Selected annotated bibliography. (Featured CME Topic: Osteoporosis).

I. DIAGNOSIS

A. BONE MINERAL DENSITY 

* Theodorou DJ, Theodorou SJ: Dual-energy x-ray absorptiometry in clinical practice: application and interpretation of scans beyond the numbers. Clin Imaging 2002; 26:43-49

Bone mineral density measurements by dual-energy x-ray absorptiometry (DXA) may be influenced by various artifacts and pathologic processes. Accurate interpretation of the scan findings requires careful analysis of these factors. This review of the published literature includes a discussion of incidental findings that can influence bone mineral density measurements and common pitfalls of DXA scan interpretation.

* Abrahamsen B, Stilgren LS, Hermann AP, et al: Discordance between changes in bone mineral density measured at different skeletal sites in peri-menopausal women - implications for assessment of bone loss and response to therapy: The Danish Osteoporosis Prevention Study. J Bone Miner Res 2001; 16:1212-1219

* Adler RA, Funkhouser HL, Holt CM: Utility of heel ultrasound bone density in men. J Clin Densitom 2001; 4:225-230

* Alonso CG, Curiel MD, Carranza FH, et al: Femoral bone mineral density, neck-shaft angle and mean femoral neck width as predictors of hip fracture in men and women. Multicenter Project for Research in Osteoporosis. Osteoporos Int 2000; 11:714-720

* Aoki TT, Grecu EO, Srinivas PR, et al: Prevalence of osteoporosis in women: variation with skeletal site of measurement of bone mineral density. Endocr Pract 2000; 6:127-131

* Bergot C, Laval-Jeantet AM, Hutchinson K, et al: A comparison of spinal quantitative computed tomography with dual energy x-ray absorptiometry in European women with vertebral and nonvertebral fractures. Calcif Tissue Int 2001; 68:74-82

* Berntsen GK, Fonnebo V, Tollan A, et al: Forearm bone mineral density by age in 7,620 men and women: the Tromso study, a population-based study. Am J Epidemiol 2001; 153:465-473

* Blake GM, Fogelman I: Monitoring treatment for osteoporosis by using bone densitometry. Semin Nucl Med 2001; 31:212-222

* Blake GM, Herd RJ, Patel R, et al: The effect of weight change on total body dual-energy x-ray absorptiometry: results from a clinical trial. Osteoporos Int 2000; 11:832-839

* Boyanov M: Diagnostic discrepancies between two closely related forearm bone density measurement sites. J Clin Densitom 2001; 4:63-71

* Cheng S, Njeh CF, Fan B, et al: Influence of region of interest and bone size on calcaneal BMD: implications for the accuracy of quantitative ultrasound assessments at the calcaneus. Br J Radiol 2002; 75:59-68

* Coin A, Sergi G, Beninca P, et al: Bone mineral density and body composition in underweight and normal elderly subjects. Osteoporos Int 2000; 11:1043-1050

* Crandall C: The role of serial bone mineral density testing for osteoporosis. J Womens Health Gend Based Med 2001; 10:887-895

* Crandall C: When to measure BMD in patients being treated for osteoporosis. Postgrad Med 2001; 109:191-192

* Dubois EF, van den Bergh JP, Smals AG, et al: Comparison of quantitative ultrasound parameters with dual energy x-ray absorptiometry in pre- and postmenopausal women. Neth J Med 2001; 58:62-70

* Economides PA, Kaklamani VG, Karavas I, et al: Assessment of physician responses to abnormal results of bone densitometry studies. Endocr Pract 2000; 6:351-356

* Ekman A, Michaelsson K, Petren-Mallmin M, et al: DXA of the hip and heel ultrasound but not densitometry of the fingers can discriminate female hip fracture patients from controls: a comparison between four different methods. Osteoporos Int 2001; 12:185-191

* Fordham JN, Chinn DJ, Kumar N: Identification of women with reduced bone density at the lumbar spine and femoral neck using BMD at the os calcis. Osteoporos Int 2000; 11:797-802

* Gass R: The early preclinical diagnosis of osteoporosis measuring the pure trabecular bone density. Eur J Med Res 2001; 6:228-230

* Greenspan SL, von Stetten E, Emond SK, et al: Instant vertebral assessment: a noninvasive dual x-ray absorptiometry technique to avoid misclassification and clinical mismanagement of osteoporosis. J Clin Densitom 2001; 4:378-380

* Gurlek A, Baraktar M, Ariyurek M: Inappropriate reference range for peak bone mineral density in dual-energy x-ray absorptiometry: implications for the interpretation of T-scores. Osteoporos Int 2000; 11:809-813

* Henry MJ, Pasco JA, Seeman E, et al: Assessment of fracture risk: value of random population-based samples - the Geelong Osteoporosis Study. J Clin Densitom 2001; 4:283-289

* Karsh J: Diagnostic challenges in osteoporosis. indications for bone densitometry and establishing secondary causes. Can Earn Physician 2001; 47:1244-1250

* Kirchengast 5, Peterson B, Hauser G, et al: Body composition characteristics are associated with the bone density of the proximal femur end in middleand old-aged women and men. Maturitas 2001; 39:133-145

* Link TM, Vieth V, Matheis J, et al: Bone structure of the distal radius and the calcaneus vs BMD of the spine and proximal femur in the prediction of osteoporotic spine fractures. EurRadiol2002; 12:401-408

* Lu Y, Genant HK, Shepherd J, et al: Classification of osteoporosis based on bone mineral densities. J Bone Miner Res 2001; 16:901-910

* Maricic M, Chen Z: Bone densitometry. Clin Lab Med 2000; 20:469-488

* MulderJE, Michaeli D, Flaster ER, et al: Comparison of bone mineral density of the phalanges, lumbar spine, hip, and forearm for the assessment of osteoporosis in postmenopausal women. J Clin Densitom 2000; 3:373-38 1

* Nguyen TV, Center JR, Eisman JA: Association between breast cancer and bone mineral density: the Dubbo Osteoporosis Epidemiology Study. Maturitas 2000; 36:27-34

* Nolla JM, Gomez-Vaquero C, FiterJ, et al: Usefulness of bone densitometry in postmenopausal women with clinically diagnosed vertebral fractures. Ann Rheum Dis 2002; 61 :73-75

* Nordin BE, Burnet RB, Fitzgerald 5, et al: Bone densitometry in clinical practice: longitudinal measurements at three sites in postmenopausal women on five treatments. Clirnacteric 2001; 4:235-242

* Petley GW, Taylor PA, Murrills AJ, et al: An investigation of the diagnostic value of bilateral femoral neck bone mineral density measurements. Osteoporos Int 2000; 11:675-679

* Phillipov G, Seaborn CJ, Phillips PJ: Reproducibility of DXA: potential impact on serial measurements and misclassification of osteoporosis. Osteoporos Int 2001; 12:49-54

* Pouilles JM, Tremollieres FA, Martinez 5, et al: Ability of peripheral DNA measurements of the forearm to predict low axial bone mineral density at menopause. Osteoporoslnt 2001; 12:71-76

* Prevrhal S, Fuerst T, Fan B, et al: Quantitative ultrasound of the tibia depends on both cortical density and thickness. Osteaporos Int 2001; 12:28-34

* Rea JA, Li J, Blake GM, et al: Visual assessment of vertebral deformity by x-ray absorptiometry: a highly predictive method to exclude vertebral deformity. Osteoporos Int 2000; 11:660-668

* Sahota 0, Pearson D, Cawte SW, et al: Site-specific variation in the classification of osteoporosis, and the diagnostic reclassification using the lowest individual lumbar vertebra T-score compared with the L1-L4 mean, in early post-menopausal women. Osteoporos Int 2000; 11:852-857

* Sim MF, Stone M, Johansen A, et al: Cost effectiveness analysis of BMD referral for DNA using ultrasound as a selective pre-screen in a group of women with low trauma Colles' fractures. Technol Health Care 2000; 8:277-284

* Siris ES, Miller PD, Barrett-Connor E, et al: Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment. JAMA 2001; 286:2815-2822

* Wachter NJ, Augat P, Mentzel M, et al: Predictive value of bone mineral density and morphology determined by peripheral quantitative computed tomography for cancellous bone strength of the proximal femur. Bone 2001; 28:133-139

* Yao WJ, Wu CH, Wang ST, et al: Differential changes in regional bone mineral density in healthy Chinese: age-related and sex-dependent. Calcif Tissue Int 2001; 68:330-336 (Please see annotation under Special Groups - Ethnic.)

B. BONE MARKERS

* Midtby M, Magnus JH,Joakimse RM: The Tromso Study: a population-based study on the variation in bone formation markers with age, gender, anthropometry and season in both men and women. Osteoporos Int 2001; 12:835-843

Menopause, body mass and seasonal changes affect the levels of bone alkaline phosphatase (S-BAP) and osteocalcin (S-OC) bone markers, which are important bone formation factors, and should be considered in the evaluation of bone loss. In order to make proper use of these bone markers, background information on how biological factors affect the level of bone turnover markers is crucial. Researchers evaluated the variations with height, weight, age, gender, and body mass index and season on a population cohort randomized from the 1994/1995 Tromso Study (n = 528 men and 605 women, aged 25 to 74 years). In men, S-BAP displayed no change with age. However, S-OC showed a decrease up to the age of 56 years with little change. Menopause was the chief factor influencing the variations in bone marker measurements in women, with the mean level of S-OC and S-BAP increasing by 21% and 41%, respectively. In both men and women, there was a negative trend in S-OC with body mass index. A 20% change in S-BAP levels was observe d in postmenopausal women. Both S-BAP and S-OC levels varied in men in relation to the seasonal conditions of a far northern latitude.

* Fassbender WJ, Balli M, Gortz B, et al: Sex steroids, biochemical markers, bone mineral density and histomorphometry in male osteoporosis patients. In Vivo 2000; 14:611-618

* Lane NE, Sanchez S, Genant HK, et al: Short-term increases in bone turnover markers predict parathyroid hormone-induced spinal bone mineral density gains in postmenopausal women with glucocorticoid-induced osteoporosis. Osteoporos Int 2000; 11:434-442 (Please see annotation under Secondary Osteoporosis - Corticosteroid-Induced.)

* Nordin BE, Burnet RB, Fitzgerald S, et al: Bone densitometry in clinical practice: longitudinal measurements at three sites in postmenopausal women on five treatments. Climacteric 2001; 4:235-242

* Xue Y, Jia W, Zhang H, et al: Urinary cross-linked N-telopeptides of type I collagen and bone metabolic diseases. Chin Med J (Engl) 1999; 112:149-152

C. CLINICAL DIAGNOSIS

* Black DM, Steinbuch M, Palermo L, et al: An assessment tool for predicting fracture risk in postmenopausal women. Osteoporos Int 200l; 12:519-528

The FRACTURE Index is useful in the assessment of 5-year risk of hip and other osteoporotic fractures in older postmenopausal women, with or without bone mineral density (BMD) testing. It also helps clinicians identify and determine further evaluation/ treatment needs for high-risk patients and is predictive of hip, vertebral, and nonvertebral fractures. The Study of Osteoporotic Fractures (SOF) in 7,782 women [greater than or equal to]65 years of age provided data for the development of the Fracture Index, which includes these variables: age, BMD T-score, fracture after 50 years of age, maternal hip fracture after age 50 years, weight [less than or equal to] 125 pounds (57 kg), smoking status, and use of arms to stand up from a chair. Ambulatory women [greater than or equal to] 65 years of age were recruited from population-based listings in Oregon, Minnesota, Maryland, and Pennsylvania; the analysis excluded Caucasians who had a previous hip fracture or bilateral hip replacement. Mean age was 73.3 years, wi th a total hip BMD T-score of-1.5. A strong relationship exists between the FRACTURE Index and hip fracture risk, and it is shown even stronger when BMD measurement is included. Age is the most important component of the index, and higher values occur more often in older women.

Further clinical evaluation is recommended for postmenopausal women with a total score of [greater than or equal to] 6 with BMD assessment or [greater than or equal to] 4 without BMD assessment.

* Dargent-Molina P, Poitiers F, Breart G: In elderly women, weight is the best predictor of a very low bone mineral density: evidence from the EPIDOS study. Ostoporos Int 2000; 11:881-888 (Please see annotation under Pathophysiology - Weight.)

* Genant HK, Li J, Wu CY, et al: Vertebral fractures in osteoporosis: a new method for clinical assessment. J Clin Densitom 2000; 3:281-290

* Greenfield DM, Eastell R: Risk factors for ankle fracture. Osteoporos Int 2001; 12:97-103

* Guthrie JR, Dennerstein L, Wark JD: Risk factors for osteoporosis: a review. Medscape Womens Health 2000; 5:E1

* Huuskonen J, Vaisanen SB, Kroger H, et al: Determinants of bone mineral density in middle aged men: a population-based study. Osteoporos Int 2000; 11:702-708

* Melton LJ III, Khosla S, Achenbach SJ, et al: Effects of body size and skeletal site on the estimated prevalence of osteoporosis in women and men. Osteoporos Int 2000; 11:977-983

* NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy: Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285:785-795

* Russell AS, Morrison RT: An assessment of the new "SCORE" index as a predictor of osteoporosis in women. Scand J Rheumatol 2001; 30:35-39

* Smerdely P, Seller M, Smith A, et al: Predictors of bone mass in healthy older men in the community. Med J Aust 2000; 173:183-186

* Trivitayaratana W, Trivitayaratana P, Kongkiatikus S: Arm span, height and forearm bone mineral density in normal young and postmenopausal women. J Med Assoc Thai 2001; 84(suppl 2):S510-S515

* Trivitayaratana W, Trivitayaratana P: Limb measurements for height and bone mineral density estimation. J Med Assoc Thai 2001; 84 (suppl 2) :S505-S509

* van der Voort DJ, Dinant GJ, Rinkens PE, et al: Construction of an algorithm for quick detection of patients with low bone mineral density and its applicability in daily general practice. J Clin Epidemiol 2000; 53:1095-1103

* Vestergaard P, Hermann AP, Gram J, et al: Evaluation of methods for prediction of bone mineral density by clinical and biochemical variables in perimenopausal women. Maturitas 2001; 40:211-220

* Yarbrough DE, Barrett-Connor E, Morton DJ: Birth weight as a predictor of adult bone mass in postmenopausal women: the Rancho Bernardo Study. Osteoporos Int 2000; 11:626-630

* Westfall G, Littlefield R, Heaton A, et al: Methodology for identifying patients at high risk for osteoporotic fracture. Clin Ther 2001; 23:1570-1588

D. ULTRASOUND

* Knapp EM, Blake GM, Spector TD, et al: Multisite quantitative ultrasound: precision, age- and menopause-related changes, fracture discrimination, and T-score equivalence with dual-energy x-ray absorptiometry. Osteoporos Int 2001; 12:456-464

* Multisite ultrasound is an innovative and promising technique for analyzing skeletal status in the clinical setting. Researchers tested the in vitro and in vivo short- and long-term precision of a new multisite ultrasound device to determine accuracy and effectiveness in evaluating bone status. The device is capable of measuring speed of sound at the radius, tibia, phalanx and metatarsal. The ultrasound proved to be capable of differentiating between pre- and postmenopausal women and has a T-score equivalence similar to that of dual-energy x-ray absorptiometry.

* Adler RA, Funkhouser HL, Holt CM: Utility of heel ultrasound bone density in men. J Clin Densitom 2001; 4:225-230 (Please see annotation under Special Groups - Men.)

* Cetin A, Erturk H, Celiker R, et al: The role of quantitative ultrasound in predicting osteoporosis defined by dual x-ray absorptiometry. Rheumatol Int 2001; 20:55-59

* Damilakis J, Perisinakis K, Gourtsoyiannis N: Imaging ultrasonometry of the calcaneus: opotimum T-score thresholds for the identification of osteoporotic subjects. Calcif Tissue Int 2001; 68:219-224

* Drozdzowska B, Pluskiewicz W: Quantitative ultrasound at the calcaneus in premenopausal women and their postmenopausal mothers. Bone 2001; 29:79-83 (Please see annotation under Pathophysiology - Genetics.)

* Frost ML, Blake GM, Fogelman I: Quantitative ultrasound and bone mineral density are equally strongly associated with risk factors for osteoporosis. J Bone Miner Res 2001; 16:406-416

* Ingle BM, Sherwood KE, Eastell R: Comparison of two methods for measuring ultrasound properties of the heel in postmenopausal women. Osteoporos Int 2001; 12:500-505

* Jorgensen HL, Warming L, Bjarnason NH, et al: How does quantitative ultrasound compare to dual x-ray absorptiometry at various skeletal sites in relation to the WHO diagnosis categories? Clin Physiol 2001; 21:51-59

* Lin JD, Chen JF, Chang HY, et al: Evaluation of bone mineral density by quantitative ultrasound of bone in 16,862 subjects during routine health examination. Br J Radiol 2001; 74:602-606

* Montagnani A, Gonnelli S, Cepollaro C, et al: Usefulness of bone quantitative ultrasound in management of osteoporosis in men. J Clin Densitom 2001; 4:231-237

* Njeh CF, Hans D, Li J, et al: Comparison of six calcaneal quantitative ultrasound devices: precision and hip fracture discrimination. Osteoporos Int 2000; 11:1051-1062

* Ohishi T, Kushida K, Yamazaki K, et al: Ultrasound measurement using CUBA clinical system can discriminate between women with and without vertebral fractures. J Clin Densitom 2000; 3:227-231

* Vanderjagt DJ, Bond B, Dulai R, et al: Assessment of the bone status of Nigerian women by ultrasound and biochemical markers. Calcif Tissue Int 2001; 68:277-284 (Please see annotation under Special Groups - Ethnic.)

* Wear KA, Armstrong DW III: Relationships among calcaneal backscatter, attenuation, sound speed, hip bone mineral density, and age in normal adult women. J Acoust Soc Am 2001; 110:573-578

* Weiss M, Ben-Shlomo AB, Hagag P, et al: Reference database for bone speed of sound measurement by a novel quantitative multi-site ultrasound device. Osteoporos Int 2000; 11:688-696

II. MANAGEMENT -- DRUG TREATMENT

A. FDA-APPROVED MEDICATIONS FOR OSTEOPOROSIS

Alendronate (Fosamax)

* Bone HG, Greenspan SL, McKeever C, et al: Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group. J Clin Endocrinol Metab 2000; 85:720-726

The combined effect of alendronate and estrogen on bone mineral density (BMD) exceeds outcomes of either agent alone and is well tolerated among postmenopausal women. A population of 425 hysterectomized postmenopausal women participated in a 2-year clinical trial designed to determine the combined efficacy and safety of alendronate and conjugated equine estrogen (CEE). The study consisted of three treatment arms: placebo, 10 mg/day alendronate alone, or 10 mg/day alendronate combined with CEE 0.625 mg/day. All subjects received 500 mg/day calcium. Participants were randomized and a subset of subjects were selected to receive bone biopsy with histomorphometry at the end of the study. Results indicate that the placebo group displayed a mean 0.6% loss in lumbar spine BMD. The patients treated with alendronate, CEE, and alendronate with CEE showed an increase in BMD of 6.0% (P<.001 vs. placebo), 6.0% (P<.001 vs. placebo), and 8.3% (P<.001 vs. placebo and CEE; P=.022 vs. alendronate), respectively. Bone marker tur nover for the biochemicals urinary N-telopeptide of type I collagen and serum alkaline phosphatase significantly decreased in the presence of alendronate and CEE. Slightly greater decreases in bone marker levels were observed in the combined agent group (alendronate + CEE) when compared to either agent alone. Normal bone histology was shown in the subset of participants undergoing bone biopsies with a significant decrease in biochemical markers and a moderately greater decrease in the combined agent group.

* Chrischilles EA, Dasbach EJ, Rubenstein LM, et al: The effect of alendronate on fracture-related healthcare utilization and costs: the fracture intervention trial. Osteoporos Int 2001; 12:654-660

Spine, forearm and hip fractures are reduced as a result of alendronate therapy. A study involving 2,027 women aged 55 to 81 with low bone mass was conducted to determine fracture-related healthcare utilization and cost between alendronate treated patients and placebo patients. Alendronate was administered to a randomized group of patients (5 mg/day for 2 years). The control group received a placebo for 3 years. The number of patients incurring fractures and the costs thereof decreased significantly in the treated group compared to the placebo group. Fracture-related healthcare cost including treatment at emergency room, hospital, rehabilitation, or nursing home fell for the alendronate group by 25 %(P= .038). Hip-fracture related healthcare costs fell 58%, or $181 per patient (P = .036) randomized. Total fracture-related costs were 35% or $190 per patient randomized when compared to the placebo group. Associated morbidity and proportion of patients utilizing healthcare resources are reduced through the use o f alendronate therapy. Information for this study was derived from the Vertebral Fracture Arm of the Fracture Intervention Trial study.

* Downs RW Jr., Bell NH, Ettinger MP, et al: Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. J Clin Endocrinol Metab 2000; 85:1783-1788

Alendronate therapy produces significantly greater increases in bone mass and lower levels of bone marker turnover in postmenopausal women when compared to intranasal calcitonin therapy. Study subjects who were postmenopausal at least 5 years (n=299) were randomized to receive 10 mg/day alendronate, 200 IU/day intranasal calcitonin, or a placebo for 12 months. BMD measurements were assessed by dual-energy x-ray absorptiometry and biochemical markers of bone turnover were assayed. Results show that bone mass in the alendronate group relative to the calcitonin group increased by 5.16% vs 1.18% (P < .00 1) in the lumbar spine, 4.73% vs 0.47% (P < .001) in the trochanter, and 2.78% vs 0.58% (P<.001) in the femoral neck, respectively. A greater decrease in serum alkaline phosphatase and urinary N-telopeptide occurred in the alendronate group compared to the calcitonin and placebo groups. BMD slightly increased in the femoral neck of the calcitonin group relative to the placebo group, but not in the trochanter or l umbar spine. Negative effects are reported with equal frequency in all groups indicating that both alendronate and calcitonin are well tolerated among postmenopausal women. This multicenter, randomized study indicates that alendronate is effective in the treatment of osteoporosis in postmenopausal women and both calcitonin and alendronate are well tolerated.

* Lanza FL, Hunt RH, Alan B, et al: Endoscopic comparison of esophageal and gastroduodenal effects of risedronate and alendronate in postmenopausal women. Gastroenterology 2000; 119:631-638

Statistical and clinical differences between risedronate and alendronate in the incidence of adverse outcomes occur, including upper gastrointestinal events. In a comparative study to determine esophageal and gastroduodenal injury associated with risedronate and alendronate therapy, researchers recruited 515 postmenopausal women and randomly assigned them to either a risedronate group (5 mg/day), or alendronate group (10 mg/ day) for 2 weeks. At the study's endpoint, it was found by endoscopy that gastric ulcers were apparent throughout the treatment period in 9 of 221 (4.1%) evaluable risedronate subjects. Of the alendronate group, 30 of 227 (13.2%) displayed gastric ulcers (P< .001). Risedronate mean gastric endoscopy scores were lower than those in the alen dronate group (P[less than or equal to] .001). Similar endoscopic and duodenal mean scores were observed at day 8 and 15 between the two groups. Three evaluable alendronate participants were noted to have esophageal ulcers relative to none in the risedr onate group. Duodenal ulcers were observed in 1 patient treated with alendronate compared to 2 in the risedronate group. This evaluator-blinded, randomized, multi-center study was conducted at 10 sites in the US and Canada.

* Lanza F, Schwartz H, Sahba B, et al: An endoscopic comparison of the effects of alendronate and risedronate on upper gastrointestinal mucosae. Am J Gastroenterol 2000; 95:3112-3117

Risedronate and alendronate induce similar endoscopic and duodenal mean scores, even at the highest approved dosage. In a study designed to compare the upper gastrointestinal (GI) safety and tolerability of risedronate and alendronate, researchers randomized men and postmenopausal women (aged 45 to 80 years) into one of three treatment groups: placebo with aspirin 650 mg qid for the last 7 days (n = 20), alendronate 40 mg/day (n = 90), or risedronate 30 mg/day (n= 89). Following 28 days of treatment it was found through the use of endoscopy that risedronate and alendronate groups had similar mean gastric and duodenal scores. Both treated groups displayed markedly lower gastroduodenal irritation compared with the placebo/aspirin group (3% vs 60%), respectively. This multicenter, double-blind, active- and placebo-controlled study indicates that risedronate and alendronate have GI tolerability and safety profiles similar to those of a placebo.

* Lowe CE, Depew WT, Vanner SJ, et al: Upper gastrointestinal toxicity of alendronate. Am J Gastroenterol 2000; 95:634-640

Alendronate, when administered at clinically applicable doses (10 mg/day), does not produce predictable upper gastrointestinal mucosal damage. The gastric, esophageal, and duodenal mucosal tolerability of alendronate was tested in a study involving 32 healthy female volunteers (aged 40 to 65 years). Before, during and after 30 days of treatment, participants were measured for gastrointestinal permeability utilizing sucrose and mannitol/ lactulose urinary excretions. Using validated endoscopic scoring, endoscopic mucosal abnormalities in the stomach, esophagus, and duodenum were taken at baseline and after treatment. Endpoint alendronate endoscopic scores were not significantly different from those taken at baseline. After treatment, no substantial variations in mucosal permeability occurred in the stomach or small intestine. Alendronate was well tolerated among participants. These results are based on a double-blind, randomized, placebo-controlled study.

* Nevitt MC, Thompson DE, Black DM, et al: Effect of alendronate on limited-activity days and bed-disabilty days caused by back pain in postmenopausal women with existing vertebral fractures. Fracture Intervention Trial Research Group. Arch Intern Med 2000; 160:77-85

Daily activities are significantly limited for women who sustain vertebral fractures after menopause. Back pain is the chief complaint, and treatment with alendronate reduces the number of days of bed rest and days of limited activity for these patients. When a daily dosage of 5 mg alendronate sodium is administered for two years and increased to 10 mg the third year, patients have an average of 11.4 fewer days of limited activity and a reduced risk of bed rest. The risk of [greater than or equal to] 7 days of bed rest is reduced to 0.44 (95% CI = 0.30 - 0.64) and risk of [greater than or equal to] 7 limited activity days reduced to 0.87 (95% CI = 0.76 - 0.99). Results are from a three-year study of 2,027 postmenopausal women ages 55 to 81 years.

* Orwoll E, Ettinger M, Weiss S, et al: Alendronate for the treatment of osteoporosis in men. N Engl J Med 2000; 343:604-610

Alendronate significantly increases bone mineral density (BMD) and helps prevent height loss and vertebral fractures in osteoporotic men. A trial designed to test the efficacy of alendronate was conducted on osteoporotic men (n = 241; mean age, 63 years). Study data indicate men who receive 10 mg/day alendronate have a mean increase in BMD at the lumbar spine (7.1 [+ or -] 0.3), at the femoral neck (2.5% [+ or -] 0.4%), and total body (2.0% [+ or -] 0.2%) compared to baseline (P<.001, for all). Men who receive placebo experience an increase in BMD at the lumbar spine (1.8% [+ or -] 0.5%); yet no significant increase is apparent in the femoral neck or total body (P< .001 in relation to baseline BMD). BMD gains are greater, and vertebral fractures are decreased in the alendronate-treated group. Men in the alendronate group have a decrease in height of 0.6 mm compared to a 2.4 mm decrease in the placebo group. The information for this trial was derived from a multicenter, multinational, placebo-controlled, doubl e-blind study.

* Rittmaster RS, Bolognese M, Ettinger MP, et al: Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate. J Clin Endocrinol Metab 2000; 85:2129-2134

Parathyroid hormone treatment followed by alendronate therapy enhances vertebral bone density in postmenopausal osteoporotic women. A study designed to determine whether human parathyroid hormone (PTH 1-84) given in a 50, 75, or 100 [micro]g dose for 1 year followed by the bisphosphonate alendronate for 1 year could preserve or increase bone mineral density (BMD) was conducted in osteoporotic postmenopausal women (n= 66). Results indicate that changes in BMD (mean [+ or -] SD) during the first year on all subjects receiving PTH (all doses combined) were 0.3% [+ or -] 6.2 % (femoral neck), 7.1% [+ or -] 5.6% (spine), and -2.3% [+ or -] 3.3% (total body). Following 1 year of PTH, the switch to alendronate was made and the mean [+ or -] SD changes in BMD were 4.4% [+ or -] 7.2% (femoral neck), 13.4% [+ or -] 6.4% (spine), and 2.6% [+ or -] 3.1% (total body). The mean increase in vertebral BMD from the subgroup with the highest dose of PTH was 14.6% [+ or -] 7.9%. During treatment with PTH biochemical markers of bone turnover increased in all groups; however, following the 1-year treatment with alendronate bone marker levels decreased to below baseline.

* Tonino RP, Meunier PJ, Emkey R, et al: Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group. J Clin Endocrinol Metab 2000; 85:3109-3115

Long-term treatment (7 years) with the bisphosphonate alendronate (5 or 10 mg/day) as opposed to short-term treatment results in enhanced spinal bone mineral density (BMD) and discontinuation of therapy does not diminish BMD gains. An extended, double-blind, placebo-controlled study to test the efficacy of alendronate on bone mass was conducted on 235 postmenopausal women. Participants were randomized into three treatment groups: placebo, 5 mg/day alendronate, or 10 mg/day alendronate. Study data indicate that continued treatment with 10 mg/day of alendronate for 7 years results in lumbar spine BMD increases of 11.4% compared to baseline. An increase of 0.8% in BMD for the 10 mg/day group and a 0.6% gain for the 5 mg/day group is observed each additional year through the seventh year, and after the initial 18 months. Substantial increases in BMD were also observed in the period between the sixth and seventh years. Of the women previously receiving alendronate over the past five years, then were switched to a placebo, no significant decrease in BMD was observed at the hip or spine; however, decreases in BMD at the total body and forearm along with small elevations in bone marker turnover were noted. Data for this study were pooled from two nearly identical multi-center studies (US and other countries).

* Biermasz NR, Hamdy NA, Janssen YJ, et al: Additional beneficial effects of alendronate in growth hormone (GH)-deficient adults with osteoporosis receiving long-term recombinant human GH replacement therapy: a randomized controlled trial. J Clin Endocrinol Metab 2001; 86:3079-3085

Alendronate in combination with recombinant human growth hormone (rhGH) therapy increases bone mineral density (BMD) at the lumbar spine. Eighteen patients who had received rhGH for four years were randomly allocated to receive either combined rhGH and alendronate treatment or to continue with rhGH for 12 months to determine the influence on BMD measurements and bone turnover after six months. Other related parameters such as age, gender, and onset of GH deficiency were equal between groups. No changes occurred in the control group, while BMD increased and all measured parameters of bone turnover decreased in the rhGH/ alendronate group. No fractures were reported in either group. More research is needed to determine if rhGH or alendronate combined with rhGH reduces fracture risk. Statistical results are listed in the Table.

* Adachi JD, Saag KG, Delmas PD, et al: Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial. Arthritis Rheum 2001; 44:202-211

* Black DM, Thompson DE, Bauer DC, et al: Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 2000; 85:4118-4124

* Bone HG, Adami S, Rizzoli R, et al: Weekly administration of alendronate: rationale and plan for clinical assessment. Clin Ther 2000; 22:15-28

* Chavassieux PM, Arlot ME, Roux JP, et al: Effects of alendronate on bone quality and remodeling in glucocorticoid-induced osteoporosis: a histomorphometric. analysis of transiliac biopsies. J Bone Miner Res 2000; 15:754-762

* Cortet B, Bera-Louville A, Gauthier P, et al: Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. effect of adding hormone replacement therapy. Joint Bone Spine 2001; 68:410-415

* Fairney A, Kyd P, Thomas E, et al: Response to alendronate in osteoporosis after previous treatment with etidronate. Osteoporos Int 2000; 11:621-625

* Lanza F, Sahba B, Schwartz H, et al: The upper GI safety and tolerability of oral alendronate at a dose of 70 milligrams once weekly: a placebo-controlled endoscopy study. Am J Gastroenterol 2002; 97:58-64

* Leder BZ, Kronenberg HM: Gastroenterologists and choosing the right bisphosphonates. Gastroenterology 2000; 119:866-871

* Ringe JD, Faber H, Dorst A: Alendronate treatment of established primary osteoporosis in men: results of a 2-year prospective study. J Clin Endocrinol Metab 2001; 86:5252-5255

* Rossini M, Gatti D, Isaia G, et al: Effects of oral alendronate in elderly patients with osteoporosis and mild primary hyperparathyroidism. J Bone Miner Res 2001; 16:113-119

* Sahota O, Fowler I, Blackwell PJ, et al: A comparison of continuous alendronate, cyclical alendronate and cyclical etidronate with calcitriol in the treatment of postmenopausal vertebral osteoporosis: a randomized controlled trial. Osteoporos Int 2000; 11:959-966

* Watts NB, Jenkins DK, Visor JM, et al: Comparison of bone and total alkaline phosphatase and bone mineral density in postmenopausal osteoporotic women treated with alendronate. Osteoporos Int 2001; 12:279-288

* Weber TJ, Drezner MK: Effect of alendronate on bone mineral density in male idiopathic osteoporosis. Metabolism 2001; 50:912-915

* Yilmaz L, Ozoran K, Gunduz OH, et al: Alendronate in rheumatoid arthritis patients treated with methotrexate and glucocorticoids. Rheumatol Int 2001; 20:65-69

Calcitonin (Miacalcin)

* Chesnut CH III, Silverman S, Andriano K, et al: A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med 2000; 109:267-276

Salmon calcitonin nasal spray is well tolerated and reduces vertebral fracture risk in osteoporotic postmenopausal women. This 5-year, double-blind, randomized, placebo-controlled study included 1,255 postmenopausal women who were randomly allocated to receive salmon calcitonin nasal spray 100 IU, 200 IU, 400 IU daily, or placebo along with 1,000 mg calcium and 400 IU vitamin D. Compared with placebo, the 200 IU dose reduced new vertebral fracture risk by 33% (relative risk = 0.67; 95% CI = 0.47 - 0.97; P = .03). The 100 IU and 400 IU groups' risk reduction was not statistically significantly different from that of placebo. Also in the 200 IU group compared with placebo, the number of women with [greater than or equal to]2 new vertebral fractures was reduced by 35% (P .13) and the number of new vertebral fractures per 1,000 participant radiograph years was reduced by 40% (P = .02). Risk of developing new vertebral fractures was reduced by 36% in women with 1-5 prevalent vertebral fractures at baseline (RR = 0 .64; 95% CI = 0.43-0.96; P = .03) and by 45% (P = .06) in those with >1 new vertebral fracture. All groups had a 1% to 1.5% increase (P< .01) in bone mineral density (BMD) in the lumbar spine. There was no significant difference in the risk of hip fracture between placebo and calcitonin groups.

These conclusions are based on results of the Prevent Recurrence of Osteoporotic Fractures (PROOF) multi-center clinical trial. Participation criteria included white, Asian, or Hispanic postmenopausal women for [greater than or equal to]1 year, with 1 - 5 thoracic or lumbar vertebral compression fractures, BMD at the lumbar spine [greater than or equal to]2 SD below normal for 30-year-old women, and no history of hip fracture. Baseline characteristics such as age, years since menopause, body mass index, lumbar spine BMD, calcium intake, smoking history, and serum C-telopeptide levels were similar in the four groups. Follow-up was obtained at 1, 3, 6, 9,12 months and every 6 months thereafter. Definition of vertebral fractures was [greater than or equal to]3 SD reduction in any height ratio and a fracture grade of [greater than or equal to]1, with 0 being no fracture and 3 being severe fracture. Dual x-ray absorptiometry was used to measure BMD. Intention-to-treat analysis was used for incident vertebral fract ure endpoint with at least one follow-up radiograph.

* Stamato FJ, Amarante EG, Furlanetto RP: Effect of combined treatment with calcitonin on bone densitometry of patients with treated hypothyroidism. Rev Assoc Med Bras 2000; 46:177-181

* Ushiroyama T, Ikeda A, Sakai M, et al: Effects of the combined use of calcitonin and 1 alpha-hydroxy-cholecalciferol on vertebral bone loss and bone turnover in women with postmenopausal osteopenia and osteoporosis: a prospective study of long-term and continuous administration with low dose calcitonin. Maturitas 2001; 40:229-238

Calcium/Vitamin D

* Ebeling PR, Wark JD, Yeung S, et al: Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double-blind, double placebo study. J Clin Endocrinol Metab 2001; 86:4098-4103

The osteoporosis preventive effects of calcitriol in men remain unconfirmed. A 2-year double masked, double placebo-controlled study to test the efficacy of calcitriol (0.25 [micro]g twice daily or calcium 500 mg twice daily [control group]) was conducted involving 41 men previously diagnosed with primary osteoporosis. Study data indicated no variations in baseline characteristics. Femoral neck bone and spinal bone mineral density remained unchanged after 2 years in both the control/placebo group and the calcitriol group. A 30% reduction in serum osteocalcin was observed in both groups (P = .05). Only the calcium group experienced a 30% decline in urine N-telopeptide cross-links. A fractional calcium absorption increase of 34% occurred after 2 years in the calcitriol group (P < .01). Vertebral fracture incidences over the 2-year trial were similar in both groups (6 vs 1; P = .097). Calcitriol, as a single agent, remains an unconfirmed treatment for osteoporosis in men.

* Hunter D, Major P, Arden N, et al: A randomized controlled trial of vitamin D supplementation on preventing postmenopausal bone loss and modifying bone metabolism using identical twin pairs. J Bone Miner Res 2000; 15:2276-2283

Vitamin D supplementation as a single agent does not prevent osteoporosis in healthy postmenopausal women <70 years of age with normal vitamin D levels. This 2-year randomized, placebo-controlled, double-blind trial included 79 monozygotic pairs of twins ages 47 to 70 years in which baseline characteristics were similar. In each pair, one twin received 800 IU cholecalciferol/day and the other received a placebo. Serum vitamin D had increased in the treatment group at 6-month follow-up (mean [+ or -] SEM intrapair difference, 14.1 [+ or -] 2.4 [micro]g/L (P< .001), but no significant differences occurred in other serum measurements or bone markers at 3 and 6 months. Bone mineral density, which was measured at spine, hip, and heel at baseline, 12 months, 18 months, and 24 months, did not change.

* Peacock M, Liu G, Carey M, et al: Effect of calcium or 25OH vitamin [D.sub.3] dietary supplementation on bone loss at the hip in men and women over the age of 60. J Clin Endocrinol Metab 2000; 85:3011-3019

A daily calcium supplement may help prevent hip fractures in the elderly. In a 4-year study of 438 men and women with mean ages of 75.9 and 73.7, respectively, a 750 mg/day calcium supplement prevented loss of bone mineral density (BMD) and reduced femoral medullary expansion, secondary hyper-parathyroidism, and high bone turnover. A 25 (OH) vitamin [D.sub.3] supplement of 15 [micro]g/day is less effective but appears to reverse calcium insufficiency. Subjects in this trial who did not receive supplements had 2% loss of BMD at total hip and 3% femoral medulla expansion during a 4-year period.

* Eisman JA: Pharmacogenetics of the vitamin D receptor and osteoporosis. Drug Metab Dispos 2001; 29:505-512

* Ushiroyama T, Ikeda A, Sakai M, et al: Effects of the combined use of calcitonin and 1 aipha-hydroxy-cholecalciferol on vertebral bone loss and bone turnover in women with postmenopausal osteopenia and osteoporosis: a prospective study of long-term and continuous administration with low dose calcitonin. Maturitas 2001; 40:229-238

Estrogen

* Mosekilde L, Beck-Nielsen H, Sorensen OH, et al: Hormonal replacement therapy reduces forearm fracture incidence in recent postmenopausal women: results of the Danish Osteoporosis Prevention Study. Maturitas 2000; 36:181-193

Hormonal replacement therapy (HRT) is effective in primary prevention of fractures in women after menopause. Reduction in forearm fracture risk and overall fracture risk is significant when HRT regimen is properly followed. In a 5-year study of 2,016 healthy postmenopausal women 45 to 58 years of age, with 9,335.3 person years followed, 140 women had 156 fractures, with 51 forearm fractures in 51 subjects. Oral HRT treatment was administered, and 65% of subjects were compliant after 5 years. Results are as follows (RR = relative risk):

                                     Forearm fracture risk

Intention-to-treat n = 2,016         RR = 0.45 (95% CI = 0.22-0.90)
Adherence to initial allocation of   RR = 0.24 (95% CI = 0.09-0.69)
 HRT (n = 395) and no HRT (n = 977)

                                     Overall fracture risk

Intention-to-treat n = 2,016         RR = 0.73(95% CI = 0.50-1.05)
Adherence to initial allocation of   RR = 0.61 (95% CI = 0.39-0.97)
 HRT (n = 395) and no HRT (n = 977)

* Bunyavejchevin S, Limpaphayom KK: The metabolic and bone density effects of continuous combined 17-beta estradiol and noresthisterone acetate treatments in Thai postmenopausal women: a double-blind placebo-controlled trial. J Med Assoc Thai 2001; 84:45-53

* Figueras F, Castelo-Branco C, Pons F, et al: Effect of continuous and sequential oral estrogen-progestogen replacement regimens on postmenopausal bone loss: a 2-year prospective study. Eur J Obstet Gynecol Reprod Biol 2001; 99:261-265

* Heikkinen J, Vaheri R, Kainulainen P, et al: Long-term continuous combined hormone replacement therapy in the prevention of postmenopausal bone loss: a comparison of high- and low-dose estrogen-progestin regimens. Osteoporos Int 2000; 11:929-937

* Leelawattana R, Ziambaras K, Roodman-Weiss J, et al: The oxidative metabolism of estradiol conditions postmenopausal bone density and bone loss. J Bone Miner Res 2000; 15:2513-2520

* Nerhood RC: Making a decision about ERT / HRT. evidence to consider in initiating and continuing protective therapy. Postgrad Med 2001; 109:167-170, 173-174, 178

* Progetto Menopausa Italia Study Group: General and medical factors associated with hormone replacement therapy among women attending menopause clinics in Italy. Menopause 2001; 8:290-295

* Thorp JM Jr., Gavin NI, Ohsfeldt RL: Hormone replacement therapy in postmenopausal women: utilization of health care resources by new users. Am J Obstet Gynecol 2001; 185:318-326

* Villareal DT, Binder EF, Williams DB, et al: Bone mineral density response to estrogen replacement in frail elderly women: a randomized controlled trial. JAMA 2001; 286:815-820

* Watts NB, Nolan JC, Brennan JJ, et al: Esterified estrogen therapy in postmenopausal women. Relationships of bone marker changes and plasma estradiol to BMD changes: a two-year study. Menopause 2000; 7:375-382

Raloxifene (Evista)

* Cauley JA, Norton L, Lippman ME, et al: Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat 2001; 65:125-134

Four years of raloxifene treatment may reduce risk of breast cancer in women with osteoporosis. Among women receiving raloxifene, there is a 72% breast cancer risk reduction (relative risk = 0.28; 95% CI = 0.17-0.46) and 84% risk reduction of estrogen receptor-positive invasive breast cancer (RR = 0.16; 95% CI 0.09-0.30). Possible side effect is throm-boembolic disease (P .003). Results are obtained from a study of 7,705 postmenopausal, osteoporotic women with a mean age of 66.5 years at baseline.

* Yaffe K, Krueger K, Sarkar S, et al: Cognitive function in postmenopausal women treated with raloxifene. N Engl J Med 2001; 344:1207-1213

Although raloxifene, a selective estrogen-receptor modulator, does not appear to have an effect on cognitive function, it may prevent decline in verbal memory and attention skills. Postmenopausal women on raloxifene and placebos have similar scores on tests of cognitive function at baseline, six months, one year, two years, and three years. Those receiving 60 mg-120 mg raloxifene per day show less decline than the placebo group on verbal memory (relative risk = 0.77) and attention (RR = 0.87) tests. This trial included 7,478 women with osteoporosis and a mean age of 66 years living in 25 different countries.

* Bjarnason NH, Sarkar S, Duong T, et al: Six- and twelve-month changes in bone turnover are related to reduction in vertebral fracture risk during 3 years of raloxifene treatment in postmenopausal osteoporosis. Osteoporos Int 2001; 12:922-930

Risedronate (Actonel)

* Wallach S, Cohen S, Reid DM, et al: Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy. Calcif Tissue Int 2000; 67:277-285

Daily risedronate therapy significantly increases bone mineral density (BMD) and decreases the frequency of vertebral fracture in both men and women regardless of duration of corticosteroid therapy and underlying disease. In a comparative trial between two similar protocol, placebo-controlled studies, men and women (n = 518) who currently receive moderate-to-high dose corticosteroids were randomly assigned to receive 2.5 mg/day risedronate, 5 mg/day of risedronate, or a placebo for 1 year. All subjects received daily calcium supplements and most received vitamin D. Bone mineral density measurements were assessed at baseline and at follow-up. The variation in BMD measurements in the lumbar spine between the treatment groups and the placebo group was the primary endpoint. Biochemical markers of bone turnover, BMD scores at other skeletal sites, and the prevalence of vertebral fractures were also assessed. Overall, BMD mean scores increased in the lumbar spine 1.9% [+ or -] 0.38% from baseline in the 5 mg risedr onate treated group (P < .001), while the placebo group displayed a reduction in BMD (lumbar spine) from baseline 1.0% [+ or -] 0.4% (P = .005). A decrease in the trochanter, femoral neck, and distal radius occurred in the placebo group; conversely, these areas displayed either an increase or maintained their level in the 5 mg treated group. BMD at the midshaft radius did not vary significantly in either treatment group. At the 1-year follow-up, the increase in BMD in the 5 mg treatment group was significant at all skeletal sites compared to the placebo group (P < .05) except at the midshaft radius. The 2.5 mg risedronate group also displayed positive effects on BMD, yet not to the same degree as did the 5 mg group. Fracture rates declined by 70% in the 5 mg dose group as compared to the placebo group (P = .01).

* Dunn CJ, Goa KL: Risedronate: a review of its pharmacological properties and clinical use in resorptive bone disease. Drugs 2001; 61:685-712

* Harris S, Eriksen EF, Davidson M, et al: Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women. J Clin Endocrinol Metab 2001; 86:1890-1897

* Reid DM, Hughes RA, Laan RF, et al: Efficacy and safety of daily risedronate in the treatment of corti-costeroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study. J Bone Miner Res 2000; 15:1006-1013

B. NON-APPROVED MEDICATIONS FOR OSTEOPOROSIS

Etidronate

* Cortet B, Bera-Louville A, Gauthier P, et al: Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. Effect of adding hormone replacement therapy. Joint Bone Spine 2001; 68:410-415

* Crilly RG, Sebaldt RJ, Hodsman AB, et al: Predicting subsequent bone density response to intermittent cyclical therapy with etidronate from initial density response in patients with osteoporosis. Osteoporos Int 2000; 11:607-614

* Lindor KD, Jorgensen RA, Tiegs RD, et al: Etidronate for osteoporosis in primary biliary cirrhosis: a randomized trial. J Hepatol 2000; 33:878-882 (Please see annotation under Secondary Osteoporosis - Cirrhosis.)

Growth Hormone

* Gomez JM, Gomez N, Fiter J, et al: Effects of long-term treatment with GH in the bone mineral density of adults with hypopituitarism and GH deficiency and after discontinuation of GH replacement. Horm Metab Res 2000; 32:66-70

Pamidronate

* Aris RM, Lester GE, Renner JB, et al: Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation. Am J Respir Crit Care Med 2000; 162:941-946 (Please see annotation under Secondary Osteoporosis - Other Drug-Induced.)

* Diamond TH, Winters J, Smith A, et al: The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade: a double blind, randomized, placebo-controlled crossover study. Cancer 2001; 92:1444-1450

Parathyroid Hormone

* Cosman F, Nieves J, Woelfert L, et al: Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal. J Bone Miner Res 2001; 16:925-931

Parathyroid hormone (PTH) in combination with established hormone-replacement therapy (HRT) both increases and maintains bone mass and reduces the occurrence of vertebral fracture in osteoporotic women by 75%-100% one year after PTH is discontinued. Fifty-two osteoporotic women who had been on HRT for at least 2 years were randomly assigned to receive HRT alone (n = 25) or PTH (1-34) 400 U (25 [micro]g) plus HRT (n = 27) a day for 3 years. Bone mineral density (BMD), calcium homeostasis, and biochemical determinations of bone turnover were measured at baseline and every 6 months throughout the 3-year study and at the 1-year follow-up. Biochemical variables of bone marker turnover and BMD remained stable in the HRT group throughout the 3-year trial and at the 1-year follow-up. Bone marker turnover rates and BMD peaked at 6-months in the PTH-HRT group and maintained the increase at the 1-year follow-up. The percent of women suffering vertebral fractures decreased in the PTH-HRT group from 37.5% to 8.3% (using a 15% height reduction criterion) compared with women receiving HRT alone. Using a 20% reduction scale, vertebral fractures decreased from 25% to 0%. Almost all of the increase in bone mass associated with the use of PTH was maintained 1 year after discontinuation.

* Kurland ES, Cosman F, McMahon DJ, et al: Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 2000; 85:3069-3076

Lumbar spine and hip bone density increases in osteoporotic men treated with parathyroid hormone. Patients receiving 400 IU PTH (1-34) show a 13.5% increase in bone mass at the lumbar spine with no change in those who do not receive PTH (P < .001), an increase in femoral neck bone mineral density of 2.9% (P < .05), and increase in all markers of bone turnover. This 18-month trial included 23 men (30 to 68 years of age) with idiopathic osteoporosis.

* Neer RM, Arnaud CD, Zanchetta JR, et al: Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 2001; 344:1434-1441

Parathyroid hormone (PTH) lowers the risk of fractures in postmenopausal women. A daily dose of 20 [micro]g is almost as effective in increasing bone mineral density as 40 [micro]g and has fewer side effects. Although it has a greater effect on bone mineral density, the larger dose may increase risk of fracture. This study included 1,637 postmenopausal women with prior vertebral fractures randomly chosen to receive 40 [micro]g of parathyroid hormone (1-34) daily, 20 [micro]g of parathyroid hormone (1-34) daily, or a placebo. Vertebral radiographs at baseline and at 21 months revealed new vertebral fractures in 14% of the placebo group, in 5% of the 20 [micro]g PTH group, and in 4% of the 40 [micro]g PTH group. The relative risk of fracture in the 20 [micro]g group compared to the placebo group was .35 (95% CI = 0.22-0.55), and .31 (95% CI = 0.19-0.50) in the 40 [micro]g group. Rate of new nonvertebral fractures was 6% in the placebo group and 3% in the other two groups (in the 20 [micro]g group: relative risk = 0.47; 95% CI = 0.25-0.88; and in the 40 [micro]g group: relative risk = 0.46; 95% CI = 0.25-0.861). PTH 20 and 40 [micro]g increased bone mineral density by 9 and 13 percentage points in the lumbar spine, 3 and 6 percentage points in the femoral neck, respectively, and total body bone mineral by 2 to 4 percentage points more than did placebo.

* Lane NE, Sanchez S, Genant HK, et al: Short-term increases in bone turnover markers predict parathyroid hormone-induced spinal bone mineral density gains in postmenopausal women with glucocorticoid-induced osteoporosis. Osteoporos Int 2000; 11:434-442 (Please see annotation under Secondary Osteoporosis - Corticosteroid-Induced.)

* Horwitz M, Stewart A, Greenspan SL: Editorial: Sequential parathyroid hormone/alendronate therapy for osteoporosis-robbing Peter to pay Paul? J Olin Endocrinol Metab 2000; 85:2127-2128

* Sigurdsson G, Franzson L, Steingrimsdottir L, et al: The association between parathyroid hormone, vitamin D and bone mineral density in 70-year-old Icelandic women. Osteoporos Int 2000; 11:1031-1035

C. VERTEBROPLASTY/KYPHOPLASTY

* Garfin SR, Yuan HA, Reiley MA: New technologies in spine: kyphoplasty and vertebroplasty for the treatment of painful osteoporotic compression fractures. Spine 2001; 26:1511-1515

Patients who undergo kyphoplasty or vertebroplasty experience a substantial decrease in pain (95%) and a significant increase in mobility. The usefulness and acceptance rates for kyphoplasty and vertebroplasty are high. Kyphosis is improved by over 50%, and height of fractured vertebrae is increased through the percutaneous technique of kyphoplasty if the procedure is implemented within 3 months of fracture occurrence. Height is slightly increased and pain is alleviated by 95% if surgery is completed after 3 months of initial fracture diagnosis (onset of pain). Complications such as cement emboli are associated with vertebroplasty, and cement leakage has been reported in both techniques. Painful osteoporotic vertebral compression fractures that do not respond well to conventional treatments may benefit from either vertebroplasty or kyphoplasty.

* Grados F, Depriester C, Cayrolle G, et al: Long-term observations of vertebral osteoporotic fractures treated by percutaneous vertebroplasty. Rheumatology (Oxford) 2000; 39:1410-1414

Percutaneous vertebroplasty (PV) offers generally safe relief from back pain caused by vertebral fractures when maximum medical therapy has failed, although the risk of fracture around a cemented vertebra slightly increases. In this study, 40 patients with osteoporotic vertebral fracture pain received PV. Follow-up was done in 25 of those patients 17 years after treatment ended. Results were as follows:

Decrease in Pain as Assessed by Huskisson's Visual Analog Scale
(P < .05)

                             After 1 month           At end of
  Before PV treatment       of PV treatment          follow-up

80 mm [+ or -] 16 mm(SD)  37 mm [+ or -] 24 mm  34 mm [+ or -] 28 mm
Increased Risk of Vertebral Fracture

Vicinity of cemented fractured  Odds ratio = 2.27; 95% CI =
vertebra                         1.10 - 4.56
Vicinity of uncemented          Odds ratio = 1.44; 95% CI =
fractured vertebra               0.82 - 2.55

* Lieberman IH, Dudeney S, Reinhardt MK, et al: Initial outcome and efficacy of "kyphoplasty" in the treatment of painful osteoporotic vertebral compression fractures. Spine 2001; 26:1631-1638

Kyphoplasty is a safe, effective procedure for restoring vertebral height, reducing pain, and improving overall function in patients with osteoporotic fractures. Kyphoplasty is a new technique for treating vertebral compression fractures and involves the placement of inflatable bone tamps into the vertebral body. Inflation of the bone tamps increases height of the vertebral body and creates a cavity to be filled with bone cement. This Phase I study involved 70 kyphoplasty procedures in 30 patients with primary or secondary osteoporotic vertebral compression fractures. The procedures restored nearly one-half of the lost height in 70% of the vertebral bodies, with no major complications. Leakage of cement was noted in 8.6%. There was significant improvement in pain (SF-36 scores - 11.6-58.7; P = 0001) and in physical function (SF-36 scores - 11.7-47.4; P = .002).

* Watts NB, Harris ST, Genant HK: Treatment of painful osteoporotic vertebral fractures with percutaneous vertebroplasty or kyphoplasty. Osteoporos Int 2001; 12:429-437

Vertebroplasty and kyphoplasty are effective in reducing the pain of vertebral fractures, but long-term complications have not been fully investigated. Pain relief is reported in 67%-100% of cases, with some episodes of increased pain and damage from heat or pressure to the spinal cord or nerve roots. Vertebroplasty and kyphoplasty may prevent pain recurrence, and the latter restores height loss and spinal deformity in addition to improving physical function. These techniques should be considered for patients who have had vertebral fracture pain for several weeks or longer and should be performed only by experienced clinicians with high-quality equipment. Possible long-term side effects which should be determined by controlled trials include faster bone resorption and increased risk of fracture. This review includes case reports, and presentations on the use of vertebroplasty and kyphoplasty techniques in treating vertebral fractures in patients with osteoporosis.

III. PATHOPHYSIOLOGY - FACTORS AFFECTING BONE MASS

A. AGING

* Chailurkit LO, Pongchaiyakul C, Charoenkiatkul S, et al: Different mechanism of bone loss in aging women and men in Kohn Kaen Province. J Med Assoc Thai 2001; 84:1175-1182

Serum vitamin D levels remain steady with age in a group of men and women from a Khon Kaen province in Thailand. A study designed to determine the levels of biochemical markers of bone turnover and vitamin D status related to age was conducted on a population of 20- to 84-year-old women and men. Results indicate that there were no changes in levels of serum 25 hydroxyvitamin D with age in either sex. After the fourth decade, women displayed an increase in all biochemical markers of bone turnover and a sharp increase after the sixth decade, which was around the age of menopause. However, in men, all biochemical markers of bone turnover had a tendency to decrease with age, except for serum total alkaline phosphatase. A gender difference in the pathogenesis of osteoporosis was noted between men and women. No evidence of vitamin D deficiency was observed in the Khon Kaen population.

* Kado DM, Browner WS, Blackwell T, et al: Rate of bone loss is associated with mortality in older women: a prospective study. J Bone Miner Res 2000; 15:1974-1980

B. ALCOHOL

* Ganry O, Baudoin C, Fardellone P: Effect of alcohol intake on bone mineral density in elderly women: The EPIDOS Study. Epidemiologie de l'Osteoporose. Am J Epidemiol 2000; 151:773-780

Drinking one to three glasses of wine every day increases trochanteric bone mineral density in ambulatory females [greater than or equal to] 75 years of age. After adjustments for age, weight, and height, increased bone mineral density at the trochanteric site is recorded in women who drink 11 g-29 g of alcohol per day (P = .0017) but not in those who have <11 g or >30 g. Drinking >30 g/day is associated with lower total body bone mineral density (P = .047). These conclusions are based on a two-year analysis of 7,598 women with an average age of 79.9 years.

* Rapuri PB, Gallagher JC, Balhorn KE, et al: Alcohol intake and bone metabolism in elderly women. Am J Clin Nutr 2000; 72:1206-1213

C. CAFFEINE

* Conlisk AJ, Galuska DA: Is caffeine associated with bone mineral density in young adult women? Prev Med 2000; 31:562-568

Caffeine is not a risk factor for osteoporosis in young women. A study designed to test this hypothesis was conducted involving 177 healthy white women ages 19-26 years who attended a midwestern university. Utilizing self-reports, it was concluded that consumption of caffeine via coffee, decaffeinated coffee, tea, colas, chocolate products, and certain medications throughout the previous year averaged out to 99.9 mg/day per participant. Using dual-energy x-ray absorptiometry, BMD was measured at the femoral neck and the lumbar spine. Results indicate an insignificant association between caffeine intake of 100 mg/day and loss of bone mass. Femoral neck BMD decreased by 0.0069 g/[cm.sup.2] (95% CI = -0.0215 - 0.0076) and lumbar spine BMD decreased 0.0119 g/[cm.sup.2] (95% CI = -0.0271 - 0.0033). The level of calcium intake did not affect outcomes. BMD was not affected significantly by any single source of caffeine.

* Hansen SA, Folsom AR, Kushi LH, et al: Association of fractures with caffeine and alcohol in postmenopausal women: the Iowa Women's Health Study. Public Health Nutr 2000; 3:253-261

Caffeine slightly increases risk of bone fracture in females. The relative risk for combined fracture sites in postmenopausal women is 1.09 (95% CI = 0.99-1.21). Caffeine intake increases risk for wrist fracture (relative risk = 1.37; 95% CI = 1.11-1.69) but is negatively associated with upper arm fractures (RR = 0.67; 95% CI = 0.48-0.94). In this population-based sample, approximately 12.6% of subjects had at least one fracture during a six-and-a-half-year period. Results are obtained from a study of 34,703 postmenopausal women 55 to 69 years of age.

* Hegarty VM, May HM, Khaw KT: Tea drinking and bone mineral density in older women. Am J Clin Nutr 2000; 71:1003-1007

Nutrients found in tea may protect against osteoporosis in older women. Caffeine is reportedly a risk factor for osteoporosis; however, in studies conducted to support or disprove this hypothesis, caffeine is rarely subdivided into categories such as tea. Tea has naturally occurring nutrients called flavonoids, which may combat the onset of bone loss in older women. The protective effects of tea were studied in a trial involving 1,256 free living British women ages 65 to 76 years, 90.3% of which were regular tea drinkers. The remaining 122 subjects were not. Mean bone mineral density (BMD) measurements were assessed at the lumbar spine, greater trochanter, and Ward's triangle. Results indicate that tea drinkers had a significantly higher BMD level when compared to non-tea drinkers. BMD measurements for lumbar spine were 0.033 g/[cm.sup.2]; greater trochanter, 0.028 g/[cm.sup.2]; and Ward's triangle, 0.025 g/[cm.sup.2]. Evaluations of the femoral neck displayed insignificant changes in BMD overall.

* Rapuri PB, Gallagher JC, Kinyamu HK, et al: Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001; 74:694-700

D. EDUCATION

* Ribeiro V, Blakeley J, Laryea M: Women's knowledge and practices regarding the prevention and treatment of osteoporosis. Health Care Women Int 2000; 21:347-353

E. EXERCISE

* Fuchs RK, Bauer JJ, Snow CM: Jumping improves hip and lumbar spine bone mass in prepubescent children: a randomized controlled trial. J Bone Miner Res 2001; 16:148-156

Elementary school children who perform simple jumping exercises three times per week increase bone mass at the hip and spine and may reduce their risk for osteoporotic fractures later in life. Children who participate in 100 two-footed jumps off 61 cm boxes three times during their school week show more gains in bone mineral content than those performing only stretching exercises (4.5% vs 3.1% increase). In addition, bone mineral density of jumpers increases significantly at the femoral neck (1.4%; P= .085). These are results of a 7-month study of children ranging in age from 5.9 to 9.8 years.

Huuskonen J, Vaisanen SB, Kroger H, et al: Regular physical exercise and bone mineral density: a four-year controlled randomized trial in middle-aged men. The DNASCO Study. Osteoporos Int 2001; 12:349-355

In this review of the current literature, authors discuss the relationships between bone mineral density, physical exercise, and age-related changes in bone loss and cardiorespiratory fitness in middle-aged men. Potential risk factors such as alcohol, smoking, and diet are also discussed.

* Sabatini S: The female athlete triad. Am J Med Sci 2001; 322:193-195

Intervention for the disorder known as the female athlete triad requires a multidisciplinary approach, focusing on psychological counseling, limited training, and education of parents and sports officials. This syndrome of disordered eating, amenorrhea, and osteoporosis places young females at risk for Fractures, deformed growth, or osteoarthritis and may affect cardiovascular function if prolonged. Amenorrheic females have decreased bone density, which can lead to knee and wrist injuries or spondylolysis, and their risk of early osteoporosis is greater than that of the general population. Victims of the disorder include female athletes, especially gymnasts, and beauty contestants; they feel pressure from coaches, trainers, judges, and even parents to maintain a degree of thinness. As many as 15%-62% of female athletes are thought to have eating disorders, compared to 1%-3% in the general population. Treatments such as hormone replacement, oral contraceptives, estrogen, dietary calcium, bisphosphonates, and c alcitonin may not be advisable for the affected age group. This review of the published literature includes a discussion of the three aspects of this disorder (disordered eating, amenorrhea, and osteoporosis) and recommendations for therapy.

* Andreoli A, Monteleone M, Van Loan M, et al: Effects of different sports on bone density and muscle mass in highly trained athletes. Med Sci Sports Exerc 2001; 33:507-511

* Carter ND, Khan KM, Petit MA, et al: Results of a 10-week community based strength and balance training programme to reduce fall risk factors: a randomised controlled trial in 65- to 75-year-old women with osteoporosis. Br J Sports Med 2001; 35:348-351

* Chien MY, Wu YT, Hsu AT, et al: Efficacy of a 24-week aerobic exercise program for osteopenic postmenopausal women. Calcif Tissue Int 2000; 67:443-448

* Gremion G, Rizzoli R, Slosman D, et al: Oligo-amenorrheic long-distance runners may lose more bone in spine than in femur. Med Sci Sports Exerc 2001; 33:15-21

* Hagberg JM, Zmuda JM, McCole SD, et al: Moderate physical activity is associated with higher bone mineral density in postmenopausal women. J Am Geriatr Soc 2001; 49:1411-1417

* Kohrt WM: Osteoprotective benefits of exercise: more pain, less gain? J Am Geriatr Soc 2001; 49:1565-1567

* Nattiv A: Stress fractures and bone health in track and field athletes. J Sci Med Sport 2000; 3:268-279

* Snow CM, Shaw JM, Winters KM, et al: Long-term exercise using weighted vests prevents hip bone loss in postmenopausal women. J Gerontol A Biol Sci Med Sci 2000; 55: M489-M491

* Sundberg M, Gardsell P, Johnell O, et al: Peripubertal moderate exercise increases bone mass in boys but not in girls: a population-based intervention study. Osteoporos Int 2001; 12:230-238

F. GENETICS

* Drozdzowska B, Pluskiewicz W: Quantitative ultrasound at the calcaneus in premenopausal women and their postmenopausal mothers. Bone 2001; 29:79-83

The daughters of postmenopausal mothers who have experienced nontraumatic fractures may inherit osteoporosis. A study involving 48 postmenopausal women and their premenopausal daughters was conducted to determine the risk for gene-related osteoporosis. The entire group was subdivided into 2 smaller groups containing 21 postmenopausal mothers who had experienced fractures and their 21 premenopausal daughters. The second group (control group) consisted of 27 healthy postmenopausal mothers and their 27 daughters. Ultrasound values were obtained by measurements at the heel utilizing the Achilles system. The Achilles software calculates speed of sound (SOS), broadband ultrasound attenuation (BUA [dB/MHz]) and stiffness index (SI). Compared to mothers without fractures and their daughters, the SOS, BUA, and SI were significantly higher in mothers with past fractures and their daughters. Using a stepwise, multiple regression analysis both on the whole group and separately on the two subgroups, future values were cal culated in daughters. Predictive values were lower for all daughters studied (r = 0.38-0.62; P = .03-.0001; SEE = 8.8-21.5) and high for daughters of women with past fractures (r = 0.72-0.87; P = .015-.00007; SEE 6.0-15.8). Prediction was not possible for daughters of mothers without past fractures. In daughters of mothers with past fractures, heritability of ultrasound values ranged between 52% and 76%. These values decreased significantly when the whole group was evaluated (range, 14%-40%). Under the condition where there is a history of maternal past fractures, future ultrasound values can be predicted on the basis of a single ultrasound evaluation.

* Moreira Kulak CA, Schussheim DH, McMahon DJ, et al: Osteoporosis and low bone mass in premenopausal and perimenopausal women. Endocr Pract 2000; 6:296-304

Genetic predisposition may lead to osteoporosis. One hundred and eleven women referred for evaluation of osteoporosis or osteopenia participated in a study to determine their clinical, historical and biochemical features. By dual-energy x-ray absorptiometry, participants were assessed relative to biochemical and anthropomorphic characteristics and risk factors for osteoporosis. Low bone mass was seen in all subjects. Of these, 66% had identifiable causes of bone loss. Conditions related to estrogen deficiency were the most common cause, followed by anorexia nervosa and cancer chemotherapy. Prolonged use of glucocorticoids was the prominent cause for secondary osteoporosis. A group of 21 premenopausal and 17 perimenopausal women showed no identifiable cause of bone loss. Mean T-scores for the lumbar spine were -2.18 [+ or -] 1.0 premenopausal and -2.51 [+ or -] 0.6 in perimenopausal women. Forty-two percent of the premenopausal and 18% of the perimenopausal women reported nontraumatic fractures. Seventy-one pe rcent of the premenopausal and 47% of the perimenopausal women had a family history of osteoporosis. Estrogen deficiency or another secondary cause of premature bone loss (or both) is a predictor of osteopenia and osteoporosis. Of those with no identifiable cause, it is postulated that a genetic predisposition may be a factor.

* Ishida R, Ezura Y, Iwasaki H, et al: Linkage disequilibrium and haplotype analysis among four novel single-nucleotide polymorphisms in the human leukemia inhibitory factor (LIF) gene. J Hum Genet 2001; 46:557-559

* Little RD, Garulli JP, Del Mastro RG, et al: A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet 2002; 70:11-19

* Massart F, Reginster JY, Brandi ML: Genetics of menopause-associated diseases. Maturitas 2001; 40:103-116

* Nemetz A, Toth M, Garcia-Gonzalez MA, et al: Allelic variation at the interleukin 1 beta gene is associated with decreased bone mass in patients with inflammatory bowel diseases. Gut 2001; 49:644-649

G. HEALTH AND LIFESTYLE

* Mackelvie KJ, McKay HA, Khan KM, et al: Lifestyle risk factors for osteoporosis in Asian and Caucasian girls. Med Sci Sports Exerc 2001; 33:1818-1824

As they mature, Asian girls consume lower amounts of calcium and are less likely than Caucasians to engage in extracurricular sports, which places them at greater risk for osteoporosis later in life. A total of 131 Asian and Caucasian girls at two levels of maturity were the basis for this study of ethnic differences in areal bone mineral density (aBMD). Four study groups consisted of Asian Tanner breast stages I and II and Caucasian Tanner breast stages I and II. Information on food intake, physical activity, and extracurricular sports information was compiled from questionnaires. Dual x-ray absorptiometry measured fat mass, lean mass, total body aBMD, lumbar spine aBMD, proximal femur, femoral neck, and trochanter. Although aBMD was similar in the two groups of Tanner stage I, measurements of total body, proximal femur, femoral neck, and aBMD were 9%-14% lower in the Asian Tanner II group than in its Caucasian counterpart. General physical activity score was greater for Tanner I Caucasians than for Tanner I Asians (P < .05), but general physical activity was the same for all Tanner II girls. Calcium intake was lower for both groups of Asians (P < .001).

* Horton MA: Integrin antagonists as inhibitors of bone resorption: implications for treatment. Proc Nutr Soc 2001; 60:275-281

* Szulc P, Garnero P, Claustrat B, et al: Increased bone resorption in moderate smokers with low body weight: the Minos study. J Clin Endocrinol Metab 2002; 87:666-674

H. NUTRITION

* Gennari C: Calcium and vitamin D nutrition and bone disease of the elderly. Public Health Nutrition 2001; 4:547-559

In this review article, the authors discuss the clinical and epidemiological aspects of osteoporosis as well as its socioeconomic implications. They also review the relationship between calcium, vitamin D, other nutritional factors, such as vitamin K, vitamin C, phosphorus, magnesium, fluorides, copper and bone mass and fractures. The authors also discuss the RDA for calcium and vitamin D and the available sources.

* Hannan MT, Tucker KL, Dawson-Hughes B, et al: Effect of dietary protein on bone loss in elderly men and women: the Framingham Osteoporosis Study. J Bone Miner Res 2000; 15:2504-2512

Protein in the diet may help maintain bone and minimize bone loss in the elderly. This study focuses on the relationship between baseline dietary protein and change in bone mineral density over a 4-year period. When adjusted for factors such as age, weight, height, weight change, total energy intake, smoking, alcohol intake, caffeine, physical activity, calcium intake, and women's estrogen use, those individuals with lowest protein intake had the greatest bone loss. Bone loss was particularly significant at femoral and spine sites (P [less than or equal to] 04), with effects similar to 10 lb of weight. Results are based on a study of 615 men and women aged 68 to 91 years.

* Dargent-Molina P, Poitiers F, Breart G: In elderly women, weight is the best predictor of a very low bone mineral density: evidence from the EPIDOS study. Osteoporos Int 2000;11:881-888. (Please see annotation under Pathophysiology - Weight.)

* Eisman JA: Pharmacogenetics of the vitamin D receptor and osteoporosis. Drug Metab Dispos 2001; 29:505-512

* Jones G, Riley MD, Dwyer T: Maternal diet during pregnancy is associated with bone mineral density in children: a longitudinal study. Eur J Clin Nutr 2000; 54:749-756 (Please see annotation under Special Groups - Children/Adolescents.)

* Massenkeil G, Fiene C, Rosen O, et al: Loss of bone mass and vitamin D deficiency after hematopoietic stem cell transplantation: standard prophylactic measures fail to prevent osteoporosis. Leukemia 2001; 15:1701-1705

* Monge-Rojas R, Nunez HP: Dietary calcium intake by a group of 13- to 18-year-old Costa Rican teenagers. Arch Latinoam Nutr 2001; 51:127-131

* Rapuri PB, Gallagher JC, Kinyamu HK, et al: Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. Am J Clin Nutr 2001; 74:694-700

* Zhang H, Tao G, Wu Q et al: Vitamin D receptor gene polymorphism in postmenopausal women of the Han and Uygur nationalities in China. Chin Med J 2000; 113:787-789

I. ORAL CONTRACEPTIVES

* Prior JC, Kirkland SA, Joseph L, et al: Oral contraceptive use and bone mineral density in premenopausal women: cross-sectional, population-based data from the Canadian Multicentre Osteoporosis Study. CMAJ 2001; 165:1023-1029

Bone mineral density (BMD) is lower and fracture rates are increased in premenopausal women who use oral contraceptives (OCs). A sample of 524 women enrolled in the Canadian Multicentre Osteoporosis Study were assigned to either ever used OCs ([greater than or equal to]3 months) or never used (0 to <3 months) groups. Of these, (mean age, 36.3) BMD values were significantly lower in the trochanter and spine in OC users. Mean BMD rates were lower in the OC group when compared to never users (2.3%-3.7%), respectively. Spine BMD values were lower in ever users at 1.03 g/[cm.sup.2] (SD = 0.12) versus 1.07 g/[cm.sup.2] (SD = 0.12; 95% CI = -0.07 to -0.001) when compared to never users. BMD values showed no correlation between the gynecological age at first OC use or the duration of use. Past users and current users had similar BMD rates.

J. WEIGHT

* Blake GM, Herd RJ, Patel R, et al: The effect of weight change on total body dual-energy x-ray absorptiometry: results from a clinical trial. Osteoporos Int 2000; 11:832-839

Dual-energy x-ray absorptiometry (DXA) is an effective tool in evaluating treatment and follow-up of osteoporosis, and total body DXA anomalies due to weight changes can be corrected. Spine, hip, and total body scans at baseline, 1 year, and 2 years were used in this analysis of 152 postmenopausal women who received etidronate therapy or a placebo. Many of the etidronate subjects experienced weight change after 2 years, ranging from -9.3 kg to 16.8 kg. Baseline and 2-year measurements of total body bone mineral density (BMD), total body bone mineral content (BMC), and subregional values for lumbar spine, thoracic spine, pelvis, head, ribs, arms, and legs were compared. Treatment effect at 2 years was significantly different for total body BMD, total body BMC, lumbar spine, thoracic spine, and pelvis but not for head, rib, arm, or leg BMD.

* Blum M, Harris SS, Must A, et al: Weight and body mass index at menarche are associated with premenopausal bone mass. Osteoporos Int 2001; 12:588-594

Low body weight and low body mass index (BMI) at menarche may be a predictor of reduced bone mass in healthy premenopausal women (ages 40 to 45 years). A follow-up investigative study involving 119 premenopausal women was conducted to determine the association between body size during adolescence with subsequent adult bone mass. Bone mineral density (BMD) levels for the lumbar spine, femoral neck, total hip, and ultradistal radius were determined using dual-energy x-ray absorptiometry. Bone mineral density at adulthood significantly correlated with weight at menarche. Conversely, there was no correlation between adult BMD and age at menarche. Subjects with the lowest BMI at menarche displayed an 8% - 15% lower BMD when compared to those who had a higher BMI. Information for this study was derived from a growth and sexual maturation study that took place 30 years ago.

* Dargent-Molina P, Poitiers F, Breart G: In elderly women weight is the best predictor of a very low bone mineral density: evidence from the EPIDOS study. Osteoporos Int 2000; 11:881-888

Underweight elderly women have a greater risk of fractures because of low bone mineral density (BMD). Other factors predictive of low BMD include fractures after the age of 50 years, slow gait, balance impairment, low grip strength, and dependence for instrumental activities of daily living. These criteria can be used to select elderly women for bone densitometry. Results are from a study of 6,958 women [greater than or equal to] 75 years of age.

IV. HEALTH CARE COSTS AND COMPLICATIONS

A. HEALTH CARE COSTS

* Martin BC, Chishoim MA, Kotzan JA: Isolating the cost of osteoporosis-related fracture for postmenopausal women. a population-based study. Gerontology 2001; 47:21-29

Medical costs accelerate as aging populations experience osteoporotic-related health problems. Medicaid and Medicare expenditures for femur fractures in women [greater than or equal to] 50 years of age are about $3,300 each, and per-case costs for all other fractures are $1,300. Costs are highest in the month of fracture, with baseline trends returning within a year. Administrative claims of 765 Medicaid eligible women aged 50 years were analyzed at the University of Georgia in 1993. All subjects had experienced a fracture, and 226 had a femur fracture. A time series design was used to determine the economic impact of fractures.

* Oleksik A, Lips P, Dawson A, et al: Health-related quality of life in postmenopausal women with low BMD with or without prevalent vertebral fractures. J Bone Miner Res 2000; 15:1384-1392

Postmenopausal osteoporosis results in reduced quality of life, primarily due to vertebral fractures. In this study of 751 osteoporotic women with and without vertebral fractures, subjects were asked about pain, physical function, social function, general health perception, and mental function. Those with vertebral fractures were older, were more likely to experience nonvertebral fractures, and had worse quality-of-life scores than those without vertebral fractures. Quality of life was dependent on number of vertebral fractures in postmenopausal osteoporotic women.

* Rolnick SJ, Kopher R, Jackson J, et al: What is the impact of osteoporosis education and bone mineral density testing for postmenopausal women in a managed care setting? Menopause 2001; 8:141-148

Education and bone mineral density (BMD) testing encourages women to make lifestyle changes. A total of 508 postmenopausal women were randomized into 3 groups: education class on osteoporosis (n = 301), education plus BMD measurement (n = 207), or no intervention (n = 187). Utilizing [chi square] tests and logistic regression analyses, group differences based on BMD test were assessed at 6 months. Overall, 90% responded to the follow-up survey. Nine percent reported initiation of hormone replacement therapy, and >50% reported changes in exercise, diet, or calcium intake. Vitamin D intake increased by 43%, and no noticeable group difference occurred in behavior except in relation to drug therapy. Hormone replacement therapy initiation occurred three times more frequently in the BMD/education group when compared with the education only group (P = .04). Test data indicate that women who are educated regarding osteoporosis prevention are more likely to consider drug therapy and make necessary lifestyle changes.

* Chrischilles EA, Dasbach EJ, Rubenstein LM, et al: The effect of alendronate on fracture-related healthcare utilization and costs: the fracture intervention trial. Osteoporos Int 2001;12;654-660 (Please see annotation under Management/Drug Treatment - Alendronate.)

* Progetto Menopausa Italia Study Group: General and medical factors associated with hormone replacement therapy among women attending menopause clinics in Italy. Menopause 2001; 8:290-295

* Ribeiro V, Blakeley J, Laryea M: Women's knowledge and practices regarding the prevention and treatment of osteoporosis. Health Care Women Int 2000; 21:347-353

* Thorp JM Jr, Gavin NI, Ohsfeldt RL: Hormone replacement therapy in postmenopausal women: utilization of health care resources by new users. Am J Obslet Gynecol 2001; 185:318-326

B. HIP FRACTURES

* Wiktorowicz ME, Goeree R, Papaioannou A, et al: Economic implications of hip fracture: health service use, institutional care and cost in Canada. Osteoporos Int 2001; 12:271-278

C. VERTEBRAL FRACTURES

* Garfin SR, Yuan HA, Reiley MA: New technologies in spine: kyphoplasty and vertebroplasty for the treatment of painful osteoporotic compression fractures. Spine 2001; 26:1511-1515 (Please see annotation under Management/Drug Treatment - Vertebroplasty/Kyphoplasty.)

* Grados F, Depriester C, Cayrolle G, et al: Long-term observations of vertebral osteoporotic fractures treated by percutaneous vertebroplasty. Rheumatology (Oxford) 2000; 39:1410-1414 (Please see annotation under Management/Drug Treatment - Vertebroplasty/Kyphoplasty.)

* Lieberman IH, Dudeney S, Reinhardt MK, et al: Initial outcome and efficacy of "kyphoplasty" in the treatment of painful osteoporotic vertebral compression fractures. Spine 2001; 26:1631-1638 (Please see annotation under Management/Drug Treatment Vertebroplasty/Kyphoplasty.)

* Watts NB, Harris ST, Genant HK: Treatment of painful osteoporotic vertebral fractures with percutaneous vertebroplasty or kyphoplasty. Osteoporos Int 2001; 12:429-437 (Please see annotation under Management/Drug Treatment - Vertebroplasty/Kyphoplasty.)

V. SECONDARY OSTEOPOROSIS

A. ANOREXIA NERVOSA

* Grinspoon S, Thomas E, Pitts S, et al: Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa. Ann In tern Med 2000; 133:790-794

The majority of women suffering from anorexia nervosa experience low bone mineral density (BMD) levels. An analysis designed to determine the predictive factors and prevalence for regional bone loss was conducted on 130 anorexic women. Through the use of dual-energy x-ray absorptiometry, prevalence of osteopenia (-1.0 SD [greater than or equal to] T-score > -2.5 SD) and osteoporosis (T-score [less than or equal to] -2.5 SD) was 57% and 24% for the lateral spine, 50% and 13% for the anterior-posterior spine, and 47% and 16% for the total hip, respectively. BMD decreased by 2.5 SD in 38% of patients and by at least 1.0 SD in 92% of patients at one or more skeletal sites. Current estrogen replacement therapy was observed in 23% of patients and 58% were previous users of estrogen. Estrogen use was not a predictor for low BMD. Conversely, weight significantly correlated with a lowered BMD rate and may be a predictor for osteopenia. This study was conducted at a University Hospital and was part of a prospective coh ort analysis.

* Wong JC, Lewindon P, Mortimer R, et al: Bone mineral density in adolescent females with recently diagnosed anorexia nervosa. Int J Eat Disord 2001; 29:11-16

Loss of bone mass does not appear to be associated with early anorexia nervosa (AN), although adolescent females with AN are at greater risk for osteoporosis and fractures. Weight and lumbar spine bone mineral density (BMD) are related in young anorexic girls (r = 0.60; P < .005); and lean mass is related to total body BMD (r = 0.83; P < .001), total body bone mineral content (r = 0.92), lumbar spine BMD (r = 0.81), and lumbar spine bone mineral content (r = 0.92). These conclusions are based on a study of 24 adolescent females diagnosed with AN within the previous 12 months.

* Zipfel S, Seibel MJ, Lowe B, et al: Osteoporosis in eating disorders: a follow-up study of patients with anorexia and bulimia nervosa. J Clin Endocrinol Metab 2001; 86:5227-5233

Anorexia nervosa (AN) patients run a greater risk for osteoporosis than bulimia nervosa (BN) patients. A follow-up study conducted over a 3.6-year period involving 47 female patients diagnosed with eating disorders revealed that nonrecovered AN subjects, particularly of the binge eating/purging type, are at a significantly higher risk for osteoporosis when compared to other eating disorder patients. Patients were assessed at baseline (T-1), 38 (n = 24 AN; n = 14 BN) and again at follow-up (T-2) (participation rate, 80.1%). Osteopenia occurrences at T-2 for non-recovered AN patients were -1.0 SD [greater or equal to] T-score > -2.5 SD and osteoporosis (T-score [less than or equal to] -2.5 SD) at the lumbar spine were 54.2 and 20.8%, respectively. Recovering AN patients showed a slight increase in BMD. Bone resorption increases measured by urinary desoxypyridinoline were noted in AN patients when compared to a control group (n = 42) (11.4 [+ or -] 4.4 vs. 10.4 [+ or -] 7.8 [P < .001] vs. 5.6 [+ or -] 2.4 and 10 .4 [+ or -] 7.8 nM/mm creatinine [P < .05], respectively). At T-2 the best predictors for BMD at the lumbar spine were body mass and the subtype of AN ([R.sup.2] = 0.576). Except for one, all BN subjects showed bone mineral density and markers of bone turnover within the normal range. Additional therapy to prevent bone loss may be needed for AN patients, especially the binge/purge type.

* Castro J, Lazaro L, Pons F, et al: Predictors of bone mineral density reduction in adolescents with anorexia nervosa. J Am Acad Child Adolesc Psychiatry 2000; 39:1365-1370

B. OTHER DISEASES THAT MAY PREDISPOSE TO OSTEOPOROSIS

Arthritis

* El Miedany YM, Mehanna AN, El Baddini MA: Altered bone mineral metabolism in patients with osteoarthritis. Joint Bone Spine 2000; 67:521-527

* Frediani B, Allegri A, Falsetti P, et al: Bone mineral density in patients with psoriatic arthritis. J Rheumatol 2001; 28:138-143

* Kroot EJ, Nieuwenhuizen MG, de Waal Malefijt MC, et al: Change in bone mineral density in patients with rheumatoid arthritis during the first decade of the disease. Arthritis Rheum 2001; 44:1254-1260

* Njeh CF, Genant HK: Bone loss, quantitative imaging techniques for assessing bone mass in rheumatoid arthritis. Arthritis Res 2000; 2:446-450

* Sinigaglia L, Nervetti A, Mela Q, et al: A multicenter cross sectional study on bone mineral density in rheumatoid arthritis. Italian Study Group on Bone Mass in Rheumatoid Arthritis. J Rheumatol 2000; 27:2582-2589

* Solomon DH, Kuntz EM: Should postmenopausal women with rheumatoid arthritis who are starting corticosteroid treatment be screened for osteoporosis? a cost-effectiveness analysis. Arthritis Rheum 2000; 43:1967-1975

Celiac Disease 

* Arnala I, Kemppainen T, Kroger H, et al: Bone histomorphometry in celiac disease. Ann Chir Gynaecol 2001; 90:100-104

* Lemieux B, Boivin M, Brossard JH, et al: Normal parathyroid function with decreased bone mineral density in treated celiac disease. Can J Gastroenterol 2001; 15:302-307

* Meyer D, Stavropolous S, Diamond B, et al: Osteoporosis in a North American adult population with celiac disease. Am J Gastroenterol 2001; 96:112-119

* Szathmari M, Tulassay T, Arato A, et al: Bone mineral content and density in asymptomatic children with coeliac disease on a gluten-free diet. Eur J Gastroenterol Hepatol 2001; 13:419-424

Cirrhosis

* Lindor KD, Jorgensen RA, Tiegs RD, et al: Etidronate for osteoporosis in primary biliary cirrhosis: a randomized trial. J Hepatol 2000; 33:878-882

Etidronate in combination with calcium supplements does not increase bone density in primary biliary cirrhosis patients with osteoporosis. In this randomized trial, 67 patients with osteopenia (T-score <-2.0) associated with primary biliary cirrhosis either received 400 mg etidronate daily for 14 days every 3 months for at least a year and calcium on all other days, or a placebo in place of etidronate. Bone density changes were similar in all subjects. Of 60 patients completing at least a year of therapy, 8 experienced fractures, 4 of whom had received etidronate. There was a reduction in bone turnover markers in those subjects receiving etidronate, but the decreases were not correlated to bone density changes.

* Newton J, Francis R, Prince M, et al: Osteoporosis in primary biliary cirrhosis revisited. Gut 2001; 49:282-287

Crohn's Disease 

* Schoon EJ, van Nunen AB, Wouters RS, et al: Osteopenia and osteoporosis in Crohn's disease: prevalence in a Dutch population-based cohort. Scand J Gastroenterol Suppl 2000; 232:43-47

Cystic Fibrosis

* Hardin DS, Arumugam R, Seilheimer DK, et al: Normal bone mineral density in cystic fibrosis. Arch Dis Child 2001; 84:363-368

Gastrectomy 

* Heiskanen JT, Kroger H, Paakkonen M, et al: Bone mineral metabolism after total gastrectomy. Bone 2001; 28:123-127

Heart Transplantation 

* Braith RW, Howard C, Fricker FJ, et al: Glucocorticoid-induced osteopenia in adolescent heart transplant recipients. J Heart Lung Transplant 2000; 19:840-845

Hemiplegia 

* Ikai T, Uematsu M, Eun SS, et al: Prevention of secondary osteoporosis postmenopause in hemiplegia. Am J Phys Med Rehabil 2001; 80:169-174

Hemodialysis

* Fontaine MA, Albert A, Dubois B, et al: Fracture and bone mineral density in hemodialysis patients. Clin Nephrol 2000; 54:218-226

Liver Transplantation 

* Hamburg SM, Piers DA, van den Berg AP, et al:

Bone mineral density in the long term after liver transplantation. Osteoporos Int 2000;11:600-606

Paralysis

* Sabo D, Blaich S, Wenz W, et al: Osteoporosis in patients with paralysis after spinal cord injury, a cross sectional study in 46 male patients with dual-energy x-ray absorptiometry. Arch Orthop Trauma Surg 2001; 121:75-78

Premenstrual Dysphoric Disorder 

* Halbreich U, Kahn LS: Are women with premenstrual dysphoric disorder prone to osteoporosis? Psychosom Med 2001; 63:361-364

Renal Transplantation

* Kokado Y, Takahara S, Ichimaru N, et al: Factors influencing vertebral bone density after renal transplantation. Transpl Int 2000; 13(suppl 1):S431-S435

* Kusec V, Smalcelj R, Cvijetic S, et al: Determinants of reduced bone mineral density and increased bone turnover after kidney transplantation: cross-sectional study. CroatMedJ2000; 41:396-400

* Mondry A, Hetzel GR, Willers R, et al: Quantitative heel ultrasound in assessment of bone structure in renal transplant recipients. Am J Kidney Dis 2001; 37:932-937

Systemic Lupus Erythematosus 

* Lakshminarayanan S, Walsh S, Mohanraj M, et al: Factors associated with low bone mineral density in female patients with systemic lupus erythematosus. J Rheumatol 2001; 28:102-108

Thyroid Disease 

* Sijanovic S, Karner I: Borne loss in premenopausal women on long-term suppressive therapy with thyroid hormone. Medscape Womens Health 2001; 6:3

Long-term thyroxine therapy (~10 years) is a risk factor for osteopenia among premenopausal women. The effects of long-term suppressive therapy with thyroid hormone were studied using a select group of 19 premenopausal women suffering from differentiated thyroid gland carcinoma who had undergone total thyroidectomy. At the end of the 4-year trial it was indicated that bone mineral density measurements were significantly lowered and development of osteopenia by the beginning of menopause was strongly associated with long-term (~10 years) thyroxine therapy.

* Ben-Shlomo A, Hagag P, Evans S, et al: Early postmenopausal bone loss in hyperthyroidism. Maturitas 2001; 39:19-27

C. CORTICOSTEROID-INDUCED OSTEOPOROSIS

* Gudbjornsson B, Juliusson UI, Gudjonsson FV: Prevalence of long term steroid treatment and the frequency of decision making to prevent steroid induced osteoporosis in daily clinical practice. Ann Rheum Dis 2002; 61:32-36

Corticosteroids (CS) increase the risk of osteoporosis, and clinicians should provide osteoporotic prevention treatment concomitandy with long-term CS regimens. This study shows that only a few patients receive preventive treatment against CS-induced osteoporosis, although those options are available. Results are obtained from a study of 191 Icelandic hospital and healthcare center patients 17 to 93 years of age who had taken CS for at least three months a year. Twenty percent of the subjects had sustained an osteoporotic fracture, and 55% of the subjects were females. About a fourth of the patients were thought to have CS-induced osteoporosis. Nearly all (91%) regularly drank milk products, 52% took supplementary vitamin D, and 37% took calcium supplements. Less than 10% of patients took bisphosphonates, and only 22 of postmenopausal women received hormone replacement therapy. Information was gathered from medical records and questionnaires.

* Lane NE, Sanchez 5, Genant HK, et al: Short-term increases in bone turnover markers predict parathyroid hormone-induced spinal bone mineral density gains in postmenopausal women with glucocorticoid-induced osteoporosis. Osteoporos Int 2000; 11:434-442

Bone marker measurements prove, to be useful in the prediction of subsequent changes in bone mineral density (BMD) attributable to the use of parathyroid hormone fragment PTH 1-34. A study to determine the effects of PTH 1-34 and to ascertain if skeletal responders may be identified utilizing bone marker measurements on bone turnover was conducted. Forty-nine osteoporotic women with chronic inflammatory diseases who were treated with estrogen ([greater than or equal to] 1 year) and prednisone 5 to 20 mg/day ([greater than or equal to]1 year) participated in the study. Participants were randomized to a treatment group (human PTH 1-34) 400 IU/day or a control group and followed for one year. Of these, the BMD T-scores were [lesser than or equal to] -2.5 at the femoral neck or the lumbar spine. Urine and serum samples were assayed for three markers [osteocalcin (OC), bone alkaline phosphate (BAP), and deoxypyridinoline (DPD)] at baseline and again at 3-month intervals for 2 years. Results indicate that BMD of th e hip revealed insignificant change. Conversely, BMD of the spine and all three markers displayed significant augmentation as a result of PTH therapy. Bone formation surpassed resorption as explicated by the increase (P < .05) in the Uncoupling Index during the first 9 months of therapy. The majority of PTH-treated participants could be identified as biochemical responders via least significant change analysis. After one month of treatment, OC and BAP identified 81% and 65% as responders. Responder rates were 75% for DPD, 79% for BAP, and 79% for OC by 6 months.

* Reid DM, Hughes RA, Laan RF, et al: Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study. J Bone Miner Res 2000; 15:1006-1013

Risedronate reduces vertebral fractures in patients with corticosteroid-induced osteoporosis by as much as 70% after one year of treatment. Without treatment, bone mineral density (BMD) remains the same over 12 months; 5 mg risedronate per day increases BMD by 2.9% at the lumbar spine (P < .001), 1.8% at the femoral neck (P = .004), and 2.4% at the trochanter (P = .010). Subjects also received 1 g of calcium and vitamin D 400 IU daily. These conclusions are based on a 12-month study of 290 ambulatory adults who had received high-dose oral corticosteroid therapy for 6 months or longer.

* Adachi JD, Saag KG, Delmas PD, et al: Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticolds: a randomized, double-blind, placebo-controlled extension trial. Arthritis Rheum 2001; 44:202-211

* Boutsen Y, Jamart J, Esselinckx W, et al: Primary prevention of glucocorticoid-induced osteoporosis with intravenous pamidronate and calcium: a prospective controlled 1-year study comparing a single infusion, an infusion given once every 3 months, and calcium alone. J Bone Miner Res 2001; 16:104-112

* Fujita K, Kasayama S, Hashimoto J, et al: Inhaled corticosteroids reduce bone mineral density in early postmenopausal but not premenopausal asthmatic women. J Bone Miner Res 2001; 16:782-787

* Geusens P, Menten J, Vosse D, et al: Recovery from severe glucocorticoid-induced osteoporosis in an adolescent boy. J Clin Densitom 2001; 4:389-394

* Lindor KD, Jorgensen RA, Tiegs RD, et al: Etidronate for osteoporosis in primary biliary cirrhosis: a randomized trial. J Hepatol 2000; 33:878-882 (Please see annotation under Secondary Osteoporosis Cirrhosis.)

* Matsumoto H, Ishihara K, Hasegawa T, et al: Effects of inhaled corticosteroid and short courses of oral corticosteroids on bone mineral density in asthmatic patients: a 4-year longitudinal study. Chest 2001; 120:1468-1473

* Sambrook P, Raj A, Hunter D, et al: Osteoporosis with low dose corticosteroids: contribution of underlying disease effects and discriminatory ability of ultrasound versus bone densitometry. J Rheumatol 2001; 28:1063-1067

* Sivri A, Coplu L: Effect of the long-term use of inhaled corticosteroids on bone mineral density in asthmatic women. Respirology 2001; 6:131-134

* Smith MD, Cheah SP, Taylor K, et al: Prevention of corticosteroid induced osteoporosis in inpatients recently discharged from a tertiary teaching hospital. J Rheumatol 2001; 28:566-570

* Tsugeno H, Goto B, Fujita T, et al: Oral glucocorticoid-induced fall in cortical bone volume and density in postmenopausal asthmatic patients. Osteoporos: Int 2001; 12:266-270

* Wallach S, Cohen S, Reid DM, et al: Effects of risedronate treatment on bone density and vertebral fracture in patients on corticosteroid therapy. Calcif Tissue Int 2000; 67:277-285 (Please see annotation under Management/ Drug Treatment - Risedronate.)

D. OTHER DRUG-INDUCED OSTEOPOROSIS

* Aris RM, Lester GE, Renner JB, et al: Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation. Am J Respir Crit Care Med 2000; 162:941-946

Pamidronate improves bone mineral density (BMD) in cystic fibrosis (CF) patients after lung transplant. CF patients are severely affected by osteoporosis; bone loss, fractures, and kyphosis are complications of lung transplantation. A total of 34 patients participated in this 2-year controlled, randomized, nonblinded trial designed to increase BMD after lung transplant. Control subjects received vitamin D and calcium, while the treatment group received 30 mg pamidronate every 3 months along with 800 IU/day vitamin D and 1 g/day calcium. Factors such as age, sex, T-scores, renal function, hospitalization rates, immunosuppressant levels, lung function, and body mass index were similar in both groups. In the pamidronate-treated group, BMD increased 8.8% [+ or -] 2.5% in the spine and 8.2% [+ or -] 3.8% in the femur after 2 years; during the same time period control subjects gained only 2.6% [+ or -] 3.2% and 0.3% [+ or -] 2.2%, respectively (P[less than or equal to].015 for both). Fractures occurred in seven of the control group and in six of the pamidronate group (P< .2). Bone resorption was highest immediately following surgery but improved with time and pamidronate treatment. Poor postsurgical bone formation was temporary.

* Lee WY, Cho SW, Oh ES, et al: The effect of bone marrow transplantation on the osteoblastic differentiation of human bone marrow stromal cells. J Clin Endocrinol Metab 2002; 87:329-335

Bone marrow transplantation impairs the differentiation of bone marrow stromal cells into osteoblasts. Utilizing both ex vivo and clinical studies, researchers aimed to identify the mechanism and extent of bone loss after bone marrow transplantation (BMT). Bone mineral density (BMD) was measured at baseline on BMT preoperative patients and again at 1-year postoperative. Biochemical markers of bone turnover were measured periodically throughout the study. Human bone marrow cells of normal controls were measured for the ex vivo portion of the study. The origin of bone marrow stromal cells was investigated via DNA fingerprinting method. In the clinical study, 67 participants undergoing BMT were assessed and it was found that until the fourth week after BMT, the mean serum carboxy-terminal cross-linked telopeptide of type I collagen increased progressively and serum osteocalcin fell steadily until the third week postoperative and reached basal levels by 3 months. Lumbar spine BMD decreased by 3.3% (P < .05) one y ear after BMT and a decrease of 8.9% (P < .001) was noted in the total proximal femoral BMD. Seven healthy donors and seven transplant recipients gave bone marrow samples for the ex vivo study. Through the use of Von Kossa histochemistry and alkaline phosphatase histochemistry it was determined that the cultured cells were of osteoblastic lineage differentiating from marrow stromal cells. Of these, results indicate that near-confluence in the primary culture was 15 days for healthy donors and 22.9 days for recipients. Alkaline phosphatase activity was significantly higher in healthy donors than in bone marrow recipients at day 7 and at day 10 of the secondary cultures. Also, the time frame at which peak activity of alkaline phosphatase was reached was delayed in the bone forming cells derived from BMT recipients. The bone marrow stromal cells were of recipient origin and the peripheral mononuclear cells in the recipients were of donor origin according to the PCR analysis, which utilized YNZ 22 mini-satellite probe.

* McDermott AY, Shevitz A, Knox T, et al: Effect of highly active antiretroviral therapy on fat, lean, and bone mass in HIV-seropositive men and women. Am J Clin Nutr 2001; 74:679-686

Highly active antiretroviral therapy (HAART) adversely effects bone mineral density (BMD) and increases the risk for osteoporosis in HIV-positive men. Utilizing dual-energy x-ray absorptiometry, researchers compared the regional and total body composition of a population of 203 HIV-positive men and 62 HIV-positive women to define the magnitude and potential changes in body composition which are associated with HAART. After adjusting for potential confounders, results indicate that of those receiving HAART, trunk fat was higher in men (1.0 kg; P < .001) and women (1.4 kg; P= .005), and leg fat was lower in men (-1.0 kg; P< .001) and women (-1.5 kg; P < .005) than in those not receiving HAART. Total and regional BMD measurements were reduced in men receiving HAART as compared with those not receiving the treatment. BMD declined in relation to the duration of HAART indicating a dose-response relation.

* Shapiro CL, Manola J, Leboff M: Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer. J Clin Oncol 2001; 19:3306-3311

Women who develop chemotherapy-induced ovarian failure are at risk for osteoporosis. Four weeks before beginning adjuvant chemotherapy (baseline) and 6 and 12 months post therapy, 49 premenopausal women with stage I/II breast cancer were evaluated via dual-energy x-ray absorptiometry; biochemical markers of bone turnover (osteocalcin and bone-specific alkaline phosphatase) were assessed. Thirty-five of the participants were diagnosed with chemotherapy-induced ovarian failure. Of these, it was found that bone mineral density (BMD) in the spine significantly decreased at 6 months and continued to decline at 12 months. At 0 to 6 months the median percentage decrease of BMD in the spine was -4.0 (range, -10.4 to 1.0; P = .0001) at 6 to 12 months -3.7 (range, -10.1 to 9.2; P = .0001). In the patients who retained ovarian function, no decrease was noted. Women who developed ovarian failure displayed an increase in serum osteocalcin and bone specific alkaline phosphatase.

* de Bruin ED, Herzog R, Rozendal RH, et al: Estimation of geometric properties of cortical bone in spinal cord injury. Arch Phys Med Rehabil 2001; 81:150-156

* Diamond TH, Winters J, Smith A, et al: The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade: a double-blind, randomized, placebo-controlled crossover study. Cancer 2001; 92:1444-1450

* Gomez JM, Gomez N, Fiter J, et al: Effects of long-term treatment with GH in the bone mineral density of adults with hypopituitarism and GH deficiency and after discontinuation of GH replacement. Horm Metab Res 2000; 32:66-70

* Gyulai L, Bauer M, Garcia-Espana F, et al: Bone mineral density in pre-and post-menopausal women with affective disorder treated with long-term L-thyroxine augmentation. J Affect Disord 2001; 66:185-191

* Massenkeil G, Fiene C, Rosen O, et al: Loss of bone mass and vitamin D deficiency after hematopoietic stem cell transplantation: standard prophylactic measures fail to prevent osteoporosis. Leukemia 2001; 15:1701-1705

* Scherr D, Pitts WR Jr, Vaughn ED Jr: Diethylstilbesterol revisited: androgen deprivation, osteoporosis and prostate cancer. J Urol 2002; 167:535-538

VI. SPECIAL GROUPS

A. CHILDREN/ADOLESCENTS

* Jones G, Riley MD, Dwyer T: Maternal diet during pregnancy is associated with bone mineral density in children: a longitudinal study. Eur J Clin Nutr 2000; 54:749-756

There is substantial evidence that maternal diet during pregnancy affects bone mineral density (BMD) in young children. Total body, femoral neck, and lumbar spine BMD in children is positively affected by magnesium, potassium, phosphorus, and/or protein in the mother's diet while pregnant. Lumbar spine and total body BMD in children is negatively associated with in utero fat density (all P < .05). An optimal diet in the mother results in higher BMD for her child: +12% at the lumbar spine, +6.8% total body, and +5.5% at the femoral neck. Results are obtained from a 1988-1996 longitudinal bone mineralization study of 173 Tasmanian children 8 years of age. Further research is needed to determine which dietary components are most important.

* Kauffman RP, Overton TH, Shiflett M, et al: Osteoporosis in children and adolescent girls: case report of idiopathic juvenile osteoporosis and review of the literature. Obstet Cynecol Surv 2001; 56:492-504

The diagnosis and treatment of idiopathic juvenile osteoporosis (IJO) are the focus of this review of the published literature. Although this rare disease gradually improves after puberty, a number of therapeutic options may be indicated, such as activity restriction, calcium, vitamin D, and bisphosphonates. The discussion of 114 articles includes such topics as diagnosis, pathogenesis, imaging methods, laboratory evaluation, treatment, reproductive concerns, and a case report involving IJO.

* Fuchs RK, Bauer JJ, Snow CM: Jumping improves hip and lumbar spine bone mass in prepubescent children: a randomized controlled trial. J Bone Miner Res 2001; 16:148-156 (Please see annotation under Pahthophysiology - Exercise.)

* Monge-Rojas R, Nunez HP: Dietary calcium intake by a group of 13- to 18-year-old Costa Rican teenagers. Arch Latinoam Nutr 2001; 51:127-131

B. ELDERLY

* Robbins J, Hirsch C, Whitmer R, et al: The association of bone mineral density and depression in an older Population. J Am Geriatr Soc 2001; 49:732-736

C. ETHNIC GROUPS

* Vanderjagt DJ, Bond B, Dulai R, et al: Assessment of the bone status of Nigerian women by ultrasound and biochemical markers. Calcif Tissue Int 2001; 68:277-284

Bone quality decreases and bone turnover increases in postmenopausal Nigerian women similar to that of North American Caucasian women. Sub-Saharan West Africa is an area where dietary calcium intake and estrogen therapy replacement are limited. A study utilizing calcaneus and serum markers of bone turnover to examine bone quality in Nigerian women was conducted on a total of 218 women participants (110 postmenopausal and 108 premenopausal). Using broadband ultrasound attenuation and speed of sound velocity to measure the stiffness index (SI) of the calcaneus, researchers determined that Nigerian women display a marked age-dependent drop in SI explicated by the regression equation SI = 105.9 - 6.62E-3 x Age2. SI was notably correlated with serum NTx levels (r = -0.26; P < .001) and age (r = -0.41; P < .001). There was no correlation with serum concentrations of bone-specific alkaline phosphatase. SI was also significantly correlated with years since menopause (r = 0.40; P < .001). A significant decrease in SI levels occurred at least a decade before an increase in serum NTx concentrations developed. Based on US reference data, 9% of the participants had T-scores indicative of osteoporonis, and 24% had T-scores indicative of osteopenia.

* Yao WJ, Wu CH, Wang ST, et al: Differential changes in regional bone mineral density in healthy Chinese: age-related and sexdependent. Calcif Tissue mt 2001; 68:330-336

Bone mineral density (BMD) reduction is both age- and sex-related, and bone loss is three times greater in Chinese women than that of men. A study to investigate the relationship of age-related and sex-dependent BMD variations in six skeletal sectors was conducted on 697 healthy Chinese men and women (310 women, 387 men) aged 20 to 80 years. Researchers utilized dual-energy x-ray absorptiometry (DXA) to measure total-body and regional BMD. Results indicate a five-phase change in the axial bones of women. No obvious peak was observed in appendicular bones. At 50 to 54 years of age a significant bone decrease was noted in women. The overall total body bone decrease was 19.3%, 20.4% for the legs, 23.9% for the anns, 29% for the spine, 23% for the pelvis, 18.2% for the ribs and 16.4% for the head. Men displayed a maximal bone mass at 35 to 39 and 30 to 34 years old for appendicular and axial bones, respectively. An insignificant age-related bone loss in all skeletal sectors was noted, except from ages 60 to 64 an d 65 to 69 years. In each region the overall bone decrease from maximal bone mass to 70 to 80 years old was 6.7% for total body, 10.4% for legs, 7.8% for arms, 7.6% for spine, 11.3% for the pelvis, 9.5% for the ribs, and 1.7% for the head. This study data indicate that regional and age/sex dependent variations of BMD occur within the Chinese population.

* Mackelvie KJ, McKay HA, Khan KM, et al: Lifestyle risk factors for osteoporosis in Asian and Caucasian girls. Med Sci Sports Exerc 2001; 33:1818-1824 (Please see annotation under Pathophysiology - Health and Lifestyle.)

* Marquez MA, Melton LJ III, Muhs JM, et al: Bone density in an immigrant population from Southeast Asia. osteoporos Int 2001; 12:595-604

D. MEN

* Adler RA, Funkhouser HL, I-Jolt CM: Utility of heel ultrasound bone density in men. J Clin Densitom 2001; 4:225-230

* Although there is a stro.ng correlation between the spine and hip bone mineral density (BMD) by dual x-ray absorptiometry (DXA) and the heel quantitative ultrasound index, no heel T-score can be used with good sensitivity and specificity to predict osteopenia or osteoporosis in men. This study to ascertain whether a heel ultrasound measurement could accurately predict central BMD was conducted on 185 men (136 Caucasian, 1 Asian, and 48 African-American), mean age, 63 years. Researchers utilized DXA to determine BMD of the spine and hip of participants using heel US T-score predictive values for osteopenia and osteoporosis.

* Orwoll ES, Bevan L, Phipps KR: Determinants of bone mineral density in older men. Osteoporos Int 2000; 11:815-821

Alcohol, osteoarthritis, and thiazide are associated with higher bone density in men >60 years, after adjustment for weight and age. Hypertension, rheumatoid arthritis, gastrectomy, previous fracture, and age are associated with lower density. There is a scarcity of data on the determinants of bone mass in men, and this study may help identify men at risk for osteopenia. Bone mineral density was measured by dual-energy x-ray absorptiometry in this study of 355 men with a mean age of 71.5 years.

* Seeman E: Unresolved issues in osteoporosis in men. Rev Endocr Metab Disord 2001; 2:45-64

In this review article, the authors discuss the clinical and epidemiological aspects of osteoporosis in men as well as the prevalence of fracture incidence in men as compared to women. Morbidity, mortality, and cost are reviewed. Innovative treatments and the effects of antiresorptive agents, hormones, bone mass, size, and bone mineral density in men are also analyzed.

* Carlsen CG, Soerensen TH, Eriksen EF: Prevalence of low serum estradiol levels in male osteoporosis. Osteoporos Int 2000; 11:697-701

* Chailurkit LO, Pongchaiyakul C, Charoenkiatkul S, et al: Different mechanism of bone loss in aging women and men in Kohn Kaen Province. J Med Assoc Thai 2001; 84:1175-1182 (Please see annotation under Pathophysiology - Aging.)

* Daniell HW: Osteoporosis due to androgen deprivation therapy in men with prostate cancer. Urology 2001; 58:101-107

* Ebeling PR, Wark JD, Yeung S, et al: Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double blind, double placebo study. J Clin Endocrinol Metab 2001; 86:4098-4103 (Please see annotation under Management/Drug Treatment - Calcium/Vitamin D.)

* Kurland ES, Cosman F, McMahon DJ, et al: Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab 2000; 85:3069-3076 (Please see annotation under Management/Drug Treatment - Parathyroid Hormone.)

* Montagnani A, Gonnelli S, Cepollaro C, et al: Usefulness of bone quantitative ultrasound in management of osteoporosis in men. J Clin Densitom 2001; 4:231-237

* Orwoll E, Ettinger M, Weiss S, et al: Alendronate for the treatment of osteoporosis in men. N Engl J Med 2000; 343:604-610 (Please see annotation under Management/ Drug Treatment - Alendronate.)

* Pande I, O'Neill TW, Pritchard C, et al: Bone mineral density, hip axis length and risk of hip fracture in men: results from the Cornwall Hip Fracture Study. Osteoporos Int 2000; 11:866-870

* Szulc P, Munoz F, Claustrat B, et al: Bioavailable estradiol may be an important determinant of osteoporosis in men: the MINOS study. J Clin Endocrinol Metab 2001; 86:192-199

* Weber TJ, Drezner MK: Effect of alendronate on bone mineral density in male idiopathic osteoporosis. Metabolism 2001; 50:912-915

E. PREGNANCY

* Karlsson C, Obrant KJ, Karlsson M: Pregnancy and lactation confer reversible bone loss in humans. Osteoporos Int 2001; 12:828-834

Multiple pregnancies and extended lactation are not risk factors for osteoporosis. Bone mineral density (BMD) was evaluated in 73 postpartum women using dual-energy x-ray absorptiometry. The effect of lactation was measured in 65 of the delivered women and 55 age-matched women were used as controls. In 39 premenopausal women the influence of multiple pregnancies was evaluated (minimum of 4 pregnancies) with 58 premenopausal women serving as controls (maximum of 2 pregnancies). A lower lumbar spine BMD was observed in postpartum women when compared with controls (7.6% [+ or -] 0.1% and total body BMD 3.9% [+ or -] 0.1%, respectively; P < .001 for both). No significant decrease was detected in non-breast feeding mothers. Femoral neck BMD was decreased by 2.0% [+ or -] 1.0% during the first 5 months postpartum (P < .001), and no further loss was observed between 5 and 12 months postpartum. When compared to breast-feeding mothers 1 to 6 months postpartum, femoral neck BMD 12 months after delivery was 1.3% [+ or - ] 0.8% lower (P = .05). Ward's triangle BMD was decreased in mothers breast-feeding for more than 6 months by 8.5% [+ or -] 1.0%; during the first 5 months postpartum, lumbar spine BMD was lowered by 4.1% [+ or -] 0.8% (both P < .05). When compared to non-lactating women, lactating women had a BMD loss higher during the first 5 months postpartum. BMD loss differences were not observed in women with 4 pregnancies compared with women with [less than or equal to] 2 pregnancies. Results of this study indicate that pregnancy seems to confer a reversible BMD loss during the first 5 months of lactation.

* Ensom MH, Liu PY, Stephenson MD: Effect of pregnancy on bone mineral density in healthy women. Obstet Gynecol Surv 2002; 57:99-111

* Phillips AJ, Ostlere SJ, Smith R: Pregnancy-associated osteoporosis: does the skeleton recover? Osteoporos Int 2000; 11:449-454

F. PREMENOPAUSAL WOMEN

* Sijanovic S, Earner I: Bone loss in premenopausal women on long-term suppressive therapy with thyroid hormone. Medscape Womens Health 2001;6:3 (Please see annotation under Secondary Osteoporosis - Thyroid Disease.)

VII. PREVENTION

* Cleghorn DB, O'Loughlin PD, Schroeder BJ, et al: An open, crossover trial of calcium-fortified milk in prevention of early postmenopausal bone loss. Med J Aust 2001; 175:242-245

* Gallagher TC, Geling O, Comite F: Missed opportunities for prevention of osteoporotic fracture. Arch Intern Med 2002; 162-450-456

* Lunt M, Masaryk P, Scheidt-Nave C, et al: The effects of lifestyle, dietary dairy intake and diabetes on bone density and vertebral deformity prevalence: the EVOS study. Osteoporos Int 2002; 12:688-698

TABLE. rhGH/Alendronate-Treated Patients

                                              Baseline

Decrease in serum bone-specific     10.9 [micro]g/L [+ or -] 0.9
 alkaline phosphatase (P < .001)             [micro]g/L
Decrease in serum osteocalcin
 (P < .001)                         3.9 [micro]g/L [+ or -] 0.4
                                             [micro]g/L
Decrease in urinary N-telopeptide/  27.3 nmol/mmol [+ or -] 7.0
 creatinine ratio (P = .01)                  nmol/mmol

                                              6 months

Increase in lumbar spine BMD
 (P = .001)                                     3.4%
Femoral neck BMD                             no change

                                             6 months

Decrease in serum bone-specific     6.8 [micro]g/L [+ or -] 0.7
 alkaline phosphatase (P < .001)            [micro]g/L
Decrease in serum osteocalcin
 (P < .001)                         1.7 [micro]g/L [+ or -] 0.3
                                            [micro]g/L
Decrease in urinary N-telopeptide/   6.4nmol/mmol [+ or -] 0.8
 creatinine ratio (P = .01)                  nmol/mmol

                                             12 months

Increase in lumbar spine BMD
 (P = .001)                                    4.4%
Femoral neck BMD                             no change