Osteoporosis treatment in 2005.

In the detailed review (1) by Hamdy et al, it is clear that there are many choices for osteoporosis therapy. Although ibandronate is appealing because of the availability of monthly dosing and teriparatide is potentially a good choice for the drug naive patient at very high fracture risk, two oral bisphosphonates, alendronate and risedronate, remain the mainstays of therapy for most patients. There are likely small differences between them, and there are plenty of papers to argue for one or the other. The question is, how much does it matter? If, from the Fosamax Actonel Comparison Trial, (2) alendronate increases bone density more and decreases bone turnover markers more, does this mean it lowers fracture risk more? There are studies (3) to show that after a given suppression of bone turnover markers, there is no further vertebral fracture reduction. However, there are also studies (4) showing greater fracture risk reduction with greater bone turnover marker suppression or greater increases in bone mineral density. (5)

To me, it is more important that those women (and men) who are at greatest risk for fracture be recognized and treated first. We are moving to 10-year fracture risk calculations, (6) analogous to 10-year cardiac event rates used to determine therapy for hyperlipidemia. As in the case of serum lipids, the goals will likely change with time.

How does the practicing clinician deal with the controversies of osteoporosis treatment and the moving target of identifying patients at risk? (7) And how is this done when third party payers have varying rules of eligibility for diagnostic procedures and medication use? Let us agree on treating those patients at highest risk. First, patients who suffer an osteoporotic fracture, such as a minimal trauma fracture of the spine, hip, or radius, need to be recognized and treated. There is evidence that such fracture patients are not receiving adequate diagnosis and treatment. (8) Attention to calcium and vitamin D repletion as well as use of a bisphosphonate in most cases will lower the risk of an additional fracture. Such patients should have a bone density test to follow the response to therapy. A second group of patients is those on glucocorticoid drugs, (9) especially oral glucocorticoids. These patients are at increased fracture risk after a mere 3 months of therapy with as little as 5 mg of prednisone or its equivalent. (10) Fracture incidence increases with age, so older patients, especially those with increased fall risk, also need evaluation for osteoporosis. There is good evidence (11) that elders respond well to therapy: the number needed in order to treat to prevent one fracture is actually lower in those over age 80.

Thus, rather than argue over shares of the pie, pharmaceutical companies should be helping to expand the pie: find the patients at highest risk and get them to diagnosis and therapy. There is even evidence (12) such programs that do this save money in the long run--in addition to improving morbidity and mortality associated with fracture.

References

1. Hamdy RC, Chestnut CHIII, Gass ML, et al. Review of treatment modalities for postmenopausal osteoporosis. Southern Med J 2005;98:1000-1014.

2. Rosen CJ, Hochberg MC, Bonnick SL, et al. Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study. J Bone Miner Res 2005;20:141-151.

3. Eastell R, Barton I, Hannon RA, et al. Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 2003;18:1051-1056.

4. Bauer DC, Black DM, Garnero P, et al. Change in bone turnover and hip, nonspine, and vertebral fracture in alendronate-treated women: The Fracture Intervention Trial. J Bone Miner Res 2004;19:1250-1258.

5. Hochberg MC, Ross PD, Black D, et al. Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group. Arthritis Rheum. 1999;1246-1254.

6. Kanis JA, Johnell O, Oden A, et al. Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds. Osteoporosis Int 2001;12:989-995.

7. Raisz LG. Screening for osteoporosis. N Engl J Med 2005;353:164-171.

8. Harrington JT, Broy SB, Derosa AM, et al. Hip fracture patients are not treated for osteoporosis: a call to action. Arthritis Rheum 2002;47:651-654.

9. Adler RA, Hochberg MC. Suggested guidelines for evaluation and treatment of glucocorticoid-induced osteoporosis for the Department of Veterans Affairs. Arch Intern Med 2003;163:2619-2624.

10. Van Staa TP, Leufkens HG, Abenhaim L, et al. Use of oral corticosteroids and risk of fractures. J Bone Miner Res 2000;15:993-1000.

11. Boonen S, McClung MR, Eastell R, et al. Safety and efficacy of risedronate in reducing fracture risk in osteoporotic women aged 80 and older: implications for the use of antiresorptive agents in the old and oldest old. J Am Geriatr Soc 2004;52:1832-1839.

12. Newman ED, Ayoub WT, Starkey RH, et al. Osteoporosis disease management in a rural health care population: hip fracture reduction and reduced costs in postmenopausal women after 5 years. Osteoporosis Int 2003;14:146-151.

Robert A. Adler, MD

From the McGuire VA Medical Center, Richmond, VA.

Reprint requests to Robert A. Adler, MD, Endocrinology (111-P), McGuire VA Medical Center, 1201 Broad Rock Blvd., Richmond, VA 23249. Email: [e-mail]

The opinions expressed in this editorial belong to the author and do not necessarily reflect the views of the Department of Veterans Affairs.

Accepted August 17, 2005.