New studies demonstrate that bone markers are not a substitute for bone densitometry in monitoring bone.

MADISON, Wis.--(BUSINESS WIRE)--April 15, 1996--A study in the April issue of Calcified Tissue International(1) by prominent researchers at Helen Hayes Hospital examined biochemical markers following the menopause in estrogen-treated and untreated women.

Resorption markers, including urinary pyridinoline and deoxypyridinoline (such as those marketed by Metra Biosystems, MTRA), correlated nonsignificantly (r approximately -0.2) with changes of bone density in untreated women; the correlations were even lower in the estrogen-treated women. The research group, under the direction of Robert Lindsay, M.D., president of the National Osteoporosis Foundation, found "...these markers probably do not have adequate sensitivity for use as diagnostic screening tests. In keeping with the generally weak relationships between independent turnover markers and BMD change, even a combination of four turnover markers and demographic variables could predict less than half of the variance in bone loss in both the spine and hip in postmenopausal women (32-42 percent)." Moreover, the researchers found that "... for predicting bone loss in the hip, none of the biochemical variables individually was substantially better than age."

Another study sponsored by Ostex International (OSTX) was published in April(2). The Seattle researchers examined bone decreases over six months (-3.7 percent and -2.4 percent for spine and femur density, respectively) caused by a chemically-induced menopause. The decreases were several times more rapid than those produced by natural menopause, and hence should better show the ability of resorption markers to predict bone loss. In fact, the urinary marker, N-telopeptide, did correlate more highly with the decrease of bone density than is usual (r approximately -0.4 to 0.5 versus approximately -0.2). About 10 percent to 30 percent of the variance in density loss was explained by N-telopeptide levels. At three months after treatment stopped, estrogen and N-telopeptide returned to normal, yet bone density in the spine and femur was still reduced by 2.4 percent and 1.7 percent, respectively. In the latter circumstance, the N-telopeptide gave a misleading indication of bone density normalization.

"These studies confirm many earlier studies, including several studies of bisphosphonate treatment, that showed resorption markers explain 10 percent to 30 percent of the variance in bone density," stated Dr. Richard B. Mazess, president of Lunar. "It is possible but unlikely that improved urinary markers, such as the C-telopeptide (by Osteometer, a private Danish company) which was recently approved by the FDA, will alter these conclusions. Bone densitometry is well accepted and reimbursed, and is the diagnostic test for osteoporosis endorsed by the National Osteoporosis Foundation and the World Health Organization. Experts recognize that markers are not a substitute for bone density in initial diagnosis, but the monitoring issue has been open. It now appears that markers are not a substitute for bone density in monitoring. Moreover, the cost of a urinary marker test, coupled with the cost of the creatinine test needed for normalization, make the marker approach as expensive as densitometry." The American Association of Clinical Endocrinologists published their practice guidelines for osteoporosis management this month; the report emphasized bone densitometry for both diagnosis and monitoring, and did not mention biochemical markers as having a role in management of osteoporosis(3).

Lunar Corp. (NASDAQ:LUNR) is the leading manufacturer of bone densitometers worldwide.

REFERENCES

1. Cosman F, Nieves J, Wilkinson C, Schnering D, Shen V, Lindsay R. (1996) Bone density change and biochemical indices of skeletal turnover. Calcif Tissue Int 58:236-243. 2. Marshall LA, Cain DF, Dmowski WP, Chesnut CH III. (1996) Urinary N-telopeptides to monitor bone resorption while on GnRH agonist therapy. Obstet Gynecol 87:350-354. 3. American Association of Clinical Endocrinologists (1996) AACE clinical practice guidelines for the prevention and treatment of postmenopausal osteoporosis. Endocrine Practice 2:157-171.

CONTACT: LUNAR Corp., Madison

Richard B. Mazess, Ph.D., 608/274-2663