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Prediction of Changes in Bone Mineral Density in Postmenopausal Women Treated with Once-Weekly Bisphosphonates

Massachusetts General Hospital (S.M.B.), Boston, Massachusetts 02114; University of Alabama (K.S.), Birmingham, Alabama 35294; Arthritis Associates (A.S.), Palm Harbor, Florida 34684; Merck & Co., Inc. (A.E.d.P., E.C., E.R.), North Wales, Pennsylvania 19454; and University of Pittsburgh (S.L.G.), Pittsburgh, Pennsylvania 15260

Address all correspondence and requests for reprints to: Sherri-Ann M. Burnett-Bowie, M.D., M.P.H., Instructor in Medicine, Thier 1051, Endocrine Unit, Massachusetts General Hospital, 50 Blossom Street, Boston, Massachusetts 02114. E-mail: sburnett-bowie{at}partners.org.

Background: In clinical practice, bone mineral density (BMD) determined by dual-energy x-ray absorptiometry is used to monitor response to osteoporosis therapy. However, 1 to 2 yr are usually required to assess patients’ BMD responses. The possibility of earlier indicators of a response or nonresponse to treatment, such as changes in bone turnover markers (BTMs), is of interest to physicians and patients.

Methods: In this post hoc analysis of women treated with once-weekly bisphosphonates, we examined the association of tertile percentage change from baseline in BTMs at 3 or 6 months and association of several baseline clinical characteristics with 24-month percentage change from baseline in BMD and with percentage of patients showing BMD nonresponse (defined as BMD loss at two or more of four sites) at 24 months. Multivariable analysis was performed to determine which factors were independently associated with BMD nonresponse.

Results: Patients in the tertile with the greatest decrease in each of the BTMs had the greatest mean increase in BMD and the lowest percentage of BMD nonresponders at 24 months. Several characteristics were independently associated with BMD nonresponse, including smaller 3-month reductions from baseline in serum C-terminal telopeptide of type 1 collagen, bone-specific alkaline phosphatase, and N-terminal propeptide of type 1 procollagen; younger age of menopause; a family history of osteoporosis; and higher baseline trochanteric BMD. Baseline BTMs were not predictive of 24-month BMD response to therapy. The strongest associations were for changes in BTMs with treatment.

Conclusion: In groups of patients, short-term changes in markers of bone turnover appear to be predictors of longer term BMD response and nonresponse to bisphosphonate therapy.