The response to anti-resorptive therapy, which is primarily mediated through the reduction of bone turnover, depends on its effect on bone quality in addition to increase in bone mineral density. We reported in previous studies that 3 years of risedronate treatment reduced bone turnover, leading to the preservation of trabecular architecture (B. Borah et.al., Bone, 2004) and increased mineralization (E. L. Ritman et.al., CTI, 2003). These changes may have increased the bone's resistance to fracture. This study compares the long term effect of risedronate on trabecular architecture and mineralization in osteoporotic patients (n=7), using iliac crest bone biopsies taken sequentially at 0, 3 and 5 years from the same patient. The trabecular bone volume (BV/TV), and 3-D architectural parameters (connectivity density, trabecular number, thickness, separation, structure model index and marrow star volume) were measured by conventional bench-top 3-D Micro-CT at 30 micron resolution. These measurements at 5 years were not significantly different from those at 0 and 3 years, indicating a sustained preservation of trabecular architecture up to 5 years. High-resolution (4 micron) micro-CT with Synchrotron radiation provided quantitative delineation of trabecular bone with lower mineralization (<0.96 gm/cm3) from bone with higher mineralization (>0.96 gm/cm3). Risedronate significantly decreased the ratio of low to high mineralized bone, estimated by volume (BMR-V) and surface area (BMR-S), after 3 years of treatment (p< 0.05) and was consistent with the reduction of bone turnover. After 5 years of continuous treatment, BMR-V and BMR-S were significantly lower in comparison to baseline (p< 0.05), but were maintained at the 3-year level, indicating that there was no progressive increase in secondary mineralization of trabecular bone in the last 2 years of treatment. The degree of mineralization and the ratio of low to high mineralized bone in treated patients were comparable to those observed in transiliac biopsies of healthy pre-menopausal women (n=7, mean age 36 years). In conclusion, the results demonstrated that long-term risedronate treatment continues to be effective in preserving trabecular architecture, and changes mineralization to levels comparable to those found in normal healthy premenopausal women.
Disclosure Information:
Faculty Member's Name: B. Borah, PhD
Other Financial or Material Support: Employee of Procter & Gamble Pharmaceuticals
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