Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women

Both hormone replacement therapy (HRT) and bisphosphonates are efficacious in the prevention and treatment of postmenopausal osteoporosis. Combined th erapy with bisphosphonate and HRT is likely to be used in clinical practice , and limited data are available regarding its efficacy and safety. This was a 1-yr, double blind, placebo-controlled study in which 524 postme nopausal women received daily treatment with conjugated equine estrogens (0 .625 mg) alone or in combination with risedronate (5 mg). Women who had not undergone hysterectomy received medroxyprogesterone acetate (up to 5 mg, d aily or cyclically) at the discretion of the investigator. The primary effi cacy end point was the percent change from baseline in mean lumbar spine bo ne mineral density (BMD) at 1 yr. Changes in BMD at the proximal femur and forearm, bone turnover markers, and histology and histomorphometry were als o assessed. At 12 months, significant (P < 0.05) increases from baseline in lumbar spin e BMD were observed in both treatment groups (HRT-only, 4.6%; combined rise dronate-HRT, 5.2%); the difference between the two groups was not statistic ally significant. Both therapies led to significant increases in BMD at 12 months at the femoral neck (1.8% and 2.7%, respectively), femoral trochante r (3.2% and 3.7%), distal radius (1.7% and 1.6%), and midshaft radius (0.4% and 0.7%). The differences between groups were statistically significant ( P < 0.05) at the femoral neck and midshaft radius. Both combined risedronat e-HRT and HRT-only produced significant decreases in the biochemical marker s of bone turnover, with somewhat greater decreases in the combined treatme nt group. Bone biopsy data showed normal bone structure and normal minerali zation with either treatment. Expected decreases in bone turnover were obse rved and were greater in the combined treatment group (68-79% reduction rel ative to baseline values, P < 0.005). Overall, combined treatment had a saf ety profile similar to that of HRT-only, including bone and gastrointestina l safety profiles. In conclusion, the combined treatment with risedronate and HRT had a favora ble effect on BMD similar to that of HRT alone at the lumbar spine and slig htly, but significantly, greater than that of HRT alone at the femoral neck and midshaft radius. The combined treatment was well tolerated, and there were no adverse effects on the skeleton.