Combining bisphosphonates with hormone therapy for postmenopausal osteoporosis

Osteoporosis affects many women after menopause. It is a major health problem, as fragility fractures create significant morbidity in this population, especially with advancing age. Available therapies include estrogens, selective estrogen receptor modulators, bisphosphonates, and calcitonin. They all inhibit bone resorption, although through different mechanisms. Several combinations of these agents have been studied in order to determine their effectiveness in comparison with monotherapy. We reviewed eight prospective randomized clinical trials of hormone therapies combined with bisphosphonates (etidronate, alendronate, and risedronate) and one study of a selective estrogen receptor modulator (raloxifene) in combination with a bisphosphonate (alendronate). Bone mineral density change at the lumbar spine was the primary endpoint of all the studies, with one or more measurements of the bone density at the femur as secondary endpoints. None of the studies had the statistical power to determine the relative reduction in fracture risk. All the studies reported greater increases in bone mineral density in patients treated with combination therapies as opposed to single agents. The bone turnover markers were also suppressed to a greater degree in the combination treatment groups, remaining however within normal premenopausal ranges. Four studies reported bone histomorphometry data, indicating no impairment of bone quality by combination therapies. The combination treatments were well tolerated in all the trials and the discontinuation rates did not vary among the groups. However, most patients will not require combination therapy. Combining bisphosphonates with hormone therapy may offer an additional benefit to women who either continue to lose bone mass despite taking estrogen or who need estrogen to control postmenopausal symptoms. The benefit of adding raloxifene to a bisphosphonate is smaller. However, it may be clinically useful if raloxifene reduces the risk of breast cancer.