A review of combination regimens for osteoporosis--prevention and treatment

Two long-used interventions for reducing the morbidity and mortality associated with osteoporosis are postmenopausal hormone replacement therapy (HRT) and treatment with antiresorptive agents. Postmenopausal HRT works through prevention of osteoporosis, whereas antiresorptive agents, such as the bisphosphonates, reverse low bone mass. Because of their different mechanisms, it has been thought that combining the two therapies would yield additive improvements in bone mineral density (BMD) and in fracture risk reduction. Results from several recent clinical trials in postmenopausal women with low bone mass support this idea, demonstrating clinically relevant additive improvements in BMD after treatment with HRT (or a selective estrogen receptor modulator) plus a bisphosphonate. Data regarding fracture rates after HRT and bisphosphonate combination therapy are unavailable, however. A newer osteoporosis treatment is subcutaneously injected parathyroid hormone (PTH). Treatment with PTH stimulates new bone formation, and recent studies have shown that PTH monotherapy reduces fracture rates. Initial data from studies of HRT and PTH combination therapy have shown impressive gains in BMD, but fracture rate data have not been published. Use of HRT for osteoporosis, either alone or in combination with a bisphosphonate or PTH, has become problematic since the recent report of a small number of serious adverse effects associated with HRT in the Women's Health Initiative.