Use of bisphosphonates in the treatment of osteoporosis

Objective: To describe the mechanisms of action of bisphosphonates in the treatment of osteoporosis and compare bisphosphonate therapy with other treatments. Options: The bisphosphonates, etidronate, alendronate, clodronate, pamidronate, tiludronate, ibandronate and risedronate; combined bisphosphonates and estrogen; combined bisphosphonates and calcium supplements. Outcomes: Fracture and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures and improved quality of life associated with bisphosphonate treatment. Evidence: Relevant clinical studies and reports were examined with emphasis on recent controlled trials. The availability of treatment products in Canada was also considered. Values: Reducing fractures, increasing bone mineral density and minimizing side effects of treatment were given a high value. Benefits, harms and costs: Treatment with bisphosphonates may be an acceptable alternative to ovarian hormone therapy in increasing bone mass and decreasing fractures associated with osteoporosis. Compared with estrogens, bisphosphonates are bone-tissue specific, have equal or greater antiresorptive effect and have few side effects and no known risk for carcinogenesis. They also hold promise in treating male osteoporosis and steroid-induced bone loss. Prolonged, continuous treatment with etidronate may lead to impaired calcification of newly formed bone; therefore, etidronate is administered cyclically. This risk is not present in newer generations of bisphosphonates. Recommendations: Bisphosphonate therapies may be considered as an alternative to ovarian hormone therapy in postmenopausal osteopenic or osteoporotic women who cannot or will not tolerate ovarian hormone therapy. They should also be considered in treating male osteoporosis and steroid-induced bone loss. Combination therapy with estrogen may be effective, although more research is needed. Combination therapy with calcium supplements is recommended. Bisphosphonate therapies should be restricted to postmenopausal patients with osteopenia or established osteoporosis and are not yet recommended for younger perimenopausal women as prophylaxis. Validation: These recommendations were developed by the Scientific Advisory Board of the Osteoporosis Society of Canada at its 1995 Consensus Conference. The Health Protection Branch, Canada, has approved etidronate and alendronate in the treatment of osteoporosis, and clodronate has been approved in Canada for the treatment of hypercalcemia-complicating malignancy. Sponsors: Sponsors of the 1995 conference included the Dairy Farmers of Canada, Eli Lilly Canada, Inc., Hoffmann-La Roche Canada Limited, Merck Frosst Canada Inc. and Proctor & Gamble Pharmaceuticals Canada Inc. Additional support to assist with publication was provided by Proctor and Gamble Pharmaceuticals Canada Inc.