while maintaining the benefit to bone. The SERM raloxifene is approved for treatment of osteoporosis. Like tamoxifen, raloxifene reduces the risk of breast cancer. It protects against spine fractures but not hip fractures—unlike bisphosphonates, denosumab, and teriparatide, which protect against both. Raloxifene does not prevent hot flushes and imposes the same increased risk of venous thromboembolism as estrogen. To counter the reduced intestinal calcium transport associated with osteoporosis, vitamin D therapy is often used in combination with dietary calcium supplementation. In several large studies, vitamin D supplementation (800 IU/d) with calcium has been shown to improve bone density, reduce falls, and prevent fractures, although calcium and vitamin D are generally used as supplements with other drugs in the treatment of osteoporosis. Calcitriol and its analog, 1α(OH)D3, have also been shown to increase bone mass and reduce fractures. Use of these agents for osteoporosis is not FDA-approved, although they are used for this purpose in other countries. The 1,25(OH)2D analog eldecalcitol is approved for use in Japan, largely replacing the use of 1α( OH)D3.
Teriparatide, the recombinant form of PTH 1-34, is approved for treatment of osteoporosis. It is given in a dosage of 20 mcg subcutaneously daily. Teriparatide stimulates new bone formation, but unlike fluoride, this new bone appears structurally normal and is associated with a substantial reduction in the incidence of fractures. The drug is approved for only 2 years of use. Trials examining the sequential use of teriparatide followed by a bisphosphonate after 1 or 2 years are in progress and look promising. Use of the drug with a bisphosphonate has not shown greater efficacy than the bisphosphonate alone, although recent trials with the concomitant use of teriparatide and denosumab show promise.
Calcitonin is approved for use in the treatment of postmenopausal osteoporosis. It has been shown to increase bone mass and reduce fractures, but only in the spine. It does not appear to be as effective as bisphosphonates or teriparatide.
Denosumab, the RANKL inhibitor, is of comparable efficacy to bisphosphonates in the treatment of postmenopausal osteoporosis. It is given subcutaneously every 6 months in 60-mg doses. Like the bisphosphonates it suppresses bone resorption and secondarily bone formation. Denosumab reduces the risk of both vertebral and nonvertebral fractures with comparable effectiveness to the potent bisphosphonates.
Strontium ranelate has not been approved in the United States for the treatment of osteoporosis but is being used in Europe, generally at a dose of 2 g/d.