Anabolics in osteoporosis: the emerging therapeutic tool

Abstract

Anabolic therapy for osteoporosis has become the most desirable therapeutic option for menopausal osteoporosis. The anabolic agents currently in clinical use are reviewed. Teriparatide (recombinant human 1-34 parathyroid hormone) is used to treat women with menopausal osteoporosis and men at high risk for fractures. Despite PTH's clinical use, the mechanism underlying its anabolic action requires greater elucidation. Proteol (strontium ranelate) acts by inhibiting bone resorption and presumably promoting bone formation. Though clinical trials have shown that strontium ranelate reduces the frequency of both vertebral and non-vertebral fractures, its molecular target remains controversial. Lately, with the discontinuation of estrogen replacement therapy, phytoestrogens are gaining much attention, chiefly as prophylactic agents. Though ipriflavone stimulates osteoblast function in vitro and favorably influences bone turnover and spinal bone mineral density in peri- and postmenopausal women, its clinical use is currently rather limited. As with PTH and strontium ranelate, the mode of action of ipriflavone requires much greater elucidation. Since osteoporosis therapies are long-term, safety is a major consideration. PTH has been reported to be associated with incidence of osteosarcoma and strontium ranelate with DRESS syndrome. Therefore, target-based (and osteoblast-specific) development of molecules is expected to improve the safety profile of anabolics. Calcium-sensing receptor, insulin-like growth factor-1, members of wingless tail signaling family, and sclerostin are emerging concepts in bone anabolic therapy. We will cover the preclinical development of some bone anabolic agents under active investigation.