Anti-Resorptive Therapy

Abstract

The goal of medical management of osteoporosis is to reduce fracture risk, preferably at all skeletal sites. The two approaches to treatment of osteoporosis are decreasing bone resorption and increasing bone formation. Currently available anti-resorptive therapies include calcium plus vitamin D, selective estrogen receptor modulators, hormone replacement therapy, bisphosphonates, RANKL antagonist denosumab, and strontium ranelate. Anti-resorptive therapy may be started in patients with a prior fragility fracture or in patients with a T-score of less than −2.5. Maintaining an adequate calcium and vitamin D intake is a standard part of the treatment of osteoporosis. Calcium is required for the bone formation phase of bone remodeling, while vitamin D is necessary for calcium absorption from the intestine. Estrogen deficiency is the most recognized risk factor for the development of osteoporosis. Hormone replacement therapy is no longer recommended as a first line therapy for the treatment of prevention of osteoporosis. Prolonged use of hormone replacement therapy, especially in elderly women, increases the risk of breast cancer, thromboembolic disease, and cerebrovascular accidents. Selective estrogen receptor modulators bind to estrogen receptors and act as agonists to decrease bone resorption and normalize bone turnover. Selective estrogen receptor modulators are predominantly prescribed to women with vertebral osteoporosis. Bisphosphonates are anti-resorptive agents which act via the inhibition of osteoclasts, leading to reduced bone turnover, increased bone mass, and improved mineralization. They are generally considered first line agents in the treatment of osteoporosis. The fracture risk reduction in postmenopausal women treated with bisphosphonates has been well documented. The most frequent complications seen are GI disturbances. Osteonecrosis of the jaw is a rare complication. Atypical subtrochanteric proximal femur fractures have also been reported in patients who have received prolonged alendronate treatment. Denosumab is the first biologic agent for the treatment of osteoporosis. Denosumab is a monoclonal antibody that binds to and neutralizes the activity of RANKL, thereby inhibiting osteoclastogenesis. Its effectiveness and biannual administration make it a promising anti-resorptive agent. Strontium ranelate is a newer treatment for postmenopausal osteoporosis, which reduces both the risk of vertebral as well as non-vertebral fractures. It is the first medication that simultaneously increases bone formation as well as decreases bone resorption. There is a great interest and clinical need for developing new therapeutic targets for the treatment of osteoporosis.