How to manage postmenopausal osteoporosis?

Osteoporosis is characterized by reduced bone mass and disruption of bone architecture, resulting in increased fracture risk. Several therapeutic agents are now available to treat postmenopausal osteoporosis and prevent fractures. Combined calcium and vitamin D supplementation reduce the relative risk of non-vertebral fractures by about 18%. Hormone replacement therapy (HRT) should not be prescribed for osteoporosis in women who do not experience menopausal symptoms. The marked benefits of raloxifene on the reduction in invasive breast cancer and vertebral fracture risk are partially counterbalanced by a lack of effect on non-vertebral fracture risk, and an increased risk of venous thromboembolism and stroke. All four bisphosphonates available in Belgium, except ibandronate, have been shown to reduce the risk of vertebral, non-vertebral and hip fractures in prospective, placebo-controlled trials. Globally, the incidence of vertebral fractures is reduced by 41%-70%, and the incidence of non-vertebral fractures by 25%-39%. The anti-fracture efficacy of weekly or monthly doses of oral bisphosphonates has not been directly shown but is assumed from bridging studies based on BMD changes. To date, the various bisphosphonates have not been studied in head-to-head comparative trials with fracture endpoints. There are potential concerns that long-term suppression of bone turnover associated with bisphosphonate treatment may eventually lead to adverse effects, especially atypical femoral fractures and osteonecrosis of the jaw, but these cases are extremely rare. Teri-paratide (recombinant human 1-34 PTH) administered by daily subcutaneous injections decreases by 65% the relative risk of new vertebral fractures in patients with severe osteoporosis. Pivotal trials with strontium ranelate have shown a 41% reduction in new vertebral fractures and a 16% reduction in non-vertebral fractures over 3 years. Denosumab is a fully human monoclonal antibody to RANK Ligand that is administered as a 60-mg subcutaneous injection every 6 months. In the pivotal phase III trial, there was a 68% reduction in the incidence of new vertebral fractures, whereas the incidence of non-vertebral fractures was reduced by 20%. Several new approaches are being explored, including antibodies to sclerostin, cathepsin K inhibitors, src kinase inhibitors, and drugs that act on calcium sensing receptors.