[Update on treatment of postmenopausal osteoporosis]

The most frequent sites of osteoporotic fractures are the vertebrae, the hip, the forearm and the proximal humerus. Drugs that inhibit bone resorption constitute the mainstay for the treatment of postmenopausal osteoporosis. A recent meta-analysis indicates that vitamin D can reduce the risk of hip fractures only if calcium supplements are also administered. The effect of hormone replacement therapy on the risk of non vertebral fractures is less clear than on vertebral fractures. Raloxifene (a SERM) reduces the rate of vertebral fractures and of breast cancer, but it does not protect against hip fracture. Bisphosphonates are the most commonly used compounds to treat postmenopausal osteoporosis. The level of evidence for currently used bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) to reduce vertebral fracture rate is maximal. Results of controlled clinical trials indicate a reduction in the risk of vertebral fractures of 40-50% and of 20-40% for non vertebral fractures, including hip fractures. However, their relative efficacy on hip fractures has been less well studied and remains more controversial. Long-term compliance of bisphosphonate therapy is improved by intermittent schemes. The most recent developpements concern the intravenous administration of ibandronate and even more of zoledronate (yearly infusions). The reduction in the rate of vertebral and hip fractures has been demonstrated in the main zoledronate trial and a prolongation of survival has been shown in the study including patients with a recent hip fracture. Whereas hyperparathyroidism is a cause of bone loss, the intermittent administration of parathyroid hormone or of its 1-34 fragment (teriparatide) exerts anabolic effects on the skeleton. The treatment is demanding and costly (daily sc injections during 18 months), requires some monitoring (serum and urinary calcium) but the results, at least for vertebral fractures, are quite favorable. Strontium ranelate is a less powerful stimulator of bone formation but it also reduces bone resorption. Its daily administration for 3 years reduces the risk of vertebral fractures and, to a lesser extent, of non vertebral fractures. Lastly, denosumab is a high affinity antibody against RANK Ligand that specifically blocks the formation and the activity of osteoclasts. The efficacy of this promising compound will soon be known.