Major pharmacological interventions are the bisphosphonates, strontium ranelate, selleck chemicals raloxifene, denosumab and parathyroid hormone peptides. Interventions that are approved for the prevention and treatment of osteoporosis in Europe are shown in Table 1. They are approved only for the treatment of postmenopausal osteoporosis, but alendronate,

etidronate, risedronate and zoledronic acid are also approved for the prevention and treatment of glucocorticoid-induced osteoporosis [4, 5] and alendronate, risedronate, zoledronate and teriparatide are approved for the treatment of osteoporosis in men [3, 6]. Table 1 AZD5363 Spectrum of anti-fracture efficacy of interventions approved in Europe [3]   Fracture outcome Intervention Vertebral Non-vertebral Hip Alendronate + + + Ibandronate + +a NCE Denosumab + + + Risedronate + + + Zoledronic acid + + + Raloxifene + NCE NCE Strontium ranelate + + +a Teriparatide + + NCE PTH (1–84) + NCE NCE NCE no convincing effects. PTH recombinant human parathyroid hormone aIn subsets of patients (post hoc analysis) All these

interventions have been shown to reduce Bafilomycin A1 the risk of vertebral fracture when given with calcium and vitamin D supplements. Some have been shown also to reduce the risk of non-vertebral fractures or specifically hip fractures. Of the available options, alendronate, risedronate, zoledronic acid, denosumab and strontium ranelate reduce vertebral, non-vertebral and hip fractures [7–15] (see Table 1). Sitaxentan The reduction in vertebral fracture rate has been between 50% and 70% whereas the magnitude of reduction in non-vertebral fracture, where demonstrated, has generally been smaller and in the order of 15–25%. Because of the broader spectrum of anti-fracture efficacy, these agents are generally regarded as preferred options

in the prevention of fractures in postmenopausal women. This distinction may be important because once a fracture occurs, the risk of a subsequent fracture at most common sites is increased independently of bone mineral density, and hence, an intervention that covers all major fracture sites is preferable. Notwithstanding, there have been no head-to-head studies with fracture as the primary outcome, so that direct comparison of efficacy between agents is not possible. For this reason, many treatment guidelines did not make a distinction between these agents in terms of any recommendations for their use [16–21]. Impact of generics In recent years, the situation has changed markedly because of the advent of generic bisphosphonates with a substantial decrease in price and the impact of this on cost-effectiveness. A pan-European study from 2004 estimated the cost-effectiveness of branded alendronate in nine countries [22].