In the Fracture Intervention study, alendronate was shown to reduce the incidence of vertebral, wrist and hip fractures by approximately half in women with prevalent vertebral fractures [173–175]. In women without prevalent vertebral fractures,

there was no significant decrease in clinical fractures in the overall population, but the reduction was significant in one third of patients that had a baseline hip BMD T-score lower than −2.5 SD [176]. Risedronate in women with prevalent vertebral fractures has been shown to reduce the incidence of vertebral and non-vertebral fractures by 40–50 and 30–36 %, respectively [177, 178]. In a large population of elderly women, risedronate decreased significantly the risk of hip fractures (by 30 %), an effect that was greater in osteoporotic women aged EMD 1214063 supplier 70–79 years (−40 %), while the decrease was not significant in women over the age of Epacadostat clinical trial 80 years without documented evidence of osteoporosis [71]. Ibandronate given daily (2.5 mg) reduces the risk of vertebral fractures by 50–60 %, whereas an effect on non-vertebral fractures was only demonstrated in a post hoc analysis of women with a baseline of BMD T-score below −3 SD [179–181]. Bridging studies have shown that oral ibandronate 150 mg once monthly is equivalent or superior to

daily ibandronate in increasing BMD and decreasing biochemical markers of bone turnover, giving rise to its approval for the prevention of vertebral fracture in postmenopausal osteoporosis [182]. Similarly, bridging studies comparing intermittent intravenous

ibandronate to daily oral treatment C-X-C chemokine receptor type 7 (CXCR-7) have led to the approval of intravenous ibandronate 3 mg every 3 months for the same indication [183]. Based on the result of a phase II study [184], a large phase III trial in over 7,700 postmenopausal osteoporotic patients assessed the efficacy of yearly infusion of zoledronic acid 5 mg over 3 years. As compared to the placebo group, zoledronic acid was found to reduce the incidence of vertebral fractures by 70 % and that of hip fractures by 40 % [185], and is now available for the treatment of postmenopausal osteoporosis. Intravenous zoledronic acid has also been shown to decrease the risk of fracture and mortality when given shortly after a first hip fracture [186]. The overall safety profile of bisphosphonates is favourable. Oral bisphosphonates are associated with mild gastrointestinal disturbances, and some aminobisphosphonates (alendronate and pamidronate) can rarely cause oesophagitis. Intravenous amino-bisphosphonates can induce a transient acute-phase reaction with fever and bone and muscle pain that ameliorates or disappears after subsequent courses [187]. Osteonecrosis of the jaw has been described in cancer patients receiving high doses of intravenous pamidronate or zoledronate.