The European study [61] was continued blindly in a subset of the population, and the antifracture efficacy was maintained for at least 5 years [64], the longest available double-blind fracture data for an antiresorptive. Vertebral fracture risk reduction with OSI-027 risedronate was confirmed in women over 80 with documented Anlotinib osteoporosis (RR, 0.56; 95% CI, 0.39–0.81), providing post hoc evidence that even in patients 80 years of age or older, reducing bone resorption rate remains an effective osteoporosis treatment strategy [65]. Risedronate has also been shown to decrease the incidence of hip fractures in a controlled trial specifically designed for that purpose. Hip fracture reduction was only observed in women with documented

osteoporosis, however. In this placebo-controlled study involving 5,445 women 70–79 years old who had osteoporosis and risk factors for

falls, it was shown that risedronate at 2.5 or 5 mg/day for 3 years (the actual mean duration of treatment was 2 years) lowered the RR of hip fracture by 40% (RR, 0.60; 95% CI, 0.40–0.90). There was no dose effect and, interestingly, the effect was greater in the group of women who had a vertebral fracture at baseline (RR, 0.40; 95% CI, 0.20–0.80). In the same study, however, there was no significant effect of risedronate in 3,886 women ≥80 years old (RR, 0.80; Epoxomicin in vivo 95% CI, 0.60–1.20), but these patients were essentially selected on the basis of the presence of at least one risk factor for hip fracture, such as difficulty standing from a sitting position and a poor tandem gait, rather than on the basis of low BMD or prevalent fractures [66]. The antifracture efficacy of risedronate has been confirmed in a meta-analysis [67]. The pooled RR for vertebral fractures in women given 2.5 mg or more of risedronate daily was 0.64 (95% CI, 0.54–0.77), whereas for nonvertebral fractures, it was 0.73 (95% CI, 0.61–0.87). Like alendronate, risedronate also had a safe profile in clinical trials. The safety profile of risedronate was similar to that of placebo, despite the Alanine-glyoxylate transaminase fact that unlike in the alendronate trials, patients with a history of gastrointestinal disease or chronic use of nonsteroidal

anti-inflammatory drugs were not excluded from the risedronate studies. A weekly formulation of risedronate has also been developed and, as for alendronate, has been shown to be therapeutically equivalent to the daily formulation as judged by the effects on bone density and on bone turnover [68]. The iBandronate Osteoporosis trial in North America and Europe (BONE) has been the first study to prospectively demonstrate a reduction of vertebral fracture risk on an intermittent bisphosphonate regimen [69]. A 2.5-mg daily oral ibandronate and an intermittent oral ibandronate dosage (20 mg every other day for 12 doses every 3 months) were assessed in a 3-year placebo-controlled trial including 2,946 osteoporotic women with prevalent vertebral fracture.