After 1 year, the incidence

of proportion of patients all adverse events, treatment-related adverse events, and treatment-related adverse events that led to withdrawal was similar for the i.v. 2-mg twice monthly, 3-mg thrice monthly, and oral 2.5-mg ibandronate in the DIVA trial [72]. Renal safety has been confirmed, without clinically relevant changes in serum creatinine, creatinine clearance, or microalbuminuria, in patients with breast cancer and bone BKM120 cell line metastases receiving ibandronate 6 mg every 3–4 weeks for 6 months given over 15 min [79] or for 2 years given every 3–4 weeks over 1–2 h [80]. To date, oral alendronate, risedronate, and ibandronate have not been studied in head-to-head comparative trials with fracture endpoints. Because of evidence that differences exist in the BMD–fracture risk find more relationship between different agents and that the relationship between fracture risk reductions and BMD is not a simple linear one [77, 81], BMD endpoint trials cannot substitute for fracture endpoint trials and do not allow SN-38 price a formal comparison of the magnitude of the treatment effects of

different osteoporosis agents. ZA is the latest of the aminobisphosphonates available for parenteral osteoporosis treatment. It has the highest affinity among bisphosphonates for bone surfaces, the maximum inhibition potency to inhibit the activity of the farnesyl diphosphate synthesis, and the highest antiresorptive activity [82]. One intravenous dose of ZA (4 to 20 µg/kg) attenuated

trabecular and cortical bone loss for 32 weeks in ovariectomized rats. At 100 µg/kg, bone loss was completely suppressed. ZA was ten times more potent than alendronate in this model [83]. The increase of bone resorption Progesterone postovariectomy, measured by TRAP5b, was suppressed until the 32nd week, even for the lowest dose of ZA (0.8 µg/kg). In human, one intravenous injection of ZA decreased bone turnover for at least 1 year [84], and perhaps even for 2 years [85], opening the road for a yearly treatment in osteoporosis. A once-yearly intravenous injection of ZA was tested in two controlled studies. In the Health Outcome and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON PFT), a yearly injection of ZA (5 mg over 15 min) given at 0, 12, and 24 months was compared to a placebo infusion in more than 7,500 postmenopausal women with osteoporosis who were followed up for 3 years. All patients received daily calcium and vitamin D supplements (1,000–1,500 mg/400–1,200 IU). The markers of bone turnover were decreased by 30% to 59% at 12 months. BMD increased significantly (p < 0.001) at the femoral neck (5.06%; 95% CI, 4.76 to 6.28), total hip (6.02%; 95% CI, 5.77 to 6.28), and lumbar spine (6.71%; 95% CI, 5.69 to 7.74). The 3-year risk of morphometric vertebral fracture was reduced by 70% (RR, 0.30; 95% CI, 0.24–0.