Background A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period. Methods In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes. Results Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the ...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa067312

Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis

Summary Guidance is provided in a European setting on the assessment and treatment of postmenopausal women with or at risk from osteoporosis. Introduction The European Foundation for Osteoporosis and Bone disease (subsequently the International Osteopo- rosis Foundation) published guidelines for the diagnosis and management of osteoporosis in 1997. This manuscript updates these in a European setting. Methods The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporo- sis and assessment of fracture risk; general and pharmaco- logical management of osteoporosis; monitoring of treatment; assessment of fracture risk; case finding strategies; investigation of patients; health economics of treatment. Results and conclusions A platform is provided on which specific guidelines can be developed for national use.

/pdf/european-guidance-for-the-diagnosis-and-management-of-bexvs3o205.pdf

European guidance for the diagnosis and management of osteoporosis in postmenopausal women

In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients (mean age, 74.5 years) received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. Results The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction with zoledronic acid (P = 0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P = 0.02), and the respective rates of new nonvertebral fractures were 7.6% and 10.7% (P = 0.03). In the safety analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic acid group (P = 0.01). The most frequent adverse events in patients receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar in the two groups. Conclusions An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and with improved survival. (ClinicalTrials.gov number, NCT00046254.)

/pdf/zoledronic-acid-and-clinical-fractures-and-mortality-after-3fcy691ral.pdf

Zoledronic acid and clinical fractures and mortality after hip fracture

Summary
Bisphosphonates (BPs) are well established as the leading drugs for the treatment of osteoporosis. There is new knowledge about how they work. The differences that exist among individual BPs in terms of mineral binding and biochemical actions may explain differences in their clinical behavior and effectiveness.

Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy

Osteonecrosis of the jaws is a recently described adverse side effect of bisphosphonate therapy. Patients with multiple myeloma and metastatic carcinoma to the skeleton who are receiving intravenous, nitrogen-containing bisphosphonates are at greatest risk for osteonecrosis of the jaws; these patients represent 94% of published cases. The mandible is more commonly affected than the maxilla (2:1 ratio), and 60% of cases are preceded by a dental surgical procedure. Oversuppression of bone turnover is probably the primary mechanism for the development of this condition, although there may be contributing comorbid factors. All sites of potential jaw infection should be eliminated before bisphosphonate therapy is initiated in these patients to reduce the necessity of subsequent dentoalveolar surgery. Conservative debridement of necrotic bone, pain control, infection management, use of antimicrobial oral rinses, and withdrawal of bisphosphonates are preferable to aggressive surgical measures for treating this condition. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate, for osteoporosis is uncertain and warrants careful monitoring.

Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws

Background Bisphosphonates are effective agents for the management of osteoporosis. Their low bioavailability and low potency necessitate frequent administration on an empty stomach, which may reduce compliance. Gastrointestinal intolerance limits maximal dosing. Although intermittent intravenous treatments have been used, the optimal doses and dosing interval have not been systematically explored. Methods We studied the effects of five regimens of zoledronic acid, the most potent bisphosphonate, on bone turnover and density in 351 postmenopausal women with low bone mineral density in a one-year, randomized, double-blind, placebo-controlled trial. Women received placebo or intravenous zoledronic acid in doses of 0.25 mg, 0.5 mg, or 1 mg at three-month intervals. In addition, one group received a total annual dose of 4 mg as a single dose, and another received two doses of 2 mg each, six months apart. Lumbar-spine bone mineral density was the primary end point. Results There were similar increases in bone ...

Joachim Happ

Papers

Intravenous zoledronic acid in postmenopausal women with low bone mineral density.