BACKGROUNDRomosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. METHODSWe enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab for 12 months, at a dose of 60 mg, administered subcutaneously every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months. Secondary end points included clinical (a composite of nonvertebral and symptomatic vertebral) and nonvertebral fractures. RESULTSAt 12 months, new vertebral fractures had occurred in 16 of 3321 patients (0.5%) in the romosozumab group, as compared with 59 of 3322 (1.8%) in the placebo group (representing a 73% lower risk with romosozumab; P<0.001). Clinical fractures had occurred in 58 of 3589 patients (1.6%) in the romosozumab group, as compared with 90 of 3591 (2.5%) in the placebo group (a 36% lower risk with romosozumab; P = 0.008). Nonvertebral fractures had occurred in 56 of 3589 patients (1.6%) in the romosozumab group and in 75 of 3591 (2.1%) in the placebo group (P = 0.10). At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3325 patients] in the romosozumab group vs. 2.5% [84 of 3327] in the placebo group, a 75% lower risk with romosozumab; P<0.001). Adverse events, including instances of hyperostosis, cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group. CONCLUSIONSIn postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year. (Funded by Amgen and UCB Pharma; FRAME ClinicalTrials.gov number, NCT01575834.)

No abstract

In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532.).

Accurate radiographic diagnosis of vertebral fractures is important. This multicenter, multinational study assessed radiographic diagnoses of vertebral fracture in 2451 postmenopausal women with osteoporosis. Comparison between local and central readings yielded a false-negative rate of 34%. Underdiagnosis of vertebral fracture is a worldwide problem.Introduction: Vertebral fractures are the most common complication of osteoporosis. Although they are associated with significant morbidity, they frequently do not come to clinical attention. Accurate radiographic diagnosis is important. Materials and Methods: In a multicenter, multinational prospective study (the IMPACT trial), the accuracy of radiographic diagnosis of vertebral fracture was evaluated in postmenopausal women 65-80 years of age newly diagnosed with osteoporosis (based on BMD measurement). Lateral radiographs of the thoracolumbar spine were evaluated for identification of vertebral fractures, first locally and subsequently at a central reading center, using a validated semiquantitative method. False-positive and false-negative rates were calculated based on adjudicated discrepancies between the initial interpretation at the local site and the subsequent central reading, considered the "reference standard." Results: Of 2451 women with an evaluable radiograph both centrally and locally, 789 (32%) had at least one vertebral fracture. Adjudicated discrepancies (n ‫ס‬ 350 patients) between local and central readings because of undetected vertebral fracture (68%) or equivocal terminology in the local radiology report (32%) yielded a false-negative rate of 34%. Conclusions: Underdiagnosis of vertebral fractures was observed in all geographic regions (false-negative rates: North America, 45.2%; Latin America, 46.5%; Europe/South Africa/Australia, 29.5%). The falsepositive rate was 5% globally. Underdiagnosis of vertebral fracture is a worldwide problem attributable in part to a lack of radiographic detection, use of ambiguous terminology in the radiology report, or both. Efforts to improve accuracy and reduce variability in terminology and interpretation may increase the effectiveness of spinal radiography for detecting vertebral fractures in patients with osteoporosis.

No abstract