Jonathan D. Adachi

Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture

BACKGROUND Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. METHODS 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 [ClinicalTrials.gov].).

Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial.

Prevalent vertebral fractures and baseline bone mineral density (BMD) predict subsequent fracture risk. The objective of this analysis is to examine whether baseline vertebral fracture severity can predict new vertebral and nonvertebral fracture risk. In the randomized, double-blind 3-year Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis (low BMD or prevalent vertebral fractures) were randomly assigned to placebo, raloxifene 60 mg/day, or raloxifene 120 mg/day. Post hoc analyses studied the association between baseline fracture severity and new fracture risk in the placebo group and the effects of placebo, raloxifene 60 mg/day, and raloxifene 120 mg/day on new fracture risk in women with the most severe prevalent vertebral fractures (n = 614). Vertebral fracture severity was visually assessed using semiquantitative analysis of radiographs and categorized by estimated decreases in vertebral heights. Reported new nonvertebral fractures were radiographically confirmed. Baseline vertebral fracture severity predicted vertebral and nonvertebral fracture risk at 3 years. In women without prevalent vertebral fractures, 4.3 and 5.5% had new vertebral and nonvertebral fractures, respectively. In women with mild, moderate, and severe prevalent vertebral fractures, 10.5, 23.6, and 38.1% respectively had new vertebral fractures, whereas 7.2, 7.7, and 13.8% respectively experienced new nonvertebral fractures. Number of prevalent vertebral fractures and baseline BMD also predicted vertebral fracture risk, but the severity of prevalent vertebral fractures was the only predictor of nonvertebral fracture risk and remained a significant predictor after adjustment for baseline characteristics, including baseline BMD. In patients with severe baseline vertebral fractures, raloxifene 60 mg/day decreased the risks of new vertebral [RR 0.74 (95% Cl 0.54, 0.99); P = 0.048] and nonvertebral (clavicle, humerus, wrist, pelvis, hip, and leg) fractures [RH 0.53 (95% CI 0.29, 0.99); P = 0.046] at 3 years. To prevent one new fracture at 3 years in women with severe baseline vertebral fractures with raloxifene 60 mg/day, the number needed to treat (NNT) was 10 for vertebral and 18 for nonvertebral fractures. Similar results were observed in women receiving raloxifene 120 mg/day. In summary, baseline vertebral fracture severity was the best independent predictor for new vertebral and nonvertebral fracture risk. Raloxifene decreased new vertebral and nonvertebral fracture risk in the subgroup of women with severe vertebral fractures at baseline. These fractures may reflect architectural deterioration, independent of BMD, leading to increased skeletal fragility.

Economic implications of hip fracture: health service use, institutional care and cost in Canada.

Abstract: As the burden of illness associated with hip fracture extends beyond the initial hospitalization, a longitudinal 1 year cohort study was used to analyze levels of health service use, institutional care and their associated costs, and to examine patient and residency factors contributing to overall 1 year cost. Patients in the study were aged 50 year and over, and had been admitted to an acute care facility for hip fracture in the Hamilton–Wentworth region of Canada from 1 April 1995 to 31 March 1996. Health care resources assessed included initial hospitalization, rehospitalization, rehabilitation, chronic care, home care, long-term care (LTC) and informal care. Regression analysis was used to determine the effects of age, gender, residence, survival and days of follow-up on 1 year cost. The mean 1 year cost of hip fracture for the 504 study patients was 26.527 Canadian dollars (95% Cl:

The Efficacy and Tolerability of Risedronate Once a week for the Treatment of Postmenopausal Osteoporosis

24.564–

Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study

28.490). One year costs were significantly different for patients who returned to the community (

Obesity is not protective against fracture in postmenopausal women: GLOW

21.385), versus those who were transferred to (

Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: greater increases in bone mineral density do not relate to greater decreases in fracture risk

44.156), or readmitted to LTC facilities (

The influence of osteoporotic fractures on health-related quality of life in community-dwelling men and women across Canada.

33.729) (p<0.001). Initial hospitalization represented 58% of 1 year cost for community-dwelling patients, compared with 27% for LTC residents. Only 59.4% of community-dwelling patients resided in the community 1 year following hip fracture, and 5.6% of patients who survived their first fracture experienced a subsequent hip fracture. Linear regression indicated place of residence, age and survival were all important contributors to 1 year cost (p<0.001). While the average 1 year cost of care was

Population trends in BMD testing, treatment, and hip and wrist fracture rates: are the hip fracture projections wrong?

26.527, the overall cost varied depending on a patient”s place of residence, age, and survival to 1 year. Annual economic implications of hip fracture in Canada are

Frailty and sarcopenia: definitions and outcome parameters

650 million and are expected to rise to