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Objectives: To assess the efficacy of once-yearly zoledronic acid (ZOL) 5 mg in increasing bone mineral density (BMD) in men with a recent hip fracture participating in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once- Yearly Recurrent Fracture Trial and to compare the efficacy with that in women from the same study., Design: Randomized, placebo-controlled, double-blind trial., Setting: International multicenter., Participants: Five hundred and eight men and 1,619 women within 90 days of surgical repair of low-trauma hip fracture in the same study (for comparison)., Intervention: Once-yearly intravenous (IV) ZOL 5 mg (n = 248) or placebo (n = 260), loading dose of vitamin D, daily calcium, and vitamin D supplements., Measurement: Changes in BMD., Results: Percentage change from baseline in total hip BMD at Months 12 and 24 was significantly higher with ZOL than with placebo (between-group difference, 2.0%, P = .003, and 3.8%, P = .002, respectively). Percentage change from baseline in femoral neck BMD at Month 24 was significantly higher with ZOL than with placebo (3.8%, P = .003). The BMD benefit was comparable with that observed in women in this study. New clinical fractures occurred in 36 (7.1%) participants (ZOL, n = 16; placebo, n = 20; P = .64). The ZOL safety profile was comparable with that of placebo, with no significant differences in cardiovascular or long-term renal function and a trend toward lower mortality in ZOL-treated men., Conclusion: Once-yearly IV ZOL 5 mg increases bone mass at the hip and femoral neck in men within 90 days of repair of a low-trauma hip fracture. Increases were of a similar magnitude to those observed in women in the same study., (© 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.)

Unlabelled: Patients in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial were assessed for evidence of delayed hip fracture healing. No association was observed between zoledronic acid (ZOL) and delayed healing. We conclude that ZOL has no clinically evident effect on fracture healing, even when the drug is infused in the immediate postoperative period., Introduction: Intravenous zoledronic acid 5 mg (ZOL) given after a hip fracture reduces secondary fracture rates and mortality. It has been postulated that bisphosphonates may affect healing if given soon after a fracture. We sought to determine whether the timing of ZOL infusion affected the risk of delayed hip fracture healing., Methods: In the HORIZON Recurrent Fracture Trial, patients were randomized within 90 days of a low-trauma hip fracture to receive either once-yearly ZOL (n = 1,065) or placebo (n = 1,062). Clinical symptoms of delayed hip fracture healing were sought at randomization, 6 months and 12 months after fracture; if present, a central adjudication committee blinded to treatment assignment reviewed radiographs and clinical records. Median follow-up was 1.9 years., Results: The overall incidence of delayed healing was 3.2% (ZOL) and 2.7% (placebo; odds ratio [OR], 1.17; 95% confidence interval [CI], 0.72-1.90; p = 0.61). Logistic regression models revealed no association between ZOL and delayed healing even after adjusting for other risk factors (OR, 1.21; 95% CI, 0.74-1.99; p = 0.44). There was no interaction by timing of infusion, and nonunion rates were similar even when ZOL was given within 2 weeks of hip fracture repair. NSAID use was significantly associated with delayed fracture healing (OR, 2.55; 95% CI, 1.49-4.39; p < 0.001)., Conclusions: ZOL has no clinically evident effect on fracture healing, even when the drug is infused in the immediate postoperative period.

Additional fractures after hip fracture are common, but little is known about the risk factors associated with these events. We determined the clinical risk factors associated with fracture following a low-trauma hip fracture and whether clinical risk factors for subsequent fracture were modified by zoledronic acid (ZOL). In this post hoc analysis of the HORIZON Recurrent Fracture trial, 2,127 men and women were randomized within 90 days of surgical hip fracture repair to receive intravenous ZOL 5 mg yearly or placebo. All patients received a loading dose of vitamin D and daily oral calcium and vitamin D supplements. In the multivariable model age, sex, BMI, femoral neck T score, and one or more fall risk factors were significant predictors of subsequent fracture. Race, history of prior fracture other than the index hip fracture, T score < -2.5 as a dichotomous variable, and type of index hip fracture were not associated with a different risk of subsequent fractures. Treatment with ZOL did not modify the impact of these risk factors. Well-established risk factors for fracture risk such as age, sex, BMI, and fall risk factors will also contribute to fracture risk in patients who have already suffered a hip fracture, while other prior fractures and T score < -2.5 are not predictive of subsequent fractures. Baseline risk factors in hip fracture patients were predictive of fracture in both ZOL- and placebo-treated participants, and there is no difference in the risk of subsequent fractures based on index hip fracture type.

Objectives: To determine the efficacy of once-yearly intravenous zoledronic acid (ZOL) 5 mg in reducing risk of clinical vertebral, nonvertebral, and any clinical fractures in elderly osteoporotic postmenopausal women., Design: A post hoc subgroup analysis of pooled data from the Health Outcome and Reduced Incidence with Zoledronic Acid One Yearly (HORIZON) Pivotal Fracture Trial and the HORIZON Recurrent Fracture Trial., Setting: Multicenter, randomized, double-blind, placebo-controlled trials., Participants: Postmenopausal women (aged > or =75) with documented osteoporosis (T-score < or =-2.5 at femoral neck or >/=1 prevalent vertebral or hip fracture) or a recent hip fracture., Intervention: Patients were randomized to receive an intravenous infusion of ZOL 5 mg (n=1,961) or placebo (n=1,926) at baseline and 12 and 24 months., Measurements: Primary endpoints were incidence of clinical vertebral and nonvertebral and any clinical fracture after treatment., Results: At 3 years, incidence of any clinical, clinical vertebral, and nonvertebral fracture were significantly lower in the ZOL group than in the placebo group (10.8% vs 16.6%, 1.1% vs 3.7%, and 9.9% vs 13.7%, respectively) (hazard ratio (HR)=0.65, 95% confidence interval (CI)=0.54-0.78, P<.001; HR=0.34, 95% CI=0.21-0.55, P<.001; and HR=0.73, 95% CI=0.60-0.90, P=.002, respectively). The incidence of hip fracture was lower with ZOL but did not reach statistical significance. The incidence rate of postdose adverse events were higher with ZOL, although the rate of serious adverse events and deaths was comparable between the two groups., Conclusion: Once-yearly intravenous ZOL 5 mg was associated with a significant reduction in the risk of new clinical fractures (vertebral and nonvertebral) in elderly postmenopausal women with osteroporosis.

Aims: The efficacy of treatments for osteoporosis can be evaluated using a variety of study designs. This article aims to comprehensively review the evidence for bisphosphonate anti-fracture efficacy in postmenopausal women, discussing the strengths and limitations associated with each study method., Methods: Literature analysis included English-language publications reporting results of randomised controlled trials (RCTs), post hoc analyses, meta analyses and observational studies evaluating the efficacy of alendronate (ALN), ibandronate (IBN), risedronate (RIS) and zoledronate (ZOL), with an initial sample size > or = 100 patients, and follow-up data for at least 1 year., Results: Primary and secondary analyses of RCT data suggest differences among bisphosphonates with regard to site-specific anti-fracture efficacy and onset of fracture risk reduction. While some observational studies indicate differences in clinical outcomes among these agents, others report similar effectiveness. ALN and RIS data demonstrate sustained fracture protection for up to 10 and 7 years of treatment respectively. The efficacy of IBN and ZOL has been evaluated for up to 3 and 5 years respectively., Conclusions: Understanding of the benefits of bisphosphonate treatment can be maximised by evaluating complementary data from RCTs and observational database studies. Fracture risk reduction with bisphosphonates is shown in RCTs and in real-world clinical settings.

Bisphosphonates are the current mainstay of treatment for postmenopausal osteoporosis. Although daily oral dosing is effective, it is associated with poor compliance, partly because of the pre and postdose fasting and posture requirements. This negatively impacts treatment outcomes, leading to a reduced clinical benefit. Improved, yet still suboptimal adherence has been noticed with less frequent bisphosphonate dosing e.g. once-weekly and once-monthly oral regimens. The recently approved quarterly intravenous (i.v.) injection regimen of ibandronate and yearly i.v. infusion of zoledronic acid are attractive options in the management of postmenopausal osteoporosis. These regimens may assure quarterly and year long compliance.

Osteoporosis is a major cause of morbidity, mortality, and healthcare costs. The socioeconomic burden of osteoporosis is likely to increase dramatically if improvements in prevention are not made. Calcium supplementation effectively reduces the rate of bone loss in postmenopausal women, yet most women do not achieve an adequate calcium intake. In fact, use of calcium supplementation appears to have declined as the more effective antiresorptive therapies, such as bisphosphonates, have become available. Among patients prescribed bisphosphonates, calcium intake is often insufficient, despite the fact that adequate calcium intake may be necessary to gain the maximum benefits from antiresorptive therapy. In addition, because calcium interferes with bisphosphonate absorption, incorrect use of calcium may limit the efficacy of bisphosphonate therapy. This underscores the need for new initiatives to reduce the confusion surrounding appropriate calcium use during antiresorptive therapy. Co-packaging of bisphosphonates with calcium supplements is one strategy to help ensure that patients taking bisphosphonates not only achieve adequate calcium intake but also gain the maximum benefit from bisphosphonate therapy.

Introduction: Risedronate, a bisphosphonate for treatment and prevention of osteoporosis, has been shown in several clinical trials to reduce the risk of fractures in postmenopausal women with osteoporosis. The cost-effectiveness of risedronate treatment has previously been evaluated within different country settings using different model and analysis approaches. The objective of this study was to assess the cost-effectiveness of risedronate in postmenopausal women in four European countries-Sweden, Finland, Spain, and Belgium-by making use of the same modelling framework and analysis setup. Methods: A previously developed Markov cohort model for the evaluation of osteoporosis treatments was used to estimate the cost-effectiveness of risedronate treatment. For each country, the model was populated with local mortality, fracture incidence, and cost data. Hip fractures, clinical vertebral fractures, and wrist fractures were included in the model. Results: The incremental cost per quality-adjusted life years (QALY) gained from a 5-year intervention with risedronate compared to "no intervention" in 70-year-old women at the threshold of osteoporosis [T-score = -2.5 based on National Health and Nutrition Examination Survey (NHANES) III data] and previous vertebral fracture was estimated to be €860, €19,532, €11,782, and €32,515 in Sweden, Finland, Belgium, and Spain, respectively. Among 70-year-old women at the threshold of osteoporosis without previous fracture the estimated cost per QALY gained ranged from €21,148 (Sweden) to €80,100 (Spain). The differences in cost-effectiveness between countries are mainly explained by different costs (fracture and treatment costs), fracture risks, and discount rates. Based on cost per QALY gained threshold values found in the literature, the study results indicated risedronate to be cost effective in the treatment of elderly women with established osteoporosis in all the included countries. Conclusions: At a hypothetical threshold value of €40,000 per QALY gained, the results in this study indicate that risedronate is a cost-effective treatment in elderly women at the threshold of osteoporosis (i.e., a T-score of -2.5) with prevalent vertebral fractures in Sweden, Finland, Belgium, and Spain. [ABSTRACT FROM AUTHOR]