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

Summary
This report describes the epidemiology, burden, and treatment of osteoporosis in the 27 countries of the European Union (EU27).

/pdf/osteoporosis-in-the-european-union-medical-management-5gi5e439ck.pdf

Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA).

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1524-4733.2007.00213.x

Medication Compliance and Persistence: Terminology and Definitions

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

Background: Clinical trials have demonstrated that drug therapy can reduce osteoporosis-related fracture risk in women over 50 years of age. Noncompliance could considerably limit the effectiveness observed in actual practice, however. The objective of this study was therefore to estimate fracture risk in relation to compliance with osteoporosis medication in actual practice. Methods: Demographic, prescription drug use, physician services, and hospitalization information for women with osteoporosis who were dispensed an osteoporosis medication between 1996 and 2001 was obtained from the Saskatchewan health data files. Compliance to treatment was defined as drug available to cover 80% of the time. Subsequent fractures were identified via hospitalizations or physician contacts with a relevant diagnostic or procedure code. The risk of fractures in relation to compliance was examined using a Cox proportional hazards model with time-dependent covariates. The impact of other patient characteristics, including age, having suffered a prior fracture, and prior use of osteoporosis medication and steroids, was also examined. Results: 11,249 women suffering from osteoporosis were identified with a mean age at the time of the index prescription of 68.4 years and average follow-up of 2 years. The overall fracture rate was 4.5% per year. Patients who complied experienced a 16% lower fracture rate. This association was maintained within subgroups and after controlling for other patient characteristics that independently predict the fracture rate. Conclusion: These results indicate that improving compliance in actual practice may significantly decrease osteoporosis-related fracture risk.

The impact of compliance with osteoporosis therapy on fracture rates in actual practice

Assessment of compliance with osteoporosis treatment and its consequences in a managed care population

Awareness of the significance of peripheral arterial disease is increasing, but quantitative estimates of the ensuing burden and the impact of other risk factors remains limited. The objective of this study was to fill this need. Morbidity and mortality were examined in 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up was complete to March 1998. Crude and adjusted event rates were calculated and Kaplan-Meier survival curves estimated. Cox proportional hazards analyses were conducted to examine the effect of risk factors on these rates. Patients suffering a myocardial infarction or ischemic stroke in Saskatchewan provided two reference populations. Half of the index patients were male; the majority was over age 65; 73% had at least one additional risk factor at index diagnosis; 10% suffered a subsequent stroke, another 10% a myocardial infarction, and 49% died within the mean follow-up of 5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after a myocardial infarction (6.3%) but slightly lower than that in patients suffering a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at highest risk of death and other events. A diagnosis of peripheral arterial disease is critical evidence of more widespread atherothrombotic disease, with substantial risks of subsequent cardiovascular events and death. Given that the majority has additional comorbidities, these risks are further increased.

/pdf/the-morbidity-and-mortality-following-a-diagnosis-of-wmta63xox8.pdf

The morbidity and mortality following a diagnosis of peripheral arterial disease: long-term follow-up of a large database.

Background: Given the high costs of caring for patients with AD in Canada, it is important to evaluate the costs of new therapies that halt or delay the advancement of AD, relative to the savings associated with delaying disease progression. Methods: The Assessment of Health Economics in Alzheimer’s Disease (AHEAD) model, which uses algorithms to predict the time until patients with AD require full-time care (FTC), was adapted to Canada to compare treatment with galantamine versus no pharmacologic treatment. Data from two clinical trials provided inputs into the algorithms, and forecasts were made for up to 10 years. Drug and health care costs were evaluated according to the stage of disease based on Quebec unit costs along with follow-up data from the Canadian Study of Health and Aging. Results: Galantamine is predicted to reduce the duration of FTC by almost 10%. Approximately 5.6 patients with mild to moderate disease must be placed on treatment to avoid one year of FTC, resulting in savings averaging $788 CAD ($528 USD) per patient. For patients with moderate disease, 3.9 patients must be placed on treatment to avoid one year of FTC, with savings predicted at $3718 CAD ($2533 USD) per patient. Conclusion: Galantamine cannot only potentially increase the time before patients require FTC, but may also lead to overall savings because treatment costs are offset by reductions in other health care expenditures.

Assessment of health economics in Alzheimer's disease (AHEAD): galantamine treatment in Canada.

Compliance with refilling prescriptions for atypical antipsychotic agents and its association with the risks for hospitalization, suicide, and death in patients with schizophrenia in Quebec and Saskatchewan: a retrospective database study.

Khajak J. Ishak

Papers

The impact of compliance with osteoporosis therapy on fracture rates in actual practice

Assessment of compliance with osteoporosis treatment and its consequences in a managed care population

The morbidity and mortality following a diagnosis of peripheral arterial disease: long-term follow-up of a large database.

Assessment of health economics in Alzheimer's disease (AHEAD): galantamine treatment in Canada.

Compliance with refilling prescriptions for atypical antipsychotic agents and its association with the risks for hospitalization, suicide, and death in patients with schizophrenia in Quebec and Saskatchewan: a retrospective database study.