Before the breaking point: reducing the risk of osteoporotic fracture.

Osteoporosis is a major cause of morbidity in the United States, resulting in approximately 2 million fractures and contributing to 65,000 deaths annually. Organizations have published guidelines for the diagnosis and management of the disease. However, a degree of conflict exists among some of the recommendations. Several screening tools have been developed to identify fracture risk, and although the Fracture Risk Assessment tool developed by the World Health Organization has been widely adopted, other screening tests are also potentially useful. A range of medications are available for the prevention of osteoporosis in individuals who are at high risk for the disease and for the treatment of individuals who already have osteoporosis. Although some of these medications are highly effective, all have adverse-effect profiles and other caveats that require both familiarity with the characteristics of the medication and detailed knowledge of patient needs and preferences. Effective therapy is only possible with strong patient adherence to the regimen, which in turn requires that the patient have an understanding of the risks and benefits and can participate in the treatment-selection process.

Clinical strategies to address patients' concerns in osteoporosis management with bisphosphonates.

Approximately 44 million Americans either have, or are at risk of developing, osteoporosis, a disease associated with an increased risk of fracture and, consequently, morbidity and mortality. Osteoporosis affects 20% to 30% of postmenopausal women, and resulting fractures pose a major economic burden, with estimated annual direct costs ranging from $17 billion to $19 billion. Hip fractures account for the majority of costs (~60%) because they often require costly long-term follow-up care in addition to the direct costs of initial treatment. Screening, diagnosis, and disease management are of paramount importance when treating patients at risk for osteoporosis. The National Osteoporosis Foundation recommends that all postmenopausal women be evaluated for osteoporosis risk factors and that all women aged ≥ 65 years undergo bone mineral density testing. Once the primary care physician has identified a patient at risk for osteoporosis-related fracture, the physician must decide whether and how to treat the patient (ie, nonpharmacologic or pharmacologic options). Bisphosphonates are the first-line pharmacologic treatment for women aged ≥ 50 years with postmenopausal osteoporosis. Bisphosphonates-which have a favorable safety and tolerability profile in clinical trials-have shown efficacy in reducing fractures. However, achieved real world effectiveness is very much dependent on good treatment adherence by the patient. Media attention to rare adverse events has motivated some patients to deliberate nonadherence. Physicians should screen patients for contraindications and adverse event risk factors, educate them on the risks of fracture and benefits and risks of treatment, and monitor them during therapy. To assist primary care physicians in clinical decision making for women at risk for or with confirmed osteoporosis, this article presents a review of the guidelines for the diagnosis and treatment of postmenopausal osteoporosis, recent long-term efficacy data for extended-interval bisphosphonates, recent safety concerns with bisphosphonates, and lastly, suggests strategies for improving bisphosphonate adherence and patient outcomes.

Preventing nonvertebral osteoporotic fractures with extended-interval bisphosphonates: regimen selection and clinical application.

CONTEXT: Nonvertebral fractures (NVFs) are the most costly and disabling type of osteoporotic fractures. Bisphosphonate therapy effectively reduces the risk for NVFs; however, fracture protection depends critically on adherence and persistence. Approved bisphosphonate regimens with extended dosing intervals increase patient convenience, help patients remain on therapy, and improve fracture protection in clinical practice. EVIDENCE ACQUISITION: To assess evidence for NVF reduction with extended-interval bisphosphonates, we searched PubMed for phase 3 clinical trials, meta-analyses, and reviews of approved nitrogen-containing bisphosphonate regimens with monthly or less frequent dosing (monthly oral ibandronate, monthly or intermittent oral risedronate, quarterly intravenous [IV] ibandronate, and yearly IV zoledronic acid). These references were augmented by ISI Web of Science cited reference searches, ISI Proceedings searches, and hand searches of relevant conference proceedings and review bibliographies. EVIDENCE SYNTHESIS: Monthly oral and quarterly IV ibandronate reduce NVF risk significantly more than daily oral ibandronate and placebo, as shown by meta-analyses stratified by ibandronate dose (annual cumulative exposure). Intermittent and monthly oral risedronate have shown bone density gains similar to those seen with daily oral risedronate. Incidence rates of NVF, reported as adverse events, were also similar. Yearly IV zoledronic acid reduced NVF risk by 25% and hip fracture risk by 41% compared with placebo in its pivotal trial for postmenopausal osteoporosis. CONCLUSIONS: Extended-interval bisphosphonates offer similar or superior NVF protection with less lifestyle disruption compared with daily or weekly treatment. By removing obstacles to adherence and persistence, extended-interval oral and IV bisphosphonate regimens provide valuable therapeutic options to enhance real-world effectiveness and reduce NVF incidence.

Risk of severe gastrointestinal events in women treated with monthly ibandronate or weekly alendronate and risedronate.

BACKGROUND: Bisphosphonate (BP)-related gastrointestinal (GI) adverse events can lead to discontinuation of osteoporosis treatment. Irritation of the GI tract related to BPs may be worsened by more frequent administration. OBJECTIVE: To compare the number of women who experienced severe GI events within 3 months of starting once-monthly oral ibandronate with those starting once-weekly oral BP (alendronate or risedronate). METHODS: In a retrospective database study design, eligible women with a new prescription for monthly ibandronate were propensity-matched to women with a new weekly BP prescription. Patients had continuous health plan enrollment for 6 months prior to the index date and for 3 months after the index date. Women with previous intravenous BP treatment, Paget's disease, or oral BP treatment within the 6-month preindex period were excluded. Severe GI events (including acute events involving perforation or bleeding/perforation) within 3 months of treatment initiation were identified by ICD-9 and Current Procedural Terminology codes. A post hoc analysis assessed treatment discontinuation after severe GI events. GI-related healthcare utilization rates and costs were also compared. RESULTS: Of the 8608 patients per group, 45 (0.52%) who were receiving monthly ibandronate and 70 (0.81%) of those receiving weekly BP treatment experienced a severe GI event. Ibandronate patients had a 36% reduction in the risk of severe GI events compared with weekly BP users (OR 0.64, 95% CI 0.44 to 0.93). Significantly more women receiving a weekly BP discontinued treatment after a severe GI event compared with those receiving ibandronate (100% vs 55.6%; p < 0.001). Most healthcare utilization outcomes were not significantly different between the 2 groups; outpatient visits were significantly higher for ibandronate (p = 0.02). Costs were not significantly different between the 2 groups. CONCLUSIONS: Patients receiving monthly ibandronate therapy had a significantly reduced risk of severe GI events compared with those receiving weekly BP treatment. In addition, patients receiving a weekly BP were more likely to discontinue treatment after a severe GI event.

Improving clinical decisions for women at risk of osteoporosis: dual-femur bone mineral density testing.

CONTEXT: In bone mineral density (BMD) testing, unilateral hip analysis and lumbar spine measurement have been the clinical standard for diagnosis and treatment classification for postmenopausal women at risk of osteoporosis. OBJECTIVE: To determine if analysis of the bilateral hip in BMD testing has a clinical effect on diagnosis of osteoporosis and treatment classification of patients. METHODS: Dual-femur BMD test results from 313 postmenopausal women (mean age 61.2 years, range 32-90 years) were evaluated using standard BMD reference values for diagnosis and treatment classification. The author compared T scores for right and left femurs at three sites: femoral neck, trochanter, and total femur. RESULTS: When the bilateral hip was considered in BMD testing and compared with unilateral hip results, a clinical change in diagnosis from normal to osteopenia occurred in 5.7% of subjects. In addition, a clinical change in diagnosis from osteopenia to osteoporosis occurred in 3.3% of subjects. A clinical change in treatment classification from "no treatment required" to "treatment required if one or more risk factors are present" occurred in 3% of subjects. A change in treatment classification from "treatment required if one or more risk factors are present" to "treatment required independent of risk factors" happened in 2.4% of subjects. CONCLUSION: When compared with BMD testing of the unilateral hip, inclusion of the bilateral hip in BMD testing resulted in a change in classification to a more severe diagnosis in a total of 9% of subjects, and to a more aggressive treatment category in a total of 5.4% of subjects. Dual-femur BMD testing may improve diagnosis and treatment classification for postmenopausal women at risk of osteoporosis.

The effect of measurement of the contralateral hip if the spine is not included in the bone mineral density analysis.

The aim of this study was to determine if measurement of the contralateral femora has an effect on osteoporosis diagnosis and treatment classification if the spine is not included in the bone mineral density (BMD) scan. The method used was the T-score discordance from the dual femur BMD scans of 537 women (mean age: 61.2 yr; standard deviation: 10.5; age range: 32-90 yr) who were evaluated to determine if inclusion of the contralateral hip in the BMD study made a difference in clinical diagnosis and treatment classification when the spine was not included in the BMD scan. Clinical diagnosis and treatment classification was based on the lowest T-score at each hip of three femur sites: the neck, the trochanter, and the total femur. The results of the diagnosis classification (i.e., normal, osteopenia, and osteoporosis) differed in the right versus the left femora in 28% of subjects at one or more sites, and in 14%, 15%, and 10% of subjects at the neck, trochanter, and total femur, respectively. Diagnosis discordance increased in subjects who were aged 65 yr and older. Treatment classification (T>or=-1.5; T<-1.5; T<-2.0) differed in the right versus the left femora in 33% of subjects at one or more sites, and in 18%, 14%, and 12% of subjects at the neck, trochanter, and total femur, respectively. Treatment discordance increased in subjects age 65 yr and older. Using the lowest T-score for clinical diagnosis classification, when the contralateral hip was considered, a clinical difference in diagnosis from normal-->osteopenia occurred in 3.9% of subjects, and from osteopenia-->osteoporosis in 1.3% of subjects. A clinical difference in treatment category from T>or=-1.5-->T<-1.5 occurred in 2.7% of subjects, and from T>or=-2-->T<-2 in 2.7% of subjects. In conclusion, inclusion of the bilateral hip in the BMD study made a clinical difference in diagnosis classification in 5.2% of subjects and in treatment classification in 5.4% of subjects. T-score differences between the contralateral hips increased with age. In the subgroup of subjects age 65 yr and older, a clinical difference in classification to a more severe diagnosis or treatment category occurred in 5.35% and 7.25% of subjects, respectively.