Shuvayu S. Sen

Undertreatment with anti-osteoporotic drugs after hospitalization for fracture

This study assessed the proportion of patients treated with anti-osteoporotic drugs during the 1-year period after hospitalization for a fracture, and the influence of a guideline in the period 1998–2000 on the likelihood of receiving treatment for osteoporosis after a fracture. Patients were assessed retrospectively for anti-osteoporotic drug use during a 1-year period following hospitalization for non-traumatic fracture. The PHARMO system, a population-based database (n=865,000) containing drug and hospitalization data of community-dwelling inhabitants of defined areas in the Netherlands, was used. The study population comprised 1654 patients age 50 years and over who were admitted to hospital for a fracture resulting from a fall during the period 1998–2000. The treatment rate of newly treated patients and the change in treatment rate throughout the period 1998–2000 were the outcome measures. The majority of these patients were women (73%), and had femur fractures (51%). In total, 247 out of 1654 patients (15%) were prescribed anti-osteoporotic drugs within 1 year after discharge from the hospital. Of these 247 patients, 86 were newly treated, mainly with bisphosphonates in the year after discharge following the fracture, yielding a new treatment rate of 5%. The likelihood of receiving treatment for osteoporosis following fracture did not change with the calendar year of fracture (OR 0.95; 95% CI: 0.68–1.30). The result of this study shows that despite the introduction of an osteoporosis treatment guideline in 1999 recommending treatment for fracture patients, most of the time, fracture patients are not being treated for osteoporosis. Thus, to a large extent, osteoporosis remains under-treated.

Cost-effectiveness of alendronate in the treatment of postmenopausal women in 9 European countries - an economic evaluation based on the fracture intervention trial

SummaryTreatment with alendronate (Fosamax®) has been shown to significantly reduce the risk of fragility fractures. Cost-effectiveness of treatment was assessed in nine European countries in a Markov model and was generally found to be cost effective in women with a previous spine fracture.IntroductionTreatment with alendronate (Fosamax®) reduces the risk of osteoporotic fractures at the spine, hip and wrist in women with and without prevalent vertebral fracture. Cost-effectiveness estimates in one country may not be applicable elsewhere due to differences in fracture risks, costs and drug prices. The aim of this study was to assess the cost-effectiveness of treating postmenopausal women with alendronate in nine European countries, comprising Belgium, Denmark, France, Germany, Italy, Norway, Spain, Sweden, and the UK.MethodsA Markov model was populated with data for the nine European populations. Effect of treatment was taken from the Fracture Intervention Trial, which recruited women with low BMD alone or with a prior vertebral fracture.ResultsThe cost per QALY gained of treating postmenopausal women with prior vertebral fractures ranged in the base case from “cost saving” in the Scandinavian countries to €15,000 in Italy. Corresponding estimates for women without prior vertebral fractures ranged from “cost saving” to €40,000.ConclusionsIn relation to thresholds generally used, the analysis suggests that alendronate is very cost effective in the treatment of women with previous vertebral fracture, and in women without previous vertebral fracture, cost-effectiveness depends on the country setting, discount rates, and chosen monetary thresholds.

Efficacy of vitamin D3 supplementation in preventing fractures in elderly women: A meta-analysis

Abstract Background: The efficacy of vitamin D3 in preventing fractures and falls has been explored in a number of clinical trials. However, recent evidence revealed new questions about the adequate doses of vitamin D3 supplementation and its efficacy in fracture prevention independent of calcium supplements for various types of fractures. Objective: To conduct a meta-analysis to estimate the effectiveness of 800 IU daily vitamin D3 supplementation for increasing bone mineral density (BMD) and preventing fractures in postmenopausal women. Methods: Medline and EMBASE were searched for controlled trials comparing the effectiveness of cholecalciferol (vitamin D3) against placebo with or without background calcium supplementation in the treatment of postmenopausal women. Results: Eight controlled trials evaluating the effect of vitamin D3 supplementation with or without calcium were assessed. Of 12 658 women included in a Bayesian meta-analysis, 6089 received vitamin D3 (with or without calcium) and 6569 received placebo (with or without calcium). Compared to placebo, vitamin D3 with calcium supplementation showed beneficial effects on the incidence of non-vertebral (odds ratio [OR] 0.77, 95% credibility limit [CL] 0.6–0.93) and hip (OR 0.70, 95% CL 0.53–0.90) fractures, while the effects on non-vertebral-non-hip fractures (OR 0.84, 95% CL 0.67–1.04) % point increase) were associated with more uncertainty. Vitamin D3 supplementation showed a 70% probability of being a better treatment than placebo for the prevention of non-vertebral fractures, hip fractures, and non-vertebral, non-hip fractures. Compared to calcium supplementation, vitamin D3 plus calcium reduced non-vertebral fractures (OR 0.68, 95% CL 0.43–1.01) and non-vertebral, non-hip fractures (OR 0.64, 95% CL 0.38–0.99), but did not reduce hip fractures (OR 1.03, 95% CL 0.39–2.25). Key limitations to this analysis include a small number of studies and heterogeneity in the study populations. Conclusions: This meta-analysis supports the use of vitamin D3 of 800 IU daily to reduce the incidence of osteoporotic non-vertebral, hip, and non-vertebral-non-hip fractures in elderly women. Vitamin D3 with calcium appears to achieve benefits above those attained with calcium supplementation alone for non-vertebral and non-vertebral-non-hip fractures.

A Risk Assessment Tool (OsteoRisk) for Identifying Latin American Women with Osteoporosis

AbstractOBJECTIVE: To develop a simple and easy-to-use tool for identifying osteoporotic women (femoral neck bone mineral density [BMD] T-scores ≤−2.5) in Latin America. DESIGN: Retrospective study involving review of medical records. SETTING: Osteoporosis clinics in 6 Latin American countries. PATIENTS: Postmenopausal women ages ≥50 in Latin America who had femoral neck BMD measurements. MEASUREMENTS AND MAIN RESULTS: A risk index was developed from 1.547 patients based on least square regression using age, weight, history of fractures, and other variables as predictors for BMD T-score. The final model was simplified by reducing the number of predictors; sensitivity and specificity were evaluated before and after reducing the number of predictors to assess performance of the index. The final model included age, weight, country, estrogen use, and history of fractures as significant predictors for T-score. The resulting scoring index achieved 91% sensitivity and 47% specificity. Simplifying the index by using only age and weight yielded similar performance (sensitivity, 92%; specificity, 45%). Three risk categories were identified based on OsteoRisk, the index using only age and body weight: high-risk patients (index <=−2; 65.6% were osteoporotic), moderate-risk patients (−21; 8% were osteoporotic). Similar results were seen in a validation sample of 279 women in Brazil. CONCLUSION: Age and weight alone performed well for predicting the risk of osteoporosis among postmenopausal women. The OsteoRisk is an easy-to-use tool that effectively targets the vast majority of osteoporotic patients in Latin America for evaluation with BMD.

Consequences of inappropriate initial empiric parenteral antibiotic therapy among patients with community-acquired intra-abdominal infections in Spain

To assess the association between inappropriate antibiotic therapy and clinical outcomes for complicated community-acquired intra-abdominal infections in Spain, patient records from October 1998 to August 2002 in 24 hospitals were reviewed. Initial empiric therapy was classified appropriate if all isolates were sensitive to at least 1 of the antibiotics administered. Multivariate analyses were performed to assess associations between appropriateness of therapy and patient outcomes. Healthcare resource use was measured as hospital length of stay (LOS) and d on intravenous antibiotic therapy. A total of 425 patients were included. Of these, 387 (91%) received appropriate initial empiric therapy. Patients on inappropriate therapy were less likely to have clinical success (79% vs 26%, p<0.001), more likely to require additional antibiotic therapy (40% vs 7%, p<0.01) and more likely to be re-hospitalized within 30 d of discharge (18% vs 3%, p<0.01). Multivariate analyses also showed that inappropriate therapy was associated with an almost 16% increase in LOS (p<0.05) and 26% in d of intravenous antibiotic therapy compared with appropriate therapy (p<0.05). Inappropriate initial antibiotic therapy was associated with a significantly higher proportion of unsuccessful patient outcomes (including death, re-operation, re-hospitalization or additional parental antibiotic therapies), increased length of stay and length on therapy.

Cost and consequences of noncompliance with osteoporosis treatment among women initiating therapy.

Abstract Objective: The objective was to evaluate compliance with osteoporosis (OP) treatments and determine the fracture and healthcare burden associated with noncompliance. Methods: This retrospective analysis of a US claims database identified women initiating an OP medication from 1 January 2002 to 30 June 2009. Patients were ≥55 years and had ≥1 pharmacy claim for a bisphosphonate or non-bisphosphonate (raloxifene, calcitonin, teriparatide); the index date was the first pharmacy claim. There were three study periods: baseline (12 months pre-index); compliance period (0–12 months post-index); and follow-up period (12–24 months post-index). Medication possession ratio (MPR) was calculated during the compliance period to differentiate two cohorts: compliant (MPR ≥ 80%) and noncompliant (MPR < 80%). Outcomes during follow-up were modeled by logistic regression (presence of fracture), Poisson regression (healthcare utilization incidence rate) and gamma regression (healthcare costs), all adjusted for patient demographic and clinical characteristics. Results: Overall, 685,505 women initiating OP therapy were identified and 57,913 (8.4%) met the inclusion criteria: only 23,430 (40.5%) were compliant and 34,483 (59.5%) were noncompliant. Mean age was 64 years. Noncompliance was associated with a 20% higher risk of any fracture (odds ratio: 1.20, 95% CI = 1.07–1.35), a higher incidence rate ratio (IRR) for inpatient utilization (IRR: 1.26, 95% CI = 1.19–1.34) and a lower rate of outpatient utilization (IRR: 0.97, 95% CI = 0.95–0.98). Noncompliant patients had 13% higher medical costs (cost ratio: 1.13, 95% CI = 1.06–1.21) than compliant patients. Limitations: Inclusion in this study required 36 months of continuous healthcare coverage. Thus, the results are primarily applicable to a stable, managed care population and may not be generalizable to other populations. Conclusion: Noncompliance with OP therapy was associated with a higher risk of fracture, higher all-cause medical costs and a higher frequency of inpatient service utilization. Additional research is needed to identify barriers to compliance with OP therapy.

Physician and patient perceptions on the use of vitamin D and calcium in osteoporosis treatment : a European and Latin American perspective

ABSTRACT Objective: Although osteoporosis treatment guidelines include recommendations for calcium and vitamin D intake, routine use of adequate supplementation often is low. This study explored the attitudes of physicians and patients towards vitamin D and calcium and patient use of both supplements. Methods: A survey of randomly selected physicians in the United Kingdom, Mexico, and Austria, and the first seven eligible women with osteoporosis from each of their practices, was conducted. Physicians were asked to rate the importance of vitamin D and calcium in osteoporosis management on a scale of 1 to 10 (1 = not important at all, 10 = extremely important) and to estimate use of calcium and vitamin D supplements by their patients. Patients were asked about their own use of vitamin D and calcium, and their perceptions regarding these supplements. Results: Altogether 151 physicians (50 in Austria, 51 in the UK, and 50 in Mexico), and 910 osteoporosis patients (350 in Austria, 212 in UK, and 348 in Mexico) completed telephone surveys. Approximately, 86%, 28%, and 46% of physicians rated importance of vitamin D and calcium as being 9 or 10 in Austria, UK, and Mexico, respectively. Overall, 50% of patients reported taking calcium and vitamin D supplements (47% of these on a daily basis and 46% on a regular basis), and 19% of patients reported that they had no discussions with their physicians about calcium, while 39% reported no discussion about vitamin D. Conclusions: Despite the recognition by physicians and patients that vitamin D and calcium are important for bone health, only a small proportion of patients regularly take supplements. This is the case even when vitamin D and calcium supplements are provided free with osteoporosis drug prescriptions, as occurs in Austria. However, these results rely on patient self-report of compliance which can lead to overestimation. In addition this studys participants may not be representative of other patient populations. This study provides additional evidence that compliance with treatment guidelines is suboptimal, and highlights the need for further study to explore the discrepancy between the highly perceived importance of vitamin D and calcium and the low use of both supplements, and to improve use among osteoporosis patients.

Substantial under-treatment among women diagnosed with osteoporosis in a US managed-care population: a retrospective analysis

Abstract Background: Multiple therapies are approved for the treatment of osteoporosis (OP), but many patients with osteoporosis may not initiate treatment upon osteoporosis diagnosis. Objective: To characterize initiation of pharmacologic OP treatment among women within 1 year of OP diagnosis in a US managed care population. Research design and methods: The retrospective cohort study included women aged ≥55 years with a claims-documented diagnosis of OP who were naïve to OP medications prior to OP diagnosis (index date) during 2001–2010. Continuous enrollment for 12 months before (baseline) and after (follow-up) the index date was required. Patients who received OP medications but did not have an OP diagnosis were excluded. Differences in baseline characteristics between the treated and untreated cohorts were compared using Wilcoxon rank-sum (continuous variables) and chi-square tests (categorical variables). Main outcomes measures: During the follow-up period, the percentages of patients treated with bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid) and non-bisphosphonates (calcitonin, raloxifene, teriparatide) were determined. Results: A total of 65,344 patients, mean age 65.7 years, met study inclusion exclusion criteria. During the follow-up period, 42,033 patients (64.3%) received no OP medication and 23,311 patients (35.7%) received OP treatment. A total of 20,200 patients (30.9% of total study population) received bisphosphonates and 3111 (4.8% of total) patients received non-bisphosphonates as their index medication. At baseline, untreated patients were slightly older and had higher rates of hypertension, chronic inflammatory joint disease, diabetes mellitus, and gastrointestinal events (p ≤ 0.01) compared with treated patients. Conclusions: Among women aged ≥55 years in a US managed-care population, 64.3% received no pharmacologic treatment within 1 year after being diagnosed with OP. The authors were not able to determine if untreated patients did not receive or did not fill a prescription. Further research is needed to understand the barriers to OP treatment and reasons for non-treatment.

Estimation of resource utilization associated with osteoporotic hip fracture and level of post-acute care in China

ABSTRACT Objective: Research suggests that the incidence and cost of treating osteoporotic hip fracture (OHF) in China is rising. The purpose of this study was to estimate resource utilization associated with OHF, including hospital length of stay (LOS) and inpatient costs, and to examine the level of post-acute care for osteoporosis among patients hospitalized for OHF in Shanghai, China. Methods: This was a retrospective study of 2855 patients aged 50 years and older who were hospitalized for bone fragility hip fractures in 13 districts of Shanghai in the 2000. One hundred and one patients were randomly selected and interviewed to determine the treatments and associated costs for the 6-month period following hospitalization. Log linear regressions with bootstrapping resampling were conducted for LOS and hospital cost data to estimate the average LOS and associated costs after adjusting for demographic and comorbid characteristics. Results: Hospital records of 2855 patients (mean age, 73.6 ± 9.9 years) were reviewed. For women, mean LOS (35 days) was longer for those greater than 60 years of age; however, mean cost of hospital stay (15 082 RMB) increased to a peak at age 65–74 years (18 932 RMB). For men, mean LOS (34 days) and mean cost of hospitalization (13 149 RMB) both increased with age. Only 14% of patients hospitalized for OHF received treatment for osteoporosis. Due to the small number of patients and sampling that was taken largely for geographical convenience, care should be taken when generalizing these data into other areas of China. Conclusions: OHF is associated with substantial resource utilization in Shanghai, China. Although patients hospitalized with OHF should be considered for osteoporosis therapy to alleviate economic and patient burden, most patients with OHF received no such treatment.

Calcium and vitamin D intake by postmenopausal women with osteoporosis in France

Abstract Objective: To assess dietary calcium and vitamin D intake and their relationship with prescription medication and nutritional supplement use among postmenopausal women with osteoporosis in France. Research design and methods: Telephone interviews were conducted with 207 postmenopausal women with osteoporosis referred by a random sample of physicians from a French national list. Based on a French food frequency questionnaire, patients reported their daily food intake and frequency as well as their use of prescription medications and nutritional supplements. Results: Average daily dietary vitamin D intake was only 144.8 IU (SD 84.6, p < 0.01 compared to the recommended 800 IU), with 30% of the sample taking a vitamin D supplement. No participant had more than 500 IU vitamin D daily from food alone and 78% had less than 200 IU per day. A total of 51% of patients took no vitamin D supplements and had less than 5 hours of sun exposure in a week. Patients who were receiving osteoporosis medications and those who were not had comparable vitamin D intake. The average daily dietary calcium intake was 966.4 mg (SD 273.7, p < 0.01 compared to the 800 mg recommended). Calcium supplements were taken by 38% of participants and older patients tended to take more. Limitations of the study include convenience sampling and patient self-report. Conclusions: Daily vitamin D intake among this sample of postmenopausal osteoporotic women in France was significantly lower than recommended dosages. At least 50% of these patients might benefit by adding vitamin D to their current therapy.