Estimating the economic burden of osteoporotic fractures in a multinational study: a real-world data perspective.

Fracture-related costs vary by country. A standardized methodology and presentations were proposed to fairly assess the economic burden of osteoporotic fracture. Results indicated substantial costs of osteoporotic fractures for pharmacy, hospitalization, emergency care, and outpatient visits in women aged ≥ 50 years in Australia, Germany, South Korea, Spain, and the USA. PURPOSE: The objective of this multinational, retrospective matched cohort study was to use a standardized methodology across different healthcare systems to estimate the burden of osteoporotic fracture (OF) in women aged ≥ 50 years in Australia, Germany, South Korea, Spain, and the USA. METHODS: Within each country, healthcare resource utilization and direct costs of care were compared between patients with newly identified OF and a propensity score-matched cohort without OF during follow-up periods of up to 5 years. RESULTS: Across all five countries, the OF cohort had significantly higher rates and length of inpatient admissions compared with the non-OF cohort. In each country, the adjusted total costs of care ratio between OF and non-OF cohorts were significant. The adjusted cost ratios for pharmacy, inpatient care, emergency care, and outpatient visits were similarly higher in the OF cohort across countries. CONCLUSION: The current study demonstrates the substantial economic burden of OF across different countries when compared with matched non-OF patients. The findings would assist stakeholders and policymakers in developing appropriate health policies.

Comparative safety of flavocoxid vs prescription NSAIDs among osteoarthritis patients.

OBJECTIVE: Flavocoxid is a prescription medical food used to manage osteoarthritis (OA) symptoms. Safety concerns based on case reports raised an association with acute liver injury and hypersensitivity pneumonitis. We determined incidence rates (IR) of these safety events in a cohort of new users of flavocoxid and prescription non-steroidal anti-inflammatory drugs (NSAIDs). METHOD: MarketScan® claims data (2006-2017) was used to identify patients initiating flavocoxid or NSAIDs. Propensity score matching (1:2 ratio) was used to balance patient characteristics. Outcomes included hospitalization for hypersensitivity pneumonitis, liver injury, gastrointestinal bleeding, myocardial infarction, and acute kidney injury. Poisson regression was used to calculate IRs and Cox regression for calculating adjusted hazard ratios (aHR). RESULTS: 3,337 flavocoxid and 6,674 NSAID users met eligibility criteria. Before matching, flavocoxid users were older (mean 57 vs 51 years), had more polypharmacy (68% vs 29% taking ≥11 medications). After matching, characteristics were well balanced. The rate of hypersensitivity pneumonitis was 1.1 (95% CI 0.0-5.9) per 1,000 PY for flavocoxid and 0.0 (95% CI 0.0-2.2) for NSAIDs. For hospitalized liver injury, it was 3.2 (95% CI 0.7-9.3) for flavocoxid and 2.4 (95% CI 0.7-6.1) for NSAIDs, aHR = 1.16, 95% CI 0.23-6.01. A lower rate of GI bleed was observed, IR: 5.3 (1.7-12.3) for flavocoxid and 10.2 (5.9-16.3) for NSAIDs, aHR 0.49 (0.18-1.68). There were no significant differences for MI or AKI. CONCLUSION: The rate of hypersensitivity pneumonitis and liver injury associated with flavocoxid was low and minimally elevated compared to NSAIDs. Flavocoxid users had a significantly lower risk for hospitalized GI bleeding. The risk-benefit profile of flavocoxid may warrant reevaluation in light of these findings.

Osteoporotic fracture trends in a population of US managed care enrollees from 2007 to 2017.

This study expands on previous findings that hip fracture rates may no longer be declining. We found that age- and sex-adjusted fracture rates in the US plateaued or increased through mid-2017 in a population of commercially insured and Medicare Advantage health plan enrollees, in contrast to a decline from 2007 to 2013. INTRODUCTION: The purpose of this study was to evaluate fracture trends in US commercial and Medicare Advantage health plan members aged ≥ 50 years between 2007 and 2017. METHODS: Retrospective analysis of the Optum Research Database from January 1, 2007, to May 31, 2017. RESULTS: Of 1,841,263 patients identified with an index fracture, 930,690 were case-qualifying and included in this analysis. The overall age- and sex-adjusted fracture rate decreased from 14.67/1000 person-years (py) in 2007 to 11.79/1000 py in 2013, followed by a plateau for the next 3 years and then an increase to 12.50/1000 py in mid-2017. In females aged ≥ 65 years, fracture rates declined from 27.49/1000 py in 2007 to 22.08/1000 py in 2013, then increased to 24.92/1000 py in mid-2017. Likewise, fracture rates in males aged ≥ 65 years declined from 2007 (12.00/1000 py) to 2013 (10.72/1000 py), then increased to 12.04/1000 py in mid-2017. The age- and sex-adjusted fracture rates for most fracture sites declined from 2007 to 2013 by 3.7% per year (P = 0.310). CONCLUSIONS: Following a consistent decline in fracture rate from 2007 to 2013, trends from 2014 to 2017 indicate fracture rates are no longer declining and, for some fracture types, rates are rising.

Factors associated with the contemplative stage of readiness to initiate osteoporosis treatment.

We investigated the factors associated with readiness for initiating osteoporosis treatment in women at high risk of fracture. We found that women in the contemplative stage were more likely to report previously being told having osteoporosis or osteopenia, acknowledge concern about osteoporosis, and disclose prior osteoporosis treatment. INTRODUCTION: Understanding factors associated with reaching the contemplative stage of readiness to initiate osteoporosis treatment may inform the design of behavioral interventions to improve osteoporosis treatment uptake in women at high risk for fracture. METHODS: We measured readiness to initiate osteoporosis treatment using a modified form of the Weinstein Precaution Adoption Process Model (PAPM) among 2684 women at high risk of fracture from the Activating Patients at Risk for OsteoPOroSis (APROPOS) clinical trial. Pre-contemplative participants were those who self-classified in the unaware and unengaged stages of PAPM (stages 1 and 2). Contemplative participants were those in the undecided, decided not to act, or decided to act stages of PAPM (stages 3, 4, and 5). Using multivariable logistic regression, we evaluated participant characteristics associated with levels of readiness to initiate osteoporosis treatment. RESULTS: Overall, 24% (N = 412) self-classified in the contemplative stage of readiness to initiate osteoporosis treatment. After adjusting for age, race, education, health literacy, and major osteoporotic fracture in the past 12 months, contemplative women were more likely to report previously being told they had osteoporosis or osteopenia (adjusted odds ratio [aOR] (95% CI) 11.8 (7.8-17.9) and 3.8 (2.5-5.6), respectively), acknowledge concern about osteoporosis (aOR 3.5 (2.5-4.9)), and disclose prior osteoporosis treatment (aOR 4.5 (3.3-6.3)) than women who self-classified as pre-contemplative. CONCLUSIONS: For women at high risk for future fractures, ensuring women's recognition of their diagnosis of osteoporosis/osteopenia and addressing their concerns about osteoporosis are critical components to consider when attempting to influence stage of behavior transitions in osteoporosis treatment.

Risk of subsequent fracture after prior fracture among older women.

Among 377,561 female Medicare beneficiaries who sustained a fracture, 10% had another fracture within 1 year, 18% within 2 years, and 31% within 5 years. Timely management to reduce risk of subsequent fracture is warranted following all nontraumatic fractures, including nonhip nonvertebral fractures, in older women. INTRODUCTION: Prior fracture is a strong predictor of subsequent fracture; however, postfracture treatment rates are low. Quantifying imminent (12-24 month) risk of subsequent fracture in older women may clarify the need for early postfracture management. METHODS: This retrospective cohort study used Medicare administrative claims data. Women ≥ 65 years who sustained a clinical fracture (clinical vertebral and nonvertebral fracture; index date) and were continuously enrolled for 1-year pre-index and ≥ 1-year (≥  2 or ≥ 5 years for outcomes at those time points) post-index were included. Cumulative incidence of subsequent fracture was calculated from 30 days post-index to 1, 2, and 5 years post-index. For appendicular fractures, only those requiring hospitalization or surgical repair were counted. Death was considered a competing risk. RESULTS: Among 377,561 women (210,621 and 10,969 for 2- and 5-year outcomes), cumulative risk of subsequent fracture was 10%, 18%, and 31% at 1, 2, and 5 years post-index, respectively. Among women age 65-74 years with initial clinical vertebral, hip, pelvis, femur, or clavicle fractures and all women ≥ 75 years regardless of initial fracture site (except ankle and tibia/fibula), 7-14% fractured again within 1 year depending on initial fracture site; risk rose to 15-26% within 2 years and 28-42% within 5 years. Risk of subsequent hip fracture exceeded 3% within 5 years in all women studied, except those < 75 years with an initial tibia/fibula or ankle fracture. CONCLUSIONS: We observed a high and early risk of subsequent fracture following a broad array of initial fractures. Timely management with consideration of pharmacotherapy is warranted in older women following all fracture types evaluated.

Hip fracture trends in the United States, 2002 to 2015.

An analysis of United States (US) Medicare claims data from 2002 to 2015 for women aged ≥ 65 years found that age-adjusted hip fracture rates for 2013, 2014, and 2015 were higher than projected, resulting in an estimated increase of more than 11,000 hip fractures. INTRODUCTION: Hip fractures are a major public health concern due to high morbidity, mortality, and healthcare expenses. Previous studies have reported a decrease in the annual incidence of hip fractures in the US beginning in 1995, coincident with the introduction of modern diagnostic tools and therapeutic agents for osteoporosis. In recent years, there has been less bone density testing and fewer prescriptions for osteoporosis treatments. The large osteoporosis treatment gap raises concern of possible adverse effects on hip fracture rates. METHODS: We assessed hip fracture incidence in the US to determine if the previous decline in hip fracture incidence continued. Using 2002 to 2015 Medicare Part A and Part B claims for women ≥ 65 years old, we calculated age-adjusted hip fracture rates, weighting to the 2014 population. RESULTS: We found that hip fracture rates declined each year from 2002 to 2012 and then plateaued at levels higher than projected for years 2013, 2014, and 2015. CONCLUSIONS: The plateau in age-adjusted hip fracture incidence rate resulted in more than 11,000 additional estimated hip fractures over the time periods 2013, 2014, and 2015. We recommend further study to assess all factors contributing to this remarkable change in hip fracture rate and to develop strategies to reduce the osteoporosis treatment gap.

Correction to: Hip fracture trends in the United States, 2002 to 2015.

The name of the first author, E.M. Lewiecki, was rendered incorrectly in the original publication. The publisher regrets any inconvenience and is pleased to correct the error here.

Combining online and in-person methods to evaluate the content validity of PROMIS fatigue short forms in rheumatoid arthritis.

PURPOSE: Fatigue is frequent and often severe and disabling in RA, and there is no consensus on how to measure it. We used online surveys and in-person interviews to evaluate PROMIS Fatigue 7a and 8a short forms (SFs) in people with RA. METHODS: We recruited people with RA from an online patient community (n = 200) and three academic medical centers (n = 84) in the US. Participants completed both SFs then rated the comprehensiveness and comprehensibility of the items to their fatigue experience. Cognitive debriefing of items was conducted in a subset of 32 clinic patients. Descriptive statistics were calculated, and associations were evaluated using Pearson and Spearman correlation coefficients. RESULTS: Mean SF scores were similar (p ≥ .61) among clinic patients reflecting mild fatigue (i.e., 54.5-55.9), but were significantly higher (p < .001) in online participants. SF Fatigue scores correlated highly (r ≥ 0.82; p < .000) and moderately with patient assessments of disease activity (r ≥ 0.62; p = .000). Most (70-92%) reported that the items "completely" or "mostly" reflected their experience. Almost all (≥ 94%) could distinguish general fatigue from RA fatigue. Most (≥ 85%) rated individual items questions as "somewhat" or "very relevant" to their fatigue experience, averaged their fatigue over the past 7 days (58%), and rated fatigue impact versus severity (72 vs. 19%). 99% rated fatigue as an important symptom they considered when deciding how well their current treatment was controlling their RA. CONCLUSIONS: Results suggest that items in the single-score PROMIS Fatigue SFs demonstrate content validity and can adequately capture the wide range of fatigue experiences of people with RA.

The cost of a patient activation intervention for achieving successful outcomes: results from the PAADRN randomized controlled trial.

In a large, pragmatic clinical trial, we calculated the costs of achieving four successful patient-centered outcomes using a tailored patient activation DXA result letter accompanied by a bone health brochure. The cost to achieve one successful outcome (e.g., a 0.5 standard deviation improvement in care satisfaction) ranged from $127.41 to $222.75. INTRODUCTION: Pragmatic randomized controlled trials (RCTs) should focus on patient-centered outcomes and report the costs for achieving those outcomes. We calculated per person incremental intervention costs, the number-needed-to-treat (NNT), and incremental per patient costs (cost per NNT) for four patient-centered outcomes in a direct-to-patient bone healthcare intervention. METHODS: The Patient Activation after DXA Result Notification (PAADRN) pragmatic RCT enrolled 7749 patients presenting for DXA at three health centers between February 2012 and August 2014. Interviews occurred at baseline and 52 weeks post-DXA. Intervention subjects received an individually tailored DXA result letter accompanied by an educational bone health brochure 4 weeks post-DXA, while the usual care subjects did not. Outcomes focused on patients (a) correctly identifying their results, (b) contacting their providers, (c) discussing their results with their providers, and (d) satisfaction with their bone healthcare. NNTs were determined using intention-to-treat linear probability models, per person incremental intervention costs were calculated, and costs per NNT were computed. RESULTS: Mean age was 66.6 years old, 83.8% were women, and 75.3% were non-Hispanic whites. The incremental per patient cost (costs per NNT) to increase the ability of a patient to (a) correctly identify their DXA result was $171.07; (b) contact their provider about their DXA result was $222.75; (c) discuss their DXA result with their provider was $193.55; and (d) achieve a 0.5 SD improvement in satisfaction with their bone healthcare was $127.41. CONCLUSION: An individually tailored DXA result letter accompanied by an educational brochure can improve four patient-centered outcomes at a modest cost. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT01507662.

Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study.

The Effectiveness of Discontinuing Bisphosphonates (EDGE) study is a planned pragmatic clinical trial to guide "drug holiday" clinical decision making. This pilot study assessed work flow and feasibility of such a study. While participant recruitment and treatment adherence were suboptimal, administrative procedures were generally feasible and minimally disrupted clinic flow. INTRODUCTION: The comparative effectiveness of continuing or discontinuing long-term alendronate (ALN) on fractures is unknown. A large pragmatic ALN discontinuation study has potential to answer this question. METHODS: We conducted a 6-month pilot study of the planned the EDGE study among current long-term ALN users (women aged ≥65 with ≥3 years of ALN use) to determine study work flow and feasibility including evaluating the administrative aspects of trial conduct (e.g., time to contract, institutional review board (IRB) approval), assessing rates of site and participant recruitment, and evaluating post-randomization outcomes, including adherence, bisphosphonate-associated adverse events, and participant and site satisfaction. We assessed outcomes 1 and 6 months after randomization. RESULTS: Nine sites participated, including seven community-based medical practices and two academic medical centers. On average (SD), contract execution took 3.4 (2.3) months and IRB approval took 13.9 (4.1) days. Sites recruited 27 participants (13 to continue ALN and 14 to discontinue ALN). Over follow-up, 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported. Sites reported no issues regarding work flow, and participants were highly satisfied with the study. CONCLUSIONS: Administrative procedures of the EDGE study were generally feasible, with minimal disruption to clinic flow. In this convenience sample, participant recruitment was suboptimal across most practice sites. Accounting for low treatment arm adherence, a comprehensive recruitment approach will be needed to effectively achieve the scientific goals of the EDGE study.

Impact of neighbourhood-level inequity on paediatric diabetes care.

AIMS: To evaluate the association between neighbourhood-level inequity and glycaemic control in paediatric participants with Type 1 diabetes using the Neighbourhood Equity Index (NEI). METHODS: The NEI was linked to the clinical data of 519 children with diabetes followed at the Hospital for Sick Children (Toronto, Canada). The NEI is a composite measure of inequity developed using the World Health Organization's Urban Health Equity Assessment and Response Tool (HEART), which encompasses 15 weighted indicators evaluating economic, social, environmental and lifestyle factors. The geographic distribution of participants was determined using postal codes, and the relationship between HbA1c and NEI was evaluated using regression and spatial analysis techniques. RESULTS: Participants' mean HbA1c was significantly correlated with NEI (R = -0.24, P < 0.0001). Regression analysis demonstrated that NEI was a strong predictor of mean HbA1c (P < 0.0001), accounting for differences in HbA1c as large as 1.0% (11 mmol/mol) when controlled for age, sex, diabetes duration, insulin pump therapy and number of annual clinic visits. Geo-mapping using spatial scan testing revealed the presence of two clusters of low-equity neighbourhoods containing 3.22 (P = 0.001) and 2.83 (P = 0.02) times more participants with HbA1c ≥ 9.5% (80 mmol/mol) than expected. CONCLUSIONS: Our findings demonstrated that NEI was a significant predictor of HbA1c in our clinic population and a useful tool for investigating spatial trends related to inequities in health, providing evidence that a composite, area-based measure of overall inequity is well suited to the study of glycaemic control in urban paediatric Type 1 diabetes populations.

Glucocorticoid exposure and fracture risk in patients with new-onset rheumatoid arthritis.

Retrospective claims analysis indicated that high levels of daily and cumulative doses of systemic glucocorticoids were associated with elevated fracture risk in a large cohort of new RA patients under age 65. Heightened risk began to decline within months of discontinuation. Findings were similar among patients age <50 years. INTRODUCTION: We evaluated the impact of systemic glucocorticoid exposure on fracture risk among relatively young patients with new-onset rheumatoid arthritis (RA). METHODS: Using administrative data, we identified 42,127 RA patients diagnosed January 1, 2005-December 31, 2012, age 18-64 years, with benefits coverage for ≥12 months before RA diagnosis. Follow-up extended to clinical fracture, cancer diagnosis, or December 31, 2012. Glucocorticoid users were new to therapy. Fracture incidence rates (IR) were stratified by glucocorticoid exposure expressed as prednisone equivalent doses. Cox's proportional hazards models estimated fracture risk adjusted for demographics and baseline clinical characteristics to assess dose-response relationships with current (daily) and prior (cumulative) dose, and by time since discontinuation. RESULTS: Most patients (85 %) had glucocorticoid exposure. Exposed and unexposed patients were demographically similar (74 % female; mean age 49.7 and 48.8 years); 1 % had prior fracture. Fracture IRs (95 % confidence intervals) were 5 to 9 per 1000 person-years at doses <15 mg/day, 16.0 (11.0, 22.6) at doses ≥15 mg/day, and 13.4 (10.7, 16.7) at cumulative doses ≥5400 mg. Adjusted fracture risk was approximately 2-fold higher at highest dose levels compared with 0 mg/day current daily dose and <675 mg cumulative dose, respectively. Fracture risk was 29 % lower at 60-182 days post-discontinuation compared with ongoing use and was similar to unexposed patients by 12 months. Findings were similar among patients age <50 years. CONCLUSIONS: Among younger, new-onset RA patients, fracture risk was significantly elevated at high levels of daily and cumulative dose, and was similar to unexposed patients by 12 months post-discontinuation.

Patient's experience with subcutaneous and oral methotrexate for the treatment of rheumatoid arthritis.

BACKGROUND: Despite the prominent position of methotrexate (MTX) in Rheumatoid Arthiris (RA) therapeutics, its real-world effectiveness may be influenced by a relative lack of tolerability or other side effects that physicians may not be aware of but that are bothersome to patients. The aim of this study is to identify suboptimal patient experience with MTX and to raise awareness for clinicians to identify opportunities to mitigate bothersome symptoms and side effects and optimize response to MTX. METHODS: We conducted a prospective, cross-sectional, online survey among RA patients who were members of Creakyjoints, a large arthritis patient community. Eligible participants must have recently initiated a new biologic, subcutaneous (SQ) MTX, or oral MTX in the last 12 months and were uniquely assigned to one of these 3 groups. Descriptive statistics were used to compare patient-reported side effects and tolerability related to MTX use in the 3 medication groups (SQ MTX, oral MTX, and biologic). RESULTS: A total of 382 (85 %) of 448 eligible patients completed the survey and were grouped as: biologic (n = 218), SQ MTX (n = 49), and oral MTX (n = 115). Demographics were mean standard deviation (SD) age 48 (10) years, 92 % white, 91 % women. Symptoms significantly more prevalent in the SQ and oral MTX groups included diarrhea, fatigue, malaise, and hair loss. Injection related pain was lower with SQ MTX compared to SQ biologics. Out of a total of 8 potential symptoms and side effects examined, higher dose MTX (> = 20 mg/week) was associated with a 2.26 (1.25-4.09) greater likelihood of more side effects referent to < =10 mg/week. CONCLUSION: Results from this real-world RA patient cohort suggest that MTX is accompanied by many patient-reported side effects and tolerability problems that may be under-recognized by physicians. These may impact both treatment satisfaction and medication adherence.

An evaluation of clinical risk factors for estimating fracture risk in postmenopausal osteoporosis using an electronic medical record database.

SUMMARY: Many of the clinical risk factors used in fracture risk assessment (FRAX) calculator are available in electronic medical record (EMR) databases and are good sources of osteoporosis risk factor information. The EPIC EMR database showed a lower prevalence of FRAX risk factors and, consequently, proportion of patients who would be deemed "high risk." INTRODUCTION: The FRAX tool is underutilized for osteoporosis screening. Many of the clinical risk factors for FRAX may be available in EMR databases and may enable health systems to perform fracture risk assessments. We intended to identify variables in an EMR database for calculating FRAX score in a cohort of postmenopausal women, to estimate absolute fracture risk, and to determine the proportions of women whose absolute fracture risks exceed the National Osteoporosis Foundation (NOF) thresholds. METHODS: Our cohort was selected using an EMR database with demographic, inpatient, outpatient, and clinical information for female patients age≥50 in a family practice, internal medicine, or obstetrics/gynecology clinic in 2007-2008. The latest physician encounter was the index date. Variables, problem and medication lists, diagnosis codes, and histories from the EMR were used to populate the 11 clinical risk factor variables used in the FRAX. These risk factor prevalence and treatment-eligible proportions were compared to those of published epidemiology studies. RESULTS: The study included 345 patients. Mean (SD) 10-year risk for any major fracture was 11.1% (6.8) when bone mineral density (BMD) was used and 11.2% (6.5) when BMI was used. About 10.1% of the cohort exceeded the NOF's 20% major fracture risk threshold and 32.5% exceeded the NOF's 3% hip fracture risk threshold when BMD was used. Overall, the number of treatment-eligible patients was slightly lower when FRAX was calculated using BMD versus BMI (13.6 and 36.8%). CONCLUSION: Our cohort using EMR data most likely underestimated the mean 10-year probability of any major fracture compared to other cohorts in published literature. The difference may be in the nature of EMRs for supporting only passive data collection of risk factor information.

Genetic variants associated with methotrexate efficacy and toxicity in early rheumatoid arthritis: results from the treatment of early aggressive rheumatoid arthritis trial.

Methotrexate (MTX) has emerged as first-line therapy for early moderate-to-severe rheumatoid arthritis (RA), but individual variation in treatment response remains unexplained. We tested the associations between 863 known pharmacogenetic variants and MTX response in 471 Treatment of Early Aggressive Rheumatoid Arthritis Trial participants with early RA. Efficacy and toxicity were modeled using multiple regression, adjusted for demographic and clinical covariates. Penalized regression models were used to test joint associations of markers and/or covariates with the outcomes. The strongest genetic associations with efficacy were in CHST11 (five markers with P<0.003), encoding carbohydrate (chondroitin 4) sulfotransferase 11. Top markers associated with MTX toxicity were in the cytochrome p450 genes CYP20A1 and CYP39A1, solute carrier genes SLC22A2 and SLC7A7, and the mitochondrial aldehyde dehydrogenase gene ALDH2. The selected markers explained a consistently higher proportion of variation in toxicity than efficacy. These findings could inform future development of personalized therapeutic approaches.

Use of pharmacologic agents for the primary prevention of osteoporosis among older women with low bone mass.

UNLABELLED: We examined the use of pharmacologic agents for the primary prevention of osteoporosis among older women with osteopenia. We found that these individuals were not managed in concordance with the National Osteoporosis Foundation (NOF) guidelines and that self-perceived osteoporosis risk and lower bone density were strongly associated with receipt of treatment. INTRODUCTION: Although osteoporosis medications are used for the primary prevention of osteoporosis among persons with low bone mass (osteopenia), their use may be discordant with clinical practice guidelines. METHODS: We studied women 55 years and older participating in the Global Longitudinal Study of Osteoporosis in Women (GLOW). Eligible participants had a dual energy x-ray absorptiometry (DXA) test performed at the University of Alabama at Birmingham hospital and had an osteopenia diagnosis based on their DXA test results. Participants' demographics, fracture risk factors, and exposure to osteoporosis medications were determined from the GLOW survey. We examined the proportions of women managed in concordance with the National Osteoporosis Foundation 2008 guidelines, and we assessed factors independently associated with osteoporosis treatment decisions. Women with a prior spine or hip fracture were excluded. RESULTS: Among 597 eligible women from GLOW, the mean age ± standard deviation (SD) was 70 ± 7 years. Among all subjects, 309 (52%) were treated in concordance with the NOF 2008 guidelines. Greater self-perceived osteoporosis risk and lower bone mineral density were significantly and consistently associated with receipt of osteoporosis treatment, both for those considered appropriate and for those considered inappropriate for treatment based on the NOF guidelines. CONCLUSIONS: We found significant discordance between NOF 2008 guidelines and pharmacologic management of women with osteopenia. A person's self-perceived osteoporosis risk and bone mineral density were most strongly associated with receipt of osteoporosis medication use among women with low bone mass.

Initiation of TNF inhibitor therapy and change in physiologic measures in psoriasis.

BACKGROUND: Psoriasis may predispose to cardiovascular disease and diabetes. However, the role of tumor necrosis factor (TNF) inhibitor in mediating this risk is controversial. OBJECTIVE: To assess this relationship, we estimated change in metabolic physiologic measures before and after initiation of TNF inhibitor therapy compared with methotrexate (MTX) therapy among psoriasis patients. METHODS: We conducted a retrospective cohort study, 2007-2012, using computerized clinical data for 1274 new users of TNF inhibitor and 979 new users of MTX therapy to compare change in blood pressure, lipids, triglycerides, fasting plasma glucose and body mass index (BMI) before and after start of TNF inhibitors or MTX. The study was restricted to new users. We computed within-person change in each measure, so that each patient served as their own control. In addition, we compared TNF inhibitor patients to MTX patients, by computing the adjusted difference in their group means. In secondary analyses, we examined phototherapy as a comparator. RESULTS: Among starters of TNF inhibitor and MTX therapy, within-person change in physiologic measures at 6 months did not differ significantly. We observed no important or significant changes in any of the physiologic measures with initiation of TNF inhibitor compared with MTX. The same results were found in subgroup analyses focused on men, and on those with hypertension, diabetes mellitus, or obesity. The same results were observed with phototherapy, except that diastolic blood pressure declined by 0.6 mmHg within person during the 6 months after starting phototherapy (P < 0.05). CONCLUSIONS: The study provides no evidence for improvement of physiologic measures associated with the metabolic syndrome resulting from TNF inhibitor use for psoriasis.

Mycobacterial diseases and antitumour necrosis factor therapy in USA.

OBJECTIVE: In North America, tuberculosis and nontuberculous mycobacterial (NTM) disease rates associated with antitumour necrosis factor α (anti-TNFα) therapy are unknown. METHODS: At Kaiser Permanente Northern California, the authors searched automated pharmacy records to identify inflammatory disease patients who received anti-TNF therapy during 2000-2008 and used validated electronic search algorithms to identify NTM and tuberculosis cases occurring during anti-TNF drug exposure. RESULTS: Of 8418 anti-TNF users identified, 60% had rheumatoid arthritis (RA). Among anti-TNF users, 18 developed NTM and 16 tuberculosis after drug start. Anti-TNF associated rates of NTM and tuberculosis were 74 (95% CI: 37 to 111) and 49 (95% CI: 18 to 79) per 100 000 person-years, respectively. Rates (per 100, 000 person-years) for NTM and tuberculosis respectively for etanercept were 35 (95% CI: 1 to 69) and 17 (95% CI: 0 to 41); infliximab, 116 (95% CI: 30 to 203) and 83 (95% CI: 10 to 156); and adalimumab, 122 (95% CI: 3 to 241) and 91 (95% CI: 19 to 267). Background rates for NTM and tuberculosis in unexposed RA-patients were 19.2 (14.2 to 25.0) and 8.7 (5.3 to 13.2), and in the general population were 4.1 (95% CI 3.9 to 4.4) and 2.8 (95% CI 2.6 to 3.0) per 100, 000 person-years. Among anti-TNF users, compared with uninfected individuals, NTM case-patients were older (median age 68 vs 50 years, p<0.01) and more likely to have RA (100% vs 60%, p<0.01); whereas, tuberculosis case-patients were more likely to have diabetes (37% vs 16%, p=0.02) or chronic renal disease (25% vs 6%, p=0.02). CONCLUSIONS: Among anti-TNF users in USA, mycobacterial disease rates are elevated, and NTM is associated with RA.

Heart failure risk among patients with rheumatoid arthritis starting a TNF antagonist.

BACKGROUND: While heart failure (HF) is associated with elevations in tumor necrosis factor (TNF)α, several trials of TNF antagonists showed no benefit and possibly worsening of disease in those with known severe HF. We studied the risk of new or recurrent HF among a group of patients receiving these agents to treat rheumatoid arthritis (RA). METHODS: We used data from four different US healthcare programmes. Subjects with RA receiving methotrexate were eligible to enter the study cohort if they added or switched to a TNF antagonist or another non-biological disease modifying antirheumatic drug (nbDMARD). These groups were compared in Cox regression models stratified by propensity score decile and adjusted for oral glucocorticoid dosage, prior HF hospitalisations, and the use of loop diuretics. RESULTS: We compared 8656 new users of a nbDMARD with 11 587 new users of a TNF antagonist with similar baseline covariates. The HR for the TNF antagonists compared with nbDMARD was 0.85 (95% CI 0.63 to 1.14). The HR was also not elevated in subjects with a history of HF. But, it was elevated prior to 2002 (HR 2.17, 95% CI 0.45 to 10.50, test for interaction p=0.036). Oral glucocorticoids were associated with a dose-related gradient of HF risk: compared with no use, 1≤5 mg HR 1.30 (95% CI 0.91 to 1.85), ≥5 mg HR 1.54 (95% CI 1.09 to 2.19). CONCLUSIONS: TNF antagonists were not associated with a risk of HF hospital admissions compared with nbDMARDs in this RA population.

Performance of FRAX in a cohort of community-dwelling, ambulatory older men: the Osteoporotic Fractures in Men (MrOS) study.

UNLABELLED: We evaluated performance of FRAX in older men who participated in the Osteoporotic Fractures in Men (MrOS) study. INTRODUCTION: FRAX has been extensively studied in women, but there are few studies of its performance in men. METHODS: FRAX estimates for 10-year hip fracture and major osteoporotic fracture (MOF; either hip, clinical spine, forearm, or shoulder) were calculated from data obtained from MrOS participants and compared to observed 10-year fracture cumulative incidence calculated using product limit estimate methods, accounting for competing mortality risk. RESULTS: Five thousand eight hundred ninety-one men were followed for an average of 8.4 years. Without bone mineral density (BMD) in the FRAX model, the mean 10-year predicted fracture probabilities for hip and MOF were 3.5% and 8.9%, respectively; addition of BMD to the calculations reduced these estimates to 2.3% and 7.6%. Using FRAX without BMD, predicted quintile probabilities closely estimated cumulative incidence of hip fracture (range of observed to predicted ratios 0.9-1.1). However, with BMD in the FRAX calculation, observed to predicted hip fracture probabilities were not close to unity and varied markedly across quintiles of predicted probability. For MOF, FRAX without BMD overestimated observed cumulative incidence (range of observed to predicted ratios 0.7-0.9) and addition of BMD did not improve this discrepancy (range of observed to predicted ratios 0.7-1.1). Addition of BMD to the calculation had mixed effects on the discriminatory performance of FRAX, depending on the analysis tool applied. CONCLUSION: Among this cohort of community-dwelling older men, the FRAX risk calculator without BMD was well calibrated to hip fracture but less well to MOF.