Efficacy of osteoporosis pharmacotherapies in preventing fracture among oral glucocorticoid users: a network meta-analysis.

UNLABELLED: Efficacy of osteoporosis medication is not well-established among patients taking oral glucocorticoids. We assessed the efficacy of approved osteoporosis pharmacotherapies in preventing fracture by combining data from randomized controlled trials. Teriparatide, risedronate, and etidronate were associated with decreased vertebral fracture risk. INTRODUCTION: Several osteoporosis drugs are approved for the prevention and treatment of glucocorticoid (GC)-induced osteoporosis. However, the efficacy of these treatments among oral GC users is still limited. We aimed to examine the comparative efficacy of osteoporosis treatments among oral GC users. METHODS: We updated a systematic review through to March 2015 to identify all double-blinded randomized controlled trials (RCTs) that examined osteoporosis treatment among oral GC users. We used a network meta-analysis with informative priors to derive comparative risk ratios (RRs) and 95 % credible intervals (95 % CrI) for vertebral and non-vertebral fracture and mean differences in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD). Treatment ranking was estimated using the surface under the cumulative ranking curve (SUCRA) statistic. A meta-regression was completed to assess a subgroup effect between patients with prior GC exposures and GC initiators. RESULTS: We identified 27 eligible RCTs examining nine active comparators. Etidronate (RR, 0.41; 95%CrI = 0.17-0.90), risedronate (RR = 0.30, 95%CrI = 0.14-0.61), and teriparatide (RR = 0.07, 95%CrI = 0.001-0.48) showed greater efficacy than placebo in preventing vertebral fractures; yet, no treatment effects were statistically significant in reducing non-vertebral fractures. Alendronate, risedronate, and etidronate increased LS BMD while alendronate and raloxifene increased FN BMD. In preventing vertebral fractures, teriparatide was ranked as the best treatment (SUCRA: 77 %), followed by risedronate (77 %) and zoledronic acid (76 %). For non-vertebral fractures, teriparatide also had the highest SUCRA (69 %), followed by risedronate (64 %). No subgroup effect was identified with regards to prior GC exposure. CONCLUSIONS: Despite weak trial evidence available for fracture prevention among GC users, we identified several drugs that are likely to prevent osteoporotic fracture. Teriparatide, risedronate, and etidronate were associated with decreased vertebral fracture risk.

Fracture risk in oral glucocorticoid users: a Bayesian meta-regression leveraging control arms of osteoporosis clinical trials.

UNLABELLED: Little data exist on the frequency of fracture among oral glucocorticoid users. We examined the effect of oral glucocorticoids on fracture incidence using data from randomized controlled trials. Patients starting glucocorticoids had a higher probability of fracture and decline in bone mineral density compared to chronic glucocorticoid users. INTRODUCTION: Oral glucocorticoids (GCs) are the leading cause of secondary osteoporosis. However, there have been few studies that quantify the rate of fracture among GC users. We sought to provide a pooled estimate of fracture risk from randomized controlled trials (RCTs) of GC-treated patients. METHODS: We updated a MEDLINE search published by the American College of Rheumatology through to March 2015 and identified RCTs of osteoporosis therapies that reported fracture and bone mineral density (BMD) among oral GC users. We restricted the analysis to placebo or control arms. RCT arms were stratified by GC exposure at enrolment to GC initiators (≤6 months) and chronic GC users (>6 months). Bayesian meta-regression was used to estimate the annual probability of vertebral fracture (primary), non-vertebral fracture and percentage change in lumbar spine and femoral neck BMD. RESULTS: The annual incidence of vertebral and non-vertebral fracture was 5.1 % (95 % CrI = 2.8-8.2) and 2.5 % (95 % CrI = 1.2--4.2) among GC initiators, and 3.2 % (95 % CrI = 1.8-5.0) and 3.0 % (95 % CrI = 0.8-5.9) among chronic GC users. Our meta-regression identified a non-significant effect of group-level variables (mean age, mean BMD, mean GC daily dose, patients with previous vertebral fractures, proportion of women and adjuvant used) on vertebral fracture rate. CONCLUSION: Our study found higher vertebral fracture incidence among GC initiators, yet a relative decline in fracture incidence with longer exposure. Our findings suggest that fracture incidence among oral GC users may be more common than previously estimated. Optimizing GC-induced osteoporosis management during early exposure to GC is essential to prevent fractures.

Glucocorticoid-induced osteoporosis management among seniors, by year, sex, and indication, 1996-2012.

UNLABELLED: We identified that glucocorticoid-induced osteoporosis management (bone mineral density testing or osteoporosis treatment) among seniors improved among men (2 to 23 %) and women (10 to 48 %) between 1996 and 2007, and then remained relatively stable through to 2012. Differences were also noted by indication (from a low of 21 % for respiratory conditions to a high of 41 % for rheumatic conditions). PURPOSE: The aim of our study was to describe the proportion of chronic oral glucocorticoid (GC) users that receive osteoporosis management (bone mineral density test or osteoporosis treatment) by sex and over time. METHODS: We identified community-dwelling older adults initiating chronic oral GC therapy in Ontario using pharmacy data from 1996 to 2012. Chronic GC use was defined as greater than or equal to two oral GC prescriptions dispensed and ≥450 mg prednisone equivalent over a 6-month period. Osteoporosis management within 6 months of starting chronic GC therapy was examined by sex, year, indication for therapy, and osteoporosis management history. Results were summarized using descriptive statistics. RESULTS: We identified 72,099 men and 95,975 women starting chronic oral GC therapy (mean age = 74.9 years, SD = 6.5). Approximately two thirds of patients (65 %) received ≥900 mg within the 6-month chronic use window. GC-induced osteoporosis management increased from 2 to 23 % (men) and 10 to 48 % (women) between 1996 and 2007, and then remained relatively stable through to 2012. A higher proportion of patients with prior osteoporosis management were managed within 6 months (56 % men, 67 % women) of chronic GC use, compared to patients without prior management (12 % men, 23 % women). Patients with rheumatic disease were managed most commonly (41 %), and patients with respiratory conditions were managed least commonly (21 %). CONCLUSIONS: GC-induced osteoporosis management improved significantly over time for both sexes yet remains low. Significant care gaps by sex and between clinical areas represent a missed opportunity for fracture prevention among patients requiring chronic GC therapy.

The accuracy of self-reported weights.

The accuracy of self-reported weights was assessed by comparing reported weights with measured weights of 1302 subjects at eight different medical and nonmedical sites across two countries (United States and Denmark), across ages, sexes, and different purposes for the weight measurements. Self-reported weights were remarkably accurate across all these variables in the American sample, even among obese people, and may obviate the need for measured weights in epidemiological investigations. Danish reports were somewhat less accurate, particularly among women over 40 yr of age.

Evaluation and modification of exercise patterns in the natural environment.

Using a new experimental paradigm to evaluate physical activity in the natural environment, the authors made of 45,694 observations of persons using stairs or an adjacent escalator at a shopping mall, train station, and bus terminal. In study 1, stair use more than doubled for both obese and nonobese persons during two-week periods when a colorful sign encouraging use of the stairs was positioned at the stairs/escalator choice point. In study 2, stair use remained elevated for 15 consecutive days while the sign was present, decreased during a 1-month follow-up period, and returned to baseline by 3 months. These results not only demonstrate the usefulness of this paradigm, but also suggest the strength of simple, inexpensive public health interventions to increase physical activity.