Atopic dermatitis and bone health: a systematic review.

Atopic dermatitis (AD) is associated with systemic inflammation and systemic corticosteroid use which can lead to poor bone health. The aim of this systematic review is to investigate the relationship between AD and bone mineral density (BMD), osteoporosis and fractures. We searched Web of Science, Cochrane Database of Systematic Reviews, MEDLINE and Embase. Title, abstract and full-text screening, and data extraction were done in duplicate. Quality appraisal was performed using the Agency for Healthcare Research and Quality Methodology Checklist (cross-sectional studies) and Newcastle-Ottawa Scale (cohort studies). We screened 3800 abstracts and included fifteen studies (twelve cross-sectional, three cohort). In cross-sectional studies, AD was associated with decreased BMD and increased fractures. In cross-sectional studies and a cohort study, AD was associated with a higher prevalence of osteoporosis compared to controls. There was inconsistency across studies, with some finding no association. In a large cohort study, AD was associated with increased risk of fractures of the hip (HR: 1.06, 95% CI: 1.02 to 1.11), spine (HR: 1.14, 95% CI: 1.06 to 1.23) and wrist (HR: 1.06, 95% CI: 1.01 to 1.10), with further increased risk with more severe AD. Differences between studies precluded quantitative synthesis. There is some evidence supporting an association between AD and poor bone health. Research is needed to clarify this association, underlying mechanisms and develop strategies to improve bone health of individuals with AD.

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.

Uptake and characteristics of zoledronic acid and denosumab patients and physicians in Ontario, Canada: impact of drug formulary access.

UNLABELLED: The addition of Limited Use criteria (less restrictive access) for zoledronic acid resulted in an immediate and significant increase in uptake and resulted in differences in patient/physician characteristics. In comparison, the uptake of denosumab (only listed with Limited Use) was rapid. Thus, formulary access restrictions have significant implications for prescribing. INTRODUCTION: We sought to describe the use of zoledronic acid and denosumab by physicians and patients over time and examine the impact of a 2012 provincial formulary modification that removed the administrative burden on physicians when prescribing zoledronic acid. METHODS: We identified users of zoledronic acid and denosumab using Ontario pharmacy claims data. The number of new patients and physicians was plotted and examined over time. Interrupted time series analysis examined the impact of a formulary modification to zoledronic acid use and prescribing. Descriptive characteristics of patients and prescribers were summarized pre- and post-formulary modification for zoledronic acid and overall for denosumab. RESULTS: We identified 1463 zoledronic acid patients treated by 627 physicians and 16,736 denosumab patients treated by 2904 physicians. In the first 2 months on the market, we identified a rapid uptake of denosumab (>450 physicians and >1200 patients) in contrast to zoledronic acid (<10 physicians and <10 patients). Zoledronic acid use increased significantly in the 2-month post-formulary change, yet no change in denosumab was observed. Prior to the formulary modification, more zoledronic acid patients had a history of osteoporosis therapy (41 vs. 26%) or bone density testing (30 vs. 10%). Compared to zoledronic patients (post-formulary modification), more denosumab patients had prior osteoporosis therapy (55 vs. 26%), yet fewer had a gastrointestinal diagnosis (6 vs. 11%). CONCLUSION: We identified a rapid uptake of denosumab in only 15 months of observation. A provincial formulary modification to zoledronic acid resulted in an increase in utilization and impacted patient characteristics.

Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a network meta-analysis.

UNLABELLED: We completed a network meta-analysis of published papers to compare bisphosphonate gastrointestinal safety. We found that zoledronic acid had the highest chance of causing gastrointestinal adverse events. Etidronate had the highest chance of discontinuation due to an adverse event. No difference was found for serious adverse events. INTRODUCTION: Bisphosphonates are first-line treatment for osteoporosis. Gastrointestinal (GI) adverse events (AE) are the primary reason for non-adherence. Little is known about the comparative GI safety of bisphosphonates. PURPOSE: Leverage published clinical trial data to examine the comparative GI safety of bisphosphonates. METHODS: We completed a systematic review of all English-language clinical trials that assessed bisphosphonate safety and/or efficacy in primary osteoporosis through to 2012. Randomized, blinded, and controlled studies were eligible. The primary outcome was any GI-related AE. Subanalyses were completed for upper GI symptoms, serious GI, nausea, esophageal-related events, and discontinuation due to AE. A Bayesian-based network meta-analysis was completed to allow for indirect comparisons. Results were reported as the probability that a specific drug had the highest number of events. RESULTS: We identified 50 studies: 32 alendronate, 12 risedronate, 5 etidronate, and 7 zoledronic acid. Zoledronic acid had the highest probability of having the highest number of any GI AE (91%) and nausea (70%). Etidronate (70%) and zoledronic acid (28%) had the highest probability of having the greatest attrition due to AE. Etidronate had the highest probability (56%) of having the greatest number of upper GI symptoms among oral bisphosphonates. CONCLUSION: Zoledronic acid had the highest probability of causing the greatest number of GI AE, possibly related to nausea. These results question the assumption that annual zoledronic acid will translate into better adherence. Little difference was found between alendronate and risedronate for serious AE. More research into real-world implications of the comparative safety of bisphosphonates is needed.