Altered Bone Material Properties in HLA‐B27 Rats Include Reduced Mineral to Matrix Ratio and Altered Collagen Cross‐Links

Spondyloarthropathy and inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, are often associated with severe osteopenia/osteoporosis in both children and adults. HLA‐B27 transgenic rats present a phenotype that includes severe colitis and severely accelerated alveolar bone loss. The purpose of this study was to evaluate long bone density status, systemic bone metabolic markers, and intrinsic bone material properties in HLA‐B27 transgenic (TG) rats, and compare them with those of age‐ and sex‐matched wild‐type (WT) animals. The results indicate that in the HLA‐B27 rat, an animal susceptible to both alveolar bone loss (ABL) and long bone osteopenia, there is a statistically significant negative correlation between ABL and long bone bone mineral density (BMD), as well as mineral/matrix ratio at active bone‐forming trabecular surfaces. The TG animals had a lower mineral/matrix ratio and higher relative proteoglycan and advanced glycation end product (?‐N‐Carboxymethyl‐L‐lysine) content and pyridinoline/divalent collagen cross‐link ratio compared with WT. These results may provide better understanding of the interrelationship between osteoporosis and oral bone loss, the underlying causes of the inferior bone strength in the HLA‐B27 transgenic animals, and could prove to be a useful model in the elucidation of the pathophysiology of spondyloarthropathy and IBD‐associated osteopenia/osteoporosis and in the evaluation of pharmacological intervention(s) against such conditions. © 2014 American Society for Bone and Mineral Research.     

An approach for modelling multiple correlated outcomes in a network of interventions using odds ratios

A multivariate meta‐analysis of two or more correlated outcomes is expected to improve precision compared with a series of independent, univariate meta‐analyses especially when there are studies reporting some but not all outcomes. Multivariate meta‐analysis requires estimates of the within‐study correlations, which are seldom available. Existing methods for analysing multiple outcomes simultaneously are limited to pairwise treatment comparisons. We propose a model for a joint, simultaneous synthesis of multiple dichotomous outcomes in a network of interventions and introduce a simple way to elicit expert opinion for the within‐study correlations by utilizing a set of conditional probability parameters. We implement our multiple‐outcomes network meta‐analysis model within a Bayesian framework, which allows incorporation of expert information. As an example, we analyse two correlated dichotomous outcomes, response to the treatment and dropout rate, in a network of pharmacological interventions for acute mania. The produced estimates have narrower confidence intervals compared with the simple network meta‐analysis. We conclude that the proposed model and the suggested prior elicitation method for correlations constitute a useful framework for performing network meta‐analysis for multiple outcomes. Copyright © 2014 John Wiley & Sons, Ltd.