Influence of Adipokines and Ghrelin on Bone Mineral Density and Fracture Risk: A Systematic Review and Meta-Analysis

Context: Adipokines (leptin, adiponectin, resistin, visfatin) and ghrelin may be implicated in bone metabolism. Objective: The aim was to perform an overview of the influence of blood levels of adipokines or ghrelin on bone mineral density (BMD), osteoporotic status, and fracture risk in healthy men and women. Data Sources: We reviewed Medline, Embase, and Cochrane databases up to March 2010 and abstracts of international meetings from 2008 to 2009. Study Selection: Fifty-nine studies meeting the inclusion criteria (healthy men or women evaluated for both BMD or fracture risk and at least one adipokine and/or ghrelin levels) were analyzed in the systematic review of the 931 references found in the electronic databases. Data Extraction: We used a predefined extraction sheet. Data Synthesis: We performed meta-analyses using the method of the inverse of the variance estimated pooled correlations between adipokines/ghrelin and BMD. Inverse correlations between adiponectin levels and BMD were highlighted (pooled r from -0.14 to -0.4). Leptin is positively associated to BMD, especially in postmenopausal women(pooled r from 0.18 to 0.33). High levels of leptin were reported to be predictive of low risk of fractures, whereas high levels of adiponectin may be predictive of high risk of vertebral fractures in men only. No discriminative capacity of osteoporotic status was reported. We found no convincing data to support an association between resistin, visfatin, or ghrelin and BMD. Conclusion: Adiponectin is the most relevant adipokine negatively associated with BMD, independent of gender and menopausal status. Inconsistent associations between adipokines and BMD are probably confounded by body composition, in particular fat mass parameters. (J Clin Endocrinol Metab 96: 2703-2713, 2011)