The relationship between adipokine levels and bone mass-A systematic review

Abstract

Introduction: Adipose tissue is the source of a broad array of signalling molecules (adipokines), which mediate interorgan communication and regulate metabolic homeostasis. Alterations in adipokine levels have been causally implicated in various metabolic disorders, including changes in bone mass. Osteoporosis is the commonest progressive metabolic bone disease, characterized by elevated risk of fragility fractures as a result of a reduced bone mass and microarchitectural deterioration. The effects of different adipokines on bone mass have been studied in an attempt to identify novel modulators of bone mass or diagnostic biomarkers of osteoporosis.

Methods: In this review, we sought to aggregate and assess evidence from independent studies that quantify specific adipokines and their effect on bone mineral density (BMD).

Results: A literature search identified 57 articles that explored associations between different adipokines and BMD. Adiponectin and leptin were the most frequently studied adipokines, with most studies demonstrating that adiponectin levels are associated with decreased BMD at the lumbar spine and femoral neck. Conversely, leptin levels are associated with increased BMD at these sites. However, extensive heterogeneity with regards to sample size, characteristics of study subjects, ethnicity, as well as direction and magnitude of effect at specific skeletal anatomical sites was identified. The broad degree of conflicting findings reported in this study can be attributed several factors. These include differences in study design and ascertainment criteria, the analytic challenges of quantifying specific adipokines and their isoforms, pre-analytical variables (in particular patient preparation) and confounding effects of co-existing disease.

Conclusions: This review highlights the biological relevance of adipokines in bone metabolism and reinforces the need for longitudinal research to elucidate the causal relationship of adipokines on bone mass.

Keywords: adipokines; adiponectin; bone mineral density; diabetes; leptin; osteoporosis.

FIGURE 1

PRISMA flow diagram summarizing the process of selecting articles to be used in this review.

FIGURE 2

Association of serum leptin levels with BMD at different anatomical sites. (A) Leptin levels in individuals with no comorbidities based on studies described in Table S1; (B) Leptin levels in individuals with comorbidities affecting bone mass based on studies described in Table S2. The first row indicates the study from which the data were derived. The column to the right denotes the site/s of BMD measurement. The studies highlighted in green were longitudinal studies, whilst the rest were case–control studies. Cells highlighted in blue indicate a positive relationship between BMD and leptin. Cells highlighted in red indicate a negative relationship between BMD and leptin. Cells highlighted in grey indicate no significant findings. Cells left blank were not tested. BUA, broadband ultrasound attenuation; FN, femoral neck; LS, lumbar spine; TB, total body; TH, total hip.

FIGURE 3

Association of serum adiponectin levels with BMD at different anatomical sites. (A) Adiponectin levels in individuals with no comorbidities based on studies described in Table S1; (B) Adiponectin levels in individuals with comorbidities affecting bone mass based on studies described in Table S2. The first row indicates the study from which the data were derived. The column to the right denotes the site/s of BMD measurement. The studies highlighted in green were longitudinal studies, whilst the rest were case–control studies. Cells highlighted in blue indicate a positive relationship between BMD and adiponectin. Cells highlighted in red indicate a negative relationship between BMD and adiponectin. Cells highlighted in grey indicate no significant findings. Cells left blank were not tested. BUA, broadband ultrasound attenuation; FN, femoral neck; LS, lumbar spine; TB, total body; TH, total hip; TS, thoracic spine.