Association of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes: systematic review and meta-analysis of observational evidence

Eur J Epidemiol. 2015 Aug;30(8):599-614. doi: 10.1007/s10654-015-0058-x. Epub 2015 Jun 18.


Serum total osteocalcin, a marker of bone formation, may regulate glucose metabolism and influence the risk of developing adverse metabolic outcomes. We conducted a systematic review and meta-analysis of published observational evidence, to assess and quantify the associations of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes [e.g., metabolic syndrome (MetS)]. Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, and reference lists of relevant studies to May 2015. Mean differences and risk estimates (odds ratios or relative risks) with 95% CIs were aggregated using random-effects models. Fifty-two observational (38 cross-sectional, eight cohort, five case-control, and one both cross-sectional and cohort) studies with data on 46,998 non-overlapping participants were included. Baseline serum total osteocalcin levels were significantly lower in type 2 diabetes compared with non-type 2 diabetes and in MetS compared with non-MetS in pooled analysis of cross-sectional evidence. Pooled risk estimates (95% CIs) for type 2 diabetes in a comparison of extreme fourths of total osteocalcin levels were 0.23 (95% CI 0.12, 0.46) and 0.89 (95% CI 0.78, 1.01) for cross-sectional and cohort studies respectively. The corresponding estimate was 0.39 (0.27, 0.56) for MetS from cross-sectional evidence. In both cross-sectional and cohort studies, a unit increase in serum total osteocalcin levels was associated with a significant mean increase in HOMA-B and mean reduction in HbA1c; with significant mean reductions in fasting plasma glucose levels, HOMA-IR, and body mass index in only cross-sectional studies. Available evidence--mainly from cross-sectional studies, supports inverse associations of serum total osteocalcin with risk of adverse metabolic outcomes. Large-scale prospective studies are needed to establish whether serum total osteocalcin may be useful in the prevention of adverse metabolic outcomes such as type 2 diabetes.

Keywords: Intermediate metabolic phenotypes; Total osteocalcin; Type 2 diabetes.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / etiology*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Metabolic Syndrome / blood*
  • Osteocalcin / blood*
  • Phenotype


  • Glycated Hemoglobin A
  • Osteocalcin