Osteoporosis International

, Volume 28, Issue 8, pp 2265–2273 | Cite as

Multifaceted interaction of bone, muscle, lifestyle interventions and metabolic and cardiovascular disease: role of osteocalcin

  • I. LevingerEmail author
  • T. C. Brennan-Speranza
  • A. Zulli
  • L. Parker
  • X. Lin
  • J.R. Lewis
  • B. B. Yeap


Undercarboxylated osteocalcin (ucOC) may play a role in glucose homeostasis and cardiometabolic health. This review examines the epidemiological and interventional evidence associating osteocalcin (OC) and ucOC with metabolic risk and cardiovascular disease. The complexity in assessing such correlations, due to the observational nature of human studies, is discussed. Several studies have reported that higher levels of ucOC and OC are correlated with lower fat mass and HbA1c. In addition, improved measures of glycaemic control via pharmacological and non-pharmacological (e.g. exercise or diet) interventions are often associated with increased circulating levels of OC and/or ucOC. There is also a relationship between lower circulating OC and ucOC and increased measures of vascular calcification and cardiovascular disease. However, not all studies have reported such relationship, some with contradictory findings. Equivocal findings may arise because of the observational nature of the studies and the inability to directly assess the relationship between OC and ucOC on glycaemic control and cardiovascular health in humans. Studying OC and ucOC in humans is further complicated due to numerous confounding factors such as sex differences, menopausal status, vitamin K status, physical activity level, body mass index, insulin sensitivity (normal/insulin resistance/T2DM), tissue-specific effects and renal function among others. Current observational and indirect interventional evidence appears to support a relationship between ucOC with metabolic and cardiovascular disease. There is also emerging evidence to suggest a direct role of ucOC in human metabolism. Further mechanistic studies are required to (a) clarify causality, (b) explore mechanisms involved and (c) define the magnitude of this effect and its clinical importance.


Cardiovascular disease Glucose uptake Insulin sensitivity Osteocalcin 



A/Prof Levinger was supported by Future Leader Fellowship (ID: 100040) from the National Heart Foundation of Australia. Dr. Tara C Brennan-Speranza was supported by an NHMRC Early Career Fellowship (ID: 1013295). Dr. Lewis is supported by a National Health and Medical Research Council of Australia Career Development Fellowship (ID: 1107474).

Compliance with ethical standards

Conflict of interest



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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2017

Authors and Affiliations

  • I. Levinger
    • 1
    Email author
  • T. C. Brennan-Speranza
    • 2
  • A. Zulli
    • 1
  • L. Parker
    • 1
  • X. Lin
    • 1
  • J.R. Lewis
    • 3
    • 4
  • B. B. Yeap
    • 4
    • 5
  1. 1.Institute of Sport, Exercise and Active Living (ISEAL)Victoria UniversityMelbourneAustralia
  2. 2.Department of Physiology and Bosch Institute for Medical ResearchUniversity of SydneySydneyAustralia
  3. 3.Centre for Kidney Research, Children’s Hospital at Westmead School of Public Health, Sydney Medical SchoolThe University of SydneySydneyAustralia
  4. 4.School of Medicine and PharmacologyUniversity of Western AustraliaPerthAustralia
  5. 5.Department of Endocrinology and DiabetesFiona Stanley HospitalPerthAustralia

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