Current Osteoporosis Reports

, Volume 17, Issue 4, pp 169–177 | Cite as

CaMKK2 Signaling in Metabolism and Skeletal Disease: a New Axis with Therapeutic Potential

  • Justin N. Williams
  • Uma SankarEmail author
Skeletal Biology and Regulation (M Forwood and A Robling, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Skeletal Biology and Regulation


Purpose of Review

Age and metabolic disorders result in the accumulation of advanced glycation endproducts (AGEs), oxidative stress, and inflammation, which cumulatively cause a decline in skeletal health. Bone becomes increasingly vulnerable to fractures and its regenerative capacity diminishes under such conditions. With a rapidly aging population in the USA and the global increase in diabetes, efficacious, multi-dimensional therapies that can treat or prevent skeletal diseases associated with metabolic dysfunction and inflammatory disorders are acutely needed.

Recent Findings

Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of nutrient intake, glucose metabolism, insulin production, and adipogenesis. Recent studies suggest a pivotal role for CaMKK2 in bone metabolism, fracture healing, and inflammation.


Aside from rekindling previous concepts of CaMKK2 as a potent regulator of whole-body energy homeostasis, this review emphasizes CaMKK2 as a potential therapeutic target to treat skeletal diseases that underlie metabolic conditions and inflammation.


CaMKK2 Diabetes Diabetic osteopathy Skeletal disease Fracture healing 



This work was supported by NAIMS/NIH R01 AR068332 to US. JN was supported through a Comprehensive Musculoskeletal T32 Training Program from NIAMS/NIH (AR065971).

Compliance with Ethical Standards

Conflict of Interest

Justin N. Williams and Uma Sankar declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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Authors and Affiliations

  1. 1.Department of Anatomy and Cell BiologyIndiana University School of MedicineIndianapolisUSA

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