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Diabetes and Impaired Fracture Healing: A Narrative Review of Recent Literature

Abstract

Purpose of the Review

Diabetes mellitus is a chronic metabolic disorder commonly encountered in orthopedic patients. Both type 1 and type 2 diabetes mellitus increase fracture risk and impair fracture healing. This review examines complex etiology of impaired fracture healing in diabetes.

Recent Findings

Recent findings point to several mechanisms leading to orthopedic complications in diabetes. Hyperglycemia and chronic inflammation lead to increased formation of advanced glycation end products and generation of reactive oxygen species, which in turn contribute to the disruption in osteoblast and osteoclast balance leading to decreased bone formation and heightening the risk of nonunion or delayed union as well as impaired fracture healing. The mechanisms attributing to this imbalance is secondary to an increase in pro-inflammatory mediators leading to premature resorption of callus cartilage and impaired bone formation due to compromised osteoblast differentiation and their apoptosis. Other mechanisms include disruption in the bone’s microenvironment supporting different stages of healing process including hematoma and callus formation, and their resolution during bone remodeling phase. Complications of diabetes including peripheral neuropathy and peripheral vascular disease also contribute to the impairment of fracture healing. Certain diabetic drugs may have adverse effects on fracture healing.

Summary

The pathophysiology of impaired fracture healing in diabetic patients is complex. This review provides an update of the most recent findings on how key mediators of bone healing are affected in diabetes.

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Fig. 1

Abbreviations

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

AGE:

Advanced glycation end products

ROS:

Reactive oxygen species

PTHrP:

Parathyroid hormone related protein

PGE2:

Prostaglandin E2

NF-κB:

Nuclear factor-κB

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Acknowledgements

We thank Karen Bach for her support with preparation and review of this article.

Funding

BLC was supported by grants from NIH R01AG071332 and American Diabetes Association Innovative Basic Science Award #1-19-IBS-029.

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Correspondence to Mina Tanios or Beata Lecka-Czernik.

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Tanios, M., Brickman, B., Cage, E. et al. Diabetes and Impaired Fracture Healing: A Narrative Review of Recent Literature. Curr Osteoporos Rep (2022). https://doi.org/10.1007/s11914-022-00740-z

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Keywords

  • Diabetes mellitus
  • Fracture healing
  • Bone fractures
  • Advanced glycation end products
  • Osteoblast
  • Osteoclast