Early effects of parathyroid hormone on bisphosphonate/steroid-associated compromised osseous wound healing

Osteoporos Int. 2014 Mar;25(3):1141-50. doi: 10.1007/s00198-013-2570-8. Epub 2013 Dec 4.

Abstract

Summary: Administration of intermittent parathyroid hormone (PTH) promoted healing of tibial osseous defects and tooth extraction wounds and prevented the development of necrotic lesions in rats on a combined bisphosphonate and steroid regimen.

Introduction: Osteonecrosis of the jaw (ONJ) has emerged in association with antiresorptive therapies. The pathophysiology of ONJ is unknown and no established cure currently exists. Our objective was to determine the effect of intermittent PTH administration on early osseous healing in the jaw and long bones of rats receiving bisphosphonate and steroid treatment.

Methods: Ovariectomized rats received the combination therapy of alendronate and dexamethasone (ALN/DEX) for 12 weeks. Osseous wounds were created in the jaw and tibia. PTH was administered intermittently and healing at 2 weeks post-op was compared between the jaw and tibia by microcomputed tomography and histomorphometric analyses.

Results: ALN/DEX treatment was associated with necrotic open wounds in the jaw but had no negative effects on healing and promoted bone fill in tibial defects. PTH therapy prevented the development of necrotic lesions in the jaw and promoted healing of the tibial defects. PTH therapy was associated with the promotion of osteocyte survival in osseous wounds both in the jaw and tibia.

Conclusions: Wound healing was impaired in the jaw in rats on a combined bisphosphonate and steroid regimen, and PTH therapy rescued necrotic lesions. These findings suggest that PTH therapy could be utilized to prevent ONJ from occurring in patients on combination antiresorptive and steroid therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate / therapeutic use
  • Alendronate / toxicity
  • Animals
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / etiology
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / prevention & control*
  • Bone Density / drug effects
  • Bone Density Conservation Agents / therapeutic use
  • Bone Density Conservation Agents / toxicity
  • Bone Regeneration / drug effects*
  • Cell Survival / drug effects
  • Dexamethasone / therapeutic use
  • Dexamethasone / toxicity
  • Drug Administration Schedule
  • Drug Evaluation / methods
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / therapeutic use
  • Glucocorticoids / toxicity
  • Osteocytes / drug effects
  • Osteoporosis / drug therapy
  • Osteoporosis / physiopathology
  • Ovariectomy
  • Parathyroid Hormone / administration & dosage
  • Parathyroid Hormone / pharmacology
  • Parathyroid Hormone / therapeutic use*
  • Rats, Sprague-Dawley
  • Tibia / injuries
  • Tibia / physiology
  • Tooth Extraction
  • Tooth Socket / drug effects
  • Tooth Socket / physiology
  • Wound Healing / drug effects*
  • X-Ray Microtomography / methods

Substances

  • Bone Density Conservation Agents
  • Glucocorticoids
  • Parathyroid Hormone
  • Dexamethasone
  • Alendronate