Fri., 10/19/07 Basic Science, Paper #38, 4:05 pm OTA-2007
Δ The Role of Parathyroid Hormone in the Mechanosensitivity of Fracture Healing
Michael J. Gardner, MD1; Marjolein C. H. van der Meulen, PhD1,2; Joshua Carson, MD1; Jonathan Zelken, MD1; Benjamin F. Ricciardi, BA1; Timothy M. Wright, PhD1;
Joseph M. Lane, MD1; Mathias P. Bostrom, MD1 (all authors: a-OTA/Stryker, OREF Grant);
1Hospital for Special Surgery, New York, New York, USA;
2Cornell University, Ithaca, New York, USA
Purpose: The mechanical environment at a fracture site can influence the course of healing. Intermittent parathyroid hormone (PTH) has been shown to accelerate fracture healing. Intact bone models show that mechanical loading and PTH have a synergistic beneficial effect on osteogenesis. We hypothesized that PTH and mechanical loading would have a similar synergistic effect on fracture healing.
Methods: Eighty mice underwent surgical osteotomy and intramedullary nailing of the tibia. The mice were divided into four groups: one underwent daily loading, one received daily subcutaneous PTH injections (30 μg/kg/day), one received both loading and PTH, and a control group received sham loading and vehicle injection. Daily loading was applied to the ends of the tibia with an external loading device for 2 weeks. Fracture healing was assessed by microcomputed tomography, histology, and biomechanical testing.
Results: The group with both loading and PTH had increased osteoblast and osteoclast activity and was the only group with a significantly larger callus mineral density and bone volume fraction. The PTH only group had significantly more osteoid in the callus compared to the control group, indicating enhanced early osteoblast activity. This group also had a significantly higher bone mineral content and total bone volume compared to controls. The group that received loading as the only intervention had significantly greater osteoclast activity versus controls.
Conclusion/Significance: The contribution of loading and PTH administration to the fracture healing cascade indicates a synergistic effect. This finding may be of potential clinical utility when weight bearing is utilized to stimulate lower extremity fracture healing.
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• The FDA has not cleared this drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an “off label” use). ◆FDA information not available at time of printing.