“We knew from previous studies that mechanical loading and parathyroid hormone (PTH) have a positive, synergistic effect on osteogenesis,” said Michael J. Gardner, MD, at the 2007 meeting of the Orthopaedic Trauma Association. “We took the next step by hypothesizing that they would have a similar synergistic effect on fracture healing in an in vivo fracture model.”
Published 3/1/2008
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Annie Hayashi
Parathyroid hormone and mechanical loading are a positive combination
The findings of that study suggest that the synergistic effect produced by the mechanical loading and PTH in vivo has important clinical significance.
Protocols for loading, pharmacologic treatments
Dr. Gardner and his colleagues performed surgical tibial osteotomies on 80 mice and inserted intramedullary nails. Following surgery, the mice were divided into 4 equal groups for the following treatment protocols:
- Daily loading (100 load cycles/day); placebo injection
- Daily subcutaneous PTH injection (30 µg/kg/day); sham loading
- Daily loading and subcutaneous PTH injection
- Daily sham loading and placebo injection (control group)
All loading and injections were administered for two weeks (5 times/week). An external loading device was applied on the ends of the tibia and microcomputed tomography, histology, and biomechanical testing were used to assess the degree of fracture healing.
A 27-gauge needle was used for intramedullary stabilization of the tibia following osteotomy. |
Two treatments are better than one
“Our results demonstrated that a combination of loading and PTH stimulated more cellular activity during fracture healing than either treatment alone,” said Dr. Gardner. The third group (daily loading and subcutaneous PTH injections) was the only group with a significant increase in osteoblast and osteoclast activity and a greater callus mineral density and bone volume fraction compared to the control group.
The authors stated that “mechanical loading contributed a substantial component of the increased osteoclast activity to the acceleration of fracture healing and later remodeling.”
“We knew from previous studies that mechanical loading and parathyroid hormone (PTH) have a positive, synergistic effect on osteogenesis,” said Michael J. Gardner, MD, at the 2007 meeting of the Orthopaedic Trauma Association. “We took the next step by hypothesizing that they would have a similar synergistic effect on fracture healing in an in vivo fracture model.”
Mechanical loading device used in study. Photos
courtesy of Michael J. Gardner, MD
“We determined bone mineral content, density, volume fraction, and callus volume,” Dr. Gardner explained. “To estimate union, we blindly evaluated midsagittal and midcoronal images with microcomputed tomography of each callus and then established the number of bridged cortices.”
The loading only group had more osteoclast activity than osteoblast activity. This was in contrast to the PTH only group that had the opposite experience—more osteoblast than osteoclast activity.
The PTH only group had considerably more osteoid in the callus when compared to the control group, suggesting enhanced early osteoblast activity.
Clinical applications?
Other studies have looked at the role of PTH and loading in fracture healing but none has examined the synergistic effect of this combination in vivo. This study confirms that this combination can be used in vivo with positive results.
As the authors noted, “This finding may be of potential clinical utility when weight bearing is utilized to stimulate lower extremity fracture healing.”
Gardner MJ, van der Meulen MC, Carson J, et al: Role of parathyroid hormone in the mechanosensitivity of fracture healing. J Orthop Res 2007;25:1474-1480.
Annie Hayashi is the senior science writer for AAOS Now. She can be reached at hayashi@aaos.org
Disclosure information for Dr. Gardner is available through www.aaos.org/disclosure