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Response of induced bone defects in horses to collagen matrix containing the human parathyroid hormone gene

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  • 1 Comparative Orthopedic Molecular Medicine Research Laboratories, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 2 Comparative Orthopedic Molecular Medicine Research Laboratories, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 3 Comparative Orthopedic Molecular Medicine Research Laboratories, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 4 Present address is the Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.
  • | 5 Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Abstract

Objective—To determine whether human parathyroid hormone (hPTH) gene in collagen matrix could safely promote bone formation in diaphyseal or subchondral bones of horses.

Animals—8 clinically normal adult horses.

Procedure—Amount, rate, and quality of bone healing for 13 weeks were determined by use of radiography, quantitative computed tomography, and histomorphometric analysis. Diaphyseal cortex and subchondral bone defects of metacarpi were filled with hPTH1-34 gene-activated matrix (GAM) or remained untreated. Joints were assessed on the basis of circumference, synovial fluid analysis, pain on flexion, lameness, and gross and histologic examination.

Results—Bone volume index was greater for cortical defects treated with hPTH1-34 GAM, compared with untreated defects. Bone production in cortical defects treated with hPTH1-34 GAM positively correlated with native bone formation in untreated defects. In contrast, less bone was detected in hPTH1-34 GAM-treated subchondral bone defects, compared with untreated defects, and histology confirmed poorer healing and residual collagen sponge.

Conclusions and Clinical Relevance—Use of hPTH1-34 GAM induced greater total bone, specifically periosteal bone, after 13 weeks of healing in cortical defects of horses. The hPTH1-34 GAM impeded healing of subchondral bone but was biocompatible with joint tissues. Promotion of periosteal bone formation may be beneficial for healing of cortical fractures in horses, but the delay in onset of bone formation may negate benefits. The hPTH1-34 GAM used in this study should not be placed in articular subchondral bone defects, but contact with articular surfaces is unlikely to cause short-term adverse effects. (Am J Vet Res 2004;65:1223–1232)

Abstract

Objective—To determine whether human parathyroid hormone (hPTH) gene in collagen matrix could safely promote bone formation in diaphyseal or subchondral bones of horses.

Animals—8 clinically normal adult horses.

Procedure—Amount, rate, and quality of bone healing for 13 weeks were determined by use of radiography, quantitative computed tomography, and histomorphometric analysis. Diaphyseal cortex and subchondral bone defects of metacarpi were filled with hPTH1-34 gene-activated matrix (GAM) or remained untreated. Joints were assessed on the basis of circumference, synovial fluid analysis, pain on flexion, lameness, and gross and histologic examination.

Results—Bone volume index was greater for cortical defects treated with hPTH1-34 GAM, compared with untreated defects. Bone production in cortical defects treated with hPTH1-34 GAM positively correlated with native bone formation in untreated defects. In contrast, less bone was detected in hPTH1-34 GAM-treated subchondral bone defects, compared with untreated defects, and histology confirmed poorer healing and residual collagen sponge.

Conclusions and Clinical Relevance—Use of hPTH1-34 GAM induced greater total bone, specifically periosteal bone, after 13 weeks of healing in cortical defects of horses. The hPTH1-34 GAM impeded healing of subchondral bone but was biocompatible with joint tissues. Promotion of periosteal bone formation may be beneficial for healing of cortical fractures in horses, but the delay in onset of bone formation may negate benefits. The hPTH1-34 GAM used in this study should not be placed in articular subchondral bone defects, but contact with articular surfaces is unlikely to cause short-term adverse effects. (Am J Vet Res 2004;65:1223–1232)