Response of induced bone defects in horses to collagen matrix containing the human parathyroid hormone gene.
OBJECTIVE
To determine whether human parathyroid hormone (hPTH) gene in collagen matrix could safely promote bone formation in diaphyseal or subchondral bones of horses.


METHODS
8 clinically normal adult horses.


METHODS
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 hPTH(1-34) 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 hPTH(1-34) GAM, compared with untreated defects. Bone production in cortical defects treated with hPTH(1-34) GAM positively correlated with native bone formation in untreated defects. In contrast, less bone was detected in hPTH(1-34) GAM-treated subchondral bone defects, compared with untreated defects, and histology confirmed poorer healing and residual collagen sponge.


CONCLUSIONS
Use of hPTH(1-34) GAM induced greater total bone, specifically periosteal bone, after 13 weeks of healing in cortical defects of horses. The hPTH(1-34) 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 hPTH(1-34) 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.
Backstrom
Kristin C
KC
Comparative Orthopedic Molecular Medicine Research Laboratories, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Bertone
Alicia L
AL
Wisner
Erik R
ER
Weisbrode
Stephen E
SE
D000704:Analysis of Variance; D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000502:physiology*; D002350:Carpus, Animal / Q000473:pathology; D003094:Collagen; D005453:Fluorescence; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D006736:Horses / Q000293:injuries* / Q000601:surgery; D006801:Humans; D010281:Parathyroid Hormone / Q000235:genetics* / Q000494:pharmacology*; D013583:Synovial Membrane / Q000473:pathology; D014057:Tomography, X-Ray Computed
D010281:Parathyroid Hormone; D003094:Collagen