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Effect of cisplatin on bone transport osteogenesis in dogs

Nicole EhrhartComparative Musculoskeletal Tumor Laboratory, the Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61801.

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 VMD, MS
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Jo Ann C. EurellDepartment of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana, IL 61801.

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 DVM, PhD
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Matteo TommasiniCentro Veterinario Gregorio, Via del Cipresso 6, 00153 Rome, Italy.

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 DVM
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Peter D. ConstableComparative Musculoskeletal Tumor Laboratory, the Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61801.

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 BVSc, PhD
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Ann L. JohnsonComparative Musculoskeletal Tumor Laboratory, the Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana, IL 61801.

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Antonio FerettiClinica Veterinaria, Via Maestri del Lavoro 29 20025 Legnano, Milan, Italy.

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 DVM

Abstract

Objective—To document effects of cisplatin on regenerate bone formation during the distraction and consolidation phases of bone transport osteogenesis.

Animals—10 skeletally mature hounds.

Procedure—Bone transport osteogenesis was performed to reconstruct a 3-cm defect in the radius of each dog. Five dogs were randomly selected to receive cisplatin (70 mg/m2, IV, q 21 d for 4 cycles), and 5 were administered saline (0.9% NaCl) solution. Bone mineral density was measured by use of dual-energy x-ray absorptiometry (DEXA) on days 24, 55, and 90 after surgery. Dogs were euthanatized 90 days after surgery. Histomorphometry was performed on nondecalcified sections of regenerate bone. Bone mineral density and histomorphometric indices of newly formed bone were compared between groups.

Results—Densitometric differences in regenerate bone mineral density were not detected between groups at any time period. Cisplatin-treated dogs had decreased mineralized bone volume, decreased percentage of woven bone volume, decreased percentage of osteoblast-covered bone, increased porosity, and increased percentage of osteoblast-covered surfaces, compared with values for control dogs. Lamellar bone volume and osteoid volume did not differ significantly between groups.

Conclusions and Clinical Relevance—Regenerate bone will form and remodel during administration of cisplatin. Results of histomorphometric analysis suggest that bone formation and resorption may be uncoupled in cisplatin-treated regenerate bone as a result of increased osteoclast activity or delayed secondary bone formation during remodeling. These histomorphometric differences were modest in magnitude and did not result in clinically observable complications or decreased bone mineral density as measured by use of DEXA. (Am J Vet Res 2002;63:703–711)

Abstract

Objective—To document effects of cisplatin on regenerate bone formation during the distraction and consolidation phases of bone transport osteogenesis.

Animals—10 skeletally mature hounds.

Procedure—Bone transport osteogenesis was performed to reconstruct a 3-cm defect in the radius of each dog. Five dogs were randomly selected to receive cisplatin (70 mg/m2, IV, q 21 d for 4 cycles), and 5 were administered saline (0.9% NaCl) solution. Bone mineral density was measured by use of dual-energy x-ray absorptiometry (DEXA) on days 24, 55, and 90 after surgery. Dogs were euthanatized 90 days after surgery. Histomorphometry was performed on nondecalcified sections of regenerate bone. Bone mineral density and histomorphometric indices of newly formed bone were compared between groups.

Results—Densitometric differences in regenerate bone mineral density were not detected between groups at any time period. Cisplatin-treated dogs had decreased mineralized bone volume, decreased percentage of woven bone volume, decreased percentage of osteoblast-covered bone, increased porosity, and increased percentage of osteoblast-covered surfaces, compared with values for control dogs. Lamellar bone volume and osteoid volume did not differ significantly between groups.

Conclusions and Clinical Relevance—Regenerate bone will form and remodel during administration of cisplatin. Results of histomorphometric analysis suggest that bone formation and resorption may be uncoupled in cisplatin-treated regenerate bone as a result of increased osteoclast activity or delayed secondary bone formation during remodeling. These histomorphometric differences were modest in magnitude and did not result in clinically observable complications or decreased bone mineral density as measured by use of DEXA. (Am J Vet Res 2002;63:703–711)