Effect of recombinant human bone morphogenetic protein-4 dose on bone formation in a rat calvarial defect model

Eun Kyoung Pang, Se Ung Im, Chang Sung Kim, Seong Ho Choi, Jung Kiu Chai, Chong Kwan Kim, Soo Boo Han, Kyoo Sung Cho

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Background: Bone morphogenetic proteins (BMPs) are being evaluated for periodontal and bone regenerative therapy. The objective of this study was to evaluate the effect of recombinant human bone morphogenetic protein-4 (rhBMP-4) dose on local bone formation in a rat calvaria defect model. Methods: Calvarial, 8 mm diameter, critical-size osteotomy defects were created in 140 male Sprague-Dawley rats. Seven groups of 20 animals each received either 1) rhBMP-4 (2.5 μg) in an absorbable collagen sponge (ACS) carrier, 2) rhBMP-4 (5 μg)/ACS, 3) rhBMP-4 (2.5 μg) in a β-tricalcium phosphate (β-TCP) carrier, 4) rhBMP-4 (5 μ g)/β-TCP, 5) ACS or 6) β-TCP carrier controls, or 7) a sham-surgery control, and were evaluated by histologic and histometric parameters following a 2- or 8-week healing interval (10 animals/group /healing interval). Results: Surgical implantation of rhBMP-4/ACS and rhBMP-4/β-TCP resulted in enhanced local bone formation at both 2 and 8 weeks. Within the dose range examined, rhBMP-4 did not exhibit an appreciable dose-dependent response. Defect closure was not significantly different between the rhBMP-4/ACS and rhBMP-4/β-TCP groups. New bone area of the rhBMP-4/β-TCP group was significantly greater than that of the rhBMP-4/ACS group; however, bone density in the rhBMP-4/ACS group was significantly greater than that in the rhBMP-4 /β-TCP group at 8 weeks (P <0.05). Conclusions: rhBMP-4 combined with ACS or β-TCP has a significant potential to induce bone formation in the rat calvaria defect model. Within the selected rhBMP-4 dose range and observation interval, there appeared to be no meaningful differences in bone formation.

Original languageEnglish
Pages (from-to)1364-1370
Number of pages7
JournalJournal of Periodontology
Issue number10
Publication statusPublished - 2004 Oct 1


All Science Journal Classification (ASJC) codes

  • Periodontics

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