Effect of Recombinant Human Bone Morphogenetic Protein‐4 Dose on Bone Formation in a Rat Calvarial Defect Model

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 µg)/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