Recombinant human bone morphogenetic protein-2-induced craniosynostosis and growth restriction in the immature skeleton.

Abstract:

BACKGROUND:Recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on an absorbable collagen sponge is a U.S. Food and Drug Administration-approved therapy effective at generating bone formation. In pediatric patients for whom other therapeutic options have been exhausted, rhBMP-2 is used off-label to address problematic bony defects. In the skeletally immature patient, the safety of rhBMP-2 therapy remains uncertain. Experiments are needed that investigate the effect of rhBMP-2 on growth and development in clinically relevant models. METHODS:Ten juvenile rabbits underwent creation of a parietal skull defect that was treated with either 0.2 mg/cc rhBMP-2/absorbable collagen sponge or a neutral buffer solution/absorbable collagen sponge. Amalgam markers were placed at suture confluences to track suture separation and skull growth. Cranial growth was assessed radiographically at 10, 25, 42, and 84 days of age. Means and standard deviations for the various craniofacial growth variables were calculated and compared. Mean differences were considered significant for values of p < 0.05. At 84 days, sutures were analyzed by means of micro-computed tomographic scanning and histologic staining. RESULTS:Treatment with rhBMP-2 resulted in fusion of the coronal sutures bilaterally, with variable fusion of the sagittal suture by cephalometric, radiographic, and histologic analysis. There were statistically significant changes to coronal suture growth, sagittal suture growth, skull height, craniofacial length, and intracranial volume (p < 0.05). CONCLUSIONS:The use of rhBMP-2 in this juvenile animal model resulted in skeletal changes that may be undesirable in a clinical setting. The appearance of these fused sutures suggested a direct effect of rhBMP-2. Further work is required to limit the effect of rhBMP-2 to the target defect when used in the immature skeleton.

journal_name

Plast Reconstr Surg

authors

Kinsella CR Jr,Cray JJ,Durham EL,Burrows AM,Vecchione L,Smith DM,Mooney MP,Cooper GM,Losee JE

doi

10.1097/PRS.0b013e318205f2b4

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

1173-1181

issue

3

eissn

0032-1052

issn

1529-4242

pii

00006534-201103000-00018

journal_volume

127

pub_type

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