Document Detail


Intraosseous injection of rhBMP-2/calcium phosphate matrix improves bone structure and strength in the proximal aspect of the femur in chronic ovariectomized nonhuman primates.
MedLine Citation:
PMID:  23283371     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Osteoporosis results in a decrease in bone density, bone quality, and strength throughout the skeleton. Despite systemic therapies, the morbidity and mortality that are associated with hip fractures remain a major consequence of osteoporosis.
METHODS: We used fourteen chronic ovariectomized female cynomolgus monkeys in this study. Six animals received an intraosseous injection of 0.5 mL of 1.5 mg/mL recombinant human bone morphogenetic protein-2/calcium phosphate matrix (rhBMP-2/CPM) into the femoral neck of one femur, and six animals received an intraosseous injection of 0.5 mL of CPM alone into the femoral neck of one femur. The contralateral femur of each of the animals was left untreated. The proximal aspect of each femur was evaluated monthly with use of radiography and at six months with use of peripheral quantitative computed tomography, microcomputed tomography, histological analysis, and mechanical testing. Two additional animals received an intraosseous injection of 0.5 mL of 1.5 mg/mL rhBMP-2/CPM into the femoral neck of one femur. The contralateral femur of each animal was left untreated. Bone formation in the intact specimens from these animals was histologically analyzed at one month in one animal and at three months in the other.
RESULTS: Radiographic evaluation over the six-month study period demonstrated an increase in cortical thickness and density in the rhBMP-2/CPM-treated femora as compared to the findings in the untreated contralateral femora or the femora that had been treated with CPM alone. At six months, the rhBMP-2/CPM-treated femora had decreased cortical density and increased cross-sectional area, cortical thickness, trabecular density, and trabecular volume fraction as compared with the contralateral untreated femora and the femora that had received CPM treatment alone, but the differences between the femora that had been treated with CPM alone and the contralateral untreated femora did not reach significance. Increases in bone structure resulted in a 13.7% ± 7.6% (p = 0.032) increase in the maximum bending force at the femoral neck as compared with that at the femoral neck of the contralateral untreated femora. The maximum bending force at the femoral neck was similar between the femora that had been treated with CPM alone and the contralateral untreated femora. De novo and appositional bone formation was present at one month after treatment in the rhBMP-2/CPM-treated femora.
CONCLUSIONS: This study demonstrates an increase in bone structure and mechanical properties at six months following a single injection of rhBMP-2/CPM into the femoral neck of chronic ovariectomized nonhuman primates.
Authors:
Howard J Seeherman; X Jian Li; Erica Smith; Jascha Parkington; Rebecca Li; John M Wozney
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of bone and joint surgery. American volume     Volume:  95     ISSN:  1535-1386     ISO Abbreviation:  J Bone Joint Surg Am     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-03-14     Revised Date:  2013-04-05    
Medline Journal Info:
Nlm Unique ID:  0014030     Medline TA:  J Bone Joint Surg Am     Country:  United States    
Other Details:
Languages:  eng     Pagination:  36-47     Citation Subset:  AIM; IM    
Affiliation:
Inflammation and Remodeling Research Unit, Pfizer Discovery Research, Cambridge, MA 02140, USA. hseeherman@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Morphogenetic Protein 2 / administration & dosage*
Calcium Phosphates / administration & dosage*
Female
Femur Neck / pathology
Injections, Intralesional
Macaca fascicularis
Ovariectomy
Recombinant Proteins / administration & dosage
Tomography, X-Ray Computed
Transforming Growth Factor beta / administration & dosage*
Chemical
Reg. No./Substance:
0/Bone Morphogenetic Protein 2; 0/Calcium Phosphates; 0/Recombinant Proteins; 0/Transforming Growth Factor beta; 0/recombinant human bone morphogenetic protein-2; 97Z1WI3NDX/calcium phosphate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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