Document Detail

Distal tibial fracture repair in a neurofibromatosis type 1-deficient mouse treated with recombinant bone morphogenetic protein and a bisphosphonate.
MedLine Citation:
PMID:  21768643     Owner:  NLM     Status:  MEDLINE    
Congenital pseudarthrosis of the tibia is an uncommon manifestation of neurofibromatosis type 1 (NF1), but one that remains difficult to treat due to anabolic deficiency and catabolic excess. Bone grafting and more recently recombinant human bone morphogenetic proteins (rhBMPs) have been identified as pro-anabolic stimuli with the potential to improve the outcome after surgery. As an additional pharmaceutical intervention, we describe the combined use of rhBMP-2 and the bisphosphonate zoledronic acid in a mouse model of NF1-deficient fracture repair. Fractures were generated in the distal tibiae of neurofibromatosis type 1-deficient (Nf1(+/-)) mice and control mice. Fractures were open and featured periosteal stripping. All mice received 10 μg rhBMP-2 delivered in a carboxymethylcellulose carrier around the fracture as an anabolic stimulus. Bisphosphonate-treated mice also received five doses of 0.02 mg/kg zoledronic acid given by intraperitoneal injection. When only rhBMP but no zoledronic acid was used to promote repair, 75% of fractures in Nf1(+/-) mice remained ununited at three weeks compared with 7% of controls (p < 0.001). Systemic post-operative administration of zoledronic acid halved the rate of ununited fractures to 37.5% (p < 0.07). These data support the concept that preventing bone loss in combination with anabolic stimulation may improve the outcome following surgical treatment for children with congenital pseudarthosis of the tibia and NF1.
A Schindeler; O Birke; N Y C Yu; A Morse; A Ruys; P A Baldock; D G Little
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of bone and joint surgery. British volume     Volume:  93     ISSN:  0301-620X     ISO Abbreviation:  J Bone Joint Surg Br     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-19     Completed Date:  2011-10-24     Revised Date:  2011-12-09    
Medline Journal Info:
Nlm Unique ID:  0375355     Medline TA:  J Bone Joint Surg Br     Country:  England    
Other Details:
Languages:  eng     Pagination:  1134-9     Citation Subset:  AIM; IM    
Orthopaedic Research and Biotechnology Unit, The Children's Hospital at Westmead, 212 Hawkesbury Road, Westmead, New South Wales 2145, Australia.
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MeSH Terms
Bone Density Conservation Agents / therapeutic use*
Bone Morphogenetic Protein 2 / therapeutic use*
Combined Modality Therapy
Diphosphonates / therapeutic use*
Disease Models, Animal
Drug Evaluation, Preclinical / methods
Drug Therapy, Combination
Fracture Fixation, Internal / methods
Fracture Healing / drug effects
Fractures, Ununited / prevention & control
Imidazoles / therapeutic use*
Mice, Knockout
Neurofibromatosis 1 / complications*
Postoperative Care / methods
Pseudarthrosis / complications,  congenital
Recombinant Proteins / therapeutic use
Tibial Fractures / drug therapy*,  etiology,  radiography,  surgery
Treatment Outcome
X-Ray Microtomography
Reg. No./Substance:
0/BMP2 protein, human; 0/Bone Density Conservation Agents; 0/Bone Morphogenetic Protein 2; 0/Diphosphonates; 0/Imidazoles; 0/Recombinant Proteins; 118072-93-8/zoledronic acid

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