Longitudinal in vivo monitoring of callus remodeling in BMP-7- and Zoledronate-treated fractures.
bone
fracture
repair
Journal
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
04
07
2019
revised:
20
12
2019
accepted:
11
02
2020
pubmed:
20
2
2020
medline:
15
12
2020
entrez:
20
2
2020
Statut:
ppublish
Résumé
Pharmacological interventions that combine pro-anabolic and anti-catabolic drugs to treat recalcitrant fractures have shown remarkable efficacy in augmenting the regenerative response. Specifically, in rodent models of fracture repair, treatment with BMP-7 and Zoledronate (ZA) has almost uniformally resulted in complete union. However, delayed remodeling may be problematic for ZA-treated fractures. The increase in newly formed bone is substantial but if translated in humans, delayed remodeling may delay functional recovery. Our objective was to determine if, and to what extent, bone morphogenetic protein (BMP) (in synergistically administered BMP-7 + ZA) can modulate the delayed hard callus remodeling caused by ZA. Callus remodeling in BMP-7-only and BMP-7 + ZA-treated osteotomies were monitored using in vivo µCT to follow the progression of healing at 6-week intervals over 24 weeks in an open femoral fracture rat model. None of the groups recovered baseline cortical bone volumes within 24 weeks post-osteotomy. Treatment prolonged the remodeling phase but the kinetics of remodeling appeared to differ between BMP and BMP + ZA groups. However, the mechanical characteristics were largely restored. Callus/bone volumes in BMP-only treated fractures peaked as early as week 3 suggesting that remodeling is stimulated prematurely. However, this rate of remodeling was not maintained as BMP-7 was found to exhibit negligible changes in callus/bone volumes between weeks 6 and 18, whereas declines in callus/bone volumes were present at these time points in the BMP-7 + ZA group. Our findings suggest that inclusion of ZA as an anti-catabolic agent may not be detrimental to the regenerative process despite a prolonged remodeling phase.
Substances chimiques
Bone Density Conservation Agents
0
Bone Morphogenetic Protein 7
0
Zoledronic Acid
6XC1PAD3KF
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1905-1913Informations de copyright
© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.
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