Longitudinal in vivo monitoring of callus remodeling in BMP-7- and Zoledronate-treated fractures. Mathavan, N.; Raina, D. B.; Tägil, M.; and Isaksson, H. Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 38(9):1905–1913, September, 2020. Place: United States
doi  abstract   bibtex   
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.
@article{mathavan_longitudinal_2020,
	title = {Longitudinal in vivo monitoring of callus remodeling in {BMP}-7- and  {Zoledronate}-treated fractures.},
	volume = {38},
	copyright = {© 2020 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals,  Inc. on behalf of Orthopaedic Research Society.},
	issn = {1554-527X 0736-0266},
	doi = {10.1002/jor.24632},
	abstract = {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.},
	language = {eng},
	number = {9},
	journal = {Journal of orthopaedic research : official publication of the Orthopaedic Research  Society},
	author = {Mathavan, Neashan and Raina, Deepak Bushan and Tägil, Magnus and Isaksson, Hanna},
	month = sep,
	year = {2020},
	pmid = {32073160},
	note = {Place: United States},
	keywords = {bone, fracture, repair},
	pages = {1905--1913}
}
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