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Erschienen in: Calcified Tissue International 2/2020

01.10.2019 | Original Research

Pretreatment with Pamidronate Decreases Bone Formation but Increases Callus Bone Volume in a Rat Closed Fracture Model

verfasst von: Alyson Morse, Michelle M. McDonald, Kathy Mikulec, Aaron Schindeler, Craig F. Munns, David G. Little

Erschienen in: Calcified Tissue International | Ausgabe 2/2020

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Abstract

Clinical concerns have been raised over prior exposure to bisphosphonates impairing fracture healing. To model this, groups of male Wistar rats were assigned to saline control or treatment groups receiving 0.15 mg/kg (low dose), 0.5 mg/kg (medium dose), and 5 mg/kg (high dose) Pamidronate (PAM) twice weekly for 4 weeks. At this point, closed fractures were made using an Einhorn apparatus, and bisphosphonate dosing was continued until the experimental endpoint. Specimens were analyzed at 2 and 6 weeks (N = 8 per group per time point). Twice weekly PAM dosing was found to have no effect on early soft callus remodeling at 2 weeks post fracture. At this time point, the highest dose PAM group gave significant increases in bone volume (+ 10%, p < 0.05), bone mineral content (+ 30%, p < 0.01), and bone mineral density (+ 10%, p < 0.01). This PAM dosing regimen showed more substantive effects on hard callus at 6 weeks post fracture, with PAM treatment groups showing + 46–79% increased bone volume. Dynamic bone labeling showed reduced calcein signal in the PAM-treated calluses (38–63%, p < 0.01) and reduced MAR (32–49%, p < 0.01), suggesting a compensatory reduction in bone anabolism. These data support the concept that bisphosphonates lead to profound decreases in bone turnover in fracture repair, however, this does not affect soft callus remodeling.
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Metadaten
Titel
Pretreatment with Pamidronate Decreases Bone Formation but Increases Callus Bone Volume in a Rat Closed Fracture Model
verfasst von
Alyson Morse
Michelle M. McDonald
Kathy Mikulec
Aaron Schindeler
Craig F. Munns
David G. Little
Publikationsdatum
01.10.2019
Verlag
Springer US
Erschienen in
Calcified Tissue International / Ausgabe 2/2020
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-019-00615-z

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