Investigating the synergistic efficacy of BMP-7 and zoledronate on bone allografts using an open rat osteotomy model.
Mathavan, Neashan LU ; Bosemark, Per LU ; Isaksson, Hanna LU
and Tägil, Magnus
LU
(2013)
In Bone
56(2).
p.440-448
- Abstract
- Bone grafts are well-established in the treatment of fracture non-unions but union is still not always achieved. Harvesting autograft is associated with donor site morbidity and the available amount of bone is limited. Allograft is more easily obtained and available in greater quantities but lacks the osteoinductive characteristics of autograft. We have previously shown a synergistic effect of bone morphogenetic protein (BMP-7), systemic bisphosphonates and autograft. In the present study we hypothesized that the combination of allograft+BMP-7+systemic ZA is more effective than autograft alone, which is currently the most frequently used aid in augmenting fracture and non-union healing. Femoral osteotomies were performed on 82 male Sprague... (More)
- Bone grafts are well-established in the treatment of fracture non-unions but union is still not always achieved. Harvesting autograft is associated with donor site morbidity and the available amount of bone is limited. Allograft is more easily obtained and available in greater quantities but lacks the osteoinductive characteristics of autograft. We have previously shown a synergistic effect of bone morphogenetic protein (BMP-7), systemic bisphosphonates and autograft. In the present study we hypothesized that the combination of allograft+BMP-7+systemic ZA is more effective than autograft alone, which is currently the most frequently used aid in augmenting fracture and non-union healing. Femoral osteotomies were performed on 82 male Sprague Dawley rats and fixed with intramedullary K-wires. The rats were randomized into 7 groups: i. saline, ii. autograft, iii. allograft, iv. allograft+BMP-7, v. autograft+zoledronate (ZA), vi. allograft+ZA and vii. allograft+BMP-7+ZA. Autografts were harvested from the contralateral tibia. Allografts were obtained from donor rats and frozen. BMP-7 was administered locally in the form of a putty placed circumferentially around the osteotomy. At 2weeks, the rats were injected with a single dose of either saline or ZA. The rats were sacrificed at 6weeks and the femurs were evaluated using radiography, histology, μCT and three-point bending tests. Complete radiological healing was seen in all rats in the BMP-7 groups. The callus volume was larger and the calluses were denser with allograft+BMP-7+ZA than in all other groups (μCT, p<0.001). Mechanical testing yielded a substantially higher peak force with the allograft+BMP-7+ZA combination than all other groups (p<0.01, p<0.001). This was further reinforced in the 59% increase in the peak force observed in the osteotomized femurs of the allograft+BMP-7+ZA group compared to the control femurs (p<0.01), whereas significant decreases of 22-27% were observed in the saline or bone-graft alone groups (p<0.01, p<0.05). Thus our results suggest that allograft combined with the anabolic effect of BMP-7 and the anti-catabolic effect of zoledronate is more efficient than autograft alone. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3955955
- author
- Mathavan, Neashan
LU
; Bosemark, Per
LU
; Isaksson, Hanna
LU
and Tägil, Magnus
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Bone
- volume
- 56
- issue
- 2
- pages
- 440 - 448
- publisher
- Elsevier
- external identifiers
-
- wos:000323864000030
- pmid:23845325
- scopus:84882663410
- pmid:23845325
- ISSN
- 1873-2763
- DOI
- 10.1016/j.bone.2013.06.030
- project
- Assessment of bone quality during fracture healing
- language
- English
- LU publication?
- yes
- id
- ac09feaf-c2da-4b15-9077-34cdfd7a04e6 (old id 3955955)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23845325?dopt=Abstract
- date added to LUP
- 2016-04-01 10:02:50
- date last changed
- 2023-08-30 16:23:11
@article{ac09feaf-c2da-4b15-9077-34cdfd7a04e6,
abstract = {{Bone grafts are well-established in the treatment of fracture non-unions but union is still not always achieved. Harvesting autograft is associated with donor site morbidity and the available amount of bone is limited. Allograft is more easily obtained and available in greater quantities but lacks the osteoinductive characteristics of autograft. We have previously shown a synergistic effect of bone morphogenetic protein (BMP-7), systemic bisphosphonates and autograft. In the present study we hypothesized that the combination of allograft+BMP-7+systemic ZA is more effective than autograft alone, which is currently the most frequently used aid in augmenting fracture and non-union healing. Femoral osteotomies were performed on 82 male Sprague Dawley rats and fixed with intramedullary K-wires. The rats were randomized into 7 groups: i. saline, ii. autograft, iii. allograft, iv. allograft+BMP-7, v. autograft+zoledronate (ZA), vi. allograft+ZA and vii. allograft+BMP-7+ZA. Autografts were harvested from the contralateral tibia. Allografts were obtained from donor rats and frozen. BMP-7 was administered locally in the form of a putty placed circumferentially around the osteotomy. At 2weeks, the rats were injected with a single dose of either saline or ZA. The rats were sacrificed at 6weeks and the femurs were evaluated using radiography, histology, μCT and three-point bending tests. Complete radiological healing was seen in all rats in the BMP-7 groups. The callus volume was larger and the calluses were denser with allograft+BMP-7+ZA than in all other groups (μCT, p<0.001). Mechanical testing yielded a substantially higher peak force with the allograft+BMP-7+ZA combination than all other groups (p<0.01, p<0.001). This was further reinforced in the 59% increase in the peak force observed in the osteotomized femurs of the allograft+BMP-7+ZA group compared to the control femurs (p<0.01), whereas significant decreases of 22-27% were observed in the saline or bone-graft alone groups (p<0.01, p<0.05). Thus our results suggest that allograft combined with the anabolic effect of BMP-7 and the anti-catabolic effect of zoledronate is more efficient than autograft alone.}},
author = {{Mathavan, Neashan and Bosemark, Per and Isaksson, Hanna and Tägil, Magnus}},
issn = {{1873-2763}},
language = {{eng}},
number = {{2}},
pages = {{440--448}},
publisher = {{Elsevier}},
series = {{Bone}},
title = {{Investigating the synergistic efficacy of BMP-7 and zoledronate on bone allografts using an open rat osteotomy model.}},
url = {{http://dx.doi.org/10.1016/j.bone.2013.06.030}},
doi = {{10.1016/j.bone.2013.06.030}},
volume = {{56}},
year = {{2013}},
}