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Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats.

Belfrage, Ola LU ; Isaksson, Hanna LU and Tägil, Magnus LU (2012) In BMC Musculoskeletal Disorders 13(Dec.,05).
Abstract
ABSTRACT:



BACKGROUND:



Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone chamber model, and compare that with systemic treatment.



METHODS:



Cancellous bone grafts were placed in titanium chambers and implanted in the tibia of 50 male rats, randomly divided into... (More)
ABSTRACT:



BACKGROUND:



Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone chamber model, and compare that with systemic treatment.



METHODS:



Cancellous bone grafts were placed in titanium chambers and implanted in the tibia of 50 male rats, randomly divided into five groups. The first group served as negative control and the grafts were rinsed in saline before implantation. In the second and third groups, the grafts were soaked in a zoledronic acid solution (0.5 mg/ml) for 5 seconds and 10 minutes respectively before being rinsed in saline. In the fourth group, 8 μL of zoledronic acid solution (0.5 mg/ml) was pipetted onto the freeze-dried grafts without rinsing. The fifth group served as positive control and the rats were given zoledronic acid (0.1 mg/kg) systemically as a single injection two weeks after surgery. The grafts were harvested at 6 weeks and analysed with histomorphometry, evaluating the ingrowth distance of new bone into the graft as an equivalent to the anabolic osteoblast effect and the amount (bone volume/total volume; BV/TV) of remaining bone in the remodelled graft as equivalent to the catabolic osteoclast effect.



RESULTS:



In all chambers, almost the entire graft had been revascularized but only partly remodelled at harvest. The ingrowth distance of new bone into the graft was lower in grafts soaked in zoledronic acid for 10 minutes compared to control (p = 0.007). In all groups receiving zoledronic acid, the BV/TV was higher compared to control.



CONCLUSIONS:



This study found a strong inhibitory effect on bone resorption by bisphosphonates but also a limited inhibition of the ingrowth of new bone. Local treatment at surgery resulted in stronger inhibition of both resorption and bone formation compared to systemic treatment. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
BMC Musculoskeletal Disorders
volume
13
issue
Dec.,05
publisher
BioMed Central
external identifiers
  • WOS:000312801300001
  • PMID:23217097
  • Scopus:84870317866
ISSN
1471-2474
DOI
10.1186/1471-2474-13-240
language
English
LU publication?
yes
id
76508ee9-4046-4d0e-b062-568907da2cc9 (old id 3347531)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23217097?dopt=Abstract
date added to LUP
2013-01-02 14:39:49
date last changed
2016-11-06 04:25:17
@misc{76508ee9-4046-4d0e-b062-568907da2cc9,
  abstract     = {ABSTRACT:<br/><br>
<br/><br>
BACKGROUND: <br/><br>
<br/><br>
Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone chamber model, and compare that with systemic treatment.<br/><br>
<br/><br>
METHODS: <br/><br>
<br/><br>
Cancellous bone grafts were placed in titanium chambers and implanted in the tibia of 50 male rats, randomly divided into five groups. The first group served as negative control and the grafts were rinsed in saline before implantation. In the second and third groups, the grafts were soaked in a zoledronic acid solution (0.5 mg/ml) for 5 seconds and 10 minutes respectively before being rinsed in saline. In the fourth group, 8 μL of zoledronic acid solution (0.5 mg/ml) was pipetted onto the freeze-dried grafts without rinsing. The fifth group served as positive control and the rats were given zoledronic acid (0.1 mg/kg) systemically as a single injection two weeks after surgery. The grafts were harvested at 6 weeks and analysed with histomorphometry, evaluating the ingrowth distance of new bone into the graft as an equivalent to the anabolic osteoblast effect and the amount (bone volume/total volume; BV/TV) of remaining bone in the remodelled graft as equivalent to the catabolic osteoclast effect.<br/><br>
<br/><br>
RESULTS: <br/><br>
<br/><br>
In all chambers, almost the entire graft had been revascularized but only partly remodelled at harvest. The ingrowth distance of new bone into the graft was lower in grafts soaked in zoledronic acid for 10 minutes compared to control (p = 0.007). In all groups receiving zoledronic acid, the BV/TV was higher compared to control.<br/><br>
<br/><br>
CONCLUSIONS: <br/><br>
<br/><br>
This study found a strong inhibitory effect on bone resorption by bisphosphonates but also a limited inhibition of the ingrowth of new bone. Local treatment at surgery resulted in stronger inhibition of both resorption and bone formation compared to systemic treatment.},
  author       = {Belfrage, Ola and Isaksson, Hanna and Tägil, Magnus},
  issn         = {1471-2474},
  language     = {eng},
  number       = {Dec.,05},
  publisher    = {ARRAY(0x95bb188)},
  series       = {BMC Musculoskeletal Disorders},
  title        = {Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats.},
  url          = {http://dx.doi.org/10.1186/1471-2474-13-240},
  volume       = {13},
  year         = {2012},
}