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Manipulating the anabolic and catabolic response in bone graft remodeling: Synergism by a combination of local BMP-7 and a single systemic dosis of zoledronate.

Harding, Anna Kajsa LU ; Aspenberg, Per LU ; Kataoka, Masashi LU ; Bylski, David and Tägil, Magnus LU (2008) In Journal of Orthopaedic Research 26. p.1245-1249
Abstract
Remodeling of a bone graft can be influenced both by anabolic substances, such as a bone morphogenic protein (BMP) and by anticatabolic substances, such as the bisphosphonates. BMPs are potent bone anabolic substances, but also boost catabolism and cause resorption. Bisphosphonates inhibit osteoclast function and can be used to postpone resorption. In the present study a combination of both drugs was explored in a rat bone chamber model. Cancellous bone grafts were treated with either BMP-7 or saline and placed in a bone chamber implanted in the proximal tibia. After 2 weeks, an injection of either zoledronate 0.1 mg/kg or saline was given subcutaneously. The rats were killed after 6 weeks, and bone ingrowth distance into the graft and... (More)
Remodeling of a bone graft can be influenced both by anabolic substances, such as a bone morphogenic protein (BMP) and by anticatabolic substances, such as the bisphosphonates. BMPs are potent bone anabolic substances, but also boost catabolism and cause resorption. Bisphosphonates inhibit osteoclast function and can be used to postpone resorption. In the present study a combination of both drugs was explored in a rat bone chamber model. Cancellous bone grafts were treated with either BMP-7 or saline and placed in a bone chamber implanted in the proximal tibia. After 2 weeks, an injection of either zoledronate 0.1 mg/kg or saline was given subcutaneously. The rats were killed after 6 weeks, and bone ingrowth distance into the graft and graft resorption were measured by histomorphometry. BMP-7 significantly (p = 0.007) increased new bone ingrowth distance into the graft from 2.0 mm (SD = 0.98 mm) in the controls to 3.1 mm (SD = 0.93 mm). If bisphosphonate was not given, most of the newly formed and old graft bone was resorbed. A single injection of zoledronate significantly (p < 0.001) increased the trabecular volume/total volume to 40% (SD = 9%) compared to 14% (SD = 10%) in the nonbisphosphonate treated. In total, the net amount of bone increased by 400% when BMP-7 and zoledronate combined was compared to saline. A bone graft can be treated with BMP-7 to increase new bone formation and at the same time be protected against premature catabolism by a single dose of a bisphosphonate. This combination might be useful in various conditions in orthopedic reconstruction. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Orthopaedic Research
volume
26
pages
1245 - 1249
publisher
John Wiley & Sons
external identifiers
  • wos:000258240300013
  • pmid:18404659
  • scopus:49149097693
ISSN
1554-527X
DOI
10.1002/jor.20625
language
English
LU publication?
yes
id
5146bcab-372e-4eec-a754-fcffe48ed64c (old id 1147467)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18404659?dopt=Abstract
date added to LUP
2008-05-09 09:08:35
date last changed
2017-08-06 04:45:25
@article{5146bcab-372e-4eec-a754-fcffe48ed64c,
  abstract     = {Remodeling of a bone graft can be influenced both by anabolic substances, such as a bone morphogenic protein (BMP) and by anticatabolic substances, such as the bisphosphonates. BMPs are potent bone anabolic substances, but also boost catabolism and cause resorption. Bisphosphonates inhibit osteoclast function and can be used to postpone resorption. In the present study a combination of both drugs was explored in a rat bone chamber model. Cancellous bone grafts were treated with either BMP-7 or saline and placed in a bone chamber implanted in the proximal tibia. After 2 weeks, an injection of either zoledronate 0.1 mg/kg or saline was given subcutaneously. The rats were killed after 6 weeks, and bone ingrowth distance into the graft and graft resorption were measured by histomorphometry. BMP-7 significantly (p = 0.007) increased new bone ingrowth distance into the graft from 2.0 mm (SD = 0.98 mm) in the controls to 3.1 mm (SD = 0.93 mm). If bisphosphonate was not given, most of the newly formed and old graft bone was resorbed. A single injection of zoledronate significantly (p &lt; 0.001) increased the trabecular volume/total volume to 40% (SD = 9%) compared to 14% (SD = 10%) in the nonbisphosphonate treated. In total, the net amount of bone increased by 400% when BMP-7 and zoledronate combined was compared to saline. A bone graft can be treated with BMP-7 to increase new bone formation and at the same time be protected against premature catabolism by a single dose of a bisphosphonate. This combination might be useful in various conditions in orthopedic reconstruction. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.},
  author       = {Harding, Anna Kajsa and Aspenberg, Per and Kataoka, Masashi and Bylski, David and Tägil, Magnus},
  issn         = {1554-527X},
  language     = {eng},
  pages        = {1245--1249},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Orthopaedic Research},
  title        = {Manipulating the anabolic and catabolic response in bone graft remodeling: Synergism by a combination of local BMP-7 and a single systemic dosis of zoledronate.},
  url          = {http://dx.doi.org/10.1002/jor.20625},
  volume       = {26},
  year         = {2008},
}