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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
Department of Orthopedics, Lund University Hospital, SE-221 85 Lund, Sweden.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine . Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
Department of Orthopedics, Lund University Hospital, SE-221 85 Lund, Sweden, Department of Orthopaedic Surgery, Oita University, Oita, Japan.
Department of Orthopedics, Lund University Hospital, SE-221 85 Lund, Sweden.
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2008 (English)In: Journal of Orthopaedic Research, ISSN 0736-0266, Vol. 26, no 9, 1245-1249 p.Article in journal (Refereed) Published
Abstract [en]

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. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Place, publisher, year, edition, pages
2008. Vol. 26, no 9, 1245-1249 p.
Keyword [en]
Anabolism, Bisphosphonates, Bone graft remodeling, Bone morphogenic protein (BMP), Catabolism
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-50276DOI: 10.1002/jor.20625OAI: diva2:271172
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2011-01-11

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Aspenberg, Per
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Faculty of Health SciencesOrthopaedics and Sports Medicine Department of Orthopaedics Linköping
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