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Osteoinductivity of Demineralized Bone Matrix Is Independent of Donor Bisphosphonate Use
Zvi Schwartz, DMD, PhD1; Sharon L. Hyzy, BS1; Mark A. Moore, PhD, MBA2; Shawn A. Hunter, PhD3; Chad J. Ronholdt, MBA4; MoonHae Sunwoo, PhD5; Barbara D. Boyan, PhD1
1 Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive N.W., Atlanta, GA 30332-0363. E-mail address for B.D. Boyan: barbara.boyan@bme.gatech.edu
2 LifeNet Health, Bio-Implants Division, 1864 Concert Drive, Virginia Beach, VA 23453. E-mail address: mark_moore@lifenethealth.org
3 Community Tissue Services, Center for Tissue Innovation and Research, 2900 College Drive, Kettering, OH 45420. E-mail address: shunter@communitytissue.org
4 LABS Inc., 6933-B South Revere Parkway, Centennial, CO 80112. E-mail address: cronholdt@labsinc.org
5 Musculoskeletal Transplant Foundation, 125 May Street, Edison, NJ 08837. E-mail address: moonhae_sunwoo@mtf.org
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Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. In addition, one or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

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Investigation performed at the Georgia Insitute of Technology, Atlanta, Georgia

Copyright © 2011 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2011 Dec 21;93(24):2278-2286. doi: 10.2106/JBJS.J.01469
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Demineralized bone matrix is commonly used as a bone graft substitute, either alone or to supplement an osteoconductive material, because of its osteoinductive properties. The aging of the population has led to an increase in the number of prospective donors of demineralized bone matrix who have taken bisphosphonates to prevent osteoclast-mediated bone resorption. The aim of this study was to determine whether oral bisphosphonate usage affects the osteoinductivity of demineralized bone matrix from donors.


Sex-matched and age-matched pairs of samples were provided by four tissue banks (three or four pairs per bank). Demineralized bone matrix donors without bisphosphonate treatment had a mean age (and standard deviation) of 69.1 ± 2.5 years, and donors with bisphosphonate treatment had a mean age of 68.9 ± 2.0 years. Each pair included one donor known to have taken bisphosphonates and one who had not taken bisphosphonates. Demineralized bone matrix previously confirmed as osteoinductive was the positive control, and heat-inactivated demineralized bone matrix was the negative control. Demineralized bone matrix incubated with 1 mL of phosphate-buffered saline solution containing 0, 0.002, 2.0, or 2000 ng/mL of alendronate was also tested. Gelatin capsules containing 15 mg of demineralized bone matrix were implanted bilaterally in the gastrocnemius muscle of male nude mice (eight implants per group). The mice were killed thirty-five days after implantation, and hind limbs were recovered and processed for histological analysis. Osteoinductivity was measured with use of a qualitative score and by histomorphometry.


Nine of fifteen samples from donors who had had bisphosphonate treatment and ten of fifteen samples from patients who had not had bisphosphonate treatment were osteoinductive. Qualitative mean scores were comparable (1.7 ± 0.4 for those without bisphosphonates and 1.9 ± 0.7 for those with bisphosphonates). Osteoinductive demineralized bone matrix samples produced ossicles of comparable size, regardless of bisphosphonate usage. Histomorphometric measurements of the area of new bone formation and residual demineralized bone matrix were also comparable. The addition of alendronate to control demineralized bone matrix did not affect its osteoinductivity.


Demineralized bone matrix samples from donors treated with bisphosphonates and donors not treated with bisphosphonates have the same ability to induce bone formation. However, it is not known if the quality of the new bone is affected, with subsequent consequences affecting bone remodeling.

Clinical Relevance: 

These results show that demineralized bone matrix can be safe and effective as an osteoinductive material, even when the original bone graft is obtained from donors who have used bisphosphonates.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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