Osteoinductivity of commercially available demineralized bone matrix. Preparations in a spine fusion model.

BACKGROUND Although autogenous bone is the most widely used graft material for spinal fusion, demineralized bone matrix preparations are available as alternatives or supplements to autograft. They are prepared by acid extraction of most of the mineralized component, with retention of the collagen and noncollagenous proteins, including growth factors. Differences in allograft processing methods among suppliers might yield products with different osteoinductive activities. The purpose of this study was to compare the efficacy of three different commercially available demineralized bone matrix products for inducing spinal fusion in an athymic rat model. METHODS Sixty male athymic rats underwent spinal fusion and were divided into three groups of eighteen animals each. Group I received Grafton Putty; Group II, DBX Putty; and Group III, AlloMatrix Injectable Putty. A control group of six animals (Group IV) underwent decortication alone. Six animals from each of the three experimental groups were killed at each of three intervals (two, four, and eight weeks), and the six animals from the control group were killed at eight weeks. At each of the time-points, radiographic and histologic analysis and manual testing of the explanted spines were performed. RESULTS The spines in Group I demonstrated higher rates of radiographically evident fusion at eight weeks than did the spines in Group III or Group IV (p < 0.05). Manual testing of the spines at four weeks revealed variable fusion rates (five of six in Group I, two of six in Group II, and none of six in Group III). At eight weeks, all six spines in Group I, three of the six in Group II, and no spine in Group III or IV had fused. Histologic analysis of the spines in Groups I, II, and III demonstrated varying amounts of residual demineralized bone matrix and new bone formation. Group-I spines demonstrated the most new bone formation. CONCLUSIONS This study demonstrated differences in the osteoinductive potentials of commercially available demineralized bone matrices in this animal model.

[1]  S. Frenkel,et al.  Demineralized Bone Matrix: Enhancement of Spinal Fusion , 1993, Spine.

[2]  D. Oakes,et al.  An Evaluation of Human Demineralized Bone Matrices in a Rat Femoral Defect Model , 2003, Clinical orthopaedics and related research.

[3]  S. Boden,et al.  Use of Recombinant Human Bone Morphogenetic Protein-2 to Achieve Posterolateral Lumbar Spine Fusion in Humans: A Prospective, Randomized Clinical Pilot Trial 2002 Volvo Award in Clinical Studies , 2002, Spine.

[4]  Eric E. Johnson,et al.  Human Bone Morphogenetic Protein Allografting for Reconstruction of Femoral Nonunion , 2000, Clinical orthopaedics and related research.

[5]  L. Titus,et al.  1998 Volvo Award Winner in Basic Science Studies: Lumbar Spine Fusion by Local Gene Therapy With a cDNA Encoding a Novel Osteoinductive Protein (LMP‐1) , 1998, Spine.

[6]  D. Cochran,et al.  Factors that modulate the effects of bone morphogenetic protein-induced periodontal regeneration: a critical review. , 2002, Journal of periodontology.

[7]  Marc F. Brassard,et al.  Treatment of unicameral bone cyst with demineralized bone matrix. , 1998, Journal of pediatric orthopedics.

[8]  S. Boden,et al.  Spine update. The use of animal models to study spinal fusion. , 1994, Spine.

[9]  H. An,et al.  Comparison Between Allograft Plus Demineralized Bone Matrix Versus Autograft in Anterior Cervical Fusion|A Prospective Multicenter Study , 1995, Spine.

[10]  S. Boden,et al.  Overview of the Biology of Lumbar Spine Fusion and Principles for Selecting a Bone Graft Substitute , 2002, Spine.

[11]  U. Ripamonti,et al.  Advances in biotechnology for tissue engineering of bone. , 2000, Current pharmaceutical biotechnology.

[12]  G. Mundy,et al.  Optimizing human demineralized bone matrix for clinical application. , 2000, Tissue engineering.

[13]  M. Urist,et al.  Bone morphogenetic protein augmentation grafting of resistant femoral nonunions. A preliminary report. , 1988, Clinical orthopaedics and related research.

[14]  T. Malinin,et al.  Lipids closely associated with bone morphogenetic protein (BMP)--and induced heterotopic bone formation. With preliminary observations of deficiencies in lipid and osteoinduction in lathyrism in rats. , 1997, Connective tissue research.

[15]  P. Holtom,et al.  Comparison of Anterior and Posterior Iliac Crest Bone Grafts in Terms of Harvest-Site Morbidity and Functional Outcomes , 2002, The Journal of bone and joint surgery. American volume.

[16]  S. Boden Evaluation of carriers of bone morphogenetic protein for spinal fusion. , 2001, Spine.

[17]  S. Boden,et al.  Experimental Posterolateral Lumbar Spinal Fusion With a Demineralized Bone Matrix Gel , 1998, Spine.

[18]  T. Albert,et al.  Donor Site Morbidity After Anterior Iliac Crest Bone Harvest for Single-Level Anterior Cervical Discectomy and Fusion , 2003, Spine.

[19]  D. W. Boone Complications of iliac crest graft and bone grafting alternatives in foot and ankle surgery. , 2003, Foot and ankle clinics.

[20]  S. Boden,et al.  A Rabbit Model for Nonunion of Lumbar Intertransverse Process Spine Arthrodesis , 1996, Spine.

[21]  J. Seiler,et al.  Iliac crest autogenous bone grafting: donor site complications. , 2000, Journal of the Southern Orthopaedic Association.

[22]  S. Boden,et al.  Clinical application of the BMPs. , 2001, The Journal of bone and joint surgery. American volume.

[23]  S. Ludwig,et al.  Osteoinductive bone graft substitutes for spinal fusion: a basic science summary. , 1999, The Orthopedic clinics of North America.

[24]  J. Connolly,et al.  Comparison of Bone Grafts for Posterior Spinal Fusion in Adolescent Idiopathic Scoliosis , 2003, Spine.

[25]  G. Finerman,et al.  Repair of segmental defects of the tibia with cancellous bone grafts augmented with human bone morphogenetic protein. A preliminary report. , 1988, Clinical orthopaedics and related research.

[26]  L. Titus,et al.  New formulations of demineralized bone matrix as a more effective graft alternative in experimental posterolateral lumbar spine arthrodesis. , 1999, Spine.

[27]  Freddie H Fu,et al.  Gene therapy in orthopaedic surgery. , 2002, Instructional course lectures.

[28]  H. An,et al.  The use of biologic materials in spinal fusion. , 2001, Orthopedics.

[29]  L. Titus,et al.  Overcoming the Immune Response to Permit Ex Vivo Gene Therapy for Spine Fusion With Human Type 5 Adenoviral Delivery of the LIM Mineralization Protein-1 cDNA , 2003, Spine.

[30]  J E Block,et al.  Clinical utility of demineralized bone matrix for osseous defects, arthrodesis, and reconstruction: impact of processing techniques and study methodology. , 1999, Orthopedics.

[31]  S. Boden Biology of lumbar spine fusion and use of bone graft substitutes: present, future, and next generation. , 2000, Tissue engineering.

[32]  H. Sandhu,et al.  Use of Recombinant Human Bone Morphogenetic Protein-2 in Spinal Fusion Applications , 2002, Spine.

[33]  J. Connolly,et al.  Skeletal repair in the aged: a preliminary study in rabbits. , 1988, The American journal of the medical sciences.

[34]  S. Salkeld,et al.  Histologic Analysis of Implant Sites After Grafting With Demineralized Bone Matrix Putty and Sheets , 2000, Implant dentistry.

[35]  V. J. Sammarco,et al.  Modern issues in bone graft substitutes and advances in bone tissue technology. , 2002, Foot and ankle clinics.

[36]  M. Chapman,et al.  Morbidity at bone graft donor sites. , 1989, Journal of orthopaedic trauma.

[37]  J. Andrades,et al.  Demineralized bone matrix mediates differentiation of bone marrow stromal cells in vitro: Effect of age of cell donor , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.