Keys To Optimal Selection Of Orthobiologics

Phillip E. Richardson, DPM, Brian T. Dix, DPM, Adebola T. Adeleke, DPM, John M. Baca, DPM, Robert Mendicino, DPM, FACFAS, and Alan R. Catanzariti, DPM, FACFAS

   At its core, demineralized bone matrix is comprised chiefly of collagen (93 percent), which provides its osteoconductive surface. Soluble proteins such as bone morphogenetic proteins and other synergistic proteins (PDGF, IGF, TGF and FGF) give demineralized bone matrix its inherent osteoinductivity and comprise approximately 5 percent of its makeup. The remaining 2 percent is made of residual mineralized matrix.24,25

   It is important to emphasize that demineralized bone matrix does not directly induce the formation of bone in subcutaneous or submuscular tissues.24 Demineralized bone matrix induces mesenchymal stem cells to differentiate into chondroblasts, not osteoblasts. This chondrogenesis process differs from that of classical endochondral bone formation. Although cartilage forms, resorbs and is eventually replaced by bone, the bone formation facilitated by demineralized bone matrix occurs only after the cartilage has been resorbed and not at the same time as resorption as is the case in endochondral bone formation.24-27

   All demineralized bone matrix is not created equally.28 Donor tissue is not pooled in the United States and each lot or batch of demineralized bone matrix derives from a single donor. Along with donor-to-donor variation is the proprietary nature of each demineralization process, which is neither widely published nor regulated.29 Once demineralized bone is extracted from donor bone, it is in a particulate powder form, which is easily subject to static charge which can make containment and delivery challenging.

   Accordingly, demineralized bone matrix is combined with other carriers (e.g. glycerol, gelatin, calcium sulfate, hyaluronic acid, lecithin or poloxamer) to make handling and delivery easier. In such mixtures, a significant portion of the compound is comprised of carrier material (~85 percent carrier, ~15 percent demineralized bone matrix).24 Many different forms (e.g. gel, putty, chips) are commercially produced. Accordingly, there are significant variations in concentrations of bone morphogenetic proteins when comparing preparations, even between lot numbers of the same brand.21,28

What You Should Know About Bone Morphogenetic Proteins

Bone morphogenetic proteins are a group of bioactive molecules that have been the subject of intense research over the last 50 years. Since their discovery, research has revealed increasing indications in the clinical setting. Bone morphogenetic proteins can be produced in large quantities with recombinant DNA technology and cloning techniques.30 The ability to produce bone morphogenetic proteins in the lab has been instrumental in making them commercially available for patient care.30-32

   Bone morphogenetic proteins are members of the tumor growth factor beta superfamily of molecules. These molecules function within complicated signaling pathways that modulate differentiation of mesenchymal stem cells and osteogenesis.33 BMP 2, 4, 7, 9 and 14 have shown the most promise in promoting bone healing. These complex molecules are known to incite the production of cartilage, new bone formation and angiogenesis.34,35

   Furthermore, BMP-2 and BMP-7 have shown the most promise to foot and ankle surgeons due to their direct influence on angiogenesis.33 BMP-2 is of particular interest due to its abilities to promote neovascularization and induce the differentiation of mesenchymal stem cells into osteoblasts.33 This powerful molecule has been well studied in the orthopedic literature. Large multicenter randomized trials have led to FDA approval for the use of BMP-2 in acute open tibial fractures.33

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