The potential of gene therapy for fracture healing in osteoporosis.
Osteoporosis-associated fractures impair a patient's function and quality of life and represent one of the major public health burdens. Demographic changes predict a dramatic increase in osteoporotic fractures. Experimental data have shown that osteoporosis impairs fracture healing. Clinical observations demonstrate high failure rates of implant fixation in osteoporosis. The reduced healing capacity, including impaired bone formation, in osteoporotic humans might be due to defects in mesenchymal stem cells that lead to reduced proliferation and osteoblastic differentiation. Growth factors show remarkable promise as agents that can improve the healing of bone or increase the proliferation and differentiation capacities of mesenchymal stem cells. Their clinical utility is limited by delivery problems. The attraction of gene-transfer approaches is the unique ability to deliver authentically processed gene products to precise anatomical locations at therapeutic levels for sustained periods of time. Unlike the treatment of chronic diseases, it is neither necessary nor desirable for transgene expression to persist beyond the few weeks or months needed to achieve healing. This review presents different approaches of gene therapy to enhance fracture healing and summarizes the promising results of preclinical studies. It focuses on applications of this new technique to fracture healing in osteoporosis. In our opinion, these applications represent some of the few examples in which gene therapy has a good chance of early clinical success.
Egermann
M
M
AO Research Institute, Davos, Switzerland. marcus.egermann@aofoundation.org
Schneider
E
E
Evans
C H
CH
Baltzer
A W
AW
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D017102:Fracture Healing / Q000235:genetics / Q000502:physiology*; D050723:Fractures, Bone / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology; D010024:Osteoporosis / Q000150:complications / Q000235:genetics / Q000628:therapy*; D011817:Rabbits
D019485:Bone Morphogenetic Proteins; D016207:Cytokines; D006133:Growth Substances