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Influences on long bones development growth and aging
MCH van der Meulen, PhD; ER Morey-Holton, PhD; Dennis R Carter, PhD; B Mikic, MS; DM Kingsley, PhD
Skeletal development, growth, maintenance and aging are driven by both genetic and epigenetic factors, such as mechanical stimuli, hormones, growth factors and metabolic status (Figure 1). The relative importance of these factors is poorly understood but they have an obvious impact on the pathogenesis and progression of osteoporosis, osteoarthrosis and fracture, and are responsible for an ever-increasing cost to society. An understanding of these skeletal processes will facilitate development of treatment strategies and suggest possible prophylaxis.
Figure
1. Genetic and epigenetic influences on skeletal development and growth.
Quantitative theories have been proposed that predict the effects of mechanical loading on bone structure and microstructure. The orthopaedic biomechanics group at the Rehab R&D Center has developed a time-dependent skeletal developmental mechanics theory relating bone tissue apposition or resorption to the mechanical environment to which the skeleton is exposed. This theory has recently been applied to long bone modeling during growth and aging. Efforts are now being made to accommodate biologic, as well as mechanobiologic influences. Experimental data is necessary to further develop this theory and to enable it to become a useful, predictive tool.
To enhance our understanding of factors involved in skeletal development, growth and aging, we are examining genetic regulation and hormonal effects in addition to mechanical loading. In our studies we are using theoretical and experimental approaches in conjunction with animal models to identify structural, geometric and material changes to the skeleton.
Adaptation of Long Bones to Disuse
MCH van der Meulen, PhD; ER Morey-Holton, PhD; DR Carter, PhD
The effect of immobilization on bone growth and maintenance is an important clinical issue in the treatment of spinal cord injured individuals. In spinal cord injury, bone loss in the lower extremity occurs due to the reduction of normal mechanical loading, as well as the lack of neurologically induced factors. How much of this loss is due to disuse and how much due to the associated neurological conditions is not clear.
In a collaborative study with NASA Ames Research Center we are using experimental and computer models to study the effects of disuse on the skeleton. We believe these studies will help to understand changes resulting from spinal cord injury. Decreased loading will be achieved by hindlimb suspension and possibly space flight (depending on tissue availability). The first set of experiments show that hindlimb suspension significantly decreases the femur's torsional strength (Figure 2), primarily by altering the geometry of the bone.
Figure 2. Mean maximum torque (+/- SD) plotted as a function of age and environmental duration. |
Efficacy of Growth Factors in Osteoporosis
B Mikic', MS ; MCH van der Meulen, PhD; DM Kingsley, PhD; DR Carter, PhD
Osteoporosis is a severe health problem in the United States affecting 40% of post-menopausal women and a smaller, but significant, percentage of elderly men. Post-menopausal women experience a reduction in circulating estrogen levels. Estrogen replacement therapy is the most established drug treatment to date for osteoporosis; however, only a modest decrease in the rate of bone loss is achieved. In addition, only women are candidates for estrogen therapy, and many women are not eligible for a variety of health reasons. Currently a variety of natural and synthetic potential chemical treatments are being researched. We will be examining several models and how the bone strength is affected by the treatment. Experimental testing and computer models are two approaches that can be used to assess the efficacy of treatment.
One area that shows promise for the treatment of skeletal diseases involves the use of growth factors. Growth factors are chemical compounds that affect the growth and development of a variety of skeletal tissues. One class of growth factors found naturally in the body is the bone morphogenic proteins (BMPs). These proteins are known to play a critical role in early skeletal development when bones and joints are first formed in utero. However, the role of the BMPs during adulthood is not well understood. We are investigating the effects of one member of the BMP family (BMP-5) on long bone development and adaptation in a mouse model. These types of studies may suggest the use of growth factor therapy for the treatment of osteoporosis in humans.
Republished from the 1994 Rehabilitation R&D Center Progress Report. For
current information about this project, contact
MCH van der Meulen.
