MECHANICAL MODULATION OF GROWTH IN PHYSES

骨和生长软骨的进行性畸形通常被认为是由“Hueter-Reinmann定律”控制的，该定律指出，与正常值相比，增加的机械压缩会阻碍生长，而生长板的负荷减少会加速生长。 先前的研究已经证实，恒定负载叠加在生长板的环境体内负载上将调节其生长速率。 这种现象仅对个别物种的少数个别骨骼进行了量化，并且确定特定骨骼对负荷的响应作为其生理正常生长速率、生长板细胞的尺寸和活性的函数的一般规则是未知的。 许多与骨生长速率相关（并可能决定骨生长速率）的变量已被确定。 这项工作将提供更好的理解骨生长的机械调节，并最终允许定量设计的机械治疗的技术，如支具，肌肉刺激和手术。 拟议的研究将量化在正常条件下以及机械压缩和牵引下长骨和椎骨的软骨内生长速率。 四个不同的物种将在生长的早期阶段和接近骨骼成熟时，骨骼生长缓慢进行研究。 在额外的实验中，将通过研究仅在夜间和白天的生长肌负荷的影响来研究“部分时间”治疗的可行性。 将记录生长板的特征性质（尺寸、细胞数量和细胞活性测量），并在经历不同施加机械应力的生长板之间进行比较。 统计模型将被开发，以显示如何生长的机械调制变化的关系，每个生长板的特性。这些分析将部分受到生长板特性之间已知的生理关系的指导。 这项工作的结果将是一个给定的骨骺板应如何预期响应于给定的应力的理解，这将有助于了解骨骼畸形的进展，并指导他们的治疗。

Progressive deformities in bones and growth cartilages are commonly thought to be controlled by the 'Hueter-Volkmann Law' which states that growth is retarded by increased mechanical compression, and accelerated by reduced loading of the growth plate in comparison with normal values. It has been confirmed by previous studies that a constant load, superimposed on the ambient in vivo loading of a growth plate will modulate its rate of growth. This phenomenon has only been quantified for a few individual bones of individual species, and the general rules which determine a particular bone's response to load as a function of its physiologically normal growth rate, dimensions and activity of the growth plate cells are unknown. Many of the variables which covary with (and probably govern) bone growth rates have been identified. This work will provide greater understanding of the mechanical regulation of bone growth and eventually permit quantitative design of mechanical treatment by techniques such as bracing, muscle stimulation and surgery. The proposed studies will quantity the rate of endochondral growth of long bones and vertebrae under normal conditions and with mechanical compression and distraction. Four different species will be studied at an early stage of growth and nearer to skeletal maturity when the bones are growing more slowly. In additional experiments the feasibility of 'part-time' treatment will be investigated by studying the effects of physis loading during night-time and day-time only. The characteristic properties of the growth plate (dimensions, numbers of cells and measures of cellular activity) will be documented and compared between growth plates which had experienced different applied mechanical stresses. Statistical models will be developed to show how the mechanical modulation of growth varies in relationship to characteristic properties of each growth plate. These analyses will be guided in part by known physiological relationships between properties of growth plates. The result of this work will be an understanding of how a given physis should be expected to respond to a given stress, and this will be helpful to understand the progression of skeletal deformities and to guide their treatment.