Thomsen J S, Mosekilde L, Boyce R W, Mosekilde E
Department of Physics, Technical University of Denmark, Lyngby.
Bone. 1994 Nov-Dec;15(6):655-66. doi: 10.1016/8756-3282(94)90314-x.
Bone remodeling changes bone mass, architecture, and thereby bone strength, during normal aging. These changes seem to be accelerated during the menopause. Several therapeutic agents have been used in order to delay the onset of the menopause-related changes. The effects of these agents on the remodeling process have been determined histomorphometrically in several short-term clinical studies, but data from long-term clinical studies are difficult to achieve, as are data on the influence on bone strength. The aim of this study was to develop a computer stimulation model that could assist in predicting the long-term effects of changes in the remodeling process on bone mass, trabecular thickness, and perforations. The paper presents such a stochastic model of the remodeling process in human vertebral trabecular bone. The computer model is based on histomorphometric and structural data from human studies. It is presented in terms of flow charts, and simulations performed with the model are discussed in relation to measurements on human vertebral bone samples. The results show that a menopause-related doubling of the activation frequency causes a transient, mainly reversible bone loss. If the menopause is accompanied by an increase in both activation frequency and resorption depth, then the resulting bone loss will be more pronounced and with a larger part being irreversible bone loss (perforations). The two antiresorptive agents. Etidronate and estrogen both cause a slight increase in bone mass (reducing remodeling space), and Etidronate also seems capable of preventing perforations. During fluoride therapy, an initial increase in remodeling space followed by a reduction is seen. Very few perforations are found to take place during fluoride therapy. The present model has been validated by assessing the effects of the menopause and treatment with antiresorptive or anabolic agents. It was found that the results mirrored or anabolic agents. It was found that the results mirrored very closely the results (bone mass measurements) from short-term clinical studies. It is therefore concluded that the model provides a tool for evaluating existing and new therapeutic regimens.
在正常衰老过程中，骨重塑会改变骨量、结构，进而影响骨强度。这些变化在绝经期间似乎会加速。为了延缓与绝经相关变化的发生，人们使用了多种治疗药物。在几项短期临床研究中，已通过组织形态计量学确定了这些药物对重塑过程的影响，但长期临床研究的数据很难获得，关于对骨强度影响的数据也是如此。本研究的目的是开发一种计算机模拟模型，以帮助预测重塑过程变化对骨量、小梁厚度和穿孔的长期影响。本文提出了一种人类椎骨小梁骨重塑过程的随机模型。该计算机模型基于人体研究的组织形态计量学和结构数据。它以流程图的形式呈现，并结合对人体椎骨样本的测量结果讨论了用该模型进行的模拟。结果表明，与绝经相关的激活频率翻倍会导致短暂的、主要是可逆的骨质流失。如果绝经伴随着激活频率和吸收深度的增加，那么由此导致的骨质流失将更加明显，且更大一部分是不可逆的骨质流失（穿孔）。两种抗吸收剂依替膦酸盐和雌激素都会使骨量略有增加（减少重塑空间），依替膦酸盐似乎也能够预防穿孔。在氟化物治疗期间，会先出现重塑空间增加，随后减少。在氟化物治疗期间很少发现穿孔发生。通过评估绝经以及抗吸收或促合成药物治疗的效果，对本模型进行了验证。发现结果与短期临床研究的结果（骨量测量）非常接近。因此得出结论，该模型为评估现有和新的治疗方案提供了一种工具。
