Stochastic simulation of vertebral trabecular bone remodeling.

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.

[1]  L. Mosekilde,et al.  Consequences of the remodelling process for vertebral trabecular bone structure: a scanning electron microscopy study (uncoupling of unloaded structures). , 1990, Bone and mineral.

[2]  R. Newcombe,et al.  Structural mechanisms of trabecular bone loss in man. , 1989, Bone and mineral.

[3]  F. Melsen,et al.  Trabecular bone resorption depth decreases with age: differences between normal males and females. , 1985, Bone.

[4]  William M. O'Fallon,et al.  Effect of fluoride treatment on the fracture rate in postmenopausal women with osteoporosis. , 1990 .

[5]  M. Kleerekoper,et al.  Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. , 1983, The Journal of clinical investigation.

[6]  D B Kimmel,et al.  A computer simulation of the mature skeleton. , 1985, Bone.

[7]  J. Compston,et al.  A new method for the two‐dimensional analysis of bone structure in human iliac crest biopsies , 1986, Journal of microscopy.

[8]  H. Gundersen,et al.  Marrow space star volume in the iliac crest decreases in osteoporotic patients after continuous treatment with fluoride, calcium, and vitamin D2 for five years. , 1991, Bone.

[9]  L. Mosekilde,et al.  Sex differences in age-related loss of vertebral trabecular bone mass and structure--biomechanical consequences. , 1989, Bone.

[10]  G V Cochran,et al.  A new manual method for assessing two‐dimensional cancellous bone structure: Comparison between iliac crest and lumbar vertebra , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[11]  L. Mosekilde.  Iliac crest trabecular bone volume as predictor for vertebral compressive strength, ash density and trabecular bone volume in normal individuals. , 1988, Bone.

[12]  L. Mosekilde.  Age-related changes in vertebral trabecular bone architecture--assessed by a new method. , 1988, Bone.

[13]  H. Genant,et al.  Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. , 1990, The New England journal of medicine.

[14]  E. Eriksen,et al.  Normal and pathological remodeling of human trabecular bone: three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone disease. , 1986, Endocrine reviews.

[15]  F Melsen,et al.  Effect of sodium fluoride, calcium, phosphate, and vitamin D2 on trabecular bone balance and remodeling in osteoporotics. , 1985, Bone.

[16]  Flemming Melsen,et al.  A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis. , 1989 .

[17]  N L Fazzalari,et al.  Mathematical modelling of trabecular bone structure: the evaluation of analytical and quantified surface to volume relationships in the femoral head and iliac crest. , 1989, Journal of biomechanics.

[18]  L. Mosekilde,et al.  Age- and sex-related changes in iliac cortical bone mass and remodeling. , 1993, Bone.

[19]  J. Stepan,et al.  Bone loss and biochemical indices of bone remodeling in surgically induced postmenopausal women. , 1987, Bone.

[20]  P. Meunier,et al.  Treatment of osteoporosis with fluoride, calcium, and vitamin D. , 1981, The Orthopedic clinics of North America.

[21]  L. Mosekilde,et al.  Biomechanical competence of vertebral trabecular bone in relation to ash density and age in normal individuals. , 1987, Bone.

[22]  A. Parfitt,et al.  Trabecular bone architecture in the pathogenesis and prevention of fracture. , 1987, The American journal of medicine.

[23]  L. Mosekilde,et al.  A model of vertebral trabecular bone architecture and its mechanical properties. , 1990, Bone.

[24]  A. Prost,et al.  RISK-BENEFIT RATIO OF SODIUM FLUORIDE TREATMENT IN PRIMARY VERTEBRAL OSTEOPOROSIS , 1988, The Lancet.

[25]  J. Aaron,et al.  The microanatomy of trabecular bone loss in normal aging men and women. , 1987, Clinical orthopaedics and related research.

[26]  T. Steiniche,et al.  Changes in bone histomorphometry after long‐term treatment with intermittent, cyclic etidronate for postmenopausal osteoporosis , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[27]  J. Compston,et al.  Age-related changes in iliac crest trabecular microanatomic bone structure in man. , 1987, Bone.

[28]  D. Kiel,et al.  Hip fracture and the use of estrogens in postmenopausal women. The Framingham Study. , 1987, The New England journal of medicine.

[29]  R. Recker,et al.  Menopausal changes in bone remodeling. , 1978, The Journal of laboratory and clinical medicine.

[30]  J Reeve,et al.  A stochastic analysis of iliac trabecular bone dynamics. , 1986, Clinical orthopaedics and related research.

[31]  W. Mysiw,et al.  Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. , 1990, The New England journal of medicine.

[32]  Bone turnover and trabecular plate survival after artificial menopause. , 1987 .

[33]  A. Vesterby,et al.  Star volume in bone research. A histomorphometric analysis of trabecular bone structure using vertical sections , 1993, The Anatomical record.

[34]  N. Weiss,et al.  Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. , 1980, The New England journal of medicine.

[35]  R R Recker,et al.  A comparison of iliac bone histomorphometric data in post-menopausal osteoporotic and normal subjects. , 1990, Bone and mineral.