Effects of Ethnicity and Age or Menopause on the Remodeling and Turnover of Iliac Bone: Implications for Mechanisms of Bone Loss

We measured histologic indices of bone remodeling and turnover separately on the cancellous, endocortical, and intracortical subdivisions of the endosteal envelope, and on the combined total surface, in transiliac bone biopsies obtained after double tetracycline labeling in 142 healthy women, aged 20–74 years, 34 black and 108 white, 61 premenopausal and 81 postmenopausal. The data were analyzed by two‐way analysis of variance of the four groups defined by age/menopause and ethnicity and by linear regression of the major variables on age. None of the interaction terms was significant and none of the regression slopes on age differed between blacks and whites, indicating that, as for the previously reported structural indices, the effects of ethnicity and of age/menopause are independent. Accordingly, the data were also analyzed separately for the effect of ethnicity (pre‐ and postmenopausal combined) and age/menopause (blacks and whites combined). The analyses led to the following conclusions. (1) The geometric mean bone formation rate on the combined total surface was 25% lower in blacks than in whites; other histologic differences between ethnic groups were inconsistent between surfaces. (2) Serum osteocalcin (OC) but not bone‐specific alkaline phosphatase (BSAP) was lower by about 15% in blacks than in whites. (3) The lower bone turnover in blacks is most likely in the directed rather than in the stochastic component because of a higher bone mass and consequent reduced susceptibility to fatigue damage. (4) All Class 1 bone formation variables and the three resorption indices were significantly higher in the postmenopausal compared with the premenopausal subjects, reflecting a 33% increase in activation frequency. (5) BSAP, but not OC, was increased relatively more (66%) than the bone formation rate (BFR). Consequently, BSAP is more sensitive to the effects of menopause than OC, but OC is more sensitive to the effects of ethnicity than BSAP. (6) There were highly significant differences between the three subdivisions of the endosteal envelope for every non–cell‐related variable. All Class 1 formation variables were highest on the endocortical surface, but the magnitude and pattern of the differences otherwise was inconsistent between variables. The contributions of the different subdivisions to the total bone formation rate were cancellous 54%, endocortical 13%, and intracortical 33%. (7) The previously reported changes in bone surface location, together with the presently reported changes in activation frequency and wall thickness indicated that there was no significant effect of age/menopause on erosion depth on the cancellous and intracortical surfaces but a large increase in erosion depth on the endocortical surface. (8) The increase in bone turnover that results from hormonal changes is most likely in the stochastic rather than in the directed component because it serves no purpose but has harmful effects on skeletal integrity.

[1]  M. Horowitz,et al.  Evidence for a renal calcium leak in postmenopausal women. , 1991, The Journal of clinical endocrinology and metabolism.

[2]  R. Eastell,et al.  Interrelationship among vitamin D metabolism, true calcium absorption, parathyroid function, and age in women: Evidence of an age‐related intestinal resistance to 1,25‐dihydroxyvitamin D action , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[3]  A. Parfitt,et al.  Bone resorption and formation on the periosteal envelope of the ilium: A histomorphometric study in healthy women , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[4]  J. Halse,et al.  Histomorphometric analysis of normal bone from the iliac crest of Norwegian subjects. , 1988, Bone and mineral.

[5]  Douglas G. Altman,et al.  Practical statistics for medical research , 1990 .

[6]  A. Villanueva,et al.  Identification of the mineralization front: comparison of a modified toluidine blue stain with tetracycline fluorescence. , 1983, Metabolic bone disease & related research.

[7]  J. Pettifor,et al.  Histomorphometry of iliac crest bone in 346 normal black and white South African adults. , 1990, Bone and mineral.

[8]  H. Frost,et al.  Perspectives: bone's mechanical usage windows. , 1992, Bone and mineral.

[9]  R. Heaney The bone‐remodeling transient: Implications for the interpretation of clinical studies of bone mass change , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[10]  Michael A. Parfitt,et al.  A new method for measuring cancellous bone erosion depth: Application to the cellular mechanisms of bone loss in postmenopausal osteoporosis , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[11]  L E Lanyon,et al.  The success and failure of the adaptive response to functional load-bearing in averting bone fracture. , 1992, Bone.

[12]  R. Weinstein,et al.  Diminished rates of bone formation in normal black adults. , 1988, The New England journal of medicine.

[13]  F. James Rohlf,et al.  Biometry: The Principles and Practice of Statistics in Biological Research , 1969 .

[14]  M. Kleerekoper,et al.  Structural and geometric changes in iliac bone: Relationship to normal aging and osteoporosis , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[15]  Parfitt Am Hormonal Influences on Bone Remodeling and Bone Loss: Application to the Management of Primary Hyperparathyroidism , 1996 .

[16]  S. Epstein,et al.  The effects of muscle‐building exercise on Vitamin D and mineral metabolism , 1988, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[17]  M. Drezner,et al.  Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committee , 1987, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

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

[19]  J. Stepan,et al.  Serum osteocalcin levels and bone alkaline phosphatase isoenzyme after oophorectomy and in primary hyperparathyroidism. , 1987, The Journal of clinical endocrinology and metabolism.

[20]  A. Villanueva,et al.  Relations between histologic indices of bone formation: Implications for the pathogenesis of spinal osteoporosis , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[21]  S. Epstein,et al.  Evidence for alteration of the vitamin D-endocrine system in blacks. , 1985, The Journal of clinical investigation.

[22]  A. Parfitt,et al.  Theoretical perspective: A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates , 1996 .

[23]  D. Rao,et al.  Effect of ethnicity and age or menopause on the structure and geometry of iliac bone , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[24]  K. Mann,et al.  Bone formation rate in older normal women: concurrent assessment with bone histomorphometry, calcium kinetics, and biochemical markers. , 1988, The Journal of clinical endocrinology and metabolism.

[25]  K. Mann,et al.  Concurrent assays of circulating bone Gla-protein and bone alkaline phosphatase: effects of sex, age, and metabolic bone disease. , 1988, The Journal of clinical endocrinology and metabolism.

[26]  M. Kleerekoper,et al.  Reference data for bone mass, calciotropic hormones, and biochemical markers of bone remodeling in older (55‐75) postmenopausal white and black women , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[27]  R. Jilka,et al.  Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. , 1995, The New England journal of medicine.

[28]  P. Delmas,et al.  Clinical use of biochemical markers of bone remodeling in osteoporosis. , 1992, Bone.

[29]  B. Riggs,et al.  Role of estrogen deficiency in pathogenesis of secondary hyperparathyroidism and increased bone resorption in elderly women. , 1997, Proceedings of the Association of American Physicians.

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

[31]  S. Krane,et al.  Procollagen type I carboxy‐terminal extension peptide in serum as a marker of collagen biosynthesis in bone. Correlation with iliac bone formation rates and comparison with total alkaline phosphatase , 1987, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[32]  A. Parfitt Hormonal Influences on Bone Remodeling and Bone Loss: Application to the Management of Primary Hyperparathyroidism , 1996, Annals of Internal Medicine.

[33]  D. Eyre,et al.  A specific immunoassay for monitoring human bone resorption: Quantitation of type I collagen cross‐linked N‐telopeptides in urine , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[34]  Sokal Rr,et al.  Biometry: the principles and practice of statistics in biological research 2nd edition. , 1981 .

[35]  M. Kleerekoper,et al.  Biochemical studies in the evaluation and management of osteoporosis: current status and future prospects. , 1996, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[36]  R. Sokal,et al.  Biometry: The Principles and Practice of Statistics in Biological Research (2nd ed.). , 1982 .

[37]  P. Delmas,et al.  The short-term effects of conjugated estrogen on bone turnover in older women. , 1994, The Journal of clinical endocrinology and metabolism.

[38]  M. Wiznerowicz,et al.  Interleukin‐6‐Type Cytokines and Their Receptors for Gene Therapy of Melanoma a , 1995, Annals of the New York Academy of Sciences.

[39]  J. Stepan,et al.  Age and sex dependency of the biochemical indices of bone remodelling. , 1985, Clinica chimica acta; international journal of clinical chemistry.

[40]  D. Meier,et al.  Racial differences in pre‐ and postmenopausal bone homeostasis: Association with bone density , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[41]  A. Parfitt,et al.  Frequency distributions of tetracycline‐based measurements: Implications for the interpretation of bone formation indices in the absence of double‐labeled surfaces , 1990, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[42]  A. Villanueva,et al.  Metabolic bone disease with and without osteomalacia after intestinal bypass surgery: a bone histomorphometric study. , 1985, Bone.

[43]  J. Compston,et al.  Histomorphometric analysis of dynamic parameters of trabecular bone formation in the iliac crest of normal British subjects. , 1983, Metabolic bone disease & related research.

[44]  M. Kleerekoper,et al.  Irreversible bone loss in osteomalacia. Comparison of radial photon absorptiometry with iliac bone histomorphometry during treatment. , 1985, The Journal of clinical investigation.

[45]  T. Fujita Vitamin D in the Treatment of Osteoporosis Revisited∗ , 1996, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[46]  M. Horowitz,et al.  Relative contributions of years since menopause, age, and weight to vertebral density in postmenopausal women. , 1992, The Journal of clinical endocrinology and metabolism.

[47]  J. Eisman,et al.  Age and menopause-related changes in indices of bone turnover. , 1989, The Journal of clinical endocrinology and metabolism.

[48]  M. Horowitz,et al.  Aging and bone metabolism in African American and Caucasian women. , 1996, The Journal of clinical endocrinology and metabolism.