Abstract
To assess the bone turnover abnormalities which characterize postmenopausal osteoporosis with vertebral fractures (PMOp), a transiliac bone biopsy was performed after double labeling of the mineralizing front with tetracycline in 50 untreated PMOp patients who were compared with 13 healthy age-matched volunteer females. The analysis of bone remodeling and structure parameters demonstrated that PMOp is a disease affecting both the cancellous and the endocortical envelopes and characterized by increased resorption and by a marked decrease in the osteoblastic apposition rate due to a reduced duration of bone formation. This induces a decrease in the width of both individual osteons and trabeculae. In PMOp, the wide spectrum of bone turnover as compared with the controls, associated with the typical bimodal distribution of cancellous osteoid perimeter, allowed us to identify two subsets, one with normal turnover (NT) and one with high turnover (HT) representing 30% of the cases. When compared to NT, HT was characterized by increased osteoclast number, lower bone volume, thinner osteons, increased formation at the tissue-level and markedly decreased duration of formation. In HT the marked decrease in the duration of activity of osteoblasts and the markedly increased number of osteoclasts induced a greater decrease in bone volume, despite the increase of bone formation at the tissue level. These subsets could not be distinguished by any clinical or biochemical parameter except for serum bone gla protein (osteocalcin) which was significantly higher (as a group) in HT than in NT. The underlying cause for these two subsets is unknown. We conclude that PMOp affects the cancellous and the endocortical bone. Bone loss results from a wide spectrum of bone turnover abnormalities, with two distinct subsets, one with normal turnover and one with high turnover.
Similar content being viewed by others
References
Riggs BL, Melton III LJ. Heterogeneity of involutional osteoporosis: evidence for two osteoporosis syndromes. Am J Med 1983; 75: 899–901.
Johnston CC, Norton J, Khairi MRA et al. Heterogeneity of fracture syndromes in postmenopausal women. J Clin Endocrinol Metab 1985: 61: 551–6.
Jowsey J. Quantitative microradiography. A new approach in the evaluation of metabolic bone disease. Am J Med 1966; 40: 485–91.
Nordin BC, Aaron J, Speed R, Crilly RG. Bone formation and resorption as the determinants of trabecular bone volume in postmenopausal osteoporosis. Lancet 1981; ii: 277–9.
Baron R, Vignery A, Lang R. Reversal phase and osteopenia: defective coupling of resorption to formation in the pathogenesis of osteoporosis. In: DeLuca HF, Frost M, Jee WSS, Johnston Jr CC, Parfitt AM, eds. Osteoporosis. Recent advances in pathogenesis and treatment. Baltimore; University Park Press, 1981; 311–20.
Meunier PJ, Briancon D, Sellami S, Edouard C. Chavassieux P, Arlot M. Dynamic bone histomorphometry in primary osteoporosis. In: St. J. Dixon A, ed. Osteoporosis. A mulitdisciplinary disease. London: Academic Press, 1982; 67–73.
Parfitt AM, Mathews C, Rao D, Frame B, Kleerekoper M, Villanueva AR. Impaired osteoblast function in metabolic bone disease. In: DeLuca HF, Frost HM, Jee WSS, Johnston Jr CC, Parfitt AM, eds. Osteoporosis. Recent advances in pathogenesis and treatment. Baltimore: University Park Press, 1981; 321–30.
Frost HM. Tetracycline-based analysis of bone remodeling. Calcif Tissue Res 1969; 3: 211–37.
Meunier PJ. Histomorphometry of the skeleton. In: Peck WA, ed. Bone and mineral research. Annual 1. A yearly survey of developments in the field of bone and mineral metabolism. Amsterdam: Excerpta Medica, 1983; 191–222.
Whyte MP, Bergfeld MA, Murphy WA, Avioli LV, Teitelbaum SS. Postmenopausal osteoporosis. A heterogeneous disorder as assessed by histomorphometric analysis of iliac crest bone from untreated patients. Am J Med 1982; 72: 193–202.
Teitelbaum SL, Bergfeld MA, Avioli LV, Whyte MP. Failure of routine biochemical studies to predict the histological heterogeneity of untreated postmenopausal osteoporosis. In: DeLuca HF, Frost HM, Jee WSS, Johnston Jr CC, Parfit AM, eds. Osteoporosis. Recent advances in pathogenesis and treatment. Baltimore: University Park Press, 1980; 303–9.
Minaire P, Meunier PJ, Edouard C, Bernard J, Courpron P, Bourret J. Quantitative histological data on disuse osteoporosis. Calcif Tissue Res 1974; 17: 57–73.
Garcia-Carasco M, de Vernejoul MC, Sterkers Y, Morieux C, Kuntz D, Miravet L. Decreased bone formation in osteoporotic patients compared with age-matched controls. Calcif Tissue Int 1989; 44: 173–5.
Melsen F, Mosekilde L. Tetracycline double-labeling of iliac trabecular bone in 41 normal adults. Calcif Tissue Res 1978; 26: 99–102.
Vedi S, Compton JE, Webb A, Tighe JR. Histomorphometric analysis of dynamic parameters of trabecular bone formation in the iliac crest of normal British subjects. Metab Bone Dis Rel Res 1983; 5: 69–74.
Eastell R, Delmas PD, Hodgson SF, Eriksen EF, Mann KG, Riggs BL. Bone formation rate in older normal women: concurrent assessment with bone histomorphometry, calcium kinetics, and biochemical markers. J Clin Endocrinol Metab 1988; 67: 741–8.
Recker RR, Kimmel DB, Parfitt AM, Davies KM, Kesharwarz N, Hinders S. Static and tetracycline-based bone histomorphometric data from 34 normal postmenopausal females. J Bone Min Res 1988; 3: 133–44.
Eriksen EF, Hodgson SF, Eastell R, Cedel SL, O'Fallon WM, Riggs BL. Cancellous bone remodeling in type I (postmenopausal) osteoporosis: quantitative assessment of rates of formation, resorption and bone loss at tissue and cellular levels. J Bone Min Res 1990; 5: 311–19.
Chavassieux PM, Arlot ME, Meunier PJ. Intermethod variation in bone histomorphometry: comparison between manual and computerized methods applied to iliac bone biopsies. Bone 1985; 6: 221–229.
Birkenhager DH, Birkenhager JC. Bone appositional rate and percentage of doubly and singly labeled surfaces: comparison of data from 5 and 20 µm sections. Bone 1987; 8: 7–12.
Teitelbaum SL, Rosenberg EM, Richardson CA, Avioli LV. Histological studies of bone from normocalcemic postmenopausal osteoporotic patients with increased circulating parathyroid hormone. J Clin Endocrinol Metab 1976; 42: 537–43.
Meunier PJ, Sellami S, Briançon D, Edouard C. Histological heterogeneity of apparently idiopathic osteoporosis. In: DeLuca HF, Frost HM, Jee WSS, Johnston Jr CC, Parfitt AM, eds. Osteoporosis. Recent advances in pathogenesis and treatment. Baltimore: University Park Press, 1981; 293–309.
Civitelli R, Gonnelli S, Zacchei F, Bigazzi S, Vattimo A, Avioli LV, Gennari C. Bone turnover in postmenopausal osteoporosis. J Clin Invest 1988; 82: 1268–74.
Frost HM. The dynamics of bone remodeling. In: Frost HM, ed. Bone biodynamics. Boston: Little, Brown, 1964; 315–33.
Keshawarz NM, Recker RR. Expansion of the medullary cavity at the expense of cortex in postmenopausal osteoporosis. Metab Bone Dis Rel Res 1984; 5: 223–8.
Brown JP, Delmas PD, Arlot M, Meunier PJ. Active bone turnover of the cortico-endosteal envelope in postmenopausal osteoporosis. J Clin Endocrinol Metab 1987; 64: 954–9.
Steiniche T, Vesterby A, Eriksen EF, Mosekilde L, Melsen F. A histomorphometric determination of iliac bone structure and remodeling in obese subjects. Bone 1986; 7: 77–82.
Chappard D, Alexandre CA, Camps M, Montheard JP, Riffat G. Embedding iliac bone biopsies at low temperature using glycol and methyl methacrylate. Stain Technol 1983; 58: 299–308.
Kragstrup J, Gundersen HJG, Melsen F, Mosekilde L. Estimation of the three-dimensional wall thickness of completed remodeling sites in iliac trabecular bone. Metab Bone Dis Rel Res 1982; 4: 113–119.
Parfitt AM, Mathews CHE, Villanueva AR, Kleerekoper M, Frame B, Rao DS. 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. J Clin Invest 1983; 72: 1396–1409.
Parfitt AM, Drezner MK, Glorieux FH et al. Bone histomorphometry: standardization of nomenclature, symbols and units. Report of the ASBMR histomorphometry nomenclature committee. J Bone Min Res 1987; 2: 595–610.
Melsen F, Mosekilde L. Trabecular bone mineralization lag time determined by tetracycline double-labeling in normal and certain pathological conditions. Acta Pathol Microbiol Scand (A) 1980; 88: 83–8.
Arlot ME, Edouard C, Meunier PJ, Neer RM, Reeve J. Impaired osteoblast function in osteoporosis. Comparison between calcium balance and dynamic histomorphometry. Br Med J 1984; 289: 517–20.
Delmas PD, Demiaux B, Malaval L, Chapuy MC, Edouard C, Meunier PJ. Serum bone gla-protein (osteocalcin) in primary hyperparathyroidism and in malignant hypercalcemia. Comparison with bone histomorphometry. J. Clin Invest 1986; 77: 985–91.
Delmas PD, Stenner D, Wahner HW, Mann KG, Riggs BL. Serum bone gla-protein increases with aging in normal women: implications for the mechanism of age-related bone loss. J Clin Invest 1983; 71: 1316–21.
Dagnelie P. Théorie et méthodes statistiques, vol 2. Gembloux, Belgium: Les Presses Agronomiques de Gembloux, 1975.
Meunier PJ, Edouard C, Courpron P, Toussaint F. Morphometric analysis of osteoid in iliac trabecular bone. Methodology. Dynamical significance of the osteoid parameters. In: Norman AW, Schaefer K, Grigoleit HG, Von Herrath D, Ritz E, eds. Vitamin D and problems related to uremic bone disease. Berlin: Walter de Gruyter, 1975; 149–55.
Darby AJ, Meunier PJ. Mean wall thickness and formation periods of trabecular bone packets in idiopathic osteoporosis. Calcif Tissue Int 1981; 33: 199–204.
Podenphant J, Johansen JJ, Thomsen K, Riis BJ, Leth A, Christiansen C. Bone turnover in spinal osteoporosis. J Bone Min Res 1987; 2: 497–504.
Parfitt AM. The coupling of bone formation and bone resorption: a critical analysis of the concept and its relevance to the pathogenesis of osteoporosis. Metab Bone Dis Rel Res 1982; 4: 1–6.
Heaney RP, Recker RR, Saville PD. Menopausal changes in bone remodeling. J Lab Clin Med 1978; 92: 964–70.
Brown JP, Delmas PD, Malaval L, Edouard C, Chapuy MC, Meunier PJ. Serum bone gla-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet 1984; i: 1091–3.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Arlot, M.E., Delmas, P.D., Chappard, D. et al. Trabecular and endocortical bone remodeling in postmenopausal osteoporosis: Comparison with normal postmenopausal women. Osteoporosis Int 1, 41–49 (1990). https://doi.org/10.1007/BF01880415
Issue Date:
DOI: https://doi.org/10.1007/BF01880415