Best Practice & Research Clinical Endocrinology & Metabolism
Volume 22, Issue 5 , Pages 701-722 , October 2008

Bone remodelling: its local regulation and the emergence of bone fragility

  • T. John Martin, MD, DSc, FRACP, FAA, FRS (Emeritus Professor of Medicine, University of Melbourne, and John Holt Fellow, St Vincent's Institute, Melbourne, Australia)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +61 3 9288 2480; Fax: +61 3 9416 2676.

References 

  1. J Bones Currey. Structure and Mechanics. New Jersey: Princeton UP; 2002;1–380
  2. Parfitt AM. Skeletal heterogeneity and the purposes of bone remodelling: implications for the understanding of osteoporosis. In:  Marcus R,  Feldman D,  Kelsey J editor. Osteoporosis. San Diego, CA: Academic Press; 1996;p. 315–339
  3. Haapasalo H, Kontulainen S, Sievanen H, et al. Exercise-induced bone gain is due to enlargement in bone size without a change in volumetric bone density: a peripheral quantitative computed tomography study of the upper arms of male tennis players. Bone. 2000;27(3):351–357
  4. Murray PDF, Huxley JS. Self differentiation in the grafted limb bud of the chick. Journal of Anatomy. 1925;59:379–384
  5. Hattner R, Epker BN, Frost HM. Suggested sequential mode of control of changes in cell behaviour in adult bone remodelling. Nature. 1965;206(983):489–490
  6. Parfitt AM, Travers R, Rauch F, et al. Structural and cellular changes during bone growth in healthy children. Bone. 2000;27(4):487–494
  7. Rauch F, Neu C, Manz F, et al. The development of metaphyseal cortex – implications for distal radius fractures during growth. Journal of Bone and Mineral Research. 2001;16(8):1547–1555
  8. Orwoll ES. Toward an expanded understanding of the role of the periosteum in skeletal health. Journal of Bone and Mineral Research. 2003;18(6):949–954
  9. Parfitt AM. Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone. 2002;30(1):5–7
  10. Mashiba T, Hirano T, Turner CH, et al. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. Journal of Bone and Mineral Research. 2000;15(4):613–620
  11. Odvina CV, Zerwekh JE, Rao DS, et al. Severely suppressed bone turnover: a potential complication of alendronate therapy. The Journal of Clinical Endocrinology and Metabolism. 2005;90(3):1294–1301
  12. Marotti G, Cane V, Palazzini S, Palumbo C. Structure-function relationships in the osteocyte. Italian Journal of Mineral and Electrolyte Metabolism. 1990;4:93–106
  13. Hazenberg JG, Freeley M, Foran E, et al. Microdamage: a cell transducing mechanism based on ruptured osteocyte processes. Journal of Biomechanics. 2006;39(11):2096–2103
  14. Manolagas SC. Choreography from the tomb; an emerging role of dying osteocytes in the purposeful, not so purposeful targeting of bone remodeling. BoneKey Osteovision. 2006;3(1):5–14
  15. Lane NE, Yao W, Balooch M, et al. Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice. Journal of Bone and Mineral Research. 2006;21(3):466–476
  16. Tatsumi S, Ishii K, Amizuka N, et al. Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metabolism. 2007;5(6):464–475
  17. Keller H, Kneissel M. SOST is a target gene for PTH in bone. Bone. 2005;37(2):148–158
  18. O'Brien CA, Jia D, Plotkin LI, et al. Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology. 2004;145(4):1835–1841
  19. Verborgt O, Gibson GJ, Schaffler MB. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. Journal of Bone and Mineral Research. 2000;15(1):60–67
  20. Taylor D. Bone maintenance and remodeling: a control system based on fatigue damage. Journal of Orthopaedic Research. 1997;15(4):601–606
  21. Clark WD, Smith EL, Linn KA, et al. Osteocyte apoptosis and osteoclast presence in chicken radii 0-4 days following osteotomy. Calcified Tissue International. 2005;77(5):327–336
  22. Aguirre JI, Plotkin LI, Stewart SA, et al. Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. Journal of Bone and Mineral Research. 2006;21(4):605–615
  23. Hauge EM, Qvesel D, Eriksen EF, et al. Cancellous bone remodeling occurs in specialized compartments lined by cells expressing osteoblastic markers. Journal of Bone and Mineral Research. 2001;16(9):1575–1582
  24. Chambers TJ, Darby JA, Fuller K. Mammalian collagenase predisposes bone surfaces to osteoclastic resorption. Cell and Tissue Research. 1985;241(3):671–675
  25. Chambers TJ, Fuller K. Bone cells predispose bone surfaces to resorption by exposure of mineral to osteoclastic contact. Journal of Cell Science. 1985;76:155–165
  26. Fuller K, Chambers TJ. Localisation of mRNA for collagenase in osteocytic, bone surface and chondrocytic cells but not osteoclasts. Journal of Cell Science. 1995;108(Pt 6):2221–2230
  27. Partridge NC, Jeffrey JJ, Ehlich LS, et al. Hormonal regulation of the production of collagenase and a collagenase inhibitor activity by rat osteogenic sarcoma cells. Endocrinology. 1987;120(5):1956–1962
  28. Chiusaroli R, Maier A, Knight MC, et al. Collagenase cleavage of type I collagen is essential for both basal and parathyroid hormone (PTH)/PTH-related peptide receptor-induced osteoclast activation and has differential effects on discrete bone compartments. Endocrinology. 2003;144(9):4106–4116
  29. Chambers TJ. Osteoblasts release osteoclasts from calcitonin-induced quiescence. Journal of Cell Science. 1982;57:247–260
  30. Rodan GA, Martin TJ. Role of osteoblasts in hormonal control of bone resorption – a hypothesis. Calcified Tissue International. 1981;33(4):349–351
  31. Parfitt AM. The bone remodeling compartment: a circulatory function for bone lining cells. Journal of Bone and Mineral Research. 2001;16(9):1583–1585
  32. Kurata K, Heino TJ, Higaki H, et al. Bone marrow cell differentiation induced by mechanically damaged osteocytes in 3D gel-embedded culture. Journal of Bone and Mineral Research. 2006;21(4):616–625
  33. Kogianni G, Mann V, Noble BS. Apoptotic bodies convey activity capable of initiating osteoclastogenesis and localized bone destruction. Journal of Bone and Mineral Research. 2008;23(6):915–927
  34. Suda T, Takahashi N, Udagawa N, et al. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocrine Reviews. 1999;20(3):345–357
  35. Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309–319
  36. Eriksen EF, Eghbali-Fatourechi GZ, Khosla S. Remodeling and vascular spaces in bone. Journal of Bone and Mineral Research. 2007;22(1):1–6
  37. Yamamoto Y, Udagawa N, Matsuura S, et al. Osteoblasts provide a suitable microenvironment for the action of receptor activator of nuclear factor-kappaB ligand. Endocrinology. 2006;147(7):3366–3374
  38. Eghbali-Fatourechi GZ, Modder UI, Charatcharoenwitthaya N, et al. Characterization of circulating osteoblast lineage cells in humans. Bone. 2007;40(5):1370–1377
  39. Modder UI, Khosla S. Skeletal stem/osteoprogenitor cells: current concepts, alternate hypotheses, relationship to the bone remodeling compartment. Journal of Cellular Biochemistry. 2008;103(2):393–400
  40. Compagni A, Logan M, Klein R, et al. Control of skeletal patterning by ephrinB1-EphB interactions. Developmental Cell. 2003;5(2):217–230
  41. Lu Q, Sun EE, Klein RS, et al. Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction. Cell. 2001;105(1):69–79
  42. Zhao C, Irie N, Takada Y, et al. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metabolism. 2006;4(2):111–121
  43. Allan EH, Hausler KD, Wei T, et al. EphrinB2 Regulation by Parathyroid Hormone (PTH) and PTHrP revealed by molecular profiling in differentiating osteoblasts. Journal of Bone and Mineral Research. 2008;23(8):1170–1181
  44. Pasquale EB. Eph-ephrin bidirectional signaling in physiology and disease. Cell. 2008;133(1):38–52
  45. Nakamura M, Udagawa N, Matsuura S, et al. Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption. Endocrinology. 2003;144(12):5441–5449
  46. Cleiren E, Benichou O, Van Hul E, et al. Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Human Molecular Genetics. 2001;10(25):2861–2867
  47. Chiusaroli R, Knobler H, Luxenburg C, et al. Tyrosine phosphatase epsilon is a positive regulator of osteoclast function in vitro and in vivo. Molecular Biology of the Cell. 2004;15(1):234–244
  48. Grigoriadis AE, Wang ZQ, Cecchini MG, et al. c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science. 1994;266(5184):443–448
  49. Romas E, Udagawa N, Zhou H, et al. The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures. The Journal of Experimental Medicine. 1996;183(6):2581–2591
  50. Heymann D, Rousselle AV. gp130 Cytokine family and bone cells. Cytokine. 2000;12(10):1455–1468
  51. Sims NA, Jenkins BJ, Quinn JM, et al. Glycoprotein 130 regulates bone turnover and bone size by distinct downstream signaling pathways. Journal of Clinical Investigation. 2004;113(3):379–389
  52. Hoff AO, Catala-Lehnen P, Thomas PM, et al. Increased bone mass is an unexpected phenotype associated with deletion of the calcitonin gene. Journal of Clinical Investigation. 2002;110(12):1849–1857
  53. Dacquin R, Davey RA, Laplace C, et al. Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo. Journal of Cell Biology. 2004;164(4):509–514
  54. Davey RA, Turner A, McManus JF, et al. The calcitonin receptor plays a physiological role to protect against hypercalcemia in mice. Journal of Bone and Mineral Research. 2008;23(8):1182–1193
  55. Sexton PM, Findlay DM, Martin TJ. Calcitonin. Current Medicinal Chemistry. 1999;6(11):1067–1093
  56. Karsdal MA, Neutzsky-Wulff AV, Dziegiel MH, et al. Osteoclasts secrete non-bone derived signals that induce bone formation. Biochemical and Biophysical Research Communications. 2008;366(2):483–488
  57. Demiralp B, Chen HL, Koh AJ, et al. Anabolic actions of parathyroid hormone during bone growth are dependent on c-fos. Endocrinology. 2002;143(10):4038–4047
  58. Black DM, Greenspan SL, Ensrud KE, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. New England Journal of Medicine. 2003;349(13):1207–1215
  59. Finkelstein JS, Hayes A, Hunzelman JL, et al. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. New England Journal of Medicine. 2003;349(13):1216–1226
  60. Martin TJ. Does bone resorption inhibition affect the anabolic response to parathyroid hormone?. Trends in Endocrinology and Metabolism: TEM. 2004;15(2):49–50
  61. Khosla S. Parathyroid hormone plus alendronate – a combination that does not add up. New England Journal of Medicine. 2003;349(13):1277–1279
  62. Ma YL, Cain RL, Halladay DL, et al. Catabolic effects of continuous human PTH (1–38) in vivo is associated with sustained stimulation of RANKL and inhibition of osteoprotegerin and gene-associated bone formation. Endocrinology. 2001;142(9):4047–4054
  63. Holtrop ME, King GJ, Cox KA, et al. Time-related changes in the ultrastructure of osteoclasts after injection of parathyroid hormone in young rats. Calcified Tissue International. 1979;27(2):129–135
  64. Martin TJ, Sims NA. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends in Molecular Medicine. 2005;11(2):76–81
  65. Karsdal MA, Martin TJ, Bollerslev J, et al. Are nonresorbing osteoclasts sources of bone anabolic activity?. Journal of Bone and Mineral Research. 2007;22(4):487–494
  66. Amizuka N, Karaplis AC, Henderson JE, et al. Haploinsufficiency of parathyroid hormone-related peptide (PTHrP) results in abnormal postnatal bone development. Developmental Biology. 1996;175(1):166–176
  67. Martin TJ. Osteoblast-derived PTHrP is a physiological regulator of bone formation. Journal of Clinical Investigation. 2005;115(9):2322–2324
  68. Wodarz A, Nusse R. Mechanisms of Wnt signaling in development. Annual Review of Cell and Developmental Biology. 1998;14:59–88
  69. Mao B, Wu W, Li Y, et al. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001;411(6835):321–325
  70. Mao J, Wang J, Liu B, et al. Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway. Molecular Cell. 2001;7(4):801–809
  71. Moon RT, Kohn AD, De Ferrari GV, et al. WNT and beta-catenin signalling: diseases and therapies. Nature Reviews. Genetics. 2004;5(9):691–701
  72. Gong Y, Slee RB, Fukai N, et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001;107(4):513–523
  73. Boyden LM, Mao J, Belsky J, et al. High bone density due to a mutation in LDL-receptor-related protein 5. New England Journal of Medicine. 2002;346(20):1513–1521
  74. Johnson ML, Harnish K, Nusse R, et al. LRP5 and Wnt signaling: a union made for bone. Journal of Bone and Mineral Research. 2004;19(11):1749–1757
  75. Mbalaviele G, Sheikh S, Stains JP, et al. Beta-catenin and BMP-2 synergize to promote osteoblast differentiation and new bone formation. Journal of Cellular Biochemistry. 2005;94(2):403–418
  76. Rawadi G, Vayssiere B, Dunn F, et al. BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a Wnt autocrine loop. Journal of Bone and Mineral Research. 2003;18(10):1842–1853
  77. Balemans W, Van Hul W. The genetics of low-density lipoprotein receptor-related protein 5 in bone: a story of extremes. Endocrinology. 2007;148(6):2622–2629
  78. Li J, Sarosi I, Cattley RC, et al. Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone. 2006;39(4):754–766
  79. Zhou H, Mak W, Zheng Y, et al. Osteoblasts directly control lineage commitment of mesenchymal progenitor cells through Wnt signaling. Journal of Biological Chemistry. 2008;283(4):1936–1945
  80. Balemans W, Ebeling M, Patel N, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Human Molecular Genetics. 2001;10(5):537–543
  81. Loots GG, Kneissel M, Keller H, et al. Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Research. 2005;15(7):928–935
  82. Winkler DG, Sutherland MK, Geoghegan JC, et al. Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO Journal. 2003;22(23):6267–6276
  83. Poole KE, van Bezooijen RL, Loveridge N, et al. Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB journal. 2005;19(13):1842–1844
  84. van Bezooijen RL, Roelen BA, Visser A, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. Journal of Experimental Medicine. 2004;199(6):805–814
  85. van Bezooijen RL, Svensson JP, Eefting D, et al. Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation. Journal of Bone and Mineral Research. 2007;22(1):19–28
  86. van Bezooijen RL, ten Dijke P, Papapoulos SE, et al. SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine & Growth Factor Reviews. 2005;16(3):319–327
  87. Robling AG, Bellido T, Turner CH. Mechanical stimulation in vivo reduces osteocyte expression of sclerostin. Journal of Musculoskeletal & Neuronal Interactions. 2006;6(4):354
  88. Robling AG, Niziolek PJ, Baldridge LA, et-al. Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. Journal of Biological Chemistry 283(9):5866–5875.
  89. Mohan S, Baylink DJ. Bone growth factors. Clinical Orthopaedics and Related Research. 1991;263:30–482008
  90. Hauschka PV, Mavrakos AE, Iafrati MD, et al. Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-Sepharose. Journal of Biological Chemistry. 1986;261(27):12665–12674
  91. Rodan GA. Introduction to bone biology. Bone. 1992;13(Suppl. 1):S3–S6
  92. Centrella M, McCarthy TL, Canalis E. Transforming growth factor-beta and remodeling of bone. Journal of Bone and Joint Surgery. American Volume. 1991;73(9):1418–1428
  93. Harris SE, Harris MA, Mahy P, et al. Expression of bone morphogenetic protein messenger RNAs by normal rat and human prostate and prostate cancer cells. Prostate. 1994;24(4):204–211
  94. Vukicevic S, Latin V, Chen P, et al. Localization of osteogenic protein-1 (bone morphogenetic protein-7) during human embryonic development: high affinity binding to basement membranes. Biochemical and Biophysical Research Communications. 1994;198(2):693–700
  95. Vukicevic S, Paralkar VM, Cunningham NS, et al. Autoradiographic localization of osteogenin binding sites in cartilage and bone during rat embryonic development. Developmental Biology. 1990;140(1):209–214
  96. Rydziel S, Ladd C, McCarthy TL, et al. Determination and expression of platelet-derived growth factor-AA in bone cell cultures. Endocrinology. 1992;130(4):1916–1922
  97. Spencer EM, Liu CC, Si EC, et al. In vivo actions of insulin-like growth factor-I (IGF-I) on bone formation and resorption in rats. Bone. 1991;12(1):21–26
  98. Bagi CM, Brommage R, Deleon L, et al. Benefit of systemically administered rhIGF-I and rhIGF-I/IGFBP-3 on cancellous bone in ovariectomized rats. Journal of Bone and Mineral Research. 1994;9(8):1301–1312
  99. Critchlow MA, Bland YS, Ashhurst DE. The effects of age on the response of rabbit periosteal osteoprogenitor cells to exogenous transforming growth factor-beta 2. Journal of Cell Science. 1994;107(Pt 2):499–516
  100. Joyce ME, Roberts AB, Sporn MB, et al. Transforming growth factor-beta and the initiation of chondrogenesis and osteogenesis in the rat femur. Journal of Cell Biology. 1990;110(6):2195–2207
  101. Bonewald LF, Wakefield L, Oreffo RO, et al. Latent forms of transforming growth factor-beta (TGF beta) derived from bone cultures: identification of a naturally occurring 100-kDa complex with similarity to recombinant latent TGF beta. Molecular Endocrinology. 1991;5(6):741–751
  102. Oreffo RO, Mundy GR, Seyedin SM, et al. Activation of the bone-derived latent TGF beta complex by isolated osteoclasts. Biochemical and Biophysical Research Communications. 1989;158(3):817–823
  103. Martin TJ, Allan EH, Fukumoto S. The plasminogen activator and inhibitor system in bone remodelling. Growth Regulation. 1993;3(4):209–214
  104. Campbell PG, Novak JF, Yanosick TB, et al. Involvement of the plasmin system in dissociation of the insulin-like growth factor-binding protein complex. Endocrinology. 1992;130(3):1401–1412
  105. Fuller K, Lawrence KM, Ross JL, et al. Cathepsin K inhibitors prevent matrix-derived growth factor degradation by human osteoclasts. Bone. 2008;42(1):200–211
  106. Ducy P, Amling M, Takeda S, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 2000;100(2):197–207
  107. Elefteriou F, Ahn JD, Takeda S, et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature. 2005;434(7032):514–520
  108. Takeda S, Elefteriou F, Levasseur R, et al. Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002;111(3):305–317
  109. Baldock PA, Sainsbury A, Couzens M, et al. Hypothalamic Y2 receptors regulate bone formation. Journal of Clinical Investigation. 2002;109(7):915–921
  110. Sato S, Hanada R, Kimura A, et al. Central control of bone remodeling by neuromedin U. Nature Medicine. 2007;13(10):1234–1240
  111. Lee NK, Sowa H, Hinoi E, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130(3):456–469
  112. Pasco JA, Henry MJ, Sanders KM, et al. Beta-adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density: Geelong Osteoporosis Study. Journal of Bone and Mineral Research. 2004;19(1):19–24
  113. Schlienger RG, Kraenzlin ME, Jick SS, et al. Use of beta-blockers and risk of fractures. Journal of the American Medical Association. 2004;292(11):1326–1332
  114. Reid IR, Lucas J, Wattie D, et al. Effects of a beta-blocker on bone turnover in normal postmenopausal women: a randomized controlled trial. Journal of Clinical Endocrinology and Metabolism. 2005;90(9):5212–5216
  115. Abe E, Marians RC, Yu W, et al. TSH is a negative regulator of skeletal remodeling. Cell. 2003;115(2):151–162
  116. Seeman E, Delmas PD. Bone quality – the material and structural basis of bone strength and fragility. New England Journal of Medicine. 2006;354(21):2250–2261
  117. Albright F. SPRA Postmenopausal osteoporosis. Journal of the American Medical Association. 1941;116:2465–2474
  118. Lips P, Courpron P, Meunier PJ. Mean wall thickness of trabecular bone packets in the human iliac crest: changes with age. Calcified Tissue Research. 1978;26(1):13–17
  119. Vedi S, Compston JE, Webb A, et al. Histomorphometric analysis of bone biopsies from the iliac crest of normal British subjects. Metabolic Bone Disease & Related Research. 1982;4(4):231–236
  120. Bonyadi M, Waldman SD, Liu D, et al. Mesenchymal progenitor self-renewal deficiency leads to age-dependent osteoporosis in Sca-1/Ly-6A null mice. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(10):5840–5845
  121. Nishida S, Endo N, Yamagiwa H, et al. Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation. Journal of Bone Mineral Metabolism. 1999;17(3):171–177
  122. Oreffo RO, Bord S, Triffitt JT. Skeletal progenitor cells and ageing human populations. Clinical Science (London). 1998;94(5):549–555
  123. Eriksen EF. Normal and pathological remodeling of human trabecular bone: three dimensional reconstruction of the remodeling sequence in normals and in metabolic bone disease. Endocrine Reviews. 1986;7(4):379–408
  124. Eriksen EF, Langdahl B, Vesterby A, et al. Hormone replacement therapy prevents osteoclastic hyperactivity: a histomorphometric study in early postmenopausal women. Journal of Bone and Mineral Research. 1999;14(7):1217–1221
  125. Compston JE, Yamaguchi K, Croucher PI, et al. The effects of gonadotrophin-releasing hormone agonists on iliac crest cancellous bone structure in women with endometriosis. Bone. 1995;16(2):261–267
  126. Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocrine Reviews. 2000;21(2):115–137
  127. Croucher PI, Garrahan NJ, Mellish RW, et al. Age-related changes in resorption cavity characteristics in human trabecular bone. Osteoporosis International. 1991;1(4):257–261
  128. Balena R, Shih MS, Parfitt AM. Bone resorption and formation on the periosteal envelope of the ilium: a histomorphometric study in healthy women. Journal of Bone and Mineral Research. 1992;7(12):1475–1482
  129. Seeman E. Periosteal bone formation – a neglected determinant of bone strength. New England Journal of Medicine. 2003;349(4):320–323
  130. Szulc P, Seeman E, Duboeuf F, et al. Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women. Journal of Bone and Mineral Research. 2006;21(12):1856–1863
  131. Riggs BL, Melton LJ, Robb RA, et al. A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men. Journal of Bone and Mineral Research. 2008;23(2):205–214
  132. Riggs BL, Wahner HW, Melton LJ, et al. Rates of bone loss in the appendicular and axial skeletons of women. Evidence of substantial vertebral bone loss before menopause. Journal of Clinical Investigation. 1986;77(5):1487–1491
  133. Gilsanz V, Gibbens DT, Carlson M, et al. Peak trabecular vertebral density: a comparison of adolescent and adult females. Calcified Tissue International. 1988;43(4):260–262
  134. van der Linden JC, Homminga J, Verhaar JA, et al. Mechanical consequences of bone loss in cancellous bone. Journal of Bone and Mineral Research. 2001;16(3):457–465
  135. Parfitt . A Morphological basis of bone mineral measurements: transient and steady state effects of treatment in osteoporosis. Mineral and Elecrolyte Metabolism. 1980;4:273–287
  136. Akkus O, Polyakova-Akkus A, Adar F, et al. Aging of microstructural compartments in human compact bone. Journal of Bone and Mineral Research. 2003;18(6):1012–1019
  137. Hernandez CJ, Gupta A, Keaveny TM. A biomechanical analysis of the effects of resorption cavities on cancellous bone strength. Journal of Bone and Mineral Research. 2006;21(8):1248–1255
  138. Parfitt AM. The cellular basis of bone remodeling: the quantum concept reexamined in light of recent advances in the cell biology of bone. Calcified Tissue International. 1984;36(Suppl. 1):S37–S45
  139. Brown JP, Delmas PD, Arlot M, et al. Active bone turnover of the cortico-endosteal envelope in postmenopausal osteoporosis. Journal of Clinical Endocrinology and Metabolism. 1987;64(5):954–959
  140. Arlot ME, Delmas PD, Chappard D, et al. Trabecular and endocortical bone remodeling in postmenopausal osteoporosis: comparison with normal postmenopausal women. Osteoporosis International. 1990;1(1):41–49
  141. Foldes J, Parfitt AM, Shih MS, et al. Structural and geometric changes in iliac bone: relationship to normal aging and osteoporosis. Journal of Bone and Mineral Research. 1991;6(7):759–766
  142. Martin RB. Porosity and specific surface of bone. Critical Reviews in Biomedical Engineering. 1984;10(3):179–222
  143. Brockstedt H, Kassem M, Eriksen EF, et al. Age- and sex-related changes in iliac cortical bone mass and remodeling. Bone. 1993;14(4):681–691
  144. Yeni YN, Brown CU, Wang Z, et al. The influence of bone morphology on fracture toughness of the human femur and tibia. Bone. 1997;21(5):453–459
  145. Boivin G, Lips P, Ott SM, et al. Contribution of raloxifene and calcium and vitamin D3 supplementation to the increase of the degree of mineralization of bone in postmenopausal women. Journal of Clinical Endocrinology and Metabolism. 2003;88(9):4199–4205
  146. Boivin G, Meunier PJ. Changes in bone remodeling rate influence the degree of mineralization of bone. Connective Tissue Research. 2002;43(2–3):535–537
  147. Viguet-Carrin S, Garnero P, Delmas PD. The role of collagen in bone strength. Osteoporosis International. 2006;17(3):319–336
  148. Garnero P, Borel O, Gineyts E, et al. Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone. Bone. 2006;38(3):300–309
  149. Bailey AJ, Sims TJ, Ebbesen EN, et al. Age-related changes in the biochemical properties of human cancellous bone collagen: relationship to bone strength. Calcified Tissue International. 1999;65(3):203–210
  150. Banse X, Sims TJ, Bailey AJ. Mechanical properties of adult vertebral cancellous bone: correlation with collagen intermolecular cross-links. Journal of Bone and Mineral Research. 2002;17(9):1621–1628
  151. Nalla RK, Kruzic JJ, Kinney JH, et al. Effect of aging on the toughness of human cortical bone: evaluation by R-curves. Bone. 2004;35(6):1240–1246
  152. Qiu S, Rao DS, Fyhrie DP, et al. The morphological association between microcracks and osteocyte lacunae in human cortical bone. Bone. 2005;37(1):10–15
  153. Ahlborg HG, Johnell O, Turner CH, et al. Bone loss and bone size after menopause. New England Journal of Medicine. 2003;349(4):327–334
  154. Aaron JE, Makins NB, Sagreiya K. The microanatomy of trabecular bone loss in normal aging men and women. Clinical Orthopaedics and Related Research. 1987;215:260–271
  155. Duan Y, Beck TJ, Wang XF, et al. Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging. Journal of Bone and Mineral Research. 2003;18(10):1766–1774
  156. Duan Y, Turner CH, Kim BT, et al. Sexual dimorphism in vertebral fragility is more the result of gender differences in age-related bone gain than bone loss. Journal of Bone and Mineral Research. 2001;16(12):2267–2275
  157. Duan Y, Wang XF, Evans A, et al. Structural and biomechanical basis of racial and sex differences in vertebral fragility in Chinese and Caucasians. Bone. 2005;36(6):987–998
  158. Wang XF, Duan Y, Beck TJ, et al. Varying contributions of growth and ageing to racial and sex differences in femoral neck structure and strength in old age. Bone. 2005;36(6):978–986
  159. Seeman E, Duan Y, Fong C, et al. Fracture site-specific deficits in bone size and volumetric density in men with spine or hip fractures. Journal of Bone and Mineral Research. 2001;16(1):120–127
  160. Riggs BL, Melton Iii LJ, Robb RA, et al. Population-based study of age and sex differences in bone volumetric density, size, geometry, structure at different skeletal sites. Journal of Bone and Mineral Research. 2004;19(12):1945–1954

PII: S1521-690X(08)00084-5

doi: 10.1016/j.beem.2008.07.006

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 22, Issue 5 , Pages 701-722 , October 2008