Abstract
The skeleton provides a rigid framework for the body, protecting vital organs, acting as a site for the attachment of muscles, and housing the bone marrow. It contains 99% of total body calcium, and plays a major role in the preservation of calcium and phosphate homeostasis, providing a reservoir from, or into, which these ions can be transported. Hence, in the absence of adequate amounts of calcium absorbed from the intestine, bone lysis will maintain serum calcium levels at the expense of bone strength.
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References
Bachrach BE, Smith EP. The role of sex steroids in bone growth and development: evolving new concepts. Endocrinologist 1996; 6:362–8.
Bailey DA, McKay HA, Mirwald RL et al. A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the University of Saskatchewan bone mineral accrual study. J Bone Miner Res Oct 1999; 14:1672–9.
Baron R, Rawadi G. Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton. Endocrinology 2007; 148:2635–43.
Bilezikian JP, Morishima A, Bell J et al. Increased bone mass a result of estrogen therapy in a man with aromatase deficiency. N Engl J Med 1998; 339:599–603.
Bischoff-Ferrari HA, Willett WC et al. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 2005; 293:2257–64.
Bjarnarson NH, Alexandersen P, Christiansen C. Number of years since menopause: spontaneous bone loss is dependent but response to hormone replacement therapy is independent. Bone 2002; 2002: 637–42.
Boivin G, Meunier PJ. Methodological considerations in measurement of bone mineral content. Osteoporos Int 2003; 14(Suppl 5):S22–8.
Bonewald LF. Osteocytes as dynamic multifunctional cells. Ann N Y Acad Sci 2007; 1116:281–90.
Bonjour JP, Rizzoli R. Bone acquisition in adolescence. In: Osteoporosis, volume 1, 2nd edition. Edited by R Marcus, J Kelsey, D Feldman. San Diego: Academic Press, 2001; 621–38.
Bonnet N, Pierroz DD, Ferrari SL. Adrenergic control of bone remodeling and its implications for the treatment of osteoporosis. J Musculoskelet Neuronal Interact 2008; 8:94–104.
Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003; 423:337–342.
Canalis E, Mazziotti G, Giustina A et al. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 2007; 18:1319–28.
Chapuy MC, Arlot ME, Duboeuf F et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 1992; 327:1637–42.
Chevalley T, Bonjour JP, Ferrari S et al. Influence of age at menarche on forearm bone microstructure in healthy young women. J Clin Endocrinol Metab 2008; 93:2594–601.
Christiansen C, Christensen MS, McNair PL et al. Prevention of early menopausal bone loss: conducted 2-year study. Eur J Clin Invest 1980; 10:273–9.
Clowes JA, Riggs BL, Khosla S et al. The role of the immune system in the pathophysiology of osteoporosis. Immunological Reviews 2005; 208: 207–27.
Cohen MM, Jr. The new bone biology: pathologic, molecular, and clinical correlates. Am J Med Genet A 2006; 140:2646–706.
Compston JE. Sex steroids and bone. Physiol Rev 2001; 81:419–447.
Consensus Development Conference. Diagnosis, prophylaxis and treatment of osteoporosis. Am J Med 1993; 94:646–50.
Delmas PD, Eastell R, Garnero P et al. The use of biochemical markers of bone turnover in osteoporosis. Osteoporos Int 2000; 11(Suppl 6):S2–17.
Dufresne TE, Chmielewski PA, Manhart MD et al. Risedronate Preserves Bone Architecture in Early Postmenopausal Women In 1 Year as Measured by Three-Dimensional Microcomputed Tomography. Calcif Tissue Int 2003; 73:423–32.
Eghbali-Fatourechi G, Khosla S, Sanyal A et al. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest 2003; 111:1221–30.
Ferrari S. Génétique de l’ostéoporose. In: Traité des maladies métaboliques osseuses de l’adulte. Edited by M C de Vernejoul and P Marie. Paris: Flammarion Médecine-Sciences, 2008a.
Ferrari S. Human genetics of osteoporosis. Best Pract Res Clin Endocrinol Metab 2008b; 22:723–35.
Ferrari S. Cellular and molecular mechanisms of osteoporosis. In: Innovation in skeletal medicine. Edited by JY Reginster and R Rizzoli. Issy-Les-Moulineaux: Elsevier Masson, 2008c; 19–46.
Ferrari SL, Deutsch S, Antonarakis SE. Pathogenic mutations and polymorphisms in the lipoprotein receptor-related protein 5 reveal a new biological pathway for the control of bone mass. Curr Opin Lipidol 2005; 16:207–14.
Garnero P, Sornay-Rendu E, Chapuy M et al. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 1996; 11:337–49.
Goltzman D. Studies on the mechanisms of the skeletal anabolic action of endogenous and exogenous parathyroid hormone. Arch Biochem Biophys 2008; 473:218–24.
Haaspasalo H, Kannus P, Sievannen H et al. Effect of long-term unilateral activity on bone mineral density of female junior tennis players. J Bone Miner Res 1998; 13:310–9.
Hamrick MW, Ferrari SL. Leptin and the sympathetic connection of fat to bone. Osteoporos Int 2008; 19:905–12.
Heino TJ, Hentunen TA. Differentiation of osteoblasts and osteocytes from mesenchymal stem cells. Curr Stem Cell Res Ther 2008; 3:131–45.
Hock JM, Krishnan V, Oniya JE et al. Osteoblast apoptosis and bone turnover. J Bone Miner Res 2001; 16:975–84.
Hofbauer LC, Gori F, Riggs BL et al. Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 1999; 140:4382–9.
Johnston CC, Miller JZ, Slemenda CW et al. Calcium supplementation and increases in bone mineral density in children. N Engl J Med 1992; 327:82–7.
Kanis JA, Burlet N, Cooper C et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2008; 19:399–428.
Karasik D, Ferrari SL. Contribution of gender-specific genetic factors to osteoporosis risk. Ann Hum Genet 2008; 72:696–714.
Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor kappa B ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev 2008; 29:155–92.
Khosla S. Estrogen and the death of osteoclasts: a fascinating story. BoneKey 2007; 4:267–72.
Khosla S, Riggs BL, Atkinson EJ et al. Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res 2006; 21:124–31.
Komori T. Regulation of osteoblast differentiation by transcription factors. J Cell Biochem 2006; 99:1233–9.
Lee K, Jessop H, Suswillo R et al. Endocrinology: bone adaptation requires oestrogen receptor-alpha. Nature 2003; 424:389.
Lee WT, Leung SS, Leung DM et al. Bone mineral acquisition in low calcium intake children following the withdrawal of calcium supplement. Acta Paediatr 1997; 86:570–6.
Li X, Ominsky MS, Niu QT et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 2008; 23:860–9.
Li J, Sarosi I, Cattley et al. Dkk1-mediated inhibition of Wnt signaling in bone results in osteopenia. Bone 2006; 39:754–66.
Lindsay R, Aitken JM, Anderson JB et al. Long-term prevention of postmenopausal osteoporosis by oestrogen: evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet 1976; 1:1038–41.
Lips P, Hosking D, Lippuner K et al. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med 2006; 260:245–54.
Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 2000; 21:115–37.
Marcus R. The nature of osteoporosis. In: Osteoporosis. Edited by R Marcus, D Feldman, J Kelsey. San Diego: Academic Press, 1996; 647–59.
McGuigan FEA, Ralston SH. Genetic susceptibility to osteoporosis. In: Nutritional Aspects of Bone Health. Edited by SA New, JP Bonjour. Cambridge: Royal Society of Chemistry, 2003; 37–63.
Murshed M, Harmey D, Millan JL et al. Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone. Genes Dev 2005; 19:1093–104.
Nakamura T, Imai Y, Matsumoto T et al. Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell 2007; 130:811–23.
NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 2001; 285:785–95.
Parfitt AM. Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone 2002; 30:5–7.
Pei L, Tontonoz P. Fat’s loss is bone’s gain. J Clin Invest 2004; 113:805–6.
Prince RL, Smith M, Dick IM et al. Prevention of postmenopausal osteoporosis: a comparative study of exercise, calcium supplementation, and hormonereplacement therapy. N Engl J Med 1991; 325:1189–95.
Quigley MET, Martin PL, Burnier AM et al. Estrogen therapy arrests bone loss in elderly women. Am J Obstet Gynecol 1987; 156:1516–23.
Ralston SH. Genetic control of susceptibility to osteoporosis. J Clin Endocrinol Metab 2002; 87:2460–6.
Rauch F, Travers R, Glorieux FH. Cellular activity on the seven surfaces of iliac bone: a histomorphometric study in children and adolescents. J Bone Miner Res 2006; 21:513–9.
Recker R, Lappe J, Davies KM et al. Bone remodeling increases substantially in the years after menopause and remains increased in older osteoporosis patients. J Bone Miner Res 2004; 19:1628–33.
Riggs BL, Khosla S, Melton LJ 3rd. A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res 1998; 13:763–73.
Riggs BL, Khosla S, Melton LJ 3rd et al. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev 2002; 23:279–302.
Rizzoli R, Ammann P, Chevalley T et al. Protein intake and bone disorders in the elderly. Joint Bone Spine 2001; 68:383–92.
Rizzoli R, Bonjour, J-P. Dietary Protein and Bone Health. J Bone Miner Res 2004; 19:527.
Rodan S, Duong T, Cathepsin K. A new molecular target for osteoporosis. BoneKey 2008; 5:16–24.
Schurch MA, Rizzoli R, Slosman D et al. Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1998; 128:801–9.
Seeman E. Pathogenesis of bone fragility in women and men. Lancet 2002; 359:1841–50.
Seeman E, Hopper JL. Genetic and environmental components of the population variance in bone density. Osteoporos Int 1997; 7(Suppl 3):S10–6.
Seeman E, Delmas PD. Bone quality — the material and structural basis of bone strength and fragility. N Engl J Med 2006; 354:2250–61.
Seeman E, Hopper JL, Bach LA et al. Reduced bone mass in daughters of women with osteoporosis. N Engl J Med 1989; 320:554–8.
Seibel MJ, Woitge HW. Basic principles and clinical applications of biochemical markers of bone metabolism: biochemical and technical aspects. J Clin Densitometry 1999; 2:299–322.
Sornay-Rendu E, Munoz F, Duboeuf F et al. The rate of bone loss is associated with an increased risk of fracture in postmenopausal women. The OFELY study. Osteoporos Int 2005; 16(Suppl 3):OC35.
Standring S (Ed) Gray’s anatomy — the anatomical basis of clinical practice, 39th edition. Edinburgh: Elsevier, 2004.
Steingrimsdottir L, Gunnarsson O, Indridason OS et al. Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake. JAMA 2005; 294:2336–41.
Styrkarsdottir U, Cazier J, Konng A et al. Linkage of osteoporosis to chromosome 20p12 and association to BMP2. PloS Biology 2003; 1:1–10.
Teitelbaum SL, Ross FP. Genetic regulation of osteoclast development and function. Nat Rev Genet 2003; 4:638–49.
Theintz G, Buchs B, Rizzoli R et al. Longitudinal monitoring of bone mass accumulation in healthy adolescents: evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects. J Clin Endocrinol Metab 1992; 75:1060–5.
Torgerson DJ, Campbell MK, Thomas RE et al. Prediction of perimenopausal fractures by bone mineral density and other risk factors. J Bone Miner Res 1996; 11:293–7.
Vanderschueren D, Bouillon R. Androgens and bone. Calcif Tissue Int 1995; 56:341–346.
van Meurs JB, Trikalinos T, Ralston SH et al. Large-scale analysis of association between polymorphisms in the LRP-5 and-6 genes and osteoporosis: The GENOMOS Study. JAMA 2008; 299:1277–90.
Weitzmann MN, Pacifici R. The role of T lymphocytes in bone metabolism. Immunol Rev 2005; 208:154–68.
Wiren KM, Orwell ES. Skeletal biology of androgens. In: Osteopenia. Edited by R Marcus, D Feldman and J Kelsey. San Diego: Academic Press, 2001;339–359.
Yadav VK, Ryu JH, Suda N et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 2008; 135:825–37.
Yang X, Karsenty G. Transcription factors in bone: developmental and pathological aspects. Trends Mol Med 2002; 8:340–5.
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Ferrari, S., Ringe, J.D. (2010). Pathophysiology of postmenopausal osteoporosis. In: Rizzoli, R. (eds) Atlas of Postmenopausal Osteoporosis. Springer Healthcare, Tarporley. https://doi.org/10.1007/978-1-907673-28-3_1
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DOI: https://doi.org/10.1007/978-1-907673-28-3_1
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