Osteoporosis and Osteopetrosis

Yousef Abu‐Amer, Washington University School of Medicine, Saint Louis, Missouri, USA
Isra Darwech, Washington University School of Medicine, Saint Louis, Missouri, USA
Jesse Otero, Washington University School of Medicine, Saint Louis, Missouri, USA

Published online: September 2007

DOI: 10.1002/9780470015902.a0006017

Abstract

Osteoporosis is the most prevalent among bone diseases. It is manifested by low bone mass and architectural abnormalities that lead to bone fragility and elevated fracture risk. Mechanistically, osteoporosis occurs as a result of decreased bone formation (by osteoblasts) and increased bone resorption (by osteoclasts). Thus, a tip in the balance favouring bone resorption results in osteoporosis e.g. porous bone. A wide range of factors contribute to the development of osteoporosis including genetic predisposition, ageing, reduced physical activity, diet, hormonal changes and more. Osteopetrosis, however, reflects the state of dense yet fragile bones due to dysfunctional or lack of osteoclasts.

Keywords: osteoporosis; osteopetrosis; calcium; vitamin D; osteoclast; BMD

Figure 1.

Mechanisms of cytokine regulation of osteoclasts. Under basal conditions, factors such as receptor activator of NF‐κB ligand (RANKL), (OPG) and M‐CSF are secreted by stromal and osteoblast cells and support differentiation of macrophage (also known as osteoclast precursors; OCPs) into bone resorbing osteoclasts. Other cytokines, such as TNF, IL‐1 and IL‐6, are also secreted by stromal and osteoblast cells, and modulate the process of osteoclastogenesis. Conditions of oestrogen deficiency lead to activation of T lymphocytes and to secretion of high levels of RANKL and TNF by these cells. This process exacerbates osteoclastogenesis leading to enhanced bone loss.
close

References

Black D and Rosen CJ (2006) Bisphosphonates for the prevention and treatment of osteoporosis. In: Favus MJ (ed.) Osteoporosis, Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 6th edn, pp. 277–283. Washington, DC: ASBMR Press.

Dawson‐Hughes B (2006) Calcium and Vitamin‐D. In: Favus MJ (ed.) Osteoporosis, Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 6th edn, pp. 257–259. Washington, DC: ASBMR Press.

Ferrari SL and Rizzoli R (2005) Gene variants for osteoporosis and their pleiotropic effects in aging. Molecular Aspects of Medicine 26: 145–167.

Harvey N, Earl S and Cooper C (2006) Epidemiology of osteoporotic fractures. In: Favus MJ (ed.) Osteoporosis, Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 6th edn, pp. 244–248. Washington, DC: ASBMR Press.

Marcus R (2001) Role of exercise in preventing and treating osteoporosis. Rheumatic Diseases Clinics of North America 27: 131–141.

Melzer K, Kayser B and Pichard C (2004) Physical activity: the health benefits outweigh the risks. Current Opinion in Clinical Nutrition and Metabolic Care 7: 641–647.

Mundy GR, Oyajobi B, Traianedes K, Dallas S and Chen D (2001) Cytokines and bone remodeling. In: Marcus R, Feldman D and Kelsey J (eds) Osteoporosis, 2nd edn, vol. 1, pp. 373–404. San Diego, CA: Academic Press.

Orwoll ES and Klein RF (2001) Osteoporosis in men: epidemiology, pathophysiology, and clinical characterization. In: Marcus R, Feldman D and Kelsey J (eds) Osteoporosis, 2nd edn, vol. 2, pp. 103–150. San Diego, CA: Academic Press.

Riggs BL, Khosla S and Melton LJ 3rd (2002) Sex steroids and the construction and conservation of the adult skeleton. Endocrine Reviews 23: 279–302.

Rizzoli R, Bonjour JP and Ferrari SL (2001) Osteoporosis, genetics and hormones. Journal of Molecular Endocrinology 26: 79–94.

Robling AG, Castillo AB and Turner CH (2006) Biomechanical and molecular regulation of bone remodeling. Annual Review of Biomedical Engineering 8: 455–498.

Rosen CJ (2005) Postmenopausal osteoporosis. New England Journal of Medicine 353(6): 595–603.

Rossouw JE, Anderson GL, Prentice RL et al. (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. Journal of American Medical Association 288: 321–333.

Sowers MR, Jannausch M, McConnell D et al. (2006) Hormone predictors of bone mineral density changes during the menopausal transition. Journal of Clinical Endocrinology and Metabolism 91: 1261–1267.

Further Reading

Abu‐Amer Y (2005) Advances in osteoclast differentiation and function. Current Drug Targets. Immune, Endocrine and Metabolic Disorders 5(3): 347–355.

Balemans W, Van Wesenbeeck L and Van Hul W (2005) A clinical and molecular overview of the human osteopetroses. Calcified Tissue International 77(5): 263–274.

Eisman JA (2006) Genetics of osteoporosis. In: Favus MJ (ed.) Osteoporosis, Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 6th edn, pp. 249–254. Washington, DC: ASBMR Press.

Ferrari SL and Rizzoli R (2005) Gene variants for osteoporosis and their pleiotropic effects in aging. Molecular Aspects of Medicine 26: 145–167.

Fitzpatrick LA (2002) Secondary causes of osteoporosis. Mayo Clinic Proceedings 77: 453–468.

Heaney RP (2001) Nutrition and risk for osteoporosis. In: Marcus R, Feldman D and Kelsey J (eds) Osteoporosis, 2nd edn, vol. 1, pp. 669–700. San Diego, CA: Academic Press.

Hoff A, Cote GJ and Gagel RF (2001) Calcitonin. In: Marcus R, Feldman D and Kelsey J (eds) Osteoporosis, 2nd edn, vol. 1, pp. 247–256. San Diego, CA: Academic Press.

Hochberg MC (1998) Bisphosphonates. In: Cumming SR, Cosman F and Jama SA (eds) Osteoporosis: An Evidence‐based Guide to Prevention and Management, pp. 181–195. Philadelphia, PA: American College of Physicians.

Jiang Y, Zhao JJ, Mitlak BH et al. (2003) Recombinant human parathyroid hormone (1–34) improves both cortical and cancellous bone structure. Journal of Bone and Mineral Research 18: 1932–1941.

Jin H and Ralston SH (2005) Genetics of osteoporosis. Current Rheumatology Reports 7: 66–70.

Johnell O, Gullberg B, Kanis JA et al. (1995) Risk factors for hip fracture in European women: The MEDOS study. Mediterranean Osteoporosis Study. Journal of Bone and Mineral Research 10: 1802–1815.

Kanis JA (2003) Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359: 1929–1936.

Liedert A, Kaspar D, Blakytny R, Claes L and Ignatius A (2006) Signal transduction pathways involved in mechanotransduction in bone cells. Biochemical and Biophysical Research Communications 349: 1–5.

Llorens R (2006) A review of osteoporosis: diagnosis and treatment. Missouri Medicine 103: 612–615; quiz 615–616.

Melton LJ and Cooper C (2001) Magnitude and impact of osteoporosis and fractures. In: Marcus R, Feldman D and Kelsey J (eds) Osteoporosis, 2nd edn, vol. 1, pp. 557–567. San Diego, CA: Academic Press.

Michaelson K, Melhus H, Ferm H, Ahlbom A and Pedersen NL (2005) Genetic liability to fractures in the elderly. Archives of Internal Medicine 165: 1825–1830.

National Osteoporosis Foundation (2003) Physician's Guide to Prevention and Treatment of Osteoporosis. Belle Mead, NJ: Excerpta Medica.

Neer RM, Arnaud CD, Zanchetta JR et al. (2001) Effect of parathyroid hormone (1‐34) on fractures and bone mineral density in postmenopausal women with osteoporosis. New England Journal of Medicine 344: 1434–1441.

Orwoll ES (2003) Men, bone and estrogen: unresolved issues. Osteoporosis International 14: 93–98.

Parfitt M (2002) PTH and periosteal bone expansion. Journal of Bone and Mineral Research 17: 1741–1743.

Prentice A, Schoenmakers I, Laskey MA et al. (2006) Nutrition and bone growth and development. Proceedings of the Nutrition Society 65: 348–360.

Riggs BL, O’Fallon WM, Muhs J et al. (1998) Long term effects of calcium supplementation on serum parathyroid hormone levels, bone turnover, and bone loss in elderly women. Journal of Bone and Mineral Research 13: 168–174.

Schousboe JT, Taylor BC and Ensrud KE (2006) Assessing fracture risk: who should be screened?. In: Favus MJ (ed.) Osteoporosis; Primer on the Metabolic bone Diseases and Disorders of Mineral Metabolism, 6th edn, pp. 262–267. Washington, DC: ASBMR Press.

Tolar J, Teitelbaum SL and Orchard PJ (2004) Osteopetrosis. New England Journal of Medicine 351(27): 2839–2849.

World Health Organization Study Group (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Geneva, Switzerland: World Health Organization.

Wren TA and Gilsanz V (2006) Assessing bone mass in children and adolescents. Current Osteoporosis Reports 4: 153–158.

Wren TA, Liu X, Pitukcheewanont P and Gilsanz V (2005) Bone acquisition in healthy children and adolescents: comparisons of dual‐energy X‐ray absorptiometry and computed tomography measures. Journal of Clinical Endocrinology and Metabolism 90: 1925–1928.

Related Sub-Topics:

Intracellular and Extracellular Signalling | Molecular Genetics of Common and Complex Disease | Cell Death and Cellular Senescence | Cell Biology of Organogenesis | Growth and Synthesis
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Osteoporosis and Osteopetrosis
 
How to Cite close
Abu‐Amer, Yousef, Darwech, Isra, and Otero, Jesse(Sep 2007) Osteoporosis and Osteopetrosis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006017]