[Pathophysiology and Pathomorphology of Osteoporosis]

Overview

Journal Radiologe

Specialty Radiology

Date 2006 Sep 12

PMID 16964480

Authors

M Priemel

C Munch

F T Beil

H Ritzel

M Amling

Affiliations

Soon will be listed here.

Abstract

Osteoporosis is a disease that leads to fragility fractures due to loss of bone mass and bone microstructure. This review presents an update on the fundamental pathophysiologic and pathomorphologic mechanisms of bone loss situations. Pathomorphologic characteristics such as perforations and microcallus formations are explained. The physiologic relevance of the remodeling process as well as its control by local-paracrine, systemic-endocrine and central-neural signaling pathways is discussed. Furthermore the role of hormones such as estrogen, FSH and leptin, of transcription-factors such as Runx2 and osterix and as well as that of the wnt signaling pathway for bone cell differentiation and function is presented. On the basis of current knowledge osteoporosis can be diagnosed, treated and fractures can be prevented. However, it is likely that new and even more effective diagnostic and therapeutic strategies will emerge as our understanding of the remodeling process that controls osteoblast and osteoclast function increases.

References

Grant A, Avenell A, Campbell M, McDonald A, MacLennan G, McPherson G . Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet. 2005; 365(9471):1621-8. DOI: 10.1016/S0140-6736(05)63013-9. View

Sun L, Peng Y, Sharrow A, Iqbal J, Zhang Z, Papachristou D . FSH directly regulates bone mass. Cell. 2006; 125(2):247-60. DOI: 10.1016/j.cell.2006.01.051. View

Lips P . Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev. 2001; 22(4):477-501. DOI: 10.1210/edrv.22.4.0437. View

Gong Y, Slee R, Fukai N, Rawadi G, Roman-Roman S, Reginato A . LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001; 107(4):513-23. DOI: 10.1016/s0092-8674(01)00571-2. View

Prestwood K, Pilbeam C, Burleson J, Woodiel F, Delmas P, Deftos L . The short-term effects of conjugated estrogen on bone turnover in older women. J Clin Endocrinol Metab. 1994; 79(2):366-71. DOI: 10.1210/jcem.79.2.8045949. View

Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker K . Leptin regulates bone formation via the sympathetic nervous system. Cell. 2002; 111(3):305-17. DOI: 10.1016/s0092-8674(02)01049-8. View

Rodan G, Martin T . Therapeutic approaches to bone diseases. Science. 2000; 289(5484):1508-14. DOI: 10.1126/science.289.5484.1508. View

Akhter M, Wells D, Short S, Cullen D, Johnson M, Haynatzki G . Bone biomechanical properties in LRP5 mutant mice. Bone. 2004; 35(1):162-9. DOI: 10.1016/j.bone.2004.02.018. View

Weitzmann M, Cenci S, Rifas L, Haug J, DiPersio J, Pacifici R . T cell activation induces human osteoclast formation via receptor activator of nuclear factor kappaB ligand-dependent and -independent mechanisms. J Bone Miner Res. 2001; 16(2):328-37. DOI: 10.1359/jbmr.2001.16.2.328. View

10.

Prestwood K, Kenny A, Unson C, Kulldorff M . The effect of low dose micronized 17ss-estradiol on bone turnover, sex hormone levels, and side effects in older women: a randomized, double blind, placebo-controlled study. J Clin Endocrinol Metab. 2001; 85(12):4462-9. DOI: 10.1210/jcem.85.12.7001. View

11.

Simonet W, Lacey D, Dunstan C, Kelley M, Chang M, Luthy R . Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997; 89(2):309-19. DOI: 10.1016/s0092-8674(00)80209-3. View

12.

Prior J . Perimenopause: the complex endocrinology of the menopausal transition. Endocr Rev. 1998; 19(4):397-428. DOI: 10.1210/edrv.19.4.0341. View

13.

Van Wesenbeeck L, Cleiren E, Gram J, Beals R, Benichou O, Scopelliti D . Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet. 2003; 72(3):763-71. PMC: 1180253. DOI: 10.1086/368277. View

14.

Riggs B, Wahner H, Seeman E, Offord K, Dunn W, Mazess R . Changes in bone mineral density of the proximal femur and spine with aging. Differences between the postmenopausal and senile osteoporosis syndromes. J Clin Invest. 1982; 70(4):716-23. PMC: 370279. DOI: 10.1172/jci110667. View

15.

Bollerslev J, Wilson S, Dick I, Islam F, Ueland T, Palmer L . LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women. Bone. 2005; 36(4):599-606. DOI: 10.1016/j.bone.2005.01.006. View

16.

Koay M, Woon P, Zhang Y, Miles L, Duncan E, Ralston S . Influence of LRP5 polymorphisms on normal variation in BMD. J Bone Miner Res. 2004; 19(10):1619-27. DOI: 10.1359/JBMR.040704. View

17.

Lacey D, Timms E, Tan H, Kelley M, Dunstan C, Burgess T . Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998; 93(2):165-76. DOI: 10.1016/s0092-8674(00)81569-x. View

18.

Lee K, Jessop H, Suswillo R, Zaman G, Lanyon L . Endocrinology: bone adaptation requires oestrogen receptor-alpha. Nature. 2003; 424(6947):389. DOI: 10.1038/424389a. View

19.

Kobayashi T, Kronenberg H . Minireview: transcriptional regulation in development of bone. Endocrinology. 2004; 146(3):1012-7. DOI: 10.1210/en.2004-1343. View

20.

Harada S, Rodan G . Control of osteoblast function and regulation of bone mass. Nature. 2003; 423(6937):349-55. DOI: 10.1038/nature01660. View