Top

Published in:

01-09-2003 | Original Article

Genetic determinants of bone strength and fracture in humans: dreams and realities

Author: Sergio Livio Ferrari

Published in: Osteoporosis International | Special Issue 5/2003

Excerpt

Why search for gene variants underlying susceptibility to osteoporosis? First, because we hope to improve identification of individuals predisposed to fractures. Indeed, areal bone mineral density (aBMD), as assessed by dual-energy X-ray absorptiometry (DXA), has proven a valuable tool to identify subjects at greatest risk for osteoporotic fractures (high incidence rate among those with T-score below −2.5), but the vast majority of fractures (true incidence) actually occurs among those individuals whose aBMD is above the diagnostic threshold [1]. Second, because we would like to predict individual responses to therapeutic interventions in order to design targeted prevention strategies (pharmacogenetics and nutrigenetics). Third, we may gain new insights into the pathophysiology and treatment of osteoporosis. …

Siris ES, Miller PD, Barrett-Connor E, et al (2001) Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment. JAMA 286:2815–2822PubMed

Gong Y, Slee RB, Fukai N, et al (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107:513–523PubMed

Little RD, Carulli JP, Del Mastro RG, et al (2002) A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet 70:11–19CrossRefPubMed

Eisman JA (1999) Genetics of osteoporosis. Endocr Rev 20:788–804PubMed

Seeman E, Hopper JL (1997) Genetic and environmental components of the population variance in bone density. Osteoporos Int 7 [Suppl 3]:10–16

Bouxsein MLB (2001) Biomechanics of age-related fractures. In: Marcus RFD, Kelsey, J (eds) Osteoporosis. San Diego: Academic Press, 509–526

Chesnut CH 3rd, Rose CJ (2001) Reconsidering the effects of antiresorptive therapies in reducing osteoporotic fracture. J Bone Miner Res 16:2163–2172PubMed

Duan Y, Seeman E, Turner CH (2001) The biomechanical basis of vertebral body fragility in men and women. J Bone Miner Res 16:2276–2283PubMed

Cummings SR, Karpf DB, Harris F, et al (2002) Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 112:281–289CrossRefPubMed

10.

Lee C (2002) Irresistible force meets immovable object: SNP mapping of complex diseases. Trends Genet 18:67–69CrossRefPubMed

11.

MacGregor A, Snieder H, Spector TD (2000) Genetic factors and osteoporotic fractures in elderly people. BMJ 320:1669–1670; discussion 1670–1671CrossRef

12.

Peacock M, Turner CH, Econs MJ, Foroud T(2002) Genetics of osteoporosis. Endocr Rev 23:303–326PubMed

13.

Turner CH, Hsieh YF, Muller R, et al (2000) Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice. J Bone Miner Res 15:1126–1131PubMed

14.

Gregory SG, Sekhon M, Schein J, et al (2002) A physical map of the mouse genome. Nature 418:743–750CrossRefPubMed

15.

Rizzoli R, Bonjour JP, Ferrari SL (2001) Osteoporosis, genetics and hormones. J Mol Endocrinol 26:79–94PubMed

16.

Econs MJ, Speer MC (1996) Genetic studies of complex diseases: let the reader beware. J Bone Miner Res 11:1835–1840PubMed

17.

Ferrari S, Rizzoli R, Bonjour JP (1998) The vitamin D receptor gene and calcium metabolism. Trends Endocrinol Med 9:259–264

18.

Daly MJ, Rioux JD, Schaffner SF, Hudson TJ, Lander ES (2001) High-resolution haplotype structure in the human genome. Nat Genet 29:229–232PubMed

19.

Mann V, Hobson EE, Li B, et al (2001) A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 107:899–907PubMed

20.

Uitterlinden AG, Burger H, Huang Q, et al (1998) Relation of alleles of the collagen type I alpha1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women. N Engl J Med 338:1016–1021PubMed

21.

Garnero P, Borel O, Grant SF, Ralston SH, Delmas PD (1998) Collagen Ialpha1 Sp1 polymorphism, bone mass, and bone turnover in healthy French premenopausal women: the OFELY study. J Bone Miner Res 13:813–817PubMed

22.

Ferrari SL, Garnero P, Emond S, et al (2001) A functional polymorphic variant in the interleukin-6 gene promoter associated with low bone resorption in postmenopausal women. Arthritis Rheum 44:196–201CrossRefPubMed

23.

Ferrari SL, Ahn-Luong L, Garnero P (2003) Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of c-reactive protein and markers of bone resorption in postmenopausal women. J Clin Endocrin Metab 88:255–259

24.

Nguyen TV, Eisman JA (2000) Genetics of fracture: challenges and opportunities. J Bone Miner Res 15:1253–1256

Title: Genetic determinants of bone strength and fracture in humans: dreams and realities
Author: Sergio Livio Ferrari
Publication date: 01-09-2003
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue Special Issue 5/2003
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-003-1481-5

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Genetic determinants of bone strength and fracture in humans: dreams and realities

Excerpt

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Excerpt

Please log in to get access to this content

Other articles of this Special Issue 5/2003

Bone quality: where do we go from here?

Bone quality

Matrix proteins

Bone microarchitecture and strength

Bone mineral crystal size

Methodological considerations in measurement of bone mineral content