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Calcium-Sensing Receptor Gene Polymorphism A986S Does Not Predict Serum Calcium Level, Bone Mineral Density, Calcaneal Ultrasound Indices, or Fracture Rate in a Large Cohort of Elderly Women

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Abstract

Postmenopausal osteoporosis is a complex and heterogeneous disease influenced by multiple factors and related to peak bone mass achieved in early adult life, followed by a subsequent continuous bone loss. Genetic variance and polymorphisms have been shown to be of clinical significance for osteoporotic fragility fractures. Previous studies have related variations in the calcium sensor receptor (CASR) gene to circulating Ca levels and bone mass in young women and adolescent girls. The aim of this study was to investigate the impact of the A986S polymorphism of the CASR gene on calcium homeostasis and bone metabolism in elderly women. We studied the distribution of the A986S polymorphism in a large cohort of 1252 ambulatory Australian women in relation to biochemical markers of bone metabolism, bone mass evaluated by quantitative ultrasound measurements (QUS) and DXA of the hip, prevalent and 36-month incident fracture data. No effect of the polymorphism was found on circulating calcium level, renal Ca excretion, or biochemical markers of bone turnover. Moreover, A986S was not associated with bone mass or prevalent or incident fractures. Power calculations revealed that a difference in circulating calcium levels of 0.05 mmol/l, a difference in DXA bone density of 24 mg, and a 1.6-fold difference in fracture rate could have been detected with a power of 80%. In conclusion, in a large cohort of elderly women the A986S polymorphism of the CASR gene was not found to be significant for calcium homeostasis or bone mass. It is questioned whether the polymorphism has any clinical significance for postmenopausal osteoporosis.

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References

  1. E Seeman JL Hopper LA Bach ME Cooper E Parkinson J McKay G Jerums (1989) ArticleTitleReduced bone mass in daughters of women with osteoporosis. N Engl J Med 320 554–558 Occurrence Handle1:STN:280:BiaC38jksVY%3D Occurrence Handle2915666

    CAS  PubMed  Google Scholar 

  2. AG Uitterlinden H Burger Q Huang F Yue FE McGuigan SF Grant A Hofman JP van Leeuwen HA Pols SH Ralston (1998) ArticleTitleRelation of alleles of the collagen type Ialpha1 gene to bone density and the risk of osteoporotic fractures in postmenopausal women. N Engl J Med 338 1016–1021 Occurrence Handle1:STN:280:DyaK1c7otFOqug%3D%3D Occurrence Handle9535665

    CAS  PubMed  Google Scholar 

  3. R Gueguen P Jouanny F Guillemin C Kuntz J Pourel G Siest (1995) ArticleTitleSegregation analysis and variance components analysis of bone mineral density in healthy families. J Bone Miner Res 10 2017–2022 Occurrence Handle1:STN:280:BymC1M3nt1A%3D Occurrence Handle8619384

    CAS  PubMed  Google Scholar 

  4. EM Brown G Gamba D Riccardi M Lombardi R Butters O Kifor A Sun MA Hediger J Lytton SC Hebert (1993) ArticleTitleCloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 366 575–580 Occurrence Handle1:CAS:528:DyaK2cXhvVGmtLs%3D Occurrence Handle8255296

    CAS  PubMed  Google Scholar 

  5. EM Brown SC Hebert (1997) ArticleTitleCalcium-receptor-regulated parathyroid and renal function. Bone 20 303–309 Occurrence Handle10.1016/S8756-3282(97)00002-1 Occurrence Handle1:CAS:528:DyaK2sXivVaqtrc%3D Occurrence Handle9108349

    Article  CAS  PubMed  Google Scholar 

  6. SL Godwin SP Soltoff (2002) ArticleTitleCalcium-sensing receptor-mediated activation of phospholipase C-gamma1 is downstream of phospholipase C-beta and protein kinase C in MC3T3-E1 osteoblasts. Bone 30 559–566 Occurrence Handle10.1016/S8756-3282(01)00700-1 Occurrence Handle1:CAS:528:DC%2BD38XisV2ksLs%3D Occurrence Handle11934646

    Article  CAS  PubMed  Google Scholar 

  7. T Kameda H Mano Y Yamada H Takai N Amizuka M Kobori N Izumi H Kawashima H Ozawa K Ikeda A Kameda Y Hakeda M Kumegawa (1998) ArticleTitleCalcium-sensing receptor in mature osteoclasts, which are bone resorbing cells. Biochem Biophys Res Commun 245 419–422 Occurrence Handle10.1006/bbrc.1998.8448 Occurrence Handle1:CAS:528:DyaK1cXivVOqt7w%3D Occurrence Handle9571166

    Article  CAS  PubMed  Google Scholar 

  8. DE Cole VD Peltekova LA Rubin GA Hawker R Vieth CC Liew DM Hwang J Evrovski GN Hendy (1999) ArticleTitleA986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations. Lancet 353 112–115 Occurrence Handle10.1016/S0140-6736(98)06434-4 Occurrence Handle1:STN:280:DyaK1M7ks1GjsA%3D%3D Occurrence Handle10023897

    Article  CAS  PubMed  Google Scholar 

  9. DE Cole R Vieth HM Trang BY Wong GN Hendy LA Rubin (2001) ArticleTitleAssociation between total serum calcium and the A986S polymorphism of the calcium-sensing receptor gene. Mol Genet Metab 72 168–174 Occurrence Handle10.1006/mgme.2000.3126 Occurrence Handle1:CAS:528:DC%2BD3MXnsFSmtA%3D%3D Occurrence Handle11161843

    Article  CAS  PubMed  Google Scholar 

  10. MR Pollak EM Brown YH Chou SC Hebert SJ Marx B Steinmann T Levi CE Seidman JG Seidman (1993) ArticleTitleMutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Cell 75 1297–1303 Occurrence Handle1:CAS:528:DyaK2cXhtVCjsbc%3D Occurrence Handle7916660

    CAS  PubMed  Google Scholar 

  11. M Lorentzon R Lorentzon UH Lerner P Nordstrom (2001) ArticleTitleCalcium sensing receptor gene polymorphism, circulating calcium concentrations and bone mineral density in healthy adolescent girls. Eur J Endocrinol 144 257–261 Occurrence Handle1:CAS:528:DC%2BD3MXisFagtL8%3D Occurrence Handle11248745

    CAS  PubMed  Google Scholar 

  12. K Tsukamoto H Orimo T Hosoi M Miyao N Ota T Nakajima H Yoshida S Watanabe T Suzuki M Emi (2000) ArticleTitleAssociation of bone mineral density with polymorphism of the human calcium-sensing receptor locus. Calcif Tissue Int 66 181–183 Occurrence Handle10.1007/s002230010036 Occurrence Handle1:CAS:528:DC%2BD3cXhslSiur4%3D Occurrence Handle10666491

    Article  CAS  PubMed  Google Scholar 

  13. R Young W Fiona N Van der Water R Ames G Gamble IR Reid (2003) ArticleTitleCalcium sensor receptor gene A986S polymorphism and responsiveness to calcium supplementation in postmenopausal women. J Clin Endocrinol Metab 88 697–700 Occurrence Handle10.1210/jc.2002-020355 Occurrence Handle1:CAS:528:DC%2BD3sXhtlCht78%3D Occurrence Handle12574201

    Article  CAS  PubMed  Google Scholar 

  14. I Takacs G Speer E Bajnok A Tabak Z Nagy C Horvath K Kovacs P Lakatos (2002) ArticleTitleLack of association between calcium-sensing receptor gene “A986S” polymorphism and bone mineral density in Hungarian postmenopausal women. Bone 30 849–852 Occurrence Handle10.1016/S8756-3282(02)00741-X Occurrence Handle1:CAS:528:DC%2BD38XktFyntrY%3D Occurrence Handle12052452

    Article  CAS  PubMed  Google Scholar 

  15. DG Bruce A Devine RL Prince (2002) ArticleTitleRecreational physical activity levels in healthy older women: the importance of fear of falling. J Am Geriatr Soc 50 84–89 Occurrence Handle10.1046/j.1532-5415.2002.50012.x Occurrence Handle12028251

    Article  PubMed  Google Scholar 

  16. IM Dick A Devine A Marangou SS Dhaliwal S Laws RN Martins RL Prince (2002) ArticleTitleApolipoprotein E4 is associated with reduced calcaneal quantitative ultrasound measurements and bone mineral density in elderly women. Bone 31 497–502 Occurrence Handle10.1016/S8756-3282(02)00851-7 Occurrence Handle1:CAS:528:DC%2BD38XotVequ7c%3D Occurrence Handle12398946

    Article  CAS  PubMed  Google Scholar 

  17. P Ireland D Jolley G Giles K O’Dea J Powles I Rutishauser ML Wahlqvist J Williams (1994) ArticleTitleDeveloping the Melbourne FFQ: a food frequency questionnaire for use in an Australian prospective study involving an ethnically diverse cohort. Asia Pacific J Clin Nutr 3 19–31

    Google Scholar 

  18. PA Price SK Nishimoto (1980) ArticleTitleRadioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma. Proc Natl Acad Sci USA 77 2234–2238 Occurrence Handle1:CAS:528:DyaL3cXkt1Wqu7g%3D Occurrence Handle6966406

    CAS  PubMed  Google Scholar 

  19. AS John C Davies WJ Riley GN Kent RC Brown JP Aston I Weels JS Woodhead (1988) ArticleTitleComparison of the performance and clinical utility of a carboxy-terminal assay and an intact assay for parathyroid hormone. Clin Chim Acta 178 215–223 Occurrence Handle10.1016/0009-8981(88)90227-6 Occurrence Handle3242983

    Article  PubMed  Google Scholar 

  20. AG Randall GN Kent P Garcia-Webb CI Bhagat DJ Pearce DH Gutteridge RL Prince G Stewart B Stuckey RK Will RW Retallack RI Price L Ward (1996) ArticleTitleComparison of biochemical markers of bone turnover in Paget disease treated with pamidronate and a proposed model for the relationships between measurements of the different forms of pyridinoline cross-links. J Bone Miner Res 11 1176–1184 Occurrence Handle1:CAS:528:DyaK28XlvVWisLw%3D Occurrence Handle8854254

    CAS  PubMed  Google Scholar 

  21. G Vezzolo A Tanini L Ferrucci L Soldati C Bianchin F Franceschelli C Malentacchi B Porfirio D Adamo A Terranegra A Falchetti D Cusi G Bianchi ML Brandi (2002) ArticleTitleInfluence of calcium-sensing receptor gene on urinary calcium excretion in stone-forming patients. J Am Soc Nephrol 13 2517–2523 Occurrence Handle1:CAS:528:DC%2BD38XntVyntrg%3D Occurrence Handle12239240

    CAS  PubMed  Google Scholar 

  22. A Devine SG Wilson IM Dick RL Prince (2002) ArticleTitleEffects of vitamin D metabolites on intestinal calcium absorption and bone turnover in elderly women. Am J Clin Nutr 75 283–288 Occurrence Handle1:CAS:528:DC%2BD38XovVCrug%3D%3D Occurrence Handle11815319

    CAS  PubMed  Google Scholar 

  23. H Glerup K Mikkelsen L Poulsen E Hass S Overbeck J Thomsen P Charles EF Eriksen (2000) ArticleTitleCommonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited. J Intern Med 247 260–268 Occurrence Handle10.1046/j.1365-2796.2000.00595.x Occurrence Handle1:CAS:528:DC%2BD3cXhvFGitLo%3D Occurrence Handle10692090

    Article  CAS  PubMed  Google Scholar 

  24. WM Law Jr HW Wahner H Heath III (1984) ArticleTitleBone mineral density and skeletal fractures in familial benign hypercalcemia (hypocalciuric hypercalcemia). Mayo Clin Proc 59 811–815 Occurrence Handle1:STN:280:BiqD2Mbls1A%3D Occurrence Handle6503361

    CAS  PubMed  Google Scholar 

  25. JH Kristiansen P Rodbro C Christiansen J Johansen JT Jensen (1987) ArticleTitleFamilial hypocalciuric hypercalcaemia. III: bone mineral metabolism. Clin Endocrinol (Oxf) 26 713–716 Occurrence Handle1:STN:280:BieD38jos1M%3D

    CAS  Google Scholar 

  26. S Abugassa J Nordenstrom J Jarhult (1992) ArticleTitleBone mineral density in patients with familial hypocalciuric hypercalcaemia (FHH) Eur J Surg 158 397–402 Occurrence Handle1:STN:280:ByyD3czmvVM%3D Occurrence Handle1356477

    CAS  PubMed  Google Scholar 

  27. IM Dick A Devine S Li SS Dhaliwal RL Prince (2003) ArticleTitleThe T869C TGFβ polymorphism is associated with fracture, bone mineral density and calcaneal quantitative ultrasound in elderly women . . .

    Google Scholar 

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Authors and Affiliations

  1. School of Medicine and Pharmacology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia

    J. Bollerslev, S. G. Wilson, I. M. Dick, A. Devine & R. L. Prince

  2. Department of Endocrinology and Diabetes, University of Western Australia, Western Australia, Australia

    S. G. Wilson, I. M. Dick, A. Devine, S. S. Dhaliwal & R. L. Prince

  3. Sir Charles Gairdner Hospital, Western Australian Institute of Medical Research, Perth, Western Australia, Australia

    S. G. Wilson, I. M. Dick, A. Devine & R. L. Prince

  4. Section of Endocrinology, National University Hospital, Oslo, Norway

    J. Bollerslev

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  1. J. Bollerslev
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  2. S. G. Wilson
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Bollerslev, J., Wilson, S., Dick, I. et al. Calcium-Sensing Receptor Gene Polymorphism A986S Does Not Predict Serum Calcium Level, Bone Mineral Density, Calcaneal Ultrasound Indices, or Fracture Rate in a Large Cohort of Elderly Women . Calcif Tissue Int 74, 12–17 (2004). https://doi.org/10.1007/s00223-002-0066-1

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  • DOI: https://doi.org/10.1007/s00223-002-0066-1

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