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Cooperative effect of serum 25-hydroxyvitamin D concentration and a polymorphism of transforming growth factor-β1 gene on the prevalence of vertebral fractures in postmenopausal osteoporosis

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Abstract

A T869→C polymorphism of the transforming growth factor-β1 (TGF-β1) gene is reported to be associated with genetic susceptibility to both osteoporosis and vertebral fractures. A low serum 25-hydroxyvitamin D [25(OH)D] level is known to be associated with a higher risk for hip fracture. This study aimed to assess a possible cooperative effect of the gene polymorphism and vitamin D status on vertebral fracture risk. The prevalence of vertebral fracture in 168 postmenopausal female patients with osteoporosis was analyzed, and its association with the TGF-β1 gene polymorphism and serum 25(OH)D concentration was assessed cross-sectionally. The fracture prevalence increased according to the rank order of the TGF-β1 genotypes CC < CT < TT, as expected. A significant difference was found not only between the CC and TT genotypes (P = 0.005) but also between the CC and CT genotypes (P < 0.05) when the patients with serum 25(OH)D of more than the median value [22 ng/ml (55 nmol/l)] were analyzed. On the other hand, when those with serum 25(OH)D of less than the median value were analyzed, the protective effect of the C allele against the fracture was blunted; statistical significance in the difference of the fracture prevalence was lost between the CC genotype and the other genotypes. These data suggest that vitamin D fulfillment is prerequisite for the TGF-β1 genotype in exerting its full effect on the fracture prevalence.

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References

  1. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795

    Article  Google Scholar 

  2. Orimo H, Hayashi Y, Fukunaga M, Sone T, Fujiwara M, Shiraki M, Kushida K, Miyamoto S, Soen S, Nishimura J, Oh-hashi Y, Hosoi T, Gorai I, Tanaka H, Igai T, Kishimoto H (2001) Diagnostic criteria for primary osteoporosis: year 2000 revision. J Bone Miner Metab 19:331–337

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Albagha OM, Ralston SH (2003) Genetic determinants of susceptibility to osteoporosis. Endocrinol Metab Clin N Am 32:65–81

    Article  CAS  Google Scholar 

  5. Ralston SH, de Crombrugghe B (2006) Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev 20:2492–2506

    Article  CAS  PubMed  Google Scholar 

  6. Hirschhorn JN, Gennari L (2008) Bona fide genetic associations with bone mineral density. N Engl J Med 358:2403–2405

    Article  CAS  PubMed  Google Scholar 

  7. Hughes DE, Dai A, Tiffee JC, Li HH, Mundy GR, Boyce BF (1996) Estrogen promotes apotosis of murine osteoclast mediated by TGF-β. Nat Med 2:1132–1136

    Article  CAS  PubMed  Google Scholar 

  8. Yanagisawa J, Yanagi Y, Masuhiro Y, Suzawa M, Watanabe M, Kashiwagi K, Toriyabe T, Kawabata M, Miyazono K, Kato S (1999) Convergence of transforming growth factor-β and vitamin D signaling pathways on SMAD transcriptional coactivators. Science 283:1317–1321

    Article  CAS  PubMed  Google Scholar 

  9. Yamada Y, Hosoi T, Makimoto F, Tanaka H, Seino Y, Ikeda K (1999) Transforming growth factor beta-1 gene polymorphism and bone mineral density in Japanese adolescents. Am J Med 106:477–479

    Article  CAS  PubMed  Google Scholar 

  10. Yamada Y, Miyauchi A, Goto J, Takagi Y, Okuizumi H, Kanematsu M, Hase M, Takai H, Harada A, Ikeda K (1998) Association of a polymorphism of the transforming growth factor-β1 gene with genetic susceptibility to osteoporosis in Japanese women. J Bone Miner Res 13:1569–1576

    Article  CAS  PubMed  Google Scholar 

  11. Yamada Y, Miyauchi A, Takagi Y, Nakauchi K, Miki N, Mizuno M, Harada A (2000) Association of a polymorphism of the transforming growth factor-β1 gene with prevalent vertebral fractures in Japanese women. Am J Med 109:244–247

    Article  CAS  PubMed  Google Scholar 

  12. Yamada Y, Harada A, Hosoi T, Miyauchi A, Ikeda K, Ohta H, Shiraki M (2000) Association of transforming growth factor-β1 genotype with therapeutic response to active vitamin D for postmenopausal osteoporosis. J Bone Miner Res 15:415–420

    Article  CAS  PubMed  Google Scholar 

  13. Riggs BL (2003) Role of the vitamin D-endocrine system in the pathophysiology of postmenopausal osteoporosis. J Cell Biochem 88:209–215

    Article  CAS  PubMed  Google Scholar 

  14. Lips P (2001) Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 22:477–501

    Article  CAS  PubMed  Google Scholar 

  15. Looker AC, Mussolino ME (2008) Serum 25-hydroxyvitamin D and hip fracture risk in older US white adults. J Bone Miner Res 23:143–150

    Article  CAS  PubMed  Google Scholar 

  16. Cauley JA, Lacroix AZ, Wu L, Horwitz M, Danielson ME, Bauer DC, Lee JS, Jackson RD, Robbins JA, Wu C, Stanczyk FZ, LeBoff MS, Wactawski-Wende J, Sarto G, Ockene J, Cummings SR (2008) Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med 149:242–250

    PubMed  Google Scholar 

  17. Walsh MC, Hunter GR, Livingstone MB (2006) Sarcopenia in premenopausal and postmenopausal women with osteopenia, osteoporosis and normal bone mineral density. Osteoporos Int 17:61–67

    Article  PubMed  Google Scholar 

  18. Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D, Cummings SR (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. J Bone Miner Res 11:984–996

    Article  CAS  PubMed  Google Scholar 

  19. Nishizawa Y, Nakamura T, Ohta H, Kushida K, Gorai I, Shiraki M, Fukunaga M, Hosoi T, Miki T, Chaki O, Ichimura S, Nakatsuka K, Miura M (2005) Committee on the Guidelines for the Use of Biochemical Markers of Bone Turnover in Osteoporosis Japan Osteoporosis Society: guidelines for the use of biochemical markers of bone turnover in osteoporosis (2004). J Bone Miner Metab 23:97–104

    Article  PubMed  Google Scholar 

  20. Tzakas P, Wong BY, Logan AG, Rubin LA, Cole DE (2005) Transforming growth factor beta-1 (TGFB1) and peak bone mass: association between intragenic polymorphisms and quantitative ultrasound of the heel. BMC Musculoskelet Disord 6:29

    Article  PubMed  CAS  Google Scholar 

  21. Bonewald LF (1996) Transforming growth factor-β. In: Bilezikian JP, Raisz LG, Rodan GA (eds) Principles of bone biology. Academic Press, San Diego, pp 647–659

    Google Scholar 

  22. Sterck JG, Klein-Nulend J, Burger EH, Lips P (1996) 1, 25-Dihydroxyvitamin D3-mediated TGF-beta release is impaired in cultured osteoblasts from patients with multiple pituitary hormone deficiency. J Bone Miner Res 11:367–376

    Article  CAS  PubMed  Google Scholar 

  23. Finkelman RD, Linkhart TA, Mohan S, Lau KH, Baylink DJ, Bell NH (1991) Vitamin D deficiency causes a selective reduction in deposition of TGF-beta in rat bone: possible mechanism for impaired osteoinduction. Proc Natl Acad Sci USA 88:3657–3660

    Article  CAS  PubMed  Google Scholar 

  24. Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, Roberts AB, Sporn MB, Goeddel DV (1985) Human transforming growth factor-β complementary DNA sequence and expression in normal and transformed cells. Nature (Lond) 316:701–705

    Article  CAS  Google Scholar 

  25. Langdahl BL, Uitterlinden AG, Ralston SH, Trikalinos TA, Balcells S et al (2008) Large-scale analysis of association between polymorphisms in the transforming growth factor beta 1 gene (TGFB1) and osteoporosis: the GENOMOS study. Bone (NY) 42:969–981

    CAS  Google Scholar 

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Acknowledgments

We are grateful to Dr. Yasufumi Hayashi in Tokyo Metropolitan Rehabilitation Hospital, Tokyo, Japan; Dr. Seizo Yamamoto in Toranomon Hospital, Tokyo, Japan; and Dr. Toshiyuki Horiuchi in Tokyo Metropolitan Toshima Hospital, Tokyo, Japan, for their participation in the initial stage of this study.

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Authors and Affiliations

  1. Department of Internal Medicine, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan

    Seijiro Mori, Yuko Chiba, Fumiaki Tokimura, Yoshiyuki Kimbara, Yoshiaki Tamura, Atsushi Araki & Hideki Ito

  2. Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

    Noriyuki Fuku & Masashi Tanaka

  3. National Center for Geriatrics and Gerontology, Aichi, Japan

    Takayuki Hosoi

Authors
  1. Seijiro Mori
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  2. Noriyuki Fuku
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  3. Yuko Chiba
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  4. Fumiaki Tokimura
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  5. Takayuki Hosoi
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  6. Yoshiyuki Kimbara
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  7. Yoshiaki Tamura
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  8. Atsushi Araki
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  9. Masashi Tanaka
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  10. Hideki Ito
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Correspondence to Seijiro Mori.

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Mori, S., Fuku, N., Chiba, Y. et al. Cooperative effect of serum 25-hydroxyvitamin D concentration and a polymorphism of transforming growth factor-β1 gene on the prevalence of vertebral fractures in postmenopausal osteoporosis. J Bone Miner Metab 28, 446–450 (2010). https://doi.org/10.1007/s00774-009-0147-6

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  • DOI: https://doi.org/10.1007/s00774-009-0147-6

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