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Quantitative trait locus on chromosome X affects bone loss after maturation in mice

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Abstract

Genetic programming is known to affect the peak bone mass and bone loss after maturation. However, little is known about how polymorphic genes on chromosome X (Chr X) modulate bone loss after maturation. We previously reported a quantitative trait locus (QTL) on Chr X, designated Pbd3, which had a suggestive linkage to bone mass, in male SAMP2 and SAMP6 mice. In this study, we aimed to clarify the effects of Pbd3 on the skeletal phenotype. We generated a congenic strain, P2.P6-X, carrying a 45.6-cM SAMP6-derived Chr X interval on a SAMP2 genetic background. The effects of Pbd3 on the bone phenotype were determined by microcomputed tomography (μCT), whole-body dual-energy X-ray absorptiometry (DXA), serum bone turnover markers, and histomorphometric parameters. Both the bone area fraction (BA/TA) on μCT and whole-body DXA revealed reduced bone loss in P2.P6-X compared with that in SAMP2. The serum concentrations of bone turnover markers at 4 months of age were significantly lower in P2.P6-X than in SAMP2, but did not differ at 8 months of age. These results were observed in female mice, but not in male mice. In conclusion, a QTL within a segregated 45.6-cM interval on Chr X is sex-specifically related to the rate of bone loss after maturation.

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References

  1. Riggs BL, Khosla S, Melton LJ 3rd (1998) A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res 13:763–773

    Article  CAS  PubMed  Google Scholar 

  2. Smith DM, Nance WE, Kang KW, Christian JC, Johnston CC Jr (1973) Genetic factors in determining bone mass. J Clin Invest 52:2800–2808

    Article  CAS  PubMed  Google Scholar 

  3. Pocock NA, Eisman JA, Hopper JL, Yeates MG, Sambrook PN, Eberl S (1987) Genetic determinants of bone mass in adults. A twin study. J Clin Invest 80:706–710

    Article  CAS  PubMed  Google Scholar 

  4. Liu YJ, Shen H, Xiao P, Xiong DH, Li LH, Recker RR, Deng HW (2006) Molecular genetic studies of gene identification for osteoporosis: a 2004 update. J Bone Miner Res 21:1511–1535

    Article  CAS  PubMed  Google Scholar 

  5. Kawano H, Sato T, Yamada T, Matsumoto T, Sekine K, Watanabe T, Nakamura T, Fukuda T, Yoshimura K, Yoshizawa T, Aihara K, Yamamoto Y, Nakamichi Y, Metzger D, Chambon P, Nakamura K, Kawaguchi H, Kato S (2003) Suppressive function of androgen receptor in bone resorption. Proc Natl Acad Sci USA 100:9416–9421

    Article  CAS  PubMed  Google Scholar 

  6. Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, Harada Y, Azuma Y, Krust A, Yamamoto Y, Nishina H, Takeda S, Takayanagi H, Metzger D, Kanno J, Takaoka K, Martin TJ, Chambon P, Kato S (2007) Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell 130:811–823

    Article  CAS  PubMed  Google Scholar 

  7. Kawaguchi H, Manabe N, Miyaura C, Chikuda H, Nakamura K, Kuro-o M (1999) Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia. J Clin Invest 104:229–237

    Article  CAS  PubMed  Google Scholar 

  8. Kawano K, Ogata N, Chiano M, Molloy H, Kleyn P, Spector TD, Uchida M, Hosoi T, Suzuki T, Orimo H, Inoue S, Nabeshima Y, Nakamura K, Kuro-o M, Kawaguchi H (2002) Klotho gene polymorphisms associated with bone density of aged postmenopausal women. J Bone Miner Res 17:1744–1751

    Article  CAS  PubMed  Google Scholar 

  9. Lewis DB, Liggitt HD, Effmann EL, Motley ST, Teitelbaum SL, Jepsen KJ, Goldstein SA, Bonadio J, Carpenter J, Perlmutter RM (1993) Osteoporosis induced in mice by overproduction of interleukin 4. Proc Natl Acad Sci USA 90:11618–11622

    Article  CAS  PubMed  Google Scholar 

  10. Miyaura C, Toda K, Inada M, Ohshiba T, Matsumoto C, Okada T, Ito M, Shizuta Y, Ito A (2001) Sex- and age-related response to aromatase deficiency in bone. Biochem Biophys Res Commun 280:1062–1068

    Article  CAS  PubMed  Google Scholar 

  11. Öz OK, Zerwekh JE, Fisher C, Graves K, Nanu L, Millsaps R, Simpson ER (2000) Bone has a sexually dimorphic response to aromatase deficiency. J Bone Miner Res 15:507–514

    Article  PubMed  Google Scholar 

  12. Wu XB, Li Y, Schneider A, Yu W, Rajendren G, Iqbal J, Yamamoto M, Alam M, Brunet LJ, Blair HC, Zaidi M, Abe E (2003) Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice. J Clin Invest 112:924–934

    CAS  PubMed  Google Scholar 

  13. Yoshida Y, Tanaka S, Umemori H, Minowa O, Usui M, Ikematsu N, Hosoda E, Imamura T, Kuno J, Yamashita T, Miyazono K, Noda M, Noda T, Yamamoto T (2000) Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell 103:1085–1097

    Article  CAS  PubMed  Google Scholar 

  14. Takeda T, Hosokawa M, Takeshita S, Irino M, Higuchi K, Matsushita T, Tomita Y, Yasuhira K, Hamamoto H, Shimizu K, Ishii M, Yamamuro T (1981) A new murine model of accelerated senescence. Mech Ageing Dev 17:183–194

    Article  CAS  PubMed  Google Scholar 

  15. Jilka RL, Weinstein RS, Takahashi K, Parfitt AM, Manolagas SC (1996) Linkage of decreased bone mass with impaired osteoblastogenesis in a murine model of accelerated senescence. J Clin Invest 97:1732–1740

    Article  CAS  PubMed  Google Scholar 

  16. Suda T, Miyama K, Uchiyama, Katagiri T, Yamaguchi A, Sato T (1994) Osteoporotic bone changes in SAMP6 are due to a decrease in osteoblast progenitor cells. In: Takeda T (eds) The SAM model of senescence. Elsevier (Excerpta Medica), Amsterdam, pp. 47–52

  17. Silva MJ, Brodt MD, Ettner SL (2002) Long bones from the senescence accelerated mouse SAMP6 have increased size but reduced whole-bone strength and resistance to fracture. J Bone Miner Res 17:1597–1603

    Article  PubMed  Google Scholar 

  18. Silva MJ, Brodt MD, Ko M, Abu-Amer Y (2005) Impaired marrow osteogenesis is associated with reduced endocortical bone formation but does not impair periosteal bone formation in long bones of SAMP6 mice. J Bone Miner Res 20:419–427

    Article  PubMed  Google Scholar 

  19. Shimizu M, Higuchi K, Bennett B, Xia C, Tsuboyama T, Kasai S, Chiba T, Fujisawa H, Kogishi K, Kitado H, Kimoto M, Takeda N, Matsushita M, Okumura H, Serikawa T, Nakamura T, Johnson TE, Hosokawa M (1999) Identification of peak bone mass QTL in a spontaneously osteoporotic mouse strain. Mamm Genome 10:81–87

    Article  CAS  PubMed  Google Scholar 

  20. Otsuki B, Matsumura T, Shimizu M, Mori M, Okudaira S, Nakanishi R, Higuchi K, Hosokawa M, Tsuboyama T, Nakamura T (2007) Quantitative trait locus that determines the cross-sectional shape of the femur in SAMP6 and SAMP2 mice. J Bone Miner Res 22:675–685

    Article  CAS  PubMed  Google Scholar 

  21. Nakanishi R, Shimizu M, Mori M, Akiyama H, Okudaira S, Otsuki B, Hashimoto M, Higuchi K, Hosokawa M, Tsuboyama T, Nakamura T (2006) Secreted frizzled-related protein 4 is a negative regulator of peak BMD in SAMP6 mice. J Bone Miner Res 21:1713–1721

    Article  CAS  PubMed  Google Scholar 

  22. Shimizu M, Higuchi K, Kasai S, Tsuboyama T, Matsushita M, Matsumura T, Okudaira S, Mori M, Koizumi A, Nakamura T, Hosokawa M (2002) A congenic mouse and candidate gene at the chromosome 13 locus regulating bone density. Mamm Genome 13:335–340

    Google Scholar 

  23. Flaherty L (1981) Congenic strains. In: Foster HL, Small JD, Fox JG (eds) The mouse in biomedical research, vol 1. Academic Press, New York, pp 215–221

  24. Kasai S, Shimizu M, Matsumura T, Okudaira S, Matsushita M, Tsuboyama T, Nakamura T, Hosokawa M (2004) Consistency of low bone density across bone sites in SAMP6 laboratory mice. J Bone Miner Metab 22:207–214

    Article  PubMed  Google Scholar 

  25. Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1997) The effects of androgen deficiency on murine bone remodeling and bone mineral density are mediated via cells of the osteoblastic lineage. Endocrinology 138:4013–4021

    Article  CAS  PubMed  Google Scholar 

  26. Tsuboyama T, Takahashi K, Matsushita M, Okumura H, Yamamuro T, Umezawa M, Takeda T (1989) Decreased endosteal formation during cortical bone modelling in SAM-P/6 mice with a low peak bone mass. Bone Miner 7:1–12

    Article  CAS  PubMed  Google Scholar 

  27. Parfitt AM, Drezner MK (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res 2:595–610

    Google Scholar 

  28. Winer BJ, Brown DR, Michels KM (1991) Statistical principles in experimental design, 3rd edn. McGraw-Hill, New York

    Google Scholar 

  29. Takeda T, Hosokawa M, Higuchi K (1991) Senescence-accelerated mouse (SAM): a novel murine model of accelerated senescence. J Am Geriatr Soc 39:911–919

    CAS  PubMed  Google Scholar 

  30. Beamer WG, Shultz KL, Churchill GA, Frankel WN, Baylink DJ, Rosen CJ, Donahue LR (1999) Quantitative trait loci for bone density in C57BL/6J and CAST/EiJ inbred mice. Mamm Genome 10:1043–1049

    Article  CAS  PubMed  Google Scholar 

  31. Beamer WG, Shultz KL, Donahue LR, Churchill GA, Sen S, Wergedal JR, Baylink DJ, Rosen CJ (2001) Quantitative trait loci for femoral and lumbar vertebral bone mineral density in C57BL/6J and C3H/HeJ inbred strains of mice. J Bone Miner Res 16:1195–1206

    Article  CAS  PubMed  Google Scholar 

  32. Benes H, Weinstein RS, Zheng W, Thaden JJ, Jilka RL, Manolagas SC, Shmookler Reis RJ (2000) Chromosomal mapping of osteopenia-associated quantitative trait loci using closely related mouse strains. J Bone Miner Res 15:626–633

    Article  CAS  PubMed  Google Scholar 

  33. Shultz KL, Donahue LR, Bouxsein ML, Baylink DJ, Rosen CJ, Beamer WG (2003) Congenic strains of mice for verification and genetic decomposition of quantitative trait loci for femoral bone mineral density. J Bone Miner Res 18:175–185

    Article  CAS  PubMed  Google Scholar 

  34. Abboud SL, Ghosh-Choudhury N, Liu LC, Shen V, Woodruff K (2003) Osteoblast-specific targeting of soluble colony-stimulating factor-1 increases cortical bone thickness in mice. J Bone Miner Res 18:1386–1394

    Article  CAS  PubMed  Google Scholar 

  35. Hankenson KD, Bain SD, Kyriakides TR, Smith EA, Goldstein SA, Bornstein P (2000) Increased marrow-derived osteoprogenitor cells and endosteal bone formation in mice lacking thrombospondin 2. J Bone Miner Res 15:851–862

    Article  CAS  PubMed  Google Scholar 

  36. Wang Q, Alén M, Nicholson PH, Halleen JM, Alatalo SL, Ohlsson C, Suominen H, Cheng S (2006) Differential effects of sex hormones on peri- and endocortical bone surfaces in pubertal girls. J Clin Endocrinol Metab 91:277–282

    Article  CAS  PubMed  Google Scholar 

  37. Garnero P, Sornay-Rendu E, Duboeuf F, Delmas PD (1999) Markers of bone turnover predict postmenopausal forearm bone loss over 4 years: the OFELY study. J Bone Miner Res 14:1614–1621

    Article  CAS  PubMed  Google Scholar 

  38. Garnero P, Borel O, Delmas PD (2001) Evaluation of a fully automated serum assay for C-terminal cross-linking telopeptide of type I collagen in osteoporosis. Clin Chem 47:694–702

    CAS  PubMed  Google Scholar 

  39. Ross PD, Knowlton W (1998) Rapid bone loss is associated with increased levels of biochemical markers. J Bone Miner Res 13:297–302

    Article  CAS  PubMed  Google Scholar 

  40. Dresner-Pollak R, Parker RA, Poku M, Thompson J, Seibel MJ, Greenspan SL (1996) Biochemical markers of bone turnover reflect femoral bone loss in elderly women. Calcif Tissue Int 59:328–333

    Article  CAS  PubMed  Google Scholar 

  41. Szulc P, Montella A, Delmas PD (2008) High bone turnover is associated with accelerated bone loss but not with increased fracture risk in men aged 50 and over: the prospective MINOS study. Ann Rheum Dis 67:1249–1255

    Article  CAS  PubMed  Google Scholar 

  42. Löfman O, Magnusson P, Toss G, Larsson L (2005) Common biochemical markers of bone turnover predict future bone loss: a 5-year follow-up study. Clin Chim Acta 356:67–75

    Article  PubMed  Google Scholar 

  43. Bruyere O, Collette J, Delmas P, Rouillon A, Roux C, Seidel L, Richy F, Reginster JY (2003) Interest of biochemical markers of bone turnover for long-term prediction of new vertebral fracture in postmenopausal osteoporotic women. Maturitas 44:259–265

    Article  CAS  PubMed  Google Scholar 

  44. Halleen JM, Tiitinen SL, Ylipahkala H, Fagerlund KM, Väänänen HK (2006) Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clin Lab 52:499–509

    CAS  PubMed  Google Scholar 

  45. Rissanen JP, Suominen MI, Peng Z, Halleen JM (2008) Secreted tartrate-resistant acid phosphatase 5b is a Marker of osteoclast number in human osteoclast cultures and the rat ovariectomy model. Calcif Tissue Int 82:108–115

    Article  CAS  PubMed  Google Scholar 

  46. Lian JB, Stein GS, Aubin JE (2003) Bone formation: maturation and function activities of osteoblast linage cells. In: Primer on the metabolic bone diseases and disorders of mineral metabolism, 5th edn. ASBMR, Washington, pp 13–28

  47. Calvo MS, Eyre DR, Gundberg CM (1996) Molecular basis and clinical application of biological markers of bone turnover. Endocr Rev 17:333–368

    CAS  PubMed  Google Scholar 

  48. Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G (1996) Increased bone formation in osteocalcin-deficient mice. Nature 382:448–452

    Article  CAS  PubMed  Google Scholar 

  49. Szumska D, Benes H, Kang P, Weinstein RS, Jilka RL, Manolagas SC, Shmookler Reis RJ (2007) A novel locus on the X chromosome regulates post-maturity bone density changes in mice. Bone 40:758–766

    Article  CAS  PubMed  Google Scholar 

  50. Christiansen C (1994) Postmenopausal bone loss and the risk of osteoporosis. Osteoporos Int 4(Suppl 1):47–51

    Article  PubMed  Google Scholar 

  51. Riis BJ, Hansen MA, Jensen AM, Overgaard K, Christiansen C (1996) Low bone mass and fast rate of bone loss at menopause: equal risk factors for future fracture: a 15-year follow-up study. Bone 19:9–12

    Article  CAS  PubMed  Google Scholar 

  52. Stiger F, Brändström H, Gillberg P, Melhus H, Wolk A, Michaelsson K, Kindmark A (2008) Association between repeat length of exon 1 CAG microsatellite in the androgen receptor and bone density in men is modulated by sex hormone levels. Calcif Tissue Int 82:427–435

    Article  CAS  PubMed  Google Scholar 

  53. Lai BM, Cheung CL, Luk KD, Kung AW (2008) Estrogen receptor alpha CA dinucleotide repeat polymorphism is associated with rate of bone loss in perimenopausal women and bone mineral density and risk of osteoporotic fractures in postmenopausal women. Osteoporos Int 19:571–579

    Article  CAS  PubMed  Google Scholar 

  54. Nielsen KL, Allen MR, Bloomfield SA, Andersen TL, Chen XD, Poulsen HS, Young MF, Heegaard AM (2003) Biglycan deficiency interferes with ovariectomy-induced bone loss. J Bone Miner Res 18:2152–2158

    Article  CAS  PubMed  Google Scholar 

  55. Xu T, Bianco P, Fisher LW, Longenecker G, Smith E, Goldstein S, Bonadio J, Boskey A, Heegaard AM, Sommer B, Satomura K, Dominguez P, Zhao C, Kulkarni AB, Robey PG, Young MF (1998) Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice. Nat Genet 20:78–82

    Article  CAS  PubMed  Google Scholar 

  56. Yamaguchi M, Misawa H, Uchiyama S, Morooka Y, Tsurusaki Y (2002) Role of endogenous regucalcin in bone metabolism: bone loss is induced in regucalcin transgenic rats. Int J Mol Med 10:377–383

    CAS  PubMed  Google Scholar 

  57. Sims NA, Dupont S, Krust A, Clement-Lacroix P, Minet D, Resche-Rigon M, Gaillard-Kelly M, Baron R (2002) Deletion of estrogen receptors reveals a regulatory role for estrogen receptors-beta in bone remodeling in females but not in males. Bone 30:18–25

    Article  CAS  PubMed  Google Scholar 

  58. Windahl SH, Vidal O, Andersson G, Gustafsson JA, Ohlsson C (1999) Increased cortical bone mineral content but unchanged trabecular bone mineral density in female ERbeta(−/−) mice. J Clin Invest 104:895–901

    Article  CAS  PubMed  Google Scholar 

  59. Brault BA, Meyer MH, Meyer RA Jr, Iorio RJ (1987) Mineral uptake by the femora of older female X-linked hypophosphatemic (HYP) mice but not older male HYP mice. Clin Orthop Relat Res 222:289–299

    PubMed  Google Scholar 

  60. Salih DA, Mohan S, Kasukawa Y, Tripathi G, Lovett FA, Anderson NF, Carter EJ, Wergedal JE, Baylink DJ, Pell JM (2005) Insulin-like growth factor-binding protein-5 induces a gender-related decrease in bone mineral density in transgenic mice. Endocrinology 146:931–940

    Article  CAS  PubMed  Google Scholar 

  61. Hashimoto-Gotoh T, Ohnishi H, Tsujimura A, Tsunezuka H, Imai K, Masuda H, Nakamura T (2004) Bone mass increase specific to the female in a line of transgenic mice overexpressing human osteoblast stimulating factor-1. J Bone Miner Metab 22:278–282

    Article  CAS  PubMed  Google Scholar 

  62. Yeh S, Tsai MY, Xu Q, Mu XM, Lardy H, Huang KE, Lin H, Yeh SD, Altuwaijri S, Zhou X, Xing L, Boyce BF, Hung MC, Zhang S, Gan L, Chang C (2002) Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues. Proc Natl Acad Sci USA 99:13498–13503

    Article  CAS  PubMed  Google Scholar 

  63. McDevitt MA, Shivdasani RA, Fujiwara Y, Yang H, Orkin SH (1997) A “knockdown” mutation created by cis-element gene targeting reveals the dependence of erythroid cell maturation on the level of transcription factor GATA-1. Proc Natl Acad Sci USA 94:6781–6785

    Article  CAS  PubMed  Google Scholar 

  64. Zhang Y, Kwon S, Yamaguchi T, Cubizolles F, Rousseaux S, Kneissel M, Cao C, Li N, Cheng HL, Chua K, Lombard D, Mizeracki A, Matthias G, Alt FW, Khochbin S, Matthias P (2008) Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Mol Cell Biol 28:1688–1701

    Article  CAS  PubMed  Google Scholar 

  65. Kitching R, Qi S, Li V, Raouf A, Vary CP, Seth A (2002) Coordinate gene expression patterns during osteoblast maturation and retinoic acid treatment of MC3T3–E1 cells. J Bone Miner Metab 20:269–280

    Article  CAS  PubMed  Google Scholar 

  66. Ishida R, Emi M, Ezura Y, Iwasaki H, Yoshida H, Suzuki T, Hosoi T, Inoue S, Shiraki M, Ito H, Orimo H (2003) Association of a haplotype (196Phe/532Ser) in the interleukin-1-receptor-associated kinase (IRAK1) gene with low radial bone mineral density in two independent populations. J Bone Miner Res 18:419–423

    Article  CAS  PubMed  Google Scholar 

  67. Sasaki A, Masuda Y, Iwai K, Ikeda K, Watanabe K (2002) A RING finger protein Praja1 regulates Dlx5-dependent transcription through its ubiquitin ligase activity for the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1. J Biol Chem 277:22541–22546

    Article  CAS  PubMed  Google Scholar 

  68. Liu W, Wang S, Wei S, Sun L, Feng X (2005) Receptor activator of NF-kappaB (RANK) cytoplasmic motif, 369PFQEP373, plays a predominant role in osteoclast survival in part by activating Akt/PKB and its downstream effector AFX/FOXO4. J Biol Chem 280:43064–43072

    Article  CAS  PubMed  Google Scholar 

  69. Hosaka T, Biggs WH 3rd, Tieu D, Boyer AD, Varki NM, Cavenee WK, Arden KC (2004) Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc Natl Acad Sci USA 101:2975–2980

    Article  CAS  PubMed  Google Scholar 

  70. Battaglino R, Fu J, Späte U, Ersoy U, Joe M, Sedaghat L, Stashenko P (2004) Serotonin regulates osteoclast differentiation through its transporter. J Bone Miner Res 19:1420–1431

    Article  CAS  PubMed  Google Scholar 

  71. Xiao P, Chen Y, Jiang H, Liu YZ, Pan F, Yang TL, Tang ZH, Larsen JA, Lappe JM, Recker RR, Deng HW (2008) In vivo genome-wide expression study on human circulating B cells suggests a novel ESR1 and MAPK3 network for postmenopausal osteoporosis. J Bone Miner Res 23:644–654

    Article  CAS  PubMed  Google Scholar 

  72. Kitazawa R, Kitazawa S (2007) Methylation status of a single CpG locus 3 bases upstream of TATA-box of receptor activator of nuclear factor-kappaB ligand (RANKL) gene promoter modulates cell- and tissue-specific RANKL expression and osteoclastogenesis. Mol Endocrinol 21:148–158

    Article  CAS  PubMed  Google Scholar 

  73. Tsuboyama T, Takahashi K, Yamamuro T, Hosokawa M, Takeda T (1993) Cross-mating study on bone mass in the spontaneously osteoporotic mouse (SAM-P/6). Bone Miner 23:57–64

    Article  CAS  PubMed  Google Scholar 

  74. Festing MFW (1979) Notes on genetic analysis. In: Inbred strains in biomedical research. MacMillan, London, pp. 80–103

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Acknowledgments

The authors thank Kumiko Kogishi, Tomoko Watanabe, Yoko Ikeda, Sonoko Matsuda, Yoko Uenoyama, and Misako Tonomura for technical assistance.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, 606-8507, Japan

    Shuzo Okudaira, Rika Nakanishi & Takashi Nakamura

  2. Department of Orthopaedic Surgery, Utano National Hospital, Ukyo, Kyoto, 616-8825, Japan

    Motoyuki Shimizu

  3. Department of Orthopaedic Surgery, Kobe City Medical Center General Hospital, Kobe, 650-0046, Japan

    Bungo Otsuki

  4. Department of Medical, Social and Cultural Science, Faculty of Medicine, Shimane University, Izumo, Shimane, 693-8501, Japan

    Akira Ohta

  5. Department of Aging Angiology, Research Center for Aging and Adaptation, Shinshu University, Matsumoto, 390-8621, Japan

    Keiichi Higuchi

  6. Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, 480-0392, Japan

    Masanori Hosokawa

  7. Human Health Sciences, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, 606-8507, Japan

    Tadao Tsuboyama

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  1. Shuzo Okudaira
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Correspondence to Takashi Nakamura.

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Okudaira, S., Shimizu, M., Otsuki, B. et al. Quantitative trait locus on chromosome X affects bone loss after maturation in mice. J Bone Miner Metab 28, 520–531 (2010). https://doi.org/10.1007/s00774-010-0168-1

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