Skip to main content
Log in

Familial resemblance of bone turnover rate in men aged 40 and over—the MINOS study

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Familial resemblance of bone mineral density (BMD) is well known in both sexes. Fewer data concern the familial resemblance of bone turnover markers (BTMs) and bone size in men. Our aim was to assess the correlation of BMD, bone size, BTM levels and hormones regulating bone turnover in 50 pairs of brothers aged ≥ 40 and 50 pairs of unrelated men matched for age, weight and height. BMD was measured at the lumbar spine, hip, forearm and whole body. We measured serum osteocalcin (OC), bone-specific alkaline phosphatase (bone ALP), N-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (CTX-I) as well as urinary free and total deoxypyridinoline (DPD) and CTX-I. After adjustment for age, weight, bioavailable 17β-estradiol, and parathyroid hormone, all the BTMs (except bone ALP) were significantly correlated in the brothers (ICC = 0.36–0.64). Most of these correlations were significantly stronger than in the unrelated men. Bone size correlated significantly between the brothers (ICC = 0.55–0.65). These correlations were significantly stronger than in the unrelated men. BMD correlated between the brothers at most of the skeletal sites and, for some of them, more strongly than in the unrelated men. Serum levels of LDL-cholesterol and triglycerides were significantly correlated in the brothers, but not more strongly than in the unrelated men. BTM levels correlated independently in the brothers aged ≥ 40, when their shared environment was limited. These data suggest a substantial hereditary determinism of the BTM levels in men.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Rice TK (2008) Familial resemblance and heritability. Adv Genet 60:35–49

    Article  PubMed  Google Scholar 

  2. Duncan EL, Cardon LR, Sinsheimer JS, Wass JA, Brown MA (2003) Site and gender specificity of inheritance of bone mineral density. J Bone Miner Res 18:1531–1538

    Article  PubMed  Google Scholar 

  3. Cardon LR, Garner C, Bennett ST, Mackay IJ, Edwards RM, Cornish J, Hegde M, Murray MA, Reid IR, Cundy T (2000) Evidence for a major gene for bone mineral density in idiopathic osteoporotic families. J Bone Miner Res 15:1132–1137

    Article  PubMed  CAS  Google Scholar 

  4. Guéguen R, Jouanny P, Guillemin F, Kuntz C, Pourel J, Siest G (1995) Segregation analysis and variance components analysis of bone mineral density in healthy families. J Bone Miner Res 10:2017–2022

    Article  PubMed  Google Scholar 

  5. Baudoin C, Cohen-Solal ME, Beaudreuil J, De Vernejoul MC (2002) Genetic and environmental factors affect bone density variances of families of men and women with osteoporosis. J Clin Endocrinol Metab 87:2053–2059

    Article  PubMed  CAS  Google Scholar 

  6. Fox KM, Cummings SR, Powell-Threets K, Stone K (1998) Family history and risk of osteoporotic fracture. Study of Osteoporotic Fractures Research Group. Osteoporos Int 8:557–562

    Article  PubMed  CAS  Google Scholar 

  7. Seeman E, Hopper JL, Bach LA, Cooper ME, Parkinson E, McKay J, Jerums G (1989) Reduced bone mass in daughters of women with osteoporosis. N Engl J Med 320:554–558

    Article  PubMed  CAS  Google Scholar 

  8. Rudäng R, Ohlsson C, Odén A, Johansson H, Mellström D, Lorentzon M (2010) Hip fracture prevalence in grandfathers is associated with reduced cortical cross-sectional bone area in their young adult grandsons. J Clin Endocrinol Metab 95:1105–1114

    Article  PubMed  Google Scholar 

  9. Nordström P, Lorentzon R (1999) Influence of heredity and environment on bone density in adolescent boys: a parent-offspring study. Osteoporos Int 10:271–277

    Article  PubMed  Google Scholar 

  10. Van Pottelbergh I, Goemaere S, Zmierczak H, De Bacquer D, Kaufman JM (2003) Deficient acquisition of bone during maturation underlies idiopathic osteoporosis in men: evidence from a three-generation family study. J Bone Miner Res 18:303–311

    Article  PubMed  Google Scholar 

  11. Christian JC, Yu PL, Slemenda CW, Johnston CC Jr (1989) Heritability of bone mass: a longitudinal study in aging male twins. Am J Hum Genet 44:429–433

    PubMed  CAS  Google Scholar 

  12. Livshits G, Yakovenko K, Kobyliansky E (2003) Quantitative genetic study of radiographic hand bone size and geometry. Bone 32:191–198

    Article  PubMed  CAS  Google Scholar 

  13. Ng MY, Sham PC, Paterson AD, Chan V, Kung AW (2006) Effect of environmental factors and gender on the heritability of bone mineral density and bone size. Ann Hum Genet 70(Pt 4):428–438

    Article  PubMed  CAS  Google Scholar 

  14. Garnero P, Arden NK, Griffiths G, Delmas PD, Spector TD (1996) Genetic influence on bone turnover in postmenopausal twins. J Clin Endocrinol Metab 81:140–146

    Article  PubMed  CAS  Google Scholar 

  15. Kelly PJ, Hopper JL, Macaskill GT, Pocock NA, Sambrook PN, Eisman JA (1991) Genetic factors in bone turnover. J Clin Endocrinol Metab 72:808–813

    Article  PubMed  CAS  Google Scholar 

  16. Livshits G, Yakovenko C, Kobyliansky E (2000) Quantitative genetic analysis of circulating levels of biochemical markers of bone formation. Am J Med Genet 94:324–331

    Article  PubMed  CAS  Google Scholar 

  17. Hunter D, De Lange M, Snieder H, MacGregor AJ, Swaminathan R, Thakker RV, Spector TD (2001) Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. J Bone Miner Res 16:371–378

    Article  PubMed  CAS  Google Scholar 

  18. Ring HZ, Lessov CN, Reed T, Marcus R, Holloway L, Swan GE, Carmelli D (2005) Heritability of plasma sex hormones and hormone binding globulin in adult male twins. J Clin Endocrinol Metab 90:3653–3658

    Article  PubMed  CAS  Google Scholar 

  19. Van Pottelbergh I, Goemaere S, Zmierczak H, Kaufman JM (2004) Perturbed sex steroid status in men with idiopathic osteoporosis and their sons. J Clin Endocrinol Metab 89:4949–4953

    Article  PubMed  Google Scholar 

  20. Snellman G, Melhus H, Gedeborg R, Olofsson S, Wolk A, Pedersen NL, Michaëlsson K (2009) Seasonal genetic influence on serum 25-hydroxyvitamin D levels: a twin study. PLoS ONE 4:e7747

    Article  PubMed  Google Scholar 

  21. Karohl C, Su S, Kumari M, Tangpricha V, Veledar E, Vaccarino V, Raggi P (2010) Heritability and seasonal variability of vitamin D concentrations in male twins. Am J Clin Nutr 92:1393–1398

    Article  PubMed  CAS  Google Scholar 

  22. Szulc P, Marchand F, Duboeuf F, Delmas PD (2000) Cross-sectional assessment of age-related bone loss in men: the MINOS study. Bone 26:123–129

    Article  PubMed  CAS  Google Scholar 

  23. Szulc P, Munoz F, Marchand F, Chapurlat R, Delmas PD (2010) Rapid loss of appendicular skeletal muscle mass is associated with higher all-cause mortality in older men: the prospective MINOS study. Am J Clin Nutr 91:1227–1236

    Article  PubMed  CAS  Google Scholar 

  24. Szulc P, Garnero P, Munoz F, Marchand F, Delmas PD (2001) Cross-sectional evaluation of bone metabolism in men. J Bone Miner Res 16:1642–1650

    Article  PubMed  CAS  Google Scholar 

  25. Szulc P, Uusi-Rasi K, Claustrat B, Marchand F, Beck TJ, Delmas PD (2004) Role of sex steroids in the regulation of bone morphology in men. The MINOS study. Osteoporos Int 15:909–917

    Article  PubMed  CAS  Google Scholar 

  26. Szulc P, Claustrat B, Marchand F, Delmas PD (2003) Increased risk of falls and increased bone resorption in elderly men with partial androgen deficiency: the MINOS study. J Clin Endocrinol Metab 88:5240–5247

    Article  PubMed  CAS  Google Scholar 

  27. Szulc P, Claustrat B, Munoz F, Marchand F, Delmas PD (2004) Assessment of the role of 17 betaoestradiol in bone metabolism in men: does the assay technique matter? The MINOS study. Clin Endocrinol (Oxf) 61:447–457

    Article  CAS  Google Scholar 

  28. Szulc P, Munoz F, Marchand F, Chapuy MC, Delmas PD (2003) Role of vitamin D and parathyroid hormone in the regulation of bone turnover and bone mass in men: the MINOS study. Calcif Tissue Int 73:520–530

    Article  PubMed  CAS  Google Scholar 

  29. Szulc P, Varennes A, Delmas PD, Goudable J, Chapurlat R (2010) Men with metabolic syndrome have lower bone mineral density but lower fracture risk—the MINOS study. J Bone Miner Res 25:1446–1454

    Article  PubMed  Google Scholar 

  30. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    PubMed  CAS  Google Scholar 

  31. Hsu FC, Lenchik L, Nicklas BJ, Lohman K, Register TC, Mychaleckyj J, Langefeld CD, Freedman BI, Bowden DW, Carr JJ (2005) Heritability of body composition measured by DXA in the diabetes heart study. Obes Res 13:312–319

    Article  PubMed  Google Scholar 

  32. Pérusse L, Rice T, Després JP, Rao DC, Bouchard C (1997) Cross-trait familial resemblance for body fat and blood lipids: familial correlations in the Quebec Family Study. Arterioscler Thromb Vasc Biol 17:3270–3277

    Article  PubMed  Google Scholar 

  33. Pérusse L, Rice T, Després JP, Bergeron J, Province MA, Gagnon J, Leon AS, Rao DC, Skinner JS, Wilmore JH, Bouchard C (1997) Familial resemblance of plasma lipids, lipoproteins and postheparin lipoprotein and hepatic lipases in the HERITAGE Family Study. Arterioscler Thromb Vasc Biol 17:3263–3269

    Article  PubMed  Google Scholar 

  34. Demirkan A, Amin N, Isaacs A, Jarvelin MR, Whitfield JB et al (2011) Genetic architecture of circulating lipid levels. Eur J Hum Genet 19:813–819

    Article  PubMed  CAS  Google Scholar 

  35. Roshandel D, Holliday KL, Pye SR, Boonen S, Borghs H et al (2010) Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men. J Bone Miner Res 25:1830–1838

    Article  PubMed  CAS  Google Scholar 

  36. Ferrari SL, Ahn-Luong L, Garnero P, Humphries SE, Greenspan SL (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 Endocrinol Metab 88:255–259

    Article  PubMed  CAS  Google Scholar 

  37. Mitchell BD, Cole SA, Bauer RL, Iturria SJ, Rodriguez EA, Blangero J, MacCluer JW, Hixson JE (2000) Genes influencing variation in serum osteocalcin concentrations are linked to markers on chromosomes 16q and 20q. J Clin Endocrinol Metab 85:1362–1366

    Article  PubMed  CAS  Google Scholar 

  38. 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 13:813–817

    Article  PubMed  CAS  Google Scholar 

  39. Donescu OS, Battié MC, Kaprio J, Levalahti E, Risteli J, Eyre D, Videman T (2007) Genetic and constitutional influences on bone turnover markers: a study of male twin pairs. Calcif Tissue Int 80:81–88

    Article  PubMed  CAS  Google Scholar 

  40. Kuipers AL, Gundberg C, Kammerer CM, Dressen AS, Nestlerode CS, Patrick AL, Wheeler VW, Bunker CH, Newman AB, Zmuda JM (2012) Genetic analysis of serum osteocalcin and bone mineral in multigenerational Afro-Caribbean families. Osteoporos Int 23:1521–1531

    Google Scholar 

  41. Szulc P, Kaufman JM, Delmas PD (2007) Biochemical assessment of bone turnover and bone fragility in men. Osteoporos Int 18:1451–1461

    Article  PubMed  CAS  Google Scholar 

  42. Yoshimura N, Muraki S, Oka H, Kawaguchi H, Nakamura K, Akune T (2011) Changes in serum levels of biochemical markers of bone turnover during 10 years among Japanese men and women: associated factors and birth-cohort effect. The Taiji Study. J Bone Miner Metab 29:699–708

    Article  PubMed  CAS  Google Scholar 

  43. Nyquist F, Ljunghall S, Berglund M, Obrant K (1996) Biochemical markers of bone metabolism after short and long time ethanol withdrawal in alcoholics. Bone 19:51–54

    Article  PubMed  CAS  Google Scholar 

  44. Szulc P, Garnero P, Claustrat B, Marchand F, Duboeuf F, Delmas PD (2002) Increased bone resorption in moderate smokers with low body weight: the Minos study. J Clin Endocrinol Metab 87:666–674

    Article  PubMed  CAS  Google Scholar 

  45. Bogaert V, Taes Y, Konings P, Van Steen K, De Bacquer D, Goemaere S, Zmierczak H, Crabbe P, Kaufman JM (2008) Heritability of blood concentrations of sex-steroids in relation to body composition in young adult male siblings. Clin Endocrinol (Oxf) 69:129–135

    Article  CAS  Google Scholar 

  46. Lutz J, Tesar R (1990) Mother-daughter pairs: spinal and femoral bone densities and dietary intakes. Am J Clin Nutr 52:872–877

    PubMed  CAS  Google Scholar 

  47. Blain H, Vuillemin A, Jeandel C, Jouanny P, Guillemin F, Le Bihan E (2006) Lean mass plays a gender-specific role in familial resemblance for femoral neck bone mineral density in adult subjects. Osteoporos Int 17:897–907

    Article  PubMed  CAS  Google Scholar 

  48. Peacock M, Koller DL, Fishburn T, Krishnan S, Lai D, Hui S, Johnston CC, Foroud T, Econs MJ (2005) Sex-specific and non-sex-specific quantitative trait loci contribute to normal variation in bone mineral density in men. J Clin Endocrinol Metab 90:3060–3066

    Article  PubMed  CAS  Google Scholar 

  49. Tse KY, Macias BR, Meyer RS, Hargens AR (2009) Heritability of bone density: regional and gender differences in monozygotic twins. J Orthop Res 27:150–154

    Article  PubMed  Google Scholar 

  50. Lei SF, Chen Y, Xiong DH, Li LM, Deng HW (2006) Ethnic difference in osteoporosis-related phenotypes and its potential underlying genetic determination. J Musculoskelet Neuronal Interact 6:36–46

    PubMed  CAS  Google Scholar 

  51. Leder BZ, Araujo AB, Travison TG, McKinlay JB (2007) Racial and ethnic differences in bone turnover markers in men. J Clin Endocrinol Metab 92:3453–3457

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

All the authors declare that they have no conflict of interest as concerns this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pawel Szulc.

About this article

Cite this article

Nagy, H., Feyt, C., Chapurlat, R. et al. Familial resemblance of bone turnover rate in men aged 40 and over—the MINOS study. J Bone Miner Metab 31, 222–230 (2013). https://doi.org/10.1007/s00774-012-0408-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-012-0408-7

Keywords

Navigation