Download PDF
Geburtshilfe Frauenheilkd 2016; 76(08): 895-901
DOI: 10.1055/s-0042-103751
Original Article
GebFra Science
Georg Thieme Verlag KG Stuttgart · New York

Premenopausal Trabecular Bone Loss is Associated with a Family History of Fragility Fracture

Prämenopausaler trabekulärer Knochendichteverlust ist mit einer Familienanamnese für niedrig-traumatische Frakturen assoziiert
J. C. Prior
1   Centre for Menstrual Cycle and Ovulation Research, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada
2   Dept. of Medicine, University of British Columbia, Vancouver, BC, Canada
3   Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
,
C. L. Hitchcock
1   Centre for Menstrual Cycle and Ovulation Research, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada
,
Y. M. Vigna
1   Centre for Menstrual Cycle and Ovulation Research, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada
,
V. Seifert-Klauss
4   Frauenklinik und Poliklinik, Gynecologic Endocrinology and Interdisciplinary Osteoporosis Center (IOZ), Klinikum rechts der Isar, TUM Munich, Germany
› Author Affiliations
Further Information

Publication History

received 09 December 2015
revised 19 February 2016

accepted 23 February 2016

Publication Date:
25 August 2016 (online)

Also available at
   Permissions and Reprints

Abstract

Introduction: Although a fragility fracture family history (FFFH+) has repeatedly been shown to be associated with lower bone mineral density (BMD), its relationship to human BMD change is unclear. Animal research, however, documented that different purebred strains within rodent species have wide ranges in rates of bone acquisition during growth as well as in change post-ovariectomy. Our objective was to compare the rate of premenopausal spinal trabecular BMD change between women with and without a general family history of fragility fracture. Participants and Methods: Healthy premenopausal community women participated in prospective observational studies at two academic medical research centres: Vancouver, Canada (n = 66) and Munich, Germany (n = 20). The primary outcome was annual spinal BMD change, measured by quantitative computed tomography (QCT). The two studies employed similar methodologies for assessing QCT and FFFH. Results: Volunteer community participants had a mean age of 36.0 (SD, 6.9) years, body mass index 22.5 (2.4) and baseline QCT of 150.2 (22.5) mg/cm3 trabecular bone. The rates of BMD change were similar in both cities: − 3.5 (5.1)/year Vancouver, − 2.0 (3.4)/year Munich (95 % CI of difference: − 3.9, 0.9). Over a third of the women (31 of the 86, 36 %) reported FFFH+. Those with and without a FFFH were similar in demographics, nutrition, exercise, menstrual cycle and luteal phase lengths and physiological measures (serum calcium, osteocalcin and estradiol). However, women with FFFH+ lost trabecular BMD more rapidly: FFFH+, − 4.9 (5.0), FFFH−, − 2.2 (4.4) mg/cm3/year (95 % CI diff − 0.7 to − 4.8, F1.83 = 7.88, p = 0.006). FFFH+ explained 7.7 % of the variance in QCT volumetric trabecular spinal bone change/year in these healthy premenopausal women. Conclusion: This study shows for the first time that having a history of a fragility fracture in a family member is associated with a greater rate of premenopausal spinal trabecular bone loss.

Key words

osteoporosis - QCT - bone turnover - menstrual cycle - estrogen - genetics
 

  • References

  • 1 Kanis JA, Johansson H, Oden A et al. A family history of fracture and fracture risk: a meta-analysis. Bone 2004; 35: 1029-1037
    CrossrefPubMedSearch in Google Scholar
  • 2 Peacock M, Turner CH, Econs MJ et al. Genetics of osteoporosis. Endocr Rev 2002; 23: 303-326
    CrossrefPubMedSearch in Google Scholar
  • 3 Eisman JA. Genetics of osteoporosis. Endocr Rev 1999; 20: 788-804
    CrossrefPubMedSearch in Google Scholar
  • 4 Kanis JA, Johnell O, Oden A et al. Risk of hip fracture according to the World Health Organization criteria for osteopenia and osteoporosis. Bone 2000; 27: 585-590
    CrossrefPubMedSearch in Google Scholar
  • 5 Lentle B, Cheung AM, Hanley DA et al. Scientific Advisory Council of Osteoporosis Canada. Osteoporosis Canada 2010 guidelines for the assessment of fracture risk. Can Assoc Radiol J 2011; 62: 243-250
    CrossrefPubMedSearch in Google Scholar
  • 6 Kanis JA, Oden A, Johnell O et al. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 2007; 18: 1033-1046
    CrossrefPubMedSearch in Google Scholar
  • 7 Seeman E, Hopper JL, Bach LA et al. Reduced bone mass in daughters of women with osteoporosis. N Engl J Med 1989; 320: 554-558
    CrossrefPubMedSearch in Google Scholar
  • 8 MacInnis RJ, Cassar C, Nowson CA et al. Determinants of bone density in 30- to 65-year-old women: a co-twin study. J Bone Miner Res 2003; 18: 1650-1656
    CrossrefPubMedSearch in Google Scholar
  • 9 Abrahamsen B, Hjelmborg JV, Kostenuik P et al. Circulating amounts of osteoprotegerin and RANK ligand: genetic influence and relationship with BMD assessed in female twins. Bone 2005; 36: 727-735
    CrossrefPubMedSearch in Google Scholar
  • 10 Karasik D, Myers RH, Cupples LA et al. Genome screen for quantitative trait loci contributing to normal variation in bone mineral density: the Framingham Study. J Bone Miner Res 2002; 17: 1718-1727
    CrossrefPubMedSearch in Google Scholar
  • 11 Richards JB, Rivadeneira F, Inouye M et al. Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 2008; 371: 1505-1512
    CrossrefPubMedSearch in Google Scholar
  • 12 Ichikawa S, Koller DL, Padgett LR et al. Replication of previous genome-wide association studies of bone mineral density in premenopausal American women. J Bone Miner Res 2010; 25: 1821-1829
    CrossrefPubMedSearch in Google Scholar
  • 13 Buie HR, Moore CP, Boyd SK. Postpubertal architectural developmental patterns differ between the L3 vertebra and proximal tibia in three inbred strains of mice. J Bone Miner Res 2008; 23: 2048-2059
    CrossrefPubMedSearch in Google Scholar
  • 14 Bouxsein ML, Myers KS, Shultz KL et al. Ovariectomy-induced bone loss varies among inbred strains of mice. J Bone Miner Res 2005; 20: 1085-1092
    CrossrefPubMedSearch in Google Scholar
  • 15 Garnero P, Arden NK, Griffiths G et al. Genetic influence on bone turnover in postmenopausal twins. J Clin Endocrinol Metab 1996; 81: 140-146
    PubMedSearch in Google Scholar
  • 16 Melton 3rd LJ, Khosla S, Atkinson EJ et al. Relationship of bone turnover to bone density and fractures. J Bone Miner Res 1997; 12: 1083-1091
    CrossrefPubMedSearch in Google Scholar
  • 17 Berger C, Langsetmo L, Joseph L et al. CaMos Research Group. Association between change in BMD and fragility fracture in women and men. J Bone Miner Res 2009; 24: 361-370
    CrossrefPubMedSearch in Google Scholar
  • 18 Christian JC, Yu PL, Slemenda CW et al. Heritability of bone mass: a longitudinal study in aging male twins. Am J Hum Genet 1989; 44: 429-433
    PubMedSearch in Google Scholar
  • 19 Kelly PJ, Nguyen T, Hopper J et al. Changes in axial bone density with age: a twin study. J Bone Mineral Res 1993; 8: 11-17
    PubMedSearch in Google Scholar
  • 20 Bainbridge KE, Sowers M, Lin X et al. Risk factors for low bone mineral density and the 6-year rate of bone loss among premenopausal and perimenopausal women. Osteoporos Int 2004; 15: 439-446
    PubMedSearch in Google Scholar
  • 21 Brot C, Jensen LB, Sørensen OH. Bone mass and risk factors for bone loss in perimenopausal Danish women. J Intern Med 1997; 242: 505-511
    CrossrefPubMedSearch in Google Scholar
  • 22 Prior JC, Vigna YM, Schechter MT et al. Spinal bone loss and ovulatory disturbances. N Engl J Med 1990; 323: 1221-1227
    CrossrefPubMedSearch in Google Scholar
  • 23 Prior JC, Vigna YM, Schulzer M et al. Determination of luteal phase length by quantitative basal temperature methods: validation against the midcycle LH peak. Clin Invest Med 1990; 13: 123-131
    PubMedSearch in Google Scholar
  • 24 Bedford JL, Prior JC, Hitchcock CL et al. Detecting evidence of luteal activity by least-squares quantitative basal temperature analysis against urinary progesterone metabolites and the effect of wake-time variability. Eur J Obstet Gynecol Reprod Biol 2009; 146: 76-80
    CrossrefPubMedSearch in Google Scholar
  • 25 Prior JC, Vigna YM, Barr SI et al. Ovulatory premenopausal women lose cancellous spinal bone: a five year prospective study. Bone 1996; 18: 261-267
    CrossrefPubMedSearch in Google Scholar
  • 26 Seifert-Klauss V, Mueller JE, Luppa P et al. Bone metabolism during the perimenopausal transition: a prospective study. Maturitas 2002; 41: 23-33
    CrossrefPubMedSearch in Google Scholar
  • 27 Seifert-Klauss V, Link T, Heumann C et al. Influence of pattern of menopausal transition on the amount of trabecular bone loss. Results from a 6-year prospective longitudinal study. Maturitas 2006; 55: 317-324
    CrossrefPubMedSearch in Google Scholar
  • 28 Cann CE, Genant HK, Ettinger B et al. Spinal mineral loss in oophorectomized women. Determination by quantitative computed tomography. JAMA 1980; 244: 2056-2059
    CrossrefPubMedSearch in Google Scholar
  • 29 Kalender WA, Felsenberg D, Genant HK et al. The European Spine Phantom—a tool for standardization and quality control in spinal bone mineral measurements by DXA and QCT. Eur J Radiol 1995; 20: 83-92
    CrossrefPubMedSearch in Google Scholar
  • 30 Kalender WA, Felsenberg D, Louis O et al. Reference values for trabecular and cortical vertebral bone density in single and dual-energy quantitative computed tomography. Eur J Radiol 1989; 9: 75-80
    PubMedSearch in Google Scholar
  • 31 Rosenbrock H, Seifert-Klauss V, Kaspar S et al. Changes of biochemical bone markers during the menopausal transition. Clin Chem Lab Med 2002; 40: 143-151
    PubMedSearch in Google Scholar
  • 32 Moayyeri A, Hammond CJ, Hart DJ et al. The UK Adult Twin Registry (TwinsUK Resource). Twin Res Hum Genet 2013; 16: 144-149
    CrossrefPubMedSearch in Google Scholar
  • 33 Waugh EJ, Polivy J, Ridout R et al. A prospective investigation of the relations among cognitive dietary restraint, subclinical ovulatory disturbances, physical activity, and bone mass in healthy young women. Am J Clin Nutr 2007; 86: 1791-1801
    PubMedSearch in Google Scholar
  • 34 Bedford JL, Prior JC, Barr SI. A prospective exploration of cognitive dietary restraint, subclinical ovulatory disturbances, cortisol and change in bone density over two years in healthy young women. J Clin Endocrinol Metab 2010; 95: 3291-3299
    CrossrefPubMedSearch in Google Scholar
  • 35 Li D, Hitchcock CL, Barr SI et al. Negative spinal bone mineral density changes and subclinical ovulatory disturbances—prospective data in healthy premenopausal women with regular menstrual cycles. Epidemiol Rev 2014; 36: 137-147
    CrossrefPubMedSearch in Google Scholar
  • 36 Barr SI, Prior JC. The menstrual Cycle: Effects on Bone in premenopausal Women. In: Draper HH, ed. Advances in Nutritional Research, Nutrition and Osteoporosis. New York: Plenum Press; 1993
    Search in Google Scholar
  • 37 Popat VB, Calis KA, Vanderhoof VH et al. Bone mineral density in estrogen-deficient young women. J Clin Endocrinol Metab 2009; 94: 2277-2283
    CrossrefPubMedSearch in Google Scholar
  • 38 Biver E, Durosier C, Chevalley T et al. Prior ankle fractures in postmenopausal women are associated with low areal bone mineral density and bone microstructure alterations. Osteoporos Int 2015; 26: 2147-2155
    CrossrefPubMedSearch in Google Scholar