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01-05-2016 | Original Article

Are bone turnover markers associated with volumetric bone density, size, and strength in older men and women? The AGES–Reykjavik study

Authors: E. A. Marques, V. Gudnason, G. Sigurdsson, T. Lang, F. Johannesdottir, K. Siggeirsdottir, L. Launer, G. Eiriksdottir, T. B. Harris

Published in: Osteoporosis International | Issue 5/2016

Abstract

Summary

Association between serum bone formation and resorption markers and bone mineral, structural, and strength variables derived from quantitative computed tomography (QCT) in a population-based cohort of 1745 older adults was assessed. The association was weak for lumbar spine and femoral neck areal and volumetric bone mineral density.

Introduction

The aim of this study was to examine the relationship between levels of bone turnover markers (BTMs; osteocalcin (OC), C-terminal cross-linking telopeptide of type I collagen (CTX), and procollagen type 1N propeptide (P1NP)) and quantitative computed tomography (QCT)-derived bone density, geometry, and strength indices in the lumbar spine and femoral neck (FN).

Methods

A total of 1745 older individuals (773 men and 972 women, aged 66–92 years) from the Age, Gene/Environment Susceptibility (AGES)–Reykjavik cohort were studied. QCT was performed in the lumbar spine and hip to estimate volumetric trabecular, cortical, and integral bone mineral density (BMD), areal BMD, bone geometry, and bone strength indices. Association between BTMs and QCT variables were explored using multivariable linear regression.

Results

Major findings showed that all BMD measures, FN cortical index, and compressive strength had a low negative correlation with the BTM levels in both men and women. Correlations between BTMs and bone size parameters were minimal or not significant. No associations were found between BTMs and vertebral cross-sectional area in women. BTMs alone accounted for only a relatively small percentage of the bone parameter variance (1–10 %).

Conclusion

Serum CTX, OC, and P1NP were weakly correlated with lumbar spine and FN areal and volumetric BMD and strength measures. Most of the bone size indices were not associated with BTMs; thus, the selected bone remodeling markers do not reflect periosteal bone formation. These results confirmed the limited ability of the most sensitive established BTMs to predict bone structural integrity in older adults.

Seeman E (2009) Bone modeling and remodeling. Crit Rev Eukaryot Gene Expr 19(3):219–233CrossRefPubMed

Bauer NB, Khassawna TE, Goldmann F, Stirn M, Ledieu D, Schlewitz G, Govindarajan P, Zahner D, Weisweiler D, Schliefke N, Bocker W, Schnettler R, Heiss C, Moritz A (2015) Characterization of bone turnover and energy metabolism in a rat model of primary and secondary osteoporosis. Exp Toxicol Pathol Off J Ges Toxikologische Pathol 67(4):287–296. doi:10.1016/j.etp.2015.01.004 CrossRef

Garnero P, Sornay-Rendu E, Chapuy MC, Delmas PD (1996) Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res Off J Am Soc Bone Miner Res 11(3):337–349. doi:10.1002/jbmr.5650110307 CrossRef

Khosla S, Melton LJ 3rd, Atkinson EJ, O’Fallon WM, Klee GG, Riggs BL (1998) Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab 83(7):2266–2274PubMed

Marcus R, Holloway L, Wells B, Greendale G, James MK, Wasilauskas C, Kelaghan J (1999) The relationship of biochemical markers of bone turnover to bone density changes in postmenopausal women: results from the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial. J Bone Miner Res Off J Am Soc Bone Miner Res 14(9):1583–1595. doi:10.1359/jbmr.1999.14.9.1583 CrossRef

Seeman E (2008) Bone quality: the material and structural basis of bone strength. J Bone Miner Metab 26(1):1–8. doi:10.1007/s00774-007-0793-5 CrossRefPubMed

Gerdhem P, Ivaska KK, Alatalo SL, Halleen JM, Hellman J, Isaksson A, Pettersson K, Vaananen HK, Akesson K, Obrant KJ (2004) Biochemical markers of bone metabolism and prediction of fracture in elderly women. J Bone Miner Res Off J Am Soc Bone Miner Res 19(3):386–393. doi:10.1359/JBMR.0301244 CrossRef

Ivaska KK, Gerdhem P, Vaananen HK, Akesson K, Obrant KJ (2010) Bone turnover markers and prediction of fracture: a prospective follow-up study of 1040 elderly women for a mean of 9 years. J Bone Miner Res Off J Am Soc Bone Miner Res 25(2):393–403. doi:10.1359/jbmr.091006 CrossRef

Khosla S, Melton LJ 3rd, Achenbach SJ, Oberg AL, Riggs BL (2006) Hormonal and biochemical determinants of trabecular microstructure at the ultradistal radius in women and men. J Clin Endocrinol Metab 91(3):885–891. doi:10.1210/jc.2005-2065 CrossRefPubMed

10.

Boonen S, Pye SR, O’Neill TW, Szulc P, Gielen E, Borghs H, Verschueren S, Claessens F, Adams JE, Ward KA, Bartfai G, Casanueva F, Finn JD, Forti G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Silman AJ, Tajar A, Wu FC, Vanderschueren D, Group E (2011) Influence of bone remodelling rate on quantitative ultrasound parameters at the calcaneus and DXA BMDa of the hip and spine in middle-aged and elderly European men: the European Male Ageing Study (EMAS). Eur J Endocrinol Eur Fed Endocr Soc 165(6):977–986. doi:10.1530/EJE-11-0353 CrossRef

11.

Levinger I, Scott D, Nicholson GC, Stuart AL, Duque G, McCorquodale T, Herrmann M, Ebeling PR, Sanders KM (2014) Undercarboxylated osteocalcin, muscle strength and indices of bone health in older women. Bone 64:8–12. doi:10.1016/j.bone.2014.03.008 CrossRefPubMed

12.

Genant HK, Engelke K, Prevrhal S (2008) Advanced CT bone imaging in osteoporosis. Rheumatology 47(Suppl 4):iv9–iv16. doi:10.1093/rheumatology/ken180 PubMedPubMedCentral

13.

Nishiyama KK, Shane E (2013) Clinical imaging of bone microarchitecture with HR-pQCT. Curr Osteoporos Rep 11(2):147–155. doi:10.1007/s11914-013-0142-7 CrossRefPubMedPubMedCentral

14.

Carpenter RD, Sigurdsson S, Zhao S, Lu Y, Eiriksdottir G, Sigurdsson G, Jonsson BY, Prevrhal S, Harris TB, Siggeirsdottir K, Guethnason V, Lang TF (2011) Effects of age and sex on the strength and cortical thickness of the femoral neck. Bone 48(4):741–747. doi:10.1016/j.bone.2010.12.004 CrossRefPubMedPubMedCentral

15.

Balena R, Shih MS, Parfitt AM (1992) Bone resorption and formation on the periosteal envelope of the ilium: a histomorphometric study in healthy women. J Bone Miner Res Off J Am Soc Bone Miner Res 7(12):1475–1482. doi:10.1002/jbmr.5650071216 CrossRef

16.

Szulc P, Garnero P, Marchand F, Duboeuf F, Delmas PD (2005) Biochemical markers of bone formation reflect endosteal bone loss in elderly men--MINOS study. Bone 36(1):13–21. doi:10.1016/j.bone.2004.09.004 CrossRefPubMed

17.

Harris TB, Launer LJ, Eiriksdottir G, Kjartansson O, Jonsson PV, Sigurdsson G, Thorgeirsson G, Aspelund T, Garcia ME, Cotch MF, Hoffman HJ, Gudnason V (2007) Age, gene/environment susceptibility-Reykjavik study: multidisciplinary applied phenomics. Am J Epidemiol 165(9):1076–1087. doi:10.1093/aje/kwk115 CrossRefPubMedPubMedCentral

18.

Sigurdsson G, Aspelund T, Chang M, Jonsdottir B, Sigurdsson S, Eiriksdottir G, Gudmundsson A, Harris TB, Gudnason V, Lang TF (2006) Increasing sex difference in bone strength in old age: the age, gene/environment susceptibility-Reykjavik study (AGES-REYKJAVIK). Bone 39(3):644–651. doi:10.1016/j.bone.2006.03.020 CrossRefPubMed

19.

Lang TF, Sigurdsson S, Karlsdottir G, Oskarsdottir D, Sigmarsdottir A, Chengshi J, Kornak J, Harris TB, Sigurdsson G, Jonsson BY, Siggeirsdottir K, Eiriksdottir G, Gudnason V, Keyak JH (2012) Age-related loss of proximal femoral strength in elderly men and women: the age gene/environment susceptibility study—Reykjavik. Bone 50(3):743–748. doi:10.1016/j.bone.2011.12.001 CrossRefPubMedPubMedCentral

20.

Eysteinsdottir T, Thorsdottir I, Gunnarsdottir I, Steingrimsdottir L (2012) Assessing validity of a short food frequency questionnaire on present dietary intake of elderly Icelanders. Nutr J 11:12. doi:10.1186/1475-2891-11-12 CrossRefPubMedPubMedCentral

21.

von Bonsdorff MB, Groffen DA, Vidal JS, Rantanen T, Jonsson PV, Garcia M, Aspelund T, Eiriksdottir G, Siggeirsdottir K, Launer L, Gudnason V, Harris TB, Age GES-RSI (2013) Coronary artery calcium and physical performance as determinants of mortality in older age: the AGES-Reykjavik study. Int J Cardiol 168(3):2094–2099. doi:10.1016/j.ijcard.2013.01.067 CrossRef

22.

Vidal JS, Sigurdsson S, Jonsdottir MK, Eiriksdottir G, Thorgeirsson G, Kjartansson O, Garcia ME, van Buchem MA, Harris TB, Gudnason V, Launer LJ (2010) Coronary artery calcium, brain function and structure: the AGES-Reykjavik study. Stroke J Cereb Circ 41(5):891–897. doi:10.1161/STROKEAHA.110.579581 CrossRef

23.

Szulc P, Garnero P, Munoz F, Marchand F, Delmas PD (2001) Cross-sectional evaluation of bone metabolism in men. J Bone Miner Res Off J Am Soc Bone Miner Res 16(9):1642–1650. doi:10.1359/jbmr.2001.16.9.1642 CrossRef

24.

Riggs BL, Melton Iii LJ, Melton Iii LJ 3rd, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S (2004) Population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites. J Bone Miner Res Off J Am Soc Bone Miner Res 19(12):1945–1954. doi:10.1359/JBMR.040916 CrossRef

25.

Ninomiya JT, Tracy RP, Calore JD, Gendreau MA, Kelm RJ, Mann KG (1990) Heterogeneity of human bone. J Bone Miner Res Off J Am Soc Bone Miner Res 5(9):933–938. doi:10.1002/jbmr.5650050906 CrossRef

26.

Gruber R, Mayer C, Bobacz K, Krauth MT, Graninger W, Luyten FP, Erlacher L (2001) Effects of cartilage-derived morphogenetic proteins and osteogenic protein-1 on osteochondrogenic differentiation of periosteum-derived cells. Endocrinology 142(5):2087–2094. doi:10.1210/endo.142.5.8163 PubMed

27.

Garnero P (2014) New developments in biological markers of bone metabolism in osteoporosis. Bone 66:46–55. doi:10.1016/j.bone.2014.05.016 CrossRefPubMed

28.

Rousseau JC, Sornay-Rendu E, Bertholon C, Chapurlat R, Garnero P (2014) Serum periostin is associated with fracture risk in postmenopausal women: a 7-year prospective analysis of the OFELY study. J Clin Endocrinol Metab 99(7):2533–2539. doi:10.1210/jc.2013-3893 CrossRefPubMed

29.

Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteopor Int J Established Result Coop Eur Found Osteopor Natl Osteopor Found USA 21(2):195–214. doi:10.1007/s00198-009-1066-z CrossRef

30.

Currey JD (1999) What determines the bending strength of compact bone? J Exp Biol 202(Pt 18):2495–2503PubMed

31.

Seeman E, Delmas PD (2006) Bone quality--the material and structural basis of bone strength and fragility. N Engl J Med 354(21):2250–2261. doi:10.1056/NEJMra053077 CrossRefPubMed

32.

Roschger P, Misof B, Paschalis E, Fratzl P, Klaushofer K (2014) Changes in the degree of mineralization with osteoporosis and its treatment. Curr Osteoporos Rep 12(3):338–350. doi:10.1007/s11914-014-0218-z CrossRefPubMed

33.

Chaitou A, Boutroy S, Vilayphiou N, Munoz F, Delmas PD, Chapurlat R, Szulc P (2010) Association between bone turnover rate and bone microarchitecture in men: the STRAMBO study. J Bone Miner Res Off J Am Soc Bone Miner Res 25(11):2313–2323. doi:10.1002/jbmr.124 CrossRef

34.

Bauer DC, Garnero P, Bilezikian JP, Greenspan SL, Ensrud KE, Rosen CJ, Palermo L, Black DM (2006) Short-term changes in bone turnover markers and bone mineral density response to parathyroid hormone in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 91(4):1370–1375. doi:10.1210/jc.2005-1712 CrossRefPubMed

35.

Reid IR (2002) Relationships among body mass, its components, and bone. Bone 31(5):547–555CrossRefPubMed

36.

Kung AW, Huang QY (2007) Genetic and environmental determinants of osteoporosis. J Musculoskelet Neuronal Interact 7(1):26–32PubMed

37.

Skerry TM (2008) The response of bone to mechanical loading and disuse: fundamental principles and influences on osteoblast/osteocyte homeostasis. Arch Biochem Biophys 473(2):117–123. doi:10.1016/j.abb.2008.02.028 CrossRefPubMed

38.

Garnero P, Borel O, Gineyts E, Duboeuf F, Solberg H, Bouxsein ML, Christiansen C, Delmas PD (2006) Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone. Bone 38(3):300–309. doi:10.1016/j.bone.2005.09.014 CrossRefPubMed

39.

Paschalis EP, Tatakis DN, Robins S, Fratzl P, Manjubala I, Zoehrer R, Gamsjaeger S, Buchinger B, Roschger A, Phipps R, Boskey AL, Dall’Ara E, Varga P, Zysset P, Klaushofer K, Roschger P (2011) Lathyrism-induced alterations in collagen cross-links influence the mechanical properties of bone material without affecting the mineral. Bone 49(6):1232–1241. doi:10.1016/j.bone.2011.08.027 CrossRefPubMedPubMedCentral

40.

Qiu S, Rao DS, Palnitkar S, Parfitt AM (2002) Age and distance from the surface but not menopause reduce osteocyte density in human cancellous bone. Bone 31(2):313–318CrossRefPubMed

41.

Norman TL, Wang Z (1997) Microdamage of human cortical bone: incidence and morphology in long bones. Bone 20(4):375–379CrossRefPubMed

42.

Ferreira A, Ghazali A, Galvao J, Souberbielle JC, Jehle PM, Mohan S, Descamps-Latscha B, Oprisiu R, Fournier A, Drueke TB (2001) Effect of type of dialysis membrane on bone in haemodialysis patients. Nephrol Dial Trans Off Publ Eur Dial Transpl Assoc Eur Ren Assoc 16(6):1230–1238

43.

Malluche HH, Porter DS, Pienkowski D (2013) Evaluating bone quality in patients with chronic kidney disease. Nat Rev Nephrol 9(11):671–680. doi:10.1038/nrneph.2013.198 CrossRefPubMedPubMedCentral

44.

Dhonukshe-Rutten RA, Pluijm SM, de Groot LC, Lips P, Smit JH, van Staveren WA (2005) Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J Bone Miner Res Off J Am Soc Bone Miner Res 20(6):921–929. doi:10.1359/JBMR.050202 CrossRef

45.

Gerdhem P, Ivaska KK, Isaksson A, Pettersson K, Vaananen HK, Obrant KJ, Akesson K (2007) Associations between homocysteine, bone turnover, BMD, mortality, and fracture risk in elderly women. J Bone Miner Res Off J Am Soc Bone Miner Res 22(1):127–134. doi:10.1359/jbmr.061003 CrossRef

Title: Are bone turnover markers associated with volumetric bone density, size, and strength in older men and women? The AGES–Reykjavik study
Authors: E. A. Marques
V. Gudnason
G. Sigurdsson
T. Lang
F. Johannesdottir
K. Siggeirsdottir
L. Launer
G. Eiriksdottir
T. B. Harris
Publication date: 01-05-2016
Publisher: Springer London
Published in: Osteoporosis International / Issue 5/2016
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-015-3442-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Are bone turnover markers associated with volumetric bone density, size, and strength in older men and women? The AGES–Reykjavik study

Abstract

Summary

Introduction

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

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