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.
Similar content being viewed by others
References
Seeman E (2009) Bone modeling and remodeling. Crit Rev Eukaryot Gene Expr 19(3):219–233
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
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
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):2266–2274
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
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
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
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
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
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
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
Genant HK, Engelke K, Prevrhal S (2008) Advanced CT bone imaging in osteoporosis. Rheumatology 47(Suppl 4):iv9–iv16. doi:10.1093/rheumatology/ken180
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Currey JD (1999) What determines the bending strength of compact bone? J Exp Biol 202(Pt 18):2495–2503
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
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
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
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
Reid IR (2002) Relationships among body mass, its components, and bone. Bone 31(5):547–555
Kung AW, Huang QY (2007) Genetic and environmental determinants of osteoporosis. J Musculoskelet Neuronal Interact 7(1):26–32
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
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
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
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):313–318
Norman TL, Wang Z (1997) Microdamage of human cortical bone: incidence and morphology in long bones. Bone 20(4):375–379
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
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
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
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
Acknowledgments
This study was funded by National Institutes of Health contract N01-AG-012100, the National Institute on Aging Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). EAM and TBH were supported in part by and the Intramural Research Program of the National Institutes of Health, National Institute on Aging.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
None.
Rights and permissions
About this article
Cite this article
Marques, E.A., Gudnason, V., Sigurdsson, G. et al. Are bone turnover markers associated with volumetric bone density, size, and strength in older men and women? The AGES–Reykjavik study. Osteoporos Int 27, 1765–1776 (2016). https://doi.org/10.1007/s00198-015-3442-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-015-3442-1