Among 365 Hertfordshire Cohort Study participants (aged 59–71 years at baseline), higher adiponectin and adiponectin to leptin ratios were associated with lower baseline lumbar spine and femoral neck bone mineral density (BMD). Lower IL-10 was associated with accelerated decline in lumbar spine BMD. This suggests that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis.
The aim of this study was to examine the association between indices of inflammation and BMD in a population-based cohort of older adults in the UK.
Analyses were based on a sample of 194 men and 171 women of the Hertfordshire Cohort Study (community-living, older adults). Dual energy X-ray absorptiometry (DXA) was performed at the lumbar spine and proximal femur at baseline and repeated at a median of 4.5 years (inter-quartile range 3.6 to 5.2). Inflammatory markers (CRP, TNF, IL-1β, IL-6, IL-8, IL-10, adiponectin and leptin) were ascertained at baseline using enzyme-linked immunosorbent assay (ELISA) techniques and Bio-Plex Pro Assays. Gender-adjusted linear regression was used to examine the associations between markers of inflammation and outcomes with and without adjustment for anthropometric and lifestyle factors.
The mean (SD) ages at baseline were 64.4 (2.5) and 66.5 (2.7) years for men and women respectively. Higher levels of adiponectin and adiponectin to leptin ratios were each associated with lower baseline lumbar spine and femoral neck BMD in gender-adjusted (p < 0.01) and fully adjusted (p < 0.05) analyses. Lower levels of IL-10 and TNF were each associated with accelerated decline in lumbar spine BMD in both gender-adjusted (p ≤ 0.05) and fully adjusted (p < 0.05) analyses.
In a cohort of older adults, high levels of adiponectin and adiponectin to leptin ratios were both associated with lower BMD at the lumbar spine and femoral neck at baseline, and lower IL-10 was associated with accelerated decline in BMD at the lumbar spine. This adds weight to the theory that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Harvey N, Dennison E, Cooper C (2010) Osteoporosis: impact on health and economics. Nat Rev Rheumatol 6(2):99–105. https://doi.org/10.1038/nrrheum.2009.260
Dawson A, Dennison E (2016) Measuring the musculoskeletal aging phenotype. Maturitas 93:13–17. https://doi.org/10.1016/j.maturitas.2016.04.014
Kanis JA, Hans D, Cooper C, Baim S, Bilezikian JP, Binkley N, Cauley JA, Compston JE, Dawson-Hughes B, El-Hajj Fuleihan G, Johansson H, Leslie WD, Lewiecki EM, Luckey M, Oden A, Papapoulos SE, Poiana C, Rizzoli R, Wahl DA, McCloskey EV (2011) Interpretation and use of FRAX in clinical practice. Osteoporos Int 22(9):2395–2411. https://doi.org/10.1007/s00198-011-1713-z
Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423(6937):337–342. https://doi.org/10.1038/nature01658
Nakamura K, Saito T, Kobayashi R, Oshiki R, Oyama M, Nishiwaki T, Nashimoto M, Tsuchiya Y (2011) C-reactive protein predicts incident fracture in community-dwelling elderly Japanese women: the Muramatsu study. Osteoporos Int 22(7):2145–2150. https://doi.org/10.1007/s00198-010-1425-9
Cauley JA, Barbour KE, Harrison SL, Cloonan YK, Danielson ME, Ensrud KE, Fink HA, Orwoll ES, Boudreau R (2016) Inflammatory markers and the risk of hip and vertebral fractures in men: the osteoporotic fractures in men (MrOS). J Bone Miner Res 31(12):2129–2138. https://doi.org/10.1002/jbmr.2905
Schett G, Kiechl S, Weger S, Pederiva A, Mayr A, Petrangeli M, Oberhollenzer F, Lorenzini R, Redlich K, Axmann R, Zwerina J, Willeit J (2006) High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study. Arch Intern Med 166(22):2495–2501. https://doi.org/10.1001/archinte.166.22.2495
Pasco JA, Kotowicz MA, Henry MJ, Nicholson GC, Spilsbury HJ, Box JD, Schneider HG (2006) High-sensitivity C-reactive protein and fracture risk in elderly women. JAMA 296(11):1353–1355. https://doi.org/10.1001/jama.296.11.1353
Cauley JA, Danielson ME, Boudreau RM, Forrest KY, Zmuda JM, Pahor M, Tylavsky FA, Cummings SR, Harris TB, Newman AB (2007) Inflammatory markers and incident fracture risk in older men and women: the Health Aging and Body Composition Study. J Bone Miner Res 22(7):1088–1095. https://doi.org/10.1359/jbmr.070409
Ishii S, Cauley JA, Greendale GA, Crandall CJ, Danielson ME, Ouchi Y, Karlamangla AS (2013) C-reactive protein, bone strength, and nine-year fracture risk: data from the Study of Women’s Health Across the Nation (SWAN). J Bone Miner Res 28(7):1688–1698. https://doi.org/10.1002/jbmr.1915
Dahl K, Ahmed LA, Joakimsen RM, Jorgensen L, Eggen AE, Eriksen EF, Bjornerem A (2015) High-sensitivity C-reactive protein is an independent risk factor for non-vertebral fractures in women and men: the Tromso Study. Bone 72:65–70. https://doi.org/10.1016/j.bone.2014.11.012
Barbour KE, Boudreau R, Danielson ME, Youk AO, Wactawski-Wende J, Greep NC, LaCroix AZ, Jackson RD, Wallace RB, Bauer DC, Allison MA, Cauley JA (2012) Inflammatory markers and the risk of hip fracture: the Women’s Health Initiative. J Bone Miner Res 27(5):1167–1176. https://doi.org/10.1002/jbmr.1559
Barbour KE, Lui LY, Ensrud KE, Hillier TA, LeBlanc ES, Ing SW, Hochberg MC, Cauley JA (2014) Inflammatory markers and risk of hip fracture in older white women: the study of osteoporotic fractures. J Bone Miner Res 29(9):2057–2064. https://doi.org/10.1002/jbmr.2245
Ganesan K, Teklehaimanot S, Tran TH, Asuncion M, Norris K (2005) Relationship of C-reactive protein and bone mineral density in community-dwelling elderly females. J Natl Med Assoc 97(3):329–333
Koh JM, Khang YH, Jung CH, Bae S, Kim DJ, Chung YE, Kim GS (2005) Higher circulating hsCRP levels are associated with lower bone mineral density in healthy pre- and postmenopausal women: evidence for a link between systemic inflammation and osteoporosis. Osteoporos Int 16(10):1263–1271. https://doi.org/10.1007/s00198-005-1840-5
Ding C, Parameswaran V, Udayan R, Burgess J, Jones G (2008) Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: a longitudinal study. J Clin Endocrinol Metab 93(5):1952–1958. https://doi.org/10.1210/jc.2007-2325
Lin CC, Li TC, Liu CS, Yang CW, Lin CH, Hsiao JH, Meng NH, Lin WY, Liao LN, Li CI, Wu FY (2016) Associations of TNF-alpha and IL-6 polymorphisms with osteoporosis through joint effects and interactions with LEPR gene in Taiwan: Taichung Community Health Study for Elders (TCHS-E). Mol Biol Rep 43(10):1179–1191. https://doi.org/10.1007/s11033-016-4037-4
Scheidt-Nave C, Bismar H, Leidig-Bruckner G, Woitge H, Seibel MJ, Ziegler R, Pfeilschifter J (2001) Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade past menopause. J Clin Endocrinol Metab 86(5):2032–2042. https://doi.org/10.1210/jcem.86.5.7445
Lim HS, Park YH, Kim SK (2016) Relationship between serum inflammatory marker and bone mineral density in healthy adults. J Bone Metab 23(1):27–33. https://doi.org/10.11005/jbm.2016.23.1.27
Barbour KE, Zmuda JM, Boudreau R, Strotmeyer ES, Horwitz MJ, Evans RW, Kanaya AM, Harris TB, Bauer DC, Cauley JA (2011) Adipokines and the risk of fracture in older adults. J Bone Miner Res 26(7):1568–1576. https://doi.org/10.1002/jbmr.361
Haam JH, Kim YS, Kim MJ, Koo HS, Kim HY, Kim HJ, Park KH, Joo NS, Park KC (2016) A cross-sectional study of the association between adipokine levels and bone mineral density according to obesity and menopausal status in Korean women. J Bone Miner Metab 35:642–648. https://doi.org/10.1007/s00774-016-0801-8
Barbour KE, Zmuda JM, Boudreau R, Strotmeyer ES, Horwitz MJ, Evans RW, Kanaya AM, Harris TB, Cauley JA (2012) The effects of adiponectin and leptin on changes in bone mineral density. Osteoporos Int 23(6):1699–1710. https://doi.org/10.1007/s00198-011-1768-x
Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6(10):772–783. https://doi.org/10.1038/nri1937
Procaccini C, De Rosa V, Galgani M, Carbone F, La Rocca C, Formisano L, Matarese G (2013) Role of adipokines signaling in the modulation of T cells function. Front Immunol 4:332. https://doi.org/10.3389/fimmu.2013.00332
Labouesse MA, Gertz ER, Piccolo BD, Souza EC, Schuster GU, Witbracht MG, Woodhouse LR, Adams SH, Keim NL, Van Loan MD (2014) Associations among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss. Bone 64:138–146. https://doi.org/10.1016/j.bone.2014.03.047
Syddall H, Sayer AA, Dennison E, Martin H, Barker D, Cooper C (2005) Cohort profile: the Hertfordshire cohort study. Int J Epidemiol 34(6):1234–1242
Dallosso HM, Morgan K, Bassey EJ, Ebrahim SB, Fentem PH, Arie TH (1988) Levels of customary physical activity among the old and the very old living at home. J Epidemiol Community Health 42(2):121–127
Robinson S, Syddall H, Jameson K, Batelaan S, Martin H, Dennison EM, Cooper C, Sayer AA, Group HS (2009) Current patterns of diet in community-dwelling older men and women: results from the Hertfordshire Cohort Study. Age Ageing 38:594–599
Gale CR, Dennison EM, Edwards M, Sayer AA, Cooper C (2012) Symptoms of anxiety or depression and risk of fracture in older people: the Hertfordshire Cohort Study. Arch Osteoporos 7:59–65. https://doi.org/10.1007/s11657-012-0080-5
Emberson JR, Whincup PH, Morris RW, Walker M, Lowe GD, Rumley A (2004) Extent of regression dilution for established and novel coronary risk factors: results from the British Regional Heart Study. Eur J Cardiovasc Prev Rehabil 11(2):125–134
Johansson H, Oden A, Lerner UH, Jutberger H, Lorentzon M, Barrett-Connor E, Karlsson MK, Ljunggren O, Smith U, McCloskey E, Kanis JA, Ohlsson C, Mellstrom D (2012) High serum adiponectin predicts incident fractures in elderly men: osteoporotic fractures in men (MrOS) Sweden. J Bone Miner Res 27(6):1390–1396. https://doi.org/10.1002/jbmr.1591
Franceschi C, Garagnani P, Vitale G, Capri M, Salvioli S (2016) Inflammaging and ‘Garb-aging’. Trends Endocrinol Metab 28:199–212. https://doi.org/10.1016/j.tem.2016.09.005
Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254
Gerli R, Monti D, Bistoni O, Mazzone AM, Peri G, Cossarizza A, Di Gioacchino M, Cesarotti ME, Doni A, Mantovani A, Franceschi C, Paganelli R (2000) Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians. Mech Ageing Dev 121(1–3):37–46
Demontiero O, Gunawardene P, Duque G (2014) Postoperative prevention of falls in older adults with fragility fractures. Clin Geriatr Med 30(2):333–347. https://doi.org/10.1016/j.cger.2014.01.018
Cole ZA, Harvey NC, Kim M, Ntani G, Robinson SM, Inskip HM, Godfrey KM, Cooper C, Dennison EM (2012) Increased fat mass is associated with increased bone size but reduced volumetric density in pre pubertal children. Bone 50(2):562–567. https://doi.org/10.1016/j.bone.2011.05.005
Pacifici R, Rifas L, Teitelbaum S, Slatopolsky E, McCracken R, Bergfeld M, Lee W, Avioli LV, Peck WA (1987) Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis. Proc Natl Acad Sci U S A 84(13):4616–4620
Nakashima T, Kobayashi Y, Yamasaki S, Kawakami A, Eguchi K, Sasaki H, Sakai H (2000) Protein expression and functional difference of membrane-bound and soluble receptor activator of NF-kappaB ligand: modulation of the expression by osteotropic factors and cytokines. Biochem Biophys Res Commun 275(3):768–775. https://doi.org/10.1006/bbrc.2000.3379
Hengartner NE, Fiedler J, Ignatius A, Brenner RE (2013) IL-1beta inhibits human osteoblast migration. Mol Med 19:36–42. https://doi.org/10.2119/molmed.2012.00058
Dresner-Pollak R, Gelb N, Rachmilewitz D, Karmeli F, Weinreb M (2004) Interleukin 10-deficient mice develop osteopenia, decreased bone formation, and mechanical fragility of long bones. Gastroenterology 127(3):792–801
Zhang Q, Chen B (2014) Interleukin-10 inhibits bone resorption: a potential therapeutic strategy in periodontitis and other bone loss diseases. 2014:284836. https://doi.org/10.1155/2014/284836
Park BL, Han IK, Lee HS, Kim LH, Kim SJ, Shin JS, Kim SY, Shin HD (2004) Association of interleukin 10 haplotype with low bone mineral density in Korean postmenopausal women. J Biochem Mol Biol 37(6):691–699
Stannus O, Jones G, Cicuttini F, Parameswaran V, Quinn S, Burgess J, Ding C (2010) Circulating levels of IL-6 and TNF-alpha are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults. Osteoarthr Cartil 18(11):1441–1447. https://doi.org/10.1016/j.joca.2010.08.016
This research was funded by the Medical Research Council and the University of Southampton, UK.
Conflicts of interest
About this article
Cite this article
Fuggle, N.R., Westbury, L.D., Syddall, H.E. et al. Relationships between markers of inflammation and bone density: findings from the Hertfordshire Cohort Study. Osteoporos Int 29, 1581–1589 (2018). https://doi.org/10.1007/s00198-018-4503-z
- Bone mineral density