The impact of the two adipokines, visfatin and retinol-binding protein 4 (RBP-4) on bone mineral density (BMD) has been analysed in various studies with conflicting results. Visfatin is highly expressed in visceral fat with stimulatory effect on osteoblast proliferation and inhibition on osteoclast formation, while RBP-4 acts as a transporter protein for retinol, associated with changes in insulin sensitivity, independent of obesity, with no consensus on its effect on bone metabolism. We evaluated the relationship between serum concentrations of visfatin, RBP-4, markers of insulin resistance and current BMD in treated postmenopausal osteoporosis (PO).
Demographics, previous treatment, metabolic status, anthropometry, serum Alkaline phosphatise (ALP), visfatin, RBP-4, the HOMA IR (homeostatic model assessment of insulin resistance) index and BMD were evaluated in 61 subjects with PO. Statistical analysis used SPSS v. 25.0, with a level of significance α = 0.05. Regression models were constructed to evaluate the relationship between adipokines and BMD, adjusting for covariates.
In multilinear regression analysis, the strongest predictor for current BMD was a previous BMD, followed by ALP and age. RBP4 and HOMA IR were significant predictors, while visfatin had no significant effect. A significant correlation between body mass index (BMI) and BMD at the femoral neck was observed. ALP was negatively correlated with BMD and visfatin positively with RBP4.
Data indicate a positive relationship between BMD and RBP-4, an inverse relationship between markers of insulin resistance, bone turn-over and current BMD. No significant effect of visfatin on BMD was observed.
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.
Cauley JA (2013) Public Health Impact of Osteoporosis. J Gerontol A Biol Sci Med Sci 68:1243–1251. https://doi.org/10.1093/gerona/glt093
Eastell R, O’Neill TW, Hofbauer LC et al (2016) Postmenopausal osteoporosis. Nat rev Dis Primers 2:16069. https://doi.org/10.1038/nrdp.2016.69
Holmberg AH, Johnell O, Nilsson PM et al (2006) Risk factors for fragility fracture in middle age. A prospective population-based study of 33,000 men and women. Osteoporos Int 17:1065–1077. https://doi.org/10.1007/s00198-006-0164-4
Greco EA, Lenzi A, Migliaccio S (2015) The obesity of the bone. Ther Adv Endocrinol Metab 6:273–286. https://doi.org/10.1177/2042018815611004
Compston JE, Watts NB, Chapurlat R et al (2011) Obesity is not protective against fracture in postmenopausal women: GLOW. Am J Med 124:1043–1050. https://doi.org/10.1016/j.amjmed.2011.06.013
Premaor MO, Pilbrow L, Tonkin C et al (2010) Obesity and fractures in postmenopausal women. J Bone Miner Res 25:292–297. https://doi.org/10.1359/jbmr.091004
Dimitri P, Bishop N, Walsh JS et al (2012) Obesity is a risk factor for fracture in children but is protective against fracture in adults: a paradox. Bone 50:457–466. https://doi.org/10.1016/j.bone.2011.05.011
Compston J (2015) Obesity and fractures in postmenopausal women. Curr Opin Rheumatol 27:414–419. https://doi.org/10.1097/bor.0000000000000182
Tang X, Liu G, Kang J et al (2013) Obesity and risk of hip fracture in adults: a meta-analysis of prospective cohort studies. PLoS One 8:e55077. https://doi.org/10.1371/journal.pone.0055077
Sogaard AJ, Holvik K, Omsland TK et al (2016) Age and sex differences in body mass index as a predictor of hip fracture: a NOREPOS study. Am J Epidemiol 184:510–519. https://doi.org/10.1093/aje/kww011
Shen J, Leslie WD, Nielson CM et al (2015) Associations of body mass index with incident fractures and hip structural parameters in a large Canadian cohort. J Clin Endocrinol Metab 101:476–484. https://doi.org/10.1210/jc.2015-3123
Kim SH, Yi S, Yi J et al (2018) Association between body mass index and the risk of hip fracture by sex and age: a prospective cohort study. J Bone Miner Res 33:1603–1611. https://doi.org/10.1002/jbmr.3464
Kaze AD, Rosen HN, Paik JM (2018) Osteoporos Int 29:31. https://doi.org/10.1007/s00198-017-4294-7
Katzmarzyk PT, Barreira TV, Harrington DM et al (2012) Relationship between abdominal fat and bone mineral density in white and African American adults. Bone 50:576–579. https://doi.org/10.1016/j.bone.2011.04.012
Greco EA, Lenzi A, Migliaccio S (2015) The obesity of bone. Therapeutic Advances in Endocrinology and Metabolism 6:273–286. https://doi.org/10.1177/2042018815611004
Palermo A, Tuccinardi D, Defeudis G et al (2016) BMI and BMD: the potential interplay between obesity and bone fragility. Int J Environ Res Publ Health 13:544. https://doi.org/10.3390/ijerph13060544
Moradi S, Shab-Bidar S, Alizadeh S et al (2017) Association between sleep duration and osteoporosis risk in middle-aged and elderly women: a systematic review and meta-analysis of observational studies. Metabolism 69:199–206. https://doi.org/10.1016/j.metabol.2017.01.027
Biver E, Salliot C, Combescure C et al (2011) Influence of adipokines and ghrelin on bone mineral density and fracture risk: a systematic review and meta-analysis. J Clin Endocrinol Metab 96:2703–2713. https://doi.org/10.1210/jc.2011-0047
Liu Y, Song CY, Wu SS et al (2013) Novel Adipokines and Bone Metabolism. Int J Endocrin 2013:895045. https://doi.org/10.1155/2013/895045
Zhang H, Xie H, Zhao Q et al (2010) Relationships between serum adiponectin, apelin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in post-menopausal Chinese women. J Endocrinol Invest 33:707–711. https://doi.org/10.1007/BF03346674
Wu N, Wang QP, Li H et al (2010) Relationships between serum adiponectin, leptin concentrations and bone mineral density, and bone biochemical markers in Chinese women. Clin Chim Acta 411:771–775. https://doi.org/10.1016/j.cca.2010.02.064
Rhie YJ, Lee KH, Chung SC et al (2010) Effects of body composition, leptin, and adiponectin on bone mineral density in prepubertal girls. J Korean Med Sci 25:1187–1190. https://doi.org/10.3346/jkms.2010.25.8.1187
Baek JM, Ahn SJ, Cheon YH et al (2017) Nicotinamide phosphoribosyltransferase inhibits receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation in vitro. Mol Med Rep 15:784–792. https://doi.org/10.3892/mmr.2016.6069
Graham TE, Yang Q, Bluher M et al (2006) Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Eng J Med 354:2552–2563. https://doi.org/10.1056/NEJMoa054862
Ma L, Oei L, Jiang L et al (2012) Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol 27:319–332. https://doi.org/10.1007/s10654-012-9674-x
Choo MS, Choi SR, Han JH et al (2017) Association of insulin resistance with near peak bone mass in the femur and lumbar spine of Korean adults aged 25-35: the Korean national health and nutrition examination survey 2008–2010. PLoS One 12:e0177311. https://doi.org/10.1371/journal.pone.0177311
Shanbhogue VV, Joel SF, Bouxsein ML et al (2016) Association between insulin resistance and bone structure in nondiabetic postmenopausal women. J Clin Endocrinol Metab 101:3114–3122. https://doi.org/10.1210/jc.2016-1726
Srikanthan P, Crandall CJ, Miller-Martinez D et al (2014) Insulin resistance and bone strength: findings from the study of midlife in the United States. J Bone Mineral Res 29:796–803. https://doi.org/10.1002/jbmr.2083
Zhou J, Huang N, Cheng Y et al (2018) Retinol binding protein 4 is positively associated with bone mineral density in osteopenia and osteoporosis type 2 diabetic patients. Clin Endocrinol 88:659–664. https://doi.org/10.1111/cen.13560
Crespo R, Relea P, Lozano D et al (1995) Biochemical markers of nutrition in elite-marathon runners. J Sports Med Phys Fitness 35:268–272
Tohidi M, Akbarzadeh S, Larijani B et al (2012) Omentin-1, visfatin and adiponectin levels in relation to bone mineral density in Iranian postmenopausal women. Bone 51:876–881. https://doi.org/10.1016/j.bone.2012.08.117
Khorrami-Nezhad L, Mirzaei K, Maghbooli Z et al (2018) Dietary fat intake associated with bone mineral density among visfatin genotype in obese people. Br J Nutr 119:3–11. https://doi.org/10.1017/S000711451700304X
Gonnelli S, Caffarelli C, Nuti R (2014) Obesity and fracture risk. Clin Cases Mineral Bone Metab 11:9–14. https://doi.org/10.11138/ccmbm/2014.11.1.009
Ionela Maria Pascanu and Raluca-Monica Pop were supported by an internal research grant from the University of Medicine and Pharmacy Tirgu-Mures, Romania (Nr. 17802/1/22.12.2015). The authors would like to show their gratitude to the staff of the Rehabilitation Hospital, Baile Felix for their contribution and warm support.
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Written consent was obtained from all participants before any study procedure.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Mihai, G., Gasparik, A.I., Pascanu, I.M. et al. The influence of Visfatin, RBP-4 and insulin resistance on bone mineral density in women with treated primary osteoporosis. Aging Clin Exp Res 31, 889–895 (2019). https://doi.org/10.1007/s40520-019-01206-6
- Bone mineral density