The potential associations between obesity and bone health have long been discussed, but the results of the clinical trials remain controversial.
It is known that adipose tissue affects bone metabolism through mechanical, hormonal and inflammatory factors, but it is still debated whether the total effect is positive or negative for the bone. Higher body mass is associated with greater mechanical load, which in turn can stimulate the increase in bone mass. Fat accumulation is also associated with increased production of estrogen, which has a positive effect on bone metabolism. Increased secretion of insulin and amylin further suggests a greater anabolic effect on bone tissue. On the other hand, obesity is associated with low-grade inflammation and increased secretion of cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). However, these cytokines have a negative effect on bone tissue. In addition, decreased circulating levels of 25-hydroxyvitamin D (25OHD) have been observed in obese individuals, which may lead to impaired bone formation with altered quantitative and qualitative bone characteristics. Lower levels of vitamin D further lead to increased levels of parathyroid hormone (PTH), which can separately adversely affect bone metabolism. Additional discussions arise in connection with weight reduction, as dietary restrictions and mechanical changes caused by skeletal unloading during weight loss, as well as the resulting hormonal changes can increase the risk of fractures.
Hernández JL, Olmos JM, Pariente E, Martínez J, Valero C, García-Velasco P, et al. Metabolic syndrome and bone metabolism: the Camargo Cohort study. Menopause. 2010; 17(5): 955-61.
Kim BJ, Ahn SH, Bae SJ, Kim EH, Kim TH, Lee SH, et al. Association between metabolic syndrome and bone loss at various skeletal sites in postmenopausal women: a 3-year retrospective longitudinal study. Osteoporos Int. 2013; 24(8): 2243-52.
Reid IR. Relationships between fat and bone. Osteoporos Int 2008; 19: 595-606.
De Laet C, Kanis JA, Oden A, et al. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int. 2005; 16: 1330-8.
Iepsen Е, Lundgren J, Hartmann B, et al. GLP-1 Receptor Agonist Treatment Women. J Clin Endocrinol Metab 2015; 100(8): 2909–2917
Nguyen TV, Sambrook PN, Eisman JA. Bone loss, physical activity, and weight change in elderly women: the Dubbo Osteoporosis Epidemiology Study. J Bone Miner Res. 1998; 13: 1458-67.
Lloyd JT, Alley DA, Hawkes WG et al. Body mass index positively associated with bone mineral density in US older adults. Arch. of Osteop. 2014; 9: 175.
Biver E, Salliot C, Combescure C, Gossec L, Hardouin P, Legroux-Gerot I, et al. Influence of adipokines and ghrelin on bone mineral density and fracture risk: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011; 96: 2703–13.
Evans AL, Paggiosi MA, Eastell R, Walsh JS. Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood. J. Bone Miner. Res. 2015: 30: 920–928.
Liu CT, Broe KE, Zhou Y, Boyd SK, Cupples LA, Hannan MT, et al. Visceral Adipose Tissue Is Associated With Bone Microarchitecture in the Framingham Osteoporosis Study. J. Bone Miner. Res. 2017; 32: 143–150.
Bijelic R, Balaban J, Milicevic S. Correlation of the Lipid Profile, BMI and Bone Mineral Density in Postmenopausal Women ORIGINAL PAPER. Mater Sociomed. 2016; 28(6): 412-415
Lee SJ, Lee JY, Sung J. Obesity and Bone Health Revisited: A Mendelian Randomization Study for Koreans. J. Bone Miner. Res. 2019; 34: 1058–1067.
Migliaccio S, Greco EA, Fornari R, et al. Skeletal alterations in women affected by obesity. Aging Clin Exp Res. 2013; 25(1): 35-7.
Caffareli C, Alessi C, Nuti R, Gonnelli S. Divergent effects of obesity on fragility fractures. Clin Interv Aging. 2014; 9: 1629-36.
Cohen A, Dempster DW, Recker RR, Lappe JM, Zhou H, Zwahlen A, et al. Abdominal Fat Is Associated With Lower Bone Formation and Inferior Bone Quality in Healthy Premenopausal Women: A Transiliac Bone Biopsy Study. J. C. Endocrinol. Metab. 2013; 98: 2562–2572.
Gilsanz V, Chalfant J, Mo AO, Lee DC, Dorey FJ, Mittelman SD. Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J. Clin. Endocrinol. Metab. 2009; 94: 3387–3393.
Bredella MA, Lin E, Gerweck AV, Landa MG; Thomas BJ, Torriani M, et al. Determinants of bone microarchitecture and mechanical properties in obese men. J. Clin. Endocrinol. Metab. 2012; 97: 4115–4122.
Bredella MA, Torriani M, Ghomi RH, Thomas BJ, Brick DJ, Gerweck AV, et al. Determinants of bone mineral density in obese premenopausal women. Bone 2011; 48: 748–754.
Kim JH, Choi HJ, Kim MJ, Shin CS, Cho NH. Fat mass is negatively associated with bone mineral content in Koreans. Osteoporos Int. 2012; 23: 2009–2016.
Zhang P, Peterson M, Su GL, Wang SC. Visceral adiposity is negatively associated with bone density and muscle attenuation. Am J Clin Nutr. 2015; 101: 337–43.
Garnero P, Sornay-Rendu E, Chapuy M-C, Delmas PD. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J. Bone Miner. Res. 1996; 11: 337–349
Ibrahim SE, ElShishtawy HF, Helmy A, Galal ZA, Abdel Salam MH. Serum leptin concentration, bone mineral density and bone biochemical markers in a sample of Egyptian women: A possible relationship. Egypt. Rheumatol. 2011: 33: 171–177.
Sharma DK, Anderson PH, Morris HA, Clifton PM. Visceral Fat Is a Negative Determinant of Bone Health in Obese Postmenopausal Women. Int J Environ Res Public Health. 2020; 17(11): 3996
Compston JE, Watts NB, Chapurlat R, Cooper C, Boonen S, Greenspan S, et al. Obesity is not protective against fracture in postmenopausal women: GLOW. Am. J. Med. 2011; 124: 1043–1050.
Prieto-Alhambra D, Premaor MO, Fina Avilés F, Hermosilla E, Martinez-Laguna D, Carbonell-Abella C, et al. The association between fracture and obesity is site-dependent: A population-based study in postmenopausal women. J. Bone Miner. Res. 2012; 27: 294–300.
Johansson H, Kanis JA, Oden A, McCloskey E, Chapurlat RD, Christiansen C, et al. A meta-analysis of the association of fracture risk and body mass index in women. J. Bone Miner. Res. 2014; 29: 223–233.
Beck TJ, Petit MA, Wu G, LeBoff MS, Cauley JA, Chen Z. Does Obesity Really Make the Femur Stronger? BMD, Geometry, and Fracture Incidence in the Women’s Health Initiative-Observational Study. J. Bone Miner. Res. 2009: 24: 1369–1379.
Li X, Gong X, Jiang W. Abdominal obesity and risk of hip fracture: A meta-analysis of prospective studies. Osteoporos Int. 2017; 28: 2747–2757.
Ong T, Opinder S, Tan W, Marshall L. A United Kingdom perceptive on the relationship between body mass index ( BMI) and bone health: A cross sectional analisys of data from of Nottingham Fracture Liaison Service. Bone 2014; 59: 207-10.
Jones DH, Kong Y-Y, Penninger JM. Role of RANKL and RANK in bone loss and arthritis. Ann Rheum Dis. 2002; 61: 32–39
Hofbauer LC, Schoppet M. Clinical implications of the osteoprotegerin/ RANKL/RANK system for bone and vascular diseases. JAMA 2004; 292: 490–495
Smith BJ, Lerner MR, Bu SY, Lucas EA, Hanas JS, Lightfoot SA, et al. Systemic bone loss and induction of coronary vessel disease in a rat model of chronic inflammation. Bone 2006; 38: 378–386
Rosen CJ, Klibanski A. Bone, fat, and body composition: evolving concepts in the pathogenesis of osteoporosis. Am J Med. 2009; 122: 409–14.
Drincic AT, Armas LA, Van Diest EE, Heaney RP. Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity (Silver Spring) 2012; 20(7): 1444–8.
Shapses SA, Pop C, Schneider SH. Vitamin D in Obesity and Weight Loss. In: Weaver CM, Daly RM, Bischoff-Ferrari H, editors. Nutritional Aspects of Osteoporosis. Springer; London: 2016. pp. 9–16.
Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr. 2000; 72(3): 690–3.
Bolland MJ, Grey AB, Ames RW, Horne AM, Gamble GD, Reid IR. Fat mass is an important predictor of parathyroid hormone levels in postmenopausal women. Bone. 2006; 38: 317–21.
Pitroda AP, Harris SS, Dawson-Hughes B. The association of adiposity with parathyroid hormone in healthy older adults. Endocrine. 2009; 36: 218–23.
Sukumar D, Schlussel Y, Riedt CS, Gordon C, Stahl T, Shapses SA. Obesity alters cortical and trabecular bone density and geometry in women. Osteoporos Int. 2011; 22: 635–45.
Charopoulos I, Tournis S, Trovas G, Raptou P, Kaldrymides P, Skarandavos G, et al. Effect of primary hyperparathyroidism on volumetric bone mineral density and bone geometry assessed by peripheral quantitative computed tomography in postmenopausal women. J Clin Endocrinol Metab. 2006; 91: 1748–53.
Karra E, Batterham RL. The role of gut hormones in the regulation of body weight and energy homeostasis. Mol Cell Endocrinol. 2010;316:120–28.
Clowes JA, Khosla S, Eastell R. Potential role of pancreatic and enteric hormones in regulating bone turnover. J Bone Miner Res. 2005; 20: 1497–506.
Cornish J, Callon KE, Bava U, Watson M, Xu X, Lin JM, et al. Preptin, another peptide product of the pancreatic beta-cell, is osteogenic in vitro and in vivo. Am J Physiol Endocrinol Metab. 2007; 292: E117–22.
Ishii S, Cauley JA, Crandall CJ, Srikanthan P, Greendale GA, Huang MH, et al. Diabetes and femoral neck strength: findings from the Hip Strength Across the Menopausal Transition Study. J Clin Endocrinol Metab. 2012; 97: 190–7.
Srikanthan P, Crandall CJ, Miller-Martinez D, Seeman TE, Greendale GA, Binkley N, et al. Insulin resistance and bone strength: findings from the study of midlife in the United States. J Bone Miner Res. 2014; 29: 796–803.
Gutierrez-Rojas I, Lozano D, Nuche-Berenguer B, Moreno P, Acitores A, Ramos-Alvarez I, et al. Amylin exerts osteogenic actions with different efficacy depending on the diabetic status. Mol Cell Endocrinol. 2013; 365: 309–1510.
Shapses SA, Pop LC, Wang Y. Obesity is a concern for bone health with aging. Nutr Res. 2017; 39: 1-13.
Ealey KN, Kaludjerovic J, Archer MC, Ward WE. Adiponectin is a negative regulator of bone mineral and bone strength in growing mice. Exp Biol Med (Maywood) 2008; 233: 1546–1553.
Basurto L, Galván R, Cordova N, Saucedo R, Vargas C, Campos S, et al. Adiponectin is associated with low bone mineral density in elderly men. Eur J Endocrinol. 2009; 160: 289–93.
Araneta MR, von Mühlen D, Barrett-Connor E. Sex differences in the association between adiponectin and BMD, bone loss, and fractures: the Rancho Bernardo study. J Bone Miner Res. 2009; 24: 2016–22.
Motyl KJ, Rosen CJ. Understanding leptin-dependent regulation of skeletal homeostasis. Biochimie. 2012; 94: 2089–96.
Mpalaris V, Anagnostis P, Anastasilakis AD, Goulis DG, Doumas A, Iakovou I. Serum leptin, adiponectin and ghrelin concentrations in post-menopausal women: Is there an association with bone mineral density? Maturitas. 2016; 88: 32–6.
Myers MG, Jr, Heymsfield SB, Haft C, Kahn BB, Laughlin M, Leibel RL, et al. Challenges and opportunities of defining clinical leptin resistance. Cell Metab. 2012; 15: 150–156.
Goulding A, Taylor RW. Plasma leptin values in relation to bone mass and density and to dynamic biochemical markers of bone resorption and formation in postmenopausal women. Calcif Tissue Int. 1998; 63: 456–458.
Barbour KE, Zmuda JM, Boudreau R, Strotmeyer ES, Horwitz MJ, Evans RW, et al. Adipokines and the risk of fracture in older adults. J Bone Miner Res. 2011; 26: 1568–76.
Johansson H, Oden A, Lerner UH, Jutberger H, Lorentzon M, Barrett-Connor E, et al. High serum adiponectin predicts incident fractures in elderly men: Osteoporotic Fractures in Men (MrOS) Sweden. J Bone Miner Res. 2012;27:1390–96.
Berner HS, Lyngstadaas SP, Spahr A, Monjo M, Thommesen L, Drevon CA, et al. Adiponectin and its receptors are expressed in bone-forming cells. Bone. 2004; 35: 842–849.
Jurimae J, Kums T, Jurimae T. Adipocytokine and ghrelin levels in relation to bone mineral density in physically active older women: longitudinal associations. Eur J Endocrinol. 2009; 160: 381–385.
Magni P, Dozio E, Galliera E, Ruscica M, Corsi MM. Molecular aspects of adipokine-bone interactions. Curr Mol Med. 2010; 10: 522–3210.
Braun T, Schett G. Pathways for bone loss in inflammatory disease. Curr Osteoporos Rep. 2012; 10(2): 101–8.
Cao JJ. Effects of obesity on bone
metabolism. J Orthop Surg Res. 2011; 6: 30.
Mundy GR. Osteoporosis and inflammation. Nutr Rev. 2007; 65: S147–151.
Guri AJ, Bassaganya-Riera J. Systemic effects of white adipose tissue dysregulation and obesity related inflammation. Obesity (Silver Spring) 2011; 19: 689–700.
Pfeilschifter J, Koditz R, Pfohl M, Schatz H. Changes in proinflammatory cytokine activity after menopause. Endocrine reviews. 2002; 23: 90–119.
Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology. 2001; 142: 5050–5.
Kawai M, de Paula FJ, Rosen CJ. New insights into osteoporosis: the bone-fat connection. J Intern Med. 2012; 272: 317–29.
Elbaz A, Wu X, Rivas D, Gimble JM, Duque G. Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro. J Cell Mol Med. 2010; 14: 982–91.
Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma stem cells: the role of PPAR-gamma2 transcription factor and TGF-beta⁄BMP signaling pathways. Aging Cell. 2004; 3: 379–89.
Griffith JF, Yeung DK, Antonio GE, Wong SY, Kwok TC, Woo J, et al. Vertebral marrow fat content and diffusion and perfusion indexes in women with varying bone density: MR evaluation. Radiology. 2006; 241: 831–8.
Schwartz AV, Sigurdsson S, Hue TF, Lang TF, Harris TB, Rosen CJ, et al. Vertebral bone marrow fat associated with lower trabecular BMD and prevalent vertebral fracture in older adults. J Clin Endocrinol Metab. 2013; 98: 2294–300.
Yeung DK, Griffith JF, Antonio GE, Lee FK, Woo J, Leung PC. Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study. J Magn Reson Imaging. 2005;
(2): 279–85.
Shen W, Chen J, Punyanitya M, Shapses S, Heshka S, Heymsfield SB. MRI-measured bone marrow adipose tissue is inversely related to DXA-measured bone mineral in Caucasian women. Osteoporos Int. 2007; 18(5) :641–7.
Patsch JM, Li X, Baum T, Yap SP, Karampinos DC, Schwartz AV, Link TM. Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures. J Bone Miner Res. 2013; 28(8): 1721–8.
Schwartz AV. Marrow fat and bone: review of clinical findings. Front Endocrinol (Lausanne) 2015; 6: 40.
Baum T, Yap SP, Karampinos DC, Nardo L, Kuo D, Burghardt AJ, et al. Does vertebral bone marrow fat content correlate with abdominal adipose tissue, lumbar spine bone mineral density, and blood biomarkers in women with type2 diabetes mellitus? J Magn Reson Imaging. 2012; 35: 117–24.
Langlois JA, Harris T, Looker AC, Madans J. Weight change between age 50 years and old age is associated with risk of hip fracture in white women aged 67 years and older. Arch Intern Med. 1996; 156: 989–94.
Riedt CS, Cifuentes M, Stahl T, Chowdhury HA, Schlussel Y, Shapses SA. Overweight postmenopausal women lose bone with moderate weight reduction and 1 g/day calcium intake. J Bone Miner Res. 2005; 20(3): 455–63.
Meyer HE, Tverdal A, Selmer R. Weight variability, weight change and the incidence of hip fracture: a prospective study of 39,000 middle-aged Norwegians. Osteoporos Int. 1998; 8: 373–8.
Sukumar D, Ambia-Sobhan H, Zurfluh R, Schlussel Y, Stahl TJ, Gordon CL, Shapses SA. Areal and volumetric bone mineral density and geometry at two levels of protein intake during caloric restriction: a randomized, controlled trial. J Bone Miner Res. 2011; 26(6): 1339–48.
Silverman NE, Nicklas BJ, Ryan AS. Addition of aerobic exercise to a weight loss program increases BMD, with an associated reduction in inflammation in overweight postmenopausal women. Calcif Tissue Int. 2009; 84: 257–65.
Villareal DT, Fontana L, Weiss EP, Racette SB, Steger-May K, Schechtman KB, et al. Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. Arch Intern Med. 2006; 166: 2502–10.
Beavers DP, Beavers KM, Loeser RF, Walton NR, Lyles MF, Nicklas BJ, et al. The independent and combined effects of intensive weight loss and exercise training on bone mineral density in overweight and obese older adults with osteoarthritis. Osteoarthritis Cartilage. 2014; 22(6): 726–33.
Uusi-Rasi K, Patil R, Karinkanta S, Kannus P, Tokola K, Lamberg-Allardt C, et al. Exercise and vitamin D in fall prevention among older women: a randomized clinical trial. JAMA Intern Med. 2015; 175: 703–11
