Journal of Mid-life Health Journal of Mid-life Health
Home | About us | Editorial board | Search | Ahead of print | Current Issue | Past Issues | Instructions | Online submission | Subscribe | Advertise Users Online: 148  Print this pageEmail this pageSmall font sizeDefault font sizeIncrease font size 

 Table of Contents 
Year : 2014  |  Volume : 5  |  Issue : 1  |  Page : 6-9  

Obesity: Friend or foe for osteoporosis

1 Department of Obstetrics and Gynecology, Superspeciality Hospital, GMC, Jammu, Jammu and Kashmir, India
2 Department of Pharmacology, Superspeciality Hospital, GMC, Jammu, Jammu and Kashmir, India
3 Department of Nephrology, Superspeciality Hospita,l GMC, Jammu, Jammu and Kashmir, India
4 Department of General Medicine, Government Medical College, Jammu, Jammu and Kashmir, India

Date of Web Publication24-Feb-2014

Correspondence Address:
Sudhaa Sharma
Department of Obstetrics and Gynecology, Government Medical College, Jammu, Jammu and Kashmir - 180 001
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0976-7800.127782

Rights and Permissions

Osteoporosis and obesity are worldwide health problems. Interestingly, both are associated with significant morbidity and mortality. Both the diseases have common linkage as bone marrow mesenchymal stromal cells are the common precursors for both osteoblasts and adipocytes. Aging may shift composition of bone marrow by increasing adipocytes, osteoclast activity, and decreasing osteoblast activity, resulting into osteoporosis. Adipocytes secret leptin, adiponectin, adipsin, as well as proinflammatory cytokines, that contributes in pathogenesis of osteoporosis. This new concept supports the hypothesis, that the positive correlation of weight and body mass index (BMI) with bone mineral density (BMD) is not confirmed by large population-based studies. Thus, the previous concept, that obesity is protective for osteoporosis may not stand same as bone marrow fat deposition (adipogenesis) seen in obesity, is detrimental for bone health.

Keywords: Adipocytes, adiponectin, aging, leptin, obesity of bone, osteoporosis

How to cite this article:
Sharma S, Tandon VR, Mahajan S, Mahajan V, Mahajan A. Obesity: Friend or foe for osteoporosis. J Mid-life Health 2014;5:6-9

How to cite this URL:
Sharma S, Tandon VR, Mahajan S, Mahajan V, Mahajan A. Obesity: Friend or foe for osteoporosis. J Mid-life Health [serial online] 2014 [cited 2022 Dec 8];5:6-9. Available from:

   Introduction Top

Osteoporosis and obesity are worldwide health problems associated with significant morbidity and mortality as well as both has been suggested to result from dysregulation of a common precursor cell, that is, bone marrow mesenchymal stromal cells. [1]

The ongoing debate regarding the previous concept, that obesity is protective for osteoporosis may not stand same in view of the new concept of obesity of bone (adipogenesis), which is considered detrimental for bone health. This new concept has emerged as a result of the fact that weight and body mass index (BMI) have positive correlation with bone mineral density (BMD), [2],[3] but large population-based studies did not verify and confirm such positive correlation between bone mass and BMI. [4],[5]

The major factors considered in past for obesity as protective factor for osteoporosis include increased load on the cortical skeleton, direct stimulation of bone formation by leptin, greater aromatase activity, increased estradiol leading decrease bone resorption, and stimulation of bone formation. [6]

However, recent data suggest childhood obesity is associated with increased risk of lower extremity fractures in spite of increase BMD. [7] Another study [8] suggested that obesity is associated with higher BMD, but its protective effect on fracture risk is controversial. Higher absolute values of BMD, cortical and trabecular architecture, and strength indices have not been in proportion to the excess of BMI in obese postmenopausal women. Obesity was associated with reduced risk of clinical spine, hip, pelvis, and wrist/forearm fractures, but increased risk of multiple rib fracture when compared to normal or underweight population. [9] The research findings that many if not most osteoporotic fracture occur in overweight or obese women and men, further refute that obesity is protective. [10]

   How Obesity of Bone Explain these Contradictions Top

Bone marrow mesenchymal stromal cells are the common precursors for both osteoblasts and adipocytes. Aging may shift composition of bone marrow by increasing adipocytes, osteoclast activity, and decreasing osteoblast activity, resulting into osteoporosis. [1] The factors secreted by adipocytes known to affect bone remodeling are leptin, adiponectin, and adipsin, as well as proinflammatory cytokines, such as tumor necrosis factor and interleukin-6. [6] Therefore, bone marrow adipogenesis, appear to exert lypotoxic effect on osteoblast. The role of leptin, adiponectin, and adipsin in exerting lypotoxic effect on bone is explained below [Figure 1].
Figure 1: Showing the role of Leptin, Adiponectin, and Adipsin in Osteoporosis

Click here to view

Leptin and insulin growth factor-1 have been shown to possess positive peripheral roles in preserving bone mass during postmenopause. [10] More than that serum leptin has been shown a useful indicator of risk for osteoporosis associated with diet-induced obesity. [11] However, the recent data suggested that leptin controls bone formation through a hypothalamic relay, thereby suggesting central mechanism also to be involved in its action on bone. Adrenergic receptors deficiency (i.e., beta-less) has been shown to have increased body weight and fat mass, and exhibit greater total body bone mass, trabecular bone volume, and femoral cross-sectional size. [12],[13] Thereby, indicating that the integrity of sympathetic signaling is necessary for the increase in bone resorption. Which will mean that catecholamine-deficient state might have a high bone mass and sympathomimetics administered may decrease bone formation and bone mass. Conversely, beta-blockers are likely to increase bone formation and bone mass and blunt the bone loss induced by estrogen deficient state. Thus, leptin acts similar to the estrogen.

Adiponectin has been shown to increase osteoclast formation and negatively affects osteoporosis. This action is mediated by stimulating the production of receptor activator of receptor activator of nuclear factor kappa-B ligand (RANKL) that stimulates osteoclast differentiation. Furthermore, adiponectin can inhibit the production of osteoprotegerin, a known inhibitor of osteoclastogenesis, in osteoblasts. However, its level in lean mass person is seen higher and it is on lower side in fat person. Thereby, suggesting that low levels of adiponectin in obesity may confer osteoprotection. [14]

However, contradictory evidences emerged in favor of adiponectin denying osteoprotective effect among obese persons, from recent study, wherein a unique adipokine released from adipocytes has been shown antiapoptotic, anti-inflammatory, and anti-oxidative. In one of the study, human osteoblasts have been reported to express adiponectin and its receptors and shown to increase bone mass by suppressing osteoclastogenesis and by activating osteoblastogenesis. [15]

Adipsin similarly has been shown to negatively affect osteoporosis particularly diabetes mellitus (DM) induces osteoporosis. Increased expression is seen among DM and obese patients and it has been shown to decrease bone formation. [16]

Other: Beside these factors some other important factors have been proposed in genesis of osteoporosis among obese, that is, obesity and vitamin D insufficiency decreased bioavailability of vitamin D3 because cutaneous body fat has been reported in some studies may influence on long-term negatively with osteoporosis. This factor becomes very important as there is already a high prevalence of Vitamin D deficiency. [17]

   Clinical and Diagnostic Implication of the Concept- Obesity of Bone Top

Errors in BMD determinations commonly seen in markedly obese individuals are because of fat deposition in bone marrow. Dual-energy X-ray absorptiometry measurements may be falsely elevated by increased body fat; whereas, measurements of trabecular BMD by quantitative computed tomography may be decreased by greater marrow fat. [6]

Growth failure, pubertal arrest leading to reduced final adult height, and peak bone mass is usual explanation for poor bone health in Cushing's syndrome. [18] Whereas, insulin resistance and hyperglycemia are considered the reasons for deleterious effects on osteoblast function in patients of DM. [19] Similarly, glucocorticoids are known to alter the cellular composition of bone by regulating the supply and lifespan of osteoclasts and osteoblasts. [20] Immobility contributing to osteoporosis as in  Parkinsonism More Details is considered to be a result of decreased muscle strength. [21]

However, all the secondary causes of osteoporosis, like Cushing's syndrome, DM, glucocorticoids, and immobility, are associated with obesity. It was difficult in past with pervious hypothesis that obesity is protective for osteoporosis to explain the cause of osteoporosis in such cases. However, this can now be explained on the basis of associated increase in bone marrow adiposity seen in such cases. [6] Similarly, in extremes of life, puberty, and old age, fat infiltration in the bone marrow might be detrimental for skeletal strength and may negatively affect the optimal function of the bone remodeling unit. [6]

   Treatment Implication of this Concept Top

Treatment implications are going to be immense. The present treatment options for osteoporosis primarily known are either antiosteoclastogenesis or pro-osteoblastogenesis in nature. However, recently vitamin D has been shown to act by inhibiting bone marrow adipogenesis as an additional mechanism beside its known actions on bone. [22] However, further studies in this direction demonstrated dose-dependent effects of 1,25(OH) 2 D 3 on the transdifferentiation of muscle cells into adipose cells. Low physiological concentrations (possibly mimicking a deficient state) induced adipogenesis; whereas, higher (physiological and supraphysiological) concentrations attenuated this effect. [23] Furthermore, there is evidence that vitamin D affects body fat mass by inhibiting adipogenic transcription factors and lipid accumulation during adipocyte differentiation. Some recent studies demonstrate that vitamin D metabolites also influence adipokine production and the inflammatory response in adipose tissue. [24]

Similarly alendronate, a widely used bisphosphonate recently has been reported to stimulate osteoblastic differentiation while inhibiting adipogenesis in vitro; thereby, suggesting anabolic effect on bone through the differentiation of mesenchymal stem cells. [25]

Parathyroid hormone (PTH) also has been shown in past to induce osteoblast differentiation, inhibits adipogenesis and suppresses osteoblast apoptosis. [26] Similarly, Parathyroid hormone related protein (1-36) (PTHrP(1-36)) has been shown to induce a mild osteogenic effect and inhibit adipocytic effect in human mesenchymal stem cell and thereby helping in osteoporosis beside its known action to modulate bone formation through promoting osteoblast differentiation. [27]

Strontium ranelate, has both antiresorptive and anabolic effects on bone. However, it has been recently shown that adipogenesis is negatively affected in the presence of strontium ranelate with a concomitant dose-dependent decrease in the expression of adipogenic markers and changes in adipokine profile, thereby generating a favorable osteogenic effect within the bone marrow milieu. [28]

Similarly in another current study, dietary relevant mixtures of isoflavones and their metabolites, lignans and their metabolites, coumestrol, and a mixture containing all of them have been shown to concentration-dependently inhibit adipocyte differentiation as their additional mechanism of action in preventing osteoporosis. [29]

   Conclusion Top

The previous concept that obesity is protective for osteoporosis may not stand same and new concept of bone marrow fat deposition seen in obesity has emerged supporting the detrimental effect of obesity for bone health. Thus, obesity may not be considered as protective for osteoporosis. Furthermore, exploring the connection between bone and fat at a molecular and cellular level is likely to lead to a better understanding of several risk factors and pathogenesis basis and to the development of drugs with dual mechanism for both osteoporosis and obesity in future.

   References Top

1.Horowitz MC, Lorenzo JA. The origin of osteoclasts. Curr Opin Rheumatol 2004;16:464-8.  Back to cited text no. 1
2.Greendale GA, Judd HL. The menopause: Health implications and clinical management. J Am Geriatr Soc 1993;41:426-36.  Back to cited text no. 2
3.Carranza-Lira S, Rosas M, Murillo A, Martínez N, Santos J. Osteoporosis in postmenopausal women (Mexico City): 2. Validation of a predictive clinical index. Int J Fertil Womens Med 2002;47:26-31.  Back to cited text no. 3
4.Zhao LJ, Liu YJ, Liu PY, Hamilton J, Recker RR, Deng HW. Relationship of obesity with osteoporosis. J Clin Endocrinol Metab 2007;92:1640-6.  Back to cited text no. 4
5.Janicka A, Wren TA, Sanchez MM, Dorey F, Kim PS, Mittelman SD, et al. Fat mass is not beneficial to bone in adolescents and young adults. J Clin Endocrinol Metab 2007;92:143-7.  Back to cited text no. 5
6.Rosen CJ, Bouxsein ML. Mechanisms of disease: Is osteoporosis the obesity of bone? Nat Clin Pract Rheumatol 2006;2:35-43.  Back to cited text no. 6
7.Kessler J, Koebnick C, Smith N, Adams A. Childhood obesity is associated with increased risk of lower extremity fractures. Clin Orthop Relat Res 2013;471:1199-207.  Back to cited text no. 7
8.Sornay-Rendu E, Boutroy S, Vilayphiou N, Claustrat B, Chapurlat RD. In Obese postmenopausal women, bone microarchitecture and strength are not commensurate to greater body weight: The Os des Femmes de Lyon (OFELY) Study. J Bone Miner Res 2013;28:1679-87.  Back to cited text no. 8
9.Premaor MO, Compston JE, Fina Avilés F, Pagès-Castellà A, Nogués X, Díez-Pérez A, et al. The association between fracture site and obesity in men: A population-based cohort study. J Bone Miner Res 2013;28:1771-7.  Back to cited text no. 9
10.Morcov C, Vulpoi C, Brãniºteanu D. Correlation between adiponectin, leptin, insulin growth factor-1 and bone mineral density in pre and postmenopausal women. Rev Med Chir Soc Med Nat Iasi 2012;116:785-9.  Back to cited text no. 10
11.Fujita Y, Watanabe K, Maki K. Serum leptin levels negatively correlate with trabecular bone mineral density in high-fat diet-induced obesity mice. J Musculoskelet Neuronal Interact 2012;12:84-94.  Back to cited text no. 11
12.Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 2005;434:514-20.  Back to cited text no. 12
13.Petzel M. Action of leptin on bone and its relationship to menopause. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2007;151:195-9.  Back to cited text no. 13
14.Luo XH, Guo LJ, Xie H, Yuan LQ, Wu XP, Zhou HD, et al. EY Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts through the MAPK signaling pathway. J Bone Miner Res 2006;21:1648-56.  Back to cited text no. 14
15.Takeda Y, Nakanishi K, Tachibana I, Kumanogoh A. Adiponectin: A novel link between adipocytes and COPD. Vitam Horm 2012;90:419-35.  Back to cited text no. 15
16.Botolin S, Faugere MC, Malluche H, Orth M, Meyer R, McCabe LR. Increased bone adiposity and peroxisomal proliferator-activated receptor-gamma2 expression in type I diabetic mice. Endocrinology 2005;146:3622-31.  Back to cited text no. 16
17.Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 2000;72:690-3.  Back to cited text no. 17
18.Mancini T, Doga M, Mazziotti G, Giustina A. Cushing's syndrome and bone. Pituitary 2004;7:249-52.  Back to cited text no. 18
19.Lechleitner M, Pils K, Roller-Wirnsberger R, Beubler E, Gasser R, Mrak P, et al. Diabetes and osteoporosis: Pathophysiological interactions and clinical importance for geriatric patients. Z Gerontol Geriatr 2013;46:390-7.  Back to cited text no. 19
20.Manolagas SC. Steroids and osteoporosis: The quest for mechanisms. J Clin Invest 2013;123:1919-21.  Back to cited text no. 20
21.van den Bos F, Speelman AD, Samson M, Munneke M, Bloem BR, Verhaar HJ. Parkinson's disease and osteoporosis. Age Ageing 2013;42:156-62.  Back to cited text no. 21
22.Duque G, Macoritto M, Kremer R. Vitamin D treatment of senescence accelerated mice (SAM-P/6) induces several regulators of stromal cell plasticity. Biogerontology 2004;5:421-9.  Back to cited text no. 22
23.Ryan KJ, Daniel ZC, Craggs LJ, Parr T, Brameld JM. Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells. J Endocrinol 2013;217:45-58.  Back to cited text no. 23
24.Ding C, Gao D, Wilding J, Trayhurn P, Bing C. Vitamin D signalling in adipose tissue. Br J Nutr 2012;108:1915-23.  Back to cited text no. 24
25.Duque G, Rivas D. Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells. J Bone Miner Res 2007;22:1603-11.  Back to cited text no. 25
26.Chan GK, Miao D, Deckelbaum R, Bolivar I, Karaplis A, Goltzman D. Parathyroid hormone-related peptide interacts with bone morphogenetic protein 2 to increase osteoblastogenesis and decrease adipogenesis in pluripotent C3H10T 1/2 mesenchymal cells. Endocrinology 2003;144:5511-20.  Back to cited text no. 26
27.Casado-Diaz A, Santiago-Mora R, Quesada JM. The N- and C-terminal domains of parathyroid hormone-related protein affect differently the osteogenic and adipogenic potential of human mesenchymal stem cells. Exp Mol Med 2010;42:87-98.  Back to cited text no. 27
28.Vidal C, Gunaratnam K, Tong J, Duque G. Biochemical changes induced by strontium ranelate in differentiating adipocytes. Biochimie 2013;95:793-8.  Back to cited text no. 28
29.Taxvig C, Specht IO, Boberg J, Vinggaard AM, Nellemann C. Dietary relevant mixtures of phytoestrogens inhibit adipocyte differentiation in vitro. Food Chem Toxicol 2013;55:265-71.  Back to cited text no. 29


  [Figure 1]

This article has been cited by
1 The Relationship Between Bone Mineral Density and Body Composition Among Qatari Women With High Rate of Obesity: Qatar Biobank Data
Abdelhamid Kerkadi, Shalima Lathief, Yasmen Khial, Toka Teleb, Grace Attieh, Md Mizanur Rahman, Zumin Shi, Abdelali Agouni
Frontiers in Nutrition. 2022; 9
[Pubmed] | [DOI]
2 Protective effect of Spirulina against bone fragility induced by Garcinia cambogia in high-fat diet induced obese rats
Xinyi Cho, Patrick Nwabueze Okechukwu, Norazlina Mohamed, Gabriele Ruth Anisah Froemming, Hor Kuan Chan
International Food Research Journal. 2022; 29(3): 593
[Pubmed] | [DOI]
3 Weight Change Is Associated with Osteoporosis: A Cross Sectional Study Using the Korean Community Health Survey
Hyo-Geun Choi, Bong-Cheol Kwon, Soo-Hwan Yim, Hyun Youk, Jung-Woo Lee
International Journal of Environmental Research and Public Health. 2021; 18(24): 13368
[Pubmed] | [DOI]
4 Association between Metabolic Syndrome and Osteoporosis: A Systematic Review and Meta-Analysis
Weida Liu, Chuangshi Wang, Jun Hao, Lu Yin, Yang Wang, Wei Li, Alberto Ferlin
International Journal of Endocrinology. 2021; 2021: 1
[Pubmed] | [DOI]
5 Detecting causal relationship between metabolic traits and osteoporosis using multivariable Mendelian randomization
Q. Zhang, J. Greenbaum, H. Shen, L.-J. Zhao, W.-D. Zhang, C.-Q. Sun, H.-W. Deng
Osteoporosis International. 2021; 32(4): 715
[Pubmed] | [DOI]
6 Relationships between anthropometric adiposity indexes and bone mineral density in a cross-sectional Chinese study
Guijuan Deng, Lu Yin, Kai Li, Bo Hu, Xiaoru Cheng, Ling Wang, Yong Zhang, Li Xu, Shaoqi Xu, Lei Zhu, Jiman Shao, Xiaoguang Hao, Jun Zhou, Jinhua Tang, Wei Li, Yu Jiang, Xiaoguang Cheng
The Spine Journal. 2021; 21(2): 332
[Pubmed] | [DOI]
7 Non-alcoholic fatty liver disease (NAFLD) is associated with an increased incidence of osteoporosis and bone fractures
Sven H. Loosen, Christoph Roderburg, Münevver Demir, Natalia Qvartskhava, Verena Keitel, Karel Kostev, Tom Luedde
Zeitschrift für Gastroenterologie. 2021;
[Pubmed] | [DOI]
8 Effect of Qing’e Decoction on Leptin/Leptin Receptor and Bone Metabolism in Naturally Aging Rats
Pan Sun, Yuanyuan Zhang, Zhenpu Wei, Zhiqiang Wang, Shiming Guo, Yanping Lin
Evidence-Based Complementary and Alternative Medicine. 2020; 2020: 1
[Pubmed] | [DOI]

Soluble Biomarkers of Osteoporosis and Osteoarthritis, from Pathway Mapping to Clinical Trials: An Update

Elod Nagy, Csilla Nagy-Finna, Hora?iu-Valeriu Popoviciu, Béla Kovács
Clinical Interventions in Aging. 2020; Volume 15: 501
[Pubmed] | [DOI]
10 Bone Mineral Density of Femur and Lumbar and the Relation between Fat Mass and Lean Mass of Adolescents: Based on Korea National Health and Nutrition Examination Survey (KNHNES) from 2008 to 2011
Aram Kim, Seunghui Baek, Seyeon Park, Jieun Shin
International Journal of Environmental Research and Public Health. 2020; 17(12): 4471
[Pubmed] | [DOI]
11 Relationship between serum adiponectin and bone mineral density in male patients with obstructive sleep apnea syndrome
Dong-Dong Chen,Jie-Feng Huang,Qi-Chang Lin,Gong-Ping Chen,Jian-Ming Zhao
Sleep and Breathing. 2017; 21(2): 557
[Pubmed] | [DOI]
12 Inhibiting DNA methylation switches adipogenesis to osteoblastogenesis by activating Wnt10a
Yii-Shyuan Chen,Rui Wu,Xiaosong Yang,Shuping Kou,Ormond A. MacDougald,Liqing Yu,Hang Shi,Bingzhong Xue
Scientific Reports. 2016; 6: 25283
[Pubmed] | [DOI]
13 Association of Trabecular Bone Score with Inflammation and Adiposity in Patients with Psoriasis: Effect of Adalimumab Therapy
José L. Hernández,Raquel López-Mejías,Ricardo Blanco,Trinitario Pina,Sheila Ruiz,Isabel Sierra,Begońa Ubilla,Verónica Mijares,Marcos A. González-López,Susana Armesto,Alfonso Corrales,Enar Pons,Patricia Fuentevilla,Carmen González-Vela,Miguel Á. González-Gay
Journal of Osteoporosis. 2016; 2016: 1
[Pubmed] | [DOI]
14 Regulation of Obesity and Metabolic Complications by Gamma and Delta Tocotrienols
Lu Zhao,Xiefan Fang,Maurice Marshall,Soonkyu Chung
Molecules. 2016; 21(3): 344
[Pubmed] | [DOI]
15 Serum Chemerin Levels in relation to Osteoporosis and Bone Mineral Density: A Case-Control Study
Jing He,Ji-Chun Li,Hua Xie,Zhong-Hua Xu,Ya-Wen Sun,Qiao Shan
Disease Markers. 2015; 2015: 1
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
    How Obesity of B...
    Clinical and Dia...
    Treatment Implic...
    Article Figures

 Article Access Statistics
    PDF Downloaded1105    
    Comments [Add]    
    Cited by others 15    

Recommend this journal