No retraction, correction or concern found when last checked on Oct 16, 2026.

Effects of obesity on bone metabolism

Jay J Cao

Journal of Orthopaedic Surgery and Research · 2011 · Review

Abstract

Obesity is traditionally viewed to be beneficial to bone health because of well-established positive effect of mechanical loading conferred by body weight on bone formation, despite being a risk factor for many other chronic health disorders. Although body mass has a positive effect on bone formation, whether the mass derived from an obesity condition or excessive fat accumulation is beneficial to bone remains controversial. The underline pathophysiological relationship between obesity and bone is complex and continues to be an active research area. Recent data from epidemiological and animal studies strongly support that fat accumulation is detrimental to bone mass. To our knowledge, obesity possibly affects bone metabolism through several mechanisms. Because both adipocytes and osteoblasts are derived from a common multipotential mesenchymal stem cell, obesity may increase adipocyte differentiation and fat accumulation while decrease osteoblast differentiation and bone formation. Obesity is associated with chronic inflammation. The increased circulating and tissue proinflammatory cytokines in obesity may promote osteoclast activity and bone resorption through modifying the receptor activator of NF-κB (RANK)/RANK ligand/osteoprotegerin pathway. Furthermore, the excessive secretion of leptin and/or decreased production of adiponectin by adipocytes in obesity may either directly affect bone formation or indirectly affect bone resorption through up-regulated proinflammatory cytokine production. Finally, high-fat intake may interfere with intestinal calcium absorption and therefore decrease calcium availability for bone formation. Unraveling the relationship between fat and bone metabolism at molecular level may help us to develop therapeutic agents to prevent or treat both obesity and osteoporosis. Obesity, defined as having a body mass index ≥ 30 kg/m2, is a condition in which excessive body fat accumulates to a degree that adversely affects health. The rates of obesity rates have doubled since 1980 and as of 2007, 33% of men and 35% of women in the US are obese. Obesity is positively associated to many chronic disorders such as hypertension, dyslipidemia, type 2 diabetes mellitus, coronary heart disease, and certain cancers. It is estimated that the direct medical cost associated with obesity in the United States is ~$100 billion per year.Bone mass and strength decrease during adulthood, especially in women after menopause. These changes can culminate in osteoporosis, a disease characterized by low bone mass and microarchitectural deterioration resulting in increased bone fracture risk. It is estimated that there are about 10 million Americans over the age of 50 who have osteoporosis while another 34 million people are at risk of developing the disease. In 2001, osteoporosis alone accounted for some $17 billion in direct annual healthcare expenditure. Several lines of evidence suggest that obesity and bone metabolism are interrelated. First, both osteoblasts (bone forming cells) and adipocytes (energy storing cells) are derived from a common mesenchymal stem cell and agents inhibiting adipogenesis stimulated osteoblast differentiation and vice versa, those inhibiting osteoblastogenesis increased adipogenesis. Second, decreased bone marrow osteoblastogenesis with aging is usually accompanied with increased marrow adipogenesis. Third, chronic use of steroid hormone, such as glucocorticoid, results in obesity accompanied by rapid bone loss. Fourth, both obesity and osteoporosis are associated with elevated oxidative stress and increased production of proinflammatory cytokines. At present, the mechanisms for the effects of obesity on bone metabolism are not well defined and will be the focus of this review.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 16, 2026. Paragraph numbers are ours, so an answer can point at one.

Proinflammatory cytokines are elevated in obesity

1Obesity is associated with low-grade chronic inflammation. The seminal finding that the expression of a proinflammatory cytokine, tumor necrosis factor-α (TNF-α), is elevated in the adipose tissue of obese mice provided the first evidence of a link between obesity and inflammation. Later, the discovery of leptin, a small polypeptide hormone secreted primarily by the adipocytes, further supports that adipose is not just a energy storing organ and it is also an active endocrine tissue. Since then, numerous experimental, epidemiological, and clinical studies have established that obesity is associated with a chronic inflammatory response, abnormal cytokine production, increased acute-phase reactants, and activation of inflammatory signaling pathways, and that these processes are involved in and responsible for the development of obesity-related diseases. In obesity, adipose tissue is infiltrated with an increased amount of macrophages, which are an important source of inflammatory cytokines. Obese humans express higher levels of TNF-α in adipose tissue than do lean individuals. Adipose tissue also produces other proinflammatory factors including interlukin-6 (IL-6) and C-reactive protein (CRP). Obesity has also been implicated in the development or progression of musculoskeletal diseases such as osteoarthritis, a common inflammatory bone disease. Numerous studies have confirmed that increased production of proinflammatory cytokines are critical in the development and progression of obesity-related health disorders.

2Obese individuals show abnormal circulating levels of TNF-α, IL-6, CRP, adiponectin and leptin. Adiponectin and leptin, which also mediate chronic inflammation, are adipokines produced by adipose tissue. Leptin has pleiotropic effects that modulate energy expenditure, appetite, and neuroendocrine functions. Leptin, which is increased in obesity, has been found to stimulate inflammatory responses in humans. In contrast adiponectin acts as an anti-inflammatory cytokine which suppresses TNF-α-induced NF-κB activation. It has been found that plasma adiponectin concentrations are lower in obese subjects as compared to non-obese individuals.

3In a cross-sectional study of 16,573 individuals in the third National Health and Nutrition Examination Survey (NHANES) (1984-1994), logistic regression analysis showed that odds ratios for an elevated serum CRP among individuals with a body mass index (BMI) of 25- < 30, 30- < 35, 35- < 40, and ≥40 were 1.51, 3.9, 6.11, and 9.30, respectively. In another cross-sectional study, CRP, IL-6 and leptin were significantly positively related to degree of adiposity.

Proinflammatory cytokines increase bone resorption

4Bone is a dynamic organ that continuously undergoes significant turnover, a process called modeling/remodeling involving bone resorption by osteoclasts and bone formation by osteoblasts. Therefore, bone mass at any particular time reflects the balance between bone formation and resorption. At the cellular level, osteoblast number and activity decrease while osteoclast number and activity increase with aging. It is now established that osteoblasts regulate the recruitment and activity of osteoclasts through the expression of the receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) (Figure 1). RANKL is expressed on the osteoblast/stromal cell surface and binds to its receptor, RANK, on the surface of hematopoietic precursor cells to stimulate osteoclast differentiation and maturation in the presence of macrophage colony stimulation factor (M-CSF). OPG, a decoy receptor secreted by osteoblasts, binds RANKL to prevent the activation of RANK and, therefore, to prevent osteoclast differentiation and activation. It has been demonstrated that increased osteoclastic activity and increased bone resorption in postmenopausal women is positively correlated with the upregulation of RANKL.

5Proinflammatory cytokines including TNF-α, IL-1, and IL-6 are key mediators in the process of osteoclast differentiation and bone resorption. Chronic inflammation and increased proinflammatory cytokines induce bone resorption and bone loss in patients with periodontitis, pancreatitis, inflammatory bowel disease, and rheumatoid arthritis. It has also been established that upregulated proinflammatory cytokines are primary mediators of osteopenia or osteoporosis. The accelerated bone loss at menopause is linked to increased production of proinflammatory cytokines including TNF-α, IL-1, and IL-6. These proinflammatory cytokines are capable of stimulating osteoclast activity through the regulation of the RANKL/RANK/OPG pathway. In mice lacking IL-1β and TNF genes or over-expressing soluble TNF-α decoy receptor, ovariectomy did not cause bone loss. Blocking the action of IL-1 with an IL-1 receptor antagonist, or the signaling of TNF-α with a TNF-binding protein, decreased osteoclast formation and bone resorption in ovariectomized mice. The significant increase in the development of osteoarthritis in obese human subjects is another evidence that chronic inflammation influences bone metabolism.

Obesity affects bone turnover

6Obesity is traditionally thought to be beneficial to bone and, thus, to protect against osteoporosis. Mechanical loading stimulates bone formation by decreasing apoptosis and increasing proliferation and differentiation of osteoblasts and osteocytes through the Wnt/β-catenin signaling pathway. Therefore, mechanical loading conferred by body weight is part of the assumption that has led to widespread belief that obesity may prevent bone loss and osteoporosis.

7However, recent reports have shown that excessive fat mass may not protect humans from osteoporosis and in fact, increased fat mass is associated with low total bone mineral density and total bone mineral content. In a cross-sectional study of 60 females between 10 and 19 years of age, the percent of body fat was linked to suboptimal attainment of peak bone mass. Increased adiposity may also be linked to the increased risk of bone fracture. For example, in a case-control study of 100 patients with fractures and 100 age-matched fracture-free control subjects aged 3 to 19 years, high adiposity are associated with increased risk of distal forearm fractures. In another large cross-sectional study of about 13,000 adult men, pre- and post-menopausal women, percentage of body fat was positive associated with osteopenia and nonspine fractures.

8In a leptin-deficient (ob/ob) mouse model for obesity, mice weighed twice as much as lean mice but had lower femoral bone mineral density, cortical thickness, and trabecular bone volume. Obviously the positive effect of mechanical loading of increased body weight could not overcome the detrimental effect of leptin-deficiency (or possibly obesity) on bone in these mice. The apparent competing effects of adiposity and mechanical loading on bone metabolism remain an active research area. Research findings suggest that factors other than body weight are involved in the final outcome of obesity on bone health.

9While research with obese animal model has established the negative effects of adiposity on bone metabolism, studies with human subjects continue to be controversial. Human obesity is a complex issue which in general involves excessive consumption of other nutrients, such as protein and minerals, known to influence bone metabolism. Findings of the effects of obesity on bone health in humans have been based on statistical correlation or modeling rather than controlled trials. Thus, controlled studies with the obese animal model are useful for dissecting the mechanisms upon which excessive fat accumulation affect on bone metabolism.

10Using a diet-induced obese mouse model, we demonstrated that feeding mice a high-fat diet (45% energy as fat) for 14 wks decreases trabecular bone volume and trabecular number in the proximal tibia despite a substantial increase in body weight and bone formation markers in cultured BMSC. These structural changes are accompanied by increases in serum leptin and TRAP levels, the ratio of RANKL/OPG expression in cultured osteoblasts, and the number of TRAP-positive osteoclasts. Increased osteoclast activity and decreased expression of IL-10, an anti-inflammatory cytokine, by bone marrow-derived macrophages in diet-induced obese mice have also been reported by others. High fat-induced obese animals exhibited increased bone marrow adiposity accompanied by reduced BMD in different skeletal sites, up-regulation of peroxisome proliferator-activated receptor γ, cathepsin k, IL-6 and TNF-α.

11Based on available literature, obesity appears to affect bone metabolism through several mechanisms. Obesity may decrease bone formation (osteoblastogenesis) while increasing adipogenesis because adipocyte and osteoblasts are derived from a common multi-potential mesenchymal stem cell (Figure 1). For example, mechanical loading promotes osteoblast differentiation and inhibits adipogenesis by down-regulating peroxisome proliferator-activated receptor gamma (PPARγ) or by stimulating a durable beta-catemin signal. Activation of PPARγ by thiazolidinediones decreased osteoblast differentiation, bone mineral density and trabecular bone mass while increasing adipocytes differentiation and bone marrow adipose tissue volume.

12Obesity may increase bone resorption through upregulating proinflammatory cytokines such as IL-6 and TNF-α. These proinflammatory cytokines are capable of stimulating osteoclast activity through the regulation of the RANKL/RANK/OPG pathway. Obesity is significantly associated with degenerative and inflammatory musculoskeletal system. Bone marrow adipocytes also may directly regulate the osteoclast progenitors, hematopoietic cells. For example, when expressed with a dominant-negative form of CCAAT-enhancer-binding proteins (C/EBP) under the adipocyte fatty-acid-binding protein 4 promoter, mice cannot form adipocytes. These mice lack white adipose tissue and have increased bone mineral density.

13Obesity may affect bone metabolism directly or indirectly through adipocyte-derived cytokines such as leptin and adiponectin. Obesity is associated with significant increase in serum leptin and decrease in adiponectin. The action of leptin on bone appears to be complex and both positive and negative effects have been reported. It appears that its action may depend on current leptin status and the mode of the action (central or peripheral effects). Overproduction of leptin, as seen in obese animal models, may have negative effects on bone metabolism. Increased serum leptin level has been found a negative regulator of bone mass in a mouse model. Adiponectin is another cytokine secreted by adipocytes and has anti-inflammatory effect. In animal model, adiponectin has been reported to inhibit osteoclastogenesis, reduce bone resorption, and increase bone mass. Obese subjects have low serum adiponectin concentrations as compared to those normal subjects. Increased secretion of leptin (and/or decreased production of adiponectin) by adipocytes may also contribute to macrophage accumulation by simulating transport of macrophages to adipose tissue and promoting adhesion of macrophages to endothelial cells, respectively.

14Finally, a high-fat diet, often a cause of obesity, has been reported to interfere with intestinal calcium absorption. Free fatty acids can form unabsorbable insoluble calcium soaps and therefore contributing to low calcium absorption.

15Increased body weight associated with obesity may counteract the detrimental effects of obesity on bone metabolism. It is well established that body weight or body mass index (BMI) is positively correlated with bone mineral density or bone mass and low body weight or BMI is a risk factor for low bone mass and increased bone loss in humans. However, studies indicate the positive effects of body weight could not completely offset the detrimental effects of obesity on bone, at least in obese animal models.

Conclusions

16Accumulating data suggest that obesity is detrimental to bone health despite potential positive effects of mechanical loading conferred by increased body weight with obesity on bones. The decreased bone mass with obesity may be due to increased marrow adipogenesis at the expense of osteoblastogenesis, and/or increased osteoclastogenesis because of up-regulated production of proinflammatory cytokines, and/or excessive leptin secretion, or reduced adiponectin production, and/or reduced calcium absorption associated with high fat intake. Understanding the relationship between obesity and bone metabolism may help identify new molecular targets that can increase osteoblastogenesis while inhibiting adipogenesis and/or decreasing osteoclastogenesis. Ultimately, this knowledge may lead us to develop new therapeutic interventions to prevent both obesity and osteoporosis.

List of abbreviations

17CRP: C-reactive protein; IL: interleukin; OPG: osteoprotegerin; RANK: receptor activator of nuclear transcription factor κB; RANKL: receptor activator of nuclear transcription factor κB ligand; TNF-α: tumor necrosis factor alpha; TRAP: tartrate-resistant acid phosphatase; BMI: body mass index;

Conflict of interests

18The authors declare that they have no competing interests.

Author's information

19Dr. Cao received a Doctoral degree in nutrition from the University of Florida, Gainesville, Florida, USA. He worked as a postdoctoral research fellow in mineral nutrition at the Food Science and Human Nutrition Department, University of Florida and in bone biology at the Department of Medicine, University of California at San Francisco. Dr. Cao has published more than 30 papers in nutrition and bone biology fields. He has presented his research at many national and international conferences. Currently, he is a Research Nutritionist at the USDA ARS Grand Forks Human Nutrition Research Center where he conducts research focusing on the nutritional and physical activity regulation of bone metabolism using obese animal models. Dr. Cao also investigates the effects of dietary protein and acid-base balance on calcium absorption, retention, and markers of bone metabolism in human subjects.

References 93

1.
World Health OrganizationObesity: Preventing and managing the global epidemic, no. 8942000 Geneva: WHO
Not in our library
2.
Ogden CL Carroll MD Curtin LR McDowell MA Tabak CJ Flegal KM Prevalence of overweight and obesity in the United States, 1999-2004JAMA2006 2951315491555
Not in our library10.1001/jama.295.13.1549
3.
Bessesen DH Update on obesityJ Clin Endocrinol Metab2008 93620272034
Not in our library10.1210/jc.2008-0520
4.
Messerli FH Christie B DeCarvalho JG Aristimuno GG Suarez DH Dreslinski GR Frohlich ED Obesity and essential hypertension. Hemodynamics, intravascular volume, sodium excretion, and plasma renin activityArch Intern Med1981 14118185
Not in our library10.1001/archinte.141.1.81
5.
Kopelman PG Obesity as a medical problemNature2000 4046778635643
Not in our library10.1038/35007508
6.
Mokdad AH Bowman BA Ford ES Vinicor F Marks JS Koplan JP The continuing epidemics of obesity and diabetes in the United StatesJAMA2001 2861011951200
Not in our library10.1001/jama.286.10.1195
7.
Wolf AM Colditz GA Current estimates of the economic cost of obesity in the United StatesObes Res1998 6297106
Not in our library10.1002/j.1550-8528.1998.tb00322.x
8.
Riggs BL Khosla S Melton LJ 3 Sex steroids and the construction and conservation of the adult skeletonEndocrine reviews2002 233279302
Not in our library10.1210/er.23.3.279
9.
Melton LJ The prevalence of osteoporosis: gender and racial comparisonCalcif Tissue Int2001 694179181
Not in our library10.1007/s00223-001-1043-9
10.
Gregoire FM Smas CM Sul HS Understanding adipocyte differentiationPhysiol Rev1998 783783809
Not in our library10.1152/physrev.1998.78.3.783
11.
Gimble JM Robinson CE Wu X Kelly KA Rodriguez BR Kliewer SA Lehmann JM Morris DC Peroxisome proliferator-activated receptor-gamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cellsMol Pharmacol1996 50510871094
Not in our library
12.
David V Martin A Lafage-Proust MH Malaval L Peyroche S Jones DB Vico L Guignandon A Mechanical loading down-regulates peroxisome proliferator-activated receptor gamma in bone marrow stromal cells and favors osteoblastogenesis at the expense of adipogenesisEndocrinology2007 148525532562
Not in our library10.1210/en.2006-1704
13.
Sen B Xie Z Case N Ma M Rubin C Rubin J Mechanical strain inhibits adipogenesis in mesenchymal stem cells by stimulating a durable beta-catenin signalEndocrinology2008 1491260656075
Not in our library10.1210/en.2008-0687
14.
Beresford JN Bennett JH Devlin C Leboy PS Owen ME Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell culturesJ Cell Sci1992 102Pt 2341351
Not in our library10.1242/jcs.102.2.341
15.
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 pathwaysAging Cell2004 36379389
Not in our library10.1111/j.1474-9728.2004.00127.x
16.
Meunier P Aaron J Edouard C Vignon G Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsiesClin Orthop Relat Res1971 80147154
Not in our library10.1097/00003086-197110000-00021
17.
Mussig K Remer T Maser-Gluth C Brief review: glucocorticoid excretion in obesityJ Steroid Biochem Mol Biol2010 1213-5589593
Not in our library10.1016/j.jsbmb.2010.01.008
18.
Lane NE Yao W Glucocorticoid-induced bone fragilityAnn N Y Acad Sci2010 119218183
Not in our library10.1111/j.1749-6632.2009.05228.x
19.
Wellen KE Hotamisligil GS Obesity-induced inflammatory changes in adipose tissueThe Journal of clinical investigation2003 1121217851788
Not in our library10.1172/jci20514
20.
Mundy GR Osteoporosis and inflammationNutr Rev2007 6512 Pt 2S147151
Not in our library10.1111/j.1753-4887.2007.tb00353.x
21.
Hotamisligil GS Shargill NS Spiegelman BM Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistanceScience (New York, NY)1993 25950918791
Not in our library10.1126/science.7678183
22.
Zhang Y Proenca R Maffei M Barone M Leopold L Friedman JM Positional cloning of the mouse obese gene and its human homologueNature1994 3726505425432
Not in our library10.1038/372425a0
23.
Mohamed-Ali V Pinkney JH Coppack SW Adipose tissue as an endocrine and paracrine organInt J Obes Relat Metab Disord1998 221211451158
Not in our library10.1038/sj.ijo.0800770
24.
Hotamisligil GS Inflammation and metabolic disordersNature2006 4447121860867
Not in our library10.1038/nature05485
25.
Xu H Barnes GT Yang Q Tan G Yang D Chou CJ Sole J Nichols A Ross JS Tartaglia LA Chen H Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistanceThe Journal of clinical investigation2003 1121218211830
Not in our library10.1172/jci19451
26.
Weisberg SP McCann D Desai M Rosenbaum M Leibel RL Ferrante AW Jr Obesity is associated with macrophage accumulation in adipose tissueThe Journal of clinical investigation2003 1121217961808
Not in our library10.1172/jci19246
27.
Hotamisligil GS Arner P Caro JF Atkinson RL Spiegelman BM Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistanceThe Journal of clinical investigation1995 95524092415
Not in our library10.1172/jci117936
28.
Wellen KE Hotamisligil GS Inflammation, stress, and diabetesThe Journal of clinical investigation2005 115511111119
Not in our library10.1172/jci25102
29.
Pradhan AD Manson JE Rifai N Buring JE Ridker PM C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitusJama2001 2863327334
Not in our library10.1001/jama.286.3.327
30.
Anandacoomarasamy A Caterson I Sambrook P Fransen M March L The impact of obesity on the musculoskeletal systemInternational journal of obesity (2005)2008 322211222
Not in our library10.1038/sj.ijo.0803715
31.
Shoelson SE Herrero L Naaz A Obesity, inflammation, and insulin resistanceGastroenterology2007 132621692180
Not in our library10.1053/j.gastro.2007.03.059
32.
Canavan B Salem RO Schurgin S Koutkia P Lipinska I Laposata M Grinspoon S Effects of physiological leptin administration on markers of inflammation, platelet activation, and platelet aggregation during caloric deprivationJ Clin Endocrinol Metab2005 901057795785
Not in our library10.1210/jc.2005-0780
33.
van Dielen FM van't Veer C Schols AM Soeters PB Buurman WA Greve JW Increased leptin concentrations correlate with increased concentrations of inflammatory markers in morbidly obese individualsInt J Obes Relat Metab Disord2001 251217591766
Not in our library10.1038/sj.ijo.0801825
34.
Ouchi N Kihara S Arita Y Okamoto Y Maeda K Kuriyama H Hotta K Nishida M Takahashi M Muraguchi M Ohmoto Y Nakamura T Yamashita S Funahashi T Matsuzawa Y Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathwayCirculation2000 1021112961301
Not in our library10.1161/01.cir.102.11.1296
35.
Arita Y Kihara S Ouchi N Takahashi M Maeda K Miyagawa J Hotta K Shimomura I Nakamura T Miyaoka K Kuriyama H Nishida M Yamashita S Okubo K Matsubara K Muraguchi M Ohmoto Y Funahashi T Matsuzawa Y Paradoxical decrease of an adipose-specific protein, adiponectin, in obesityBiochem Biophys Res Commun1999 25717983
Not in our library10.1006/bbrc.1999.0255
36.
Ford ES Body mass index, diabetes, and C-reactive protein among U.S. adultsDiabetes care1999 221219711977
Not in our library10.2337/diacare.22.12.1971
37.
Aeberli I Molinari L Spinas G Lehmann R l'Allemand D Zimmermann MB Dietary intakes of fat and antioxidant vitamins are predictors of subclinical inflammation in overweight Swiss childrenThe American journal of clinical nutrition2006 844748755
Not in our library10.1093/ajcn/84.4.748
38.
Novack DV Teitelbaum SL The osteoclast: friend or foe?Annual review of pathology2008 3457484
Not in our library10.1146/annurev.pathmechdis.3.121806.151431
39.
Cao JJ Wronski TJ Iwaniec U Phleger L Kurimoto P Boudignon B Halloran BP Aging increases stromal/osteoblastic cell-induced osteoclastogenesis and alters the osteoclast precursor pool in the mouseJ Bone Miner Res2005 20916591668
Not in our library10.1359/jbmr.050503
40.
Perkins SL Gibbons R Kling S Kahn AJ Age-related bone loss in mice is associated with an increased osteoclast progenitor poolBone1994 1516572
Not in our library10.1016/8756-3282(94)90893-1
41.
Lacey DL Timms E Tan HL Kelley MJ Dunstan CR Burgess T Elliott R Colombero A Elliott G Scully S Hsu H Sullivan J Hawkins N Davy E Capparelli C Eli A Qian YX Kaufman S Sarosi I Shalhoub V Senaldi G Guo J Delaney J Boyle WJ Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activationCell1998 932165176
Not in our library10.1016/s0092-8674(00)81569-x
42.
Simonet WS Lacey DL Dunstan CR Kelley M Chang MS Luthy R Nguyen HQ Wooden S Bennett L Boone T Shimamoto G DeRose M Elliott R Colombero A Tan HL Trail G Sullivan J Davy E Bucay N Renshaw-Gegg L Hughes TM Hill D Pattison W Campbell P Sander S Van G Tarpley J Derby P Lee R Boyle WJ Osteoprotegerin: a novel secreted protein involved in the regulation of bone densityCell1997 892309319
Not in our library10.1016/s0092-8674(00)80209-3
43.
Eghbali-Fatourechi G Khosla S Sanyal A Boyle WJ Lacey DL Riggs BL Role of RANK ligand in mediating increased bone resorption in early postmenopausal womenJ Clin Invest2003 111812211230
Not in our library10.1172/jci17215
44.
Cao J Venton L Sakata T Halloran BP Expression of RANKL and OPG correlates with age-related bone loss in male C57BL/6 miceJ Bone Miner Res2003 182270277
Not in our library10.1359/jbmr.2003.18.2.270
45.
Van Dyke TE Serhan CN Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseasesJ Dent Res2003 8228290
Not in our library10.1177/154405910308200202
46.
Mann ST Stracke H Lange U Klor HU Teichmann J Alterations of bone mineral density and bone metabolism in patients with various grades of chronic pancreatitisMetabolism: clinical and experimental2003 525579585
Not in our library10.1053/meta.2003.50112
47.
Bernstein CN Leslie WD Taback SP Bone density in a population-based cohort of premenopausal adult women with early onset inflammatory bowel diseaseAm J Gastroenterol2003 98510941100
Not in our library10.1111/j.1572-0241.2003.07415.x
48.
Romas E Gillespie MT Martin TJ Involvement of receptor activator of NFkappaB ligand and tumor necrosis factor-alpha in bone destruction in rheumatoid arthritisBone2002 302340346
Not in our library10.1016/s8756-3282(01)00682-2
49.
Pfeilschifter J Koditz R Pfohl M Schatz H Changes in proinflammatory cytokine activity after menopauseEndocrine reviews2002 23190119
Not in our library10.1210/er.23.1.90
50.
Khosla S Minireview: the OPG/RANKL/RANK systemEndocrinology2001 1421250505055
Not in our library10.1210/en.142.12.5050
51.
Vargas SJ Naprta A Glaccum M Lee SK Kalinowski J Lorenzo JA Interleukin-6 expression and histomorphometry of bones from mice deficient in receptors for interleukin-1 or tumor necrosis factorJ Bone Miner Res1996 111117361744
Not in our library10.1002/jbmr.5650111117
52.
Ammann P Rizzoli R Bonjour JP Bourrin S Meyer JM Vassalli P Garcia I Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiencyThe Journal of clinical investigation1997 99716991703
Not in our library10.1172/jci119333
53.
Kimble RB Matayoshi AB Vannice JL Kung VT Williams C Pacifici R Simultaneous block of interleukin-1 and tumor necrosis factor is required to completely prevent bone loss in the early postovariectomy periodEndocrinology1995 136730543061
Not in our library10.1210/en.136.7.3054
54.
Reid IR Ames R Evans MC Sharpe S Gamble G France JT Lim TM Cundy TF Determinants of total body and regional bone mineral density in normal postmenopausal women--a key role for fat massThe Journal of clinical endocrinology and metabolism1992 7514551
Not in our library10.1210/jc.75.1.45
55.
Villareal DT Apovian CM Kushner RF Klein S Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity SocietyThe American journal of clinical nutrition2005 825923934
Not in our library10.1093/ajcn/82.5.923
56.
Ehrlich PJ Lanyon LE Mechanical strain and bone cell function: a reviewOsteoporos Int2002 139688700
Not in our library10.1007/s001980200095
57.
Bonewald LF Johnson ML Osteocytes, mechanosensing and Wnt signalingBone2008 424606615
Not in our library10.1016/j.bone.2007.12.224
58.
Sawakami K Robling AG Ai M Pitner ND Liu D Warden SJ Li J Maye P Rowe DW Duncan RL Warman ML Turner CH The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatmentThe Journal of biological chemistry2006 281332369823711
Not in our library10.1074/jbc.m601000200
59.
Felson DT Zhang Y Hannan MT Anderson JJ Effects of weight and body mass index on bone mineral density in men and women: the Framingham studyJ Bone Miner Res1993 85567573
Not in our library10.1002/jbmr.5650080507
60.
Ravn P Cizza G Bjarnason NH Thompson D Daley M Wasnich RD McClung M Hosking D Yates AJ Christiansen C Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study groupJ Bone Miner Res1999 14916221627
Not in our library10.1359/jbmr.1999.14.9.1622
61.
Robling AG Castillo AB Turner CH Biomechanical and molecular regulation of bone remodelingAnnual review of biomedical engineering2006 8455498
Not in our library10.1146/annurev.bioeng.8.061505.095721
62.
Reid IR Evans MC Ames RW Volumetric bone density of the lumbar spine is related to fat mass but not lean mass in normal postmenopausal womenOsteoporos Int1994 46362367
Not in our library10.1007/bf01622199
63.
Reid IR Plank LD Evans MC Fat mass is an important determinant of whole body bone density in premenopausal women but not in menJ Clin Endocrinol Metab1992 753779782
Not in our library10.1210/jc.75.3.779
64.
Goulding A Taylor RW Jones IE McAuley KA Manning PJ Williams SM Overweight and obese children have low bone mass and area for their weightInt J Obes Relat Metab Disord2000 245627632
Not in our library10.1038/sj.ijo.0801207
65.
Blum M Harris SS Must A Naumova EN Phillips SM Rand WM Dawson-Hughes B Leptin, body composition and bone mineral density in premenopausal womenCalcif Tissue Int2003 7312732
Not in our library10.1007/s00223-002-1019-4
66.
Hsu YH Venners SA Terwedow HA Feng Y Niu T Li Z Laird N Brain JD Cummings SR Bouxsein ML Rosen CJ Xu X Relation of body composition, fat mass, and serum lipids to osteoporotic fractures and bone mineral density in Chinese men and womenAm J Clin Nutr2006 831146154
Not in our library10.1093/ajcn/83.1.146
67.
Pollock NK Laing EM Baile CA Hamrick MW Hall DB Lewis RD Is adiposity advantageous for bone strength? A peripheral quantitative computed tomography study in late adolescent femalesAm J Clin Nutr2007 86515301538
Not in our library10.1093/ajcn/86.5.1530
68.
Weiler HA Janzen L Green K Grabowski J Seshia MM Yuen KC Percent body fat and bone mass in healthy Canadian females 10 to 19 years of ageBone2000 272203207
Not in our library10.1016/s8756-3282(00)00314-8
69.
Goulding A Jones IE Taylor RW Williams SM Manning PJ Bone mineral density and body composition in boys with distal forearm fractures: a dual-energy x-ray absorptiometry studyJ Pediatr2001 1394509515
Not in our library10.1067/mpd.2001.116297
70.
Hamrick MW Pennington C Newton D Xie D Isales C Leptin deficiency produces contrasting phenotypes in bones of the limb and spineBone2004 343376383
Not in our library10.1016/j.bone.2003.11.020
71.
Palacios C The role of nutrients in bone health, from A to ZCritical reviews in food science and nutrition2006 468621628
Not in our library10.1080/10408390500466174
72.
Cao JJ Gregoire BR Gao H High-fat diet decreases cancellous bone mass but has no effect on cortical bone mass in the tibia in miceBone2009 44610971104
Not in our library10.1016/j.bone.2009.02.017
73.
Cao JJ Sun L Gao H Diet-induced obesity alters bone remodeling leading to decreased femoral trabecular bone mass in miceAnn N Y Acad Sci2010 11921292297
Not in our library10.1111/j.1749-6632.2009.05252.x
74.
Kyung TW Lee JE Phan TV Yu R Choi HS Osteoclastogenesis by bone marrow-derived macrophages is enhanced in obese miceJ Nutr2009 1393502506
Not in our library10.3945/jn.108.100032
75.
Halade GV Rahman MM Williams PJ Fernandes G High fat diet-induced animal model of age-associated obesity and osteoporosisJ Nutr Biochem2010
Not in our library10.1016/j.jnutbio.2009.10.002
76.
Rosen CJ Bouxsein ML Mechanisms of disease: is osteoporosis the obesity of bone?Nat Clin Pract Rheumatol2006 213543
Not in our library10.1038/ncprheum0070
77.
Lazarenko OP Rzonca SO Suva LJ Lecka-Czernik B Netoglitazone is a PPAR-gamma ligand with selective effects on bone and fatBone2006 3817484
Not in our library10.1016/j.bone.2005.07.008
78.
Tornvig L Mosekilde LI Justesen J Falk E Kassem M Troglitazone treatment increases bone marrow adipose tissue volume but does not affect trabecular bone volume in miceCalcif Tissue Int2001 6914650
Not in our library10.1007/s002230020018
79.
Anandacoomarasamy A Fransen M March L Obesity and the musculoskeletal systemCurr Opin Rheumatol2009 2117177
Not in our library10.1097/bor.0b013e32831bc0d7
80.
Naveiras O Nardi V Wenzel PL Hauschka PV Fahey F Daley GQ Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironmentNature2009 4607252259263
Not in our library10.1038/nature08099
81.
Moitra J Mason MM Olive M Krylov D Gavrilova O Marcus-Samuels B Feigenbaum L Lee E Aoyama T Eckhaus M Reitman ML Vinson C Life without white fat: a transgenic mouseGenes Dev1998 122031683181
Not in our library10.1101/gad.12.20.3168
82.
Reitman ML Gavrilova O A-ZIP/F-1 mice lacking white fat: a model for understanding lipoatrophic diabetesInt J Obes Relat Metab Disord2000 24Suppl 4S1114
Not in our library10.1038/sj.ijo.0801493
83.
Holloway WR Collier FM Aitken CJ Myers DE Hodge JM Malakellis M Gough TJ Collier GR Nicholson GC Leptin inhibits osteoclast generationJ Bone Miner Res2002 172200209
Not in our library10.1359/jbmr.2002.17.2.200
84.
Burguera B Hofbauer LC Thomas T Gori F Evans GL Khosla S Riggs BL Turner RT Leptin reduces ovariectomy-induced bone loss in ratsEndocrinology2001 142835463553
Not in our library10.1210/en.142.8.3546
85.
Elefteriou F Takeda S Ebihara K Magre J Patano N Kim CA Ogawa Y Liu X Ware SM Craigen WJ Robert JJ Vinson C Nakao K Capeau J Karsenty G Serum leptin level is a regulator of bone massProc Natl Acad Sci USA2004 101932583263
Not in our library10.1073/pnas.0308744101
86.
Ducy P Amling M Takeda S Priemel M Schilling AF Beil FT Shen J Vinson C Rueger JM Karsenty G Leptin inhibits bone formation through a hypothalamic relay: a central control of bone massCell2000 1002197207
Not in our library10.1016/s0092-8674(00)81558-5
87.
Oshima K Nampei A Matsuda M Iwaki M Fukuhara A Hashimoto J Yoshikawa H Shimomura I Adiponectin increases bone mass by suppressing osteoclast and activating osteoblastBiochem Biophys Res Commun2005 3312520526
Not in our library10.1016/j.bbrc.2005.03.210
88.
Sierra-Honigmann MR Nath AK Murakami C Garcia-Cardena G Papapetropoulos A Sessa WC Madge LA Schechner JS Schwabb MB Polverini PJ Flores-Riveros JR Biological action of leptin as an angiogenic factorScience (New York, NY)1998 281538316831686
Not in our library10.1126/science.281.5383.1683
89.
Maeda N Shimomura I Kishida K Nishizawa H Matsuda M Nagaretani H Furuyama N Kondo H Takahashi M Arita Y Komuro R Ouchi N Kihara S Tochino Y Okutomi K Horie M Takeda S Aoyama T Funahashi T Matsuzawa Y Diet-induced insulin resistance in mice lacking adiponectin/ACRP30Nat Med2002 87731737
Not in our library10.1038/nm724
90.
Nelson SE Frantz JA Ziegler EE Absorption of fat and calcium by infants fed a milk-based formula containing palm oleinJournal of the American College of Nutrition1998 174327332
Not in our library10.1080/07315724.1998.10718770
91.
Carnielli VP Luijendijk IH Van Goudoever JB Sulkers EJ Boerlage AA Degenhart HJ Sauer PJ Structural position and amount of palmitic acid in infant formulas: effects on fat, fatty acid, and mineral balanceJ Pediatr Gastroenterol Nutr1996 235553560
Not in our library10.1097/00005176-199612000-00007
92.
Lucas A Quinlan P Abrams S Ryan S Meah S Lucas PJ Randomised controlled trial of a synthetic triglyceride milk formula for preterm infantsArch Dis Child Fetal Neonatal Ed1997 773F178184
Not in our library10.1136/fn.77.3.f178
93.
Reid IR Relationships among body mass, its components, and boneBone2002 315547555
Not in our library10.1016/s8756-3282(02)00864-5

Cited by papers we hold 7

The Role of Macronutrients, Micronutrients and Flavonoid Polyphenols in the Prevention and Treatment of Osteoporosis · 2022
No notice
Obesity and Bone: A Complex Relationship · 2021
No notice
Association between obesity and risk of fracture, bone mineral density and bone quality in adults: A systematic review and meta-analysis · 2021
No notice
Nutrients and Dietary Patterns Related to Osteoporosis · 2020
No notice
Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity · 2018
No notice
The Relationship between Metabolic Syndrome and Osteoporosis: A Review · 2016
No notice
Physical activity during the early years of life and osteoporosis in adulthood: study among users of the Brazilian National Health System
Not checked

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.