Osteoporosis International

, Volume 24, Issue 4, pp 1513–1518 | Cite as

Cold-activated brown adipose tissue is an independent predictor of higher bone mineral density in women

  • P. LeeEmail author
  • R. J. Brychta
  • M. T. Collins
  • J. Linderman
  • S. Smith
  • P. Herscovitch
  • C. Millo
  • K. Y. Chen
  • F. S. Celi
Short Communication



In animals, defective brown adipogenesis leads to bone loss. Whether brown adipose tissue (BAT) mass relates to bone mineral density (BMD) in humans is unclear. We determined the relationship between BAT mass and BMD by cold-stimulated positron-emission tomography (PET) and dual-energy X-ray absorptiometry (DXA) in healthy volunteers. Higher BAT mass was associated with higher BMD in healthy women, but not in men, independent of age and body composition.


Contrary to the traditional belief that BAT is present only in infants, recent studies revealed significant depots of BAT present in adult humans. In animals, defective brown adipogenesis leads to bone loss. While white adipose tissue mass is a known determinant of BMD in humans, the relationship between BAT and BMD in humans is unclear. We thus examined the relationship between BAT and BMD in healthy adults.


BAT volume (ml) and activity (standard uptake value) were determined by 18F-fluorodeoxyglucose PET after overnight mild cold exposure at 19 °C, and BMD was determined by DXA.


Among 24 healthy adults (age 28 ± 1 years, F = 10), BAT volumes were 82.4 ± 99.5 ml in women and 49.7 ± 54.5 ml in men. Women manifested significantly higher BAT activity, by 9.4 ± 8.1 % (p = 0.03), than men. BAT volume correlated positively with total and spine BMD (r 2 = 0.40 and 0.49, respectively, p < 0.02) in women and remained a significant predictor after adjustment for age, fat, and lean body mass (p < 0.05). Total and spine BMD were higher in women who harbored visually detectable BAT on PET images than those without by 11 ± 2 % (p = 0.02) and 22 ± 2 % (p < 0.01), respectively. No associations were observed between BAT parameters and BMD in men.


This study demonstrated higher BMD among healthy women with more abundant BAT, independent of age and other body compositional parameters. This was not observed in men. The data suggest that brown adipogenesis may be physiologically related to modulation of bone density.


Bone mineral density Brown adipose tissue Human Metabolism Thermogenesis 



Paul Lee was supported by the Australian National Health Medical Research Council Early Career Fellowship, the Diabetes Australia Fellowship, and the Bushell Travelling Fellowship. This study was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases: programs Z01-DK047057-02 and Z01-DK071044.

Conflicts of interest


Supplementary material

198_2012_2110_MOESM1_ESM.doc (67 kb)
Table S1 Multiple regression analysis in females with age, lean body mass, and fat mass as independent variables and total bone mineral density as dependent variable (DOC 67 kb)
198_2012_2110_MOESM2_ESM.doc (67 kb)
Table S2 Multiple regression analysis in females with age, lean body mass, and fat mass as independent variables and spine bone mineral density as dependent variable (DOC 67 kb)


  1. 1.
    Nedergaard J, Bengtsson T, Cannon B (2007) Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 293:E444–E452PubMedCrossRefGoogle Scholar
  2. 2.
    Feldmann HM, Golozoubova V, Cannon B, Nedergaard J (2009) UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab 9:203–209PubMedCrossRefGoogle Scholar
  3. 3.
    Saito M, Okamatsu-Ogura Y, Matsushita M et al (2009) High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 58:1526–1531PubMedCrossRefGoogle Scholar
  4. 4.
    van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360:1500–1508PubMedCrossRefGoogle Scholar
  5. 5.
    Lee P, Zhao JT, Swarbrick MM, Gracie G, Bova R, Greenfield JR, Freund J, Ho KK (2011) High prevalence of brown adipose tissue in adult humans. J Clin Endocrinol Metab 96:2450–2455PubMedCrossRefGoogle Scholar
  6. 6.
    Lee P, Greenfield JR, Ho KK, Fulham MJ (2010) A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 299:E601–E606PubMedCrossRefGoogle Scholar
  7. 7.
    Salamone LM, Glynn N, Black D, Epstein RS, Palermo L, Meilahn E, Kuller LH, Cauley JA (1995) Body composition and bone mineral density in premenopausal and early perimenopausal women. J Bone Miner Res 10:1762–1768PubMedCrossRefGoogle Scholar
  8. 8.
    Albala C, Yanez M, Devoto E, Sostin C, Zeballos L, Santos JL (1996) Obesity as a protective factor for postmenopausal osteoporosis. Int J Obes Relat Metab Disord 20:1027–1032PubMedGoogle Scholar
  9. 9.
    Reid IR, Plank LD, Evans MC (1992) Fat mass is an important determinant of whole body bone density in premenopausal women but not in men. J Clin Endocrinol Metab 75:779–782PubMedCrossRefGoogle Scholar
  10. 10.
    Janicka A, Wren TA, Sanchez MM, Dorey F, Kim PS, Mittelman SD, Gilsanz V (2007) Fat mass is not beneficial to bone in adolescents and young adults. J Clin Endocrinol Metab 92:143–147PubMedCrossRefGoogle Scholar
  11. 11.
    Gilsanz V, Chalfant J, Mo AO, Lee DC, Dorey FJ, Mittelman SD (2009) Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. J Clin Endocrinol Metab 94:3387–3393PubMedCrossRefGoogle Scholar
  12. 12.
    Russell M, Mendes N, Miller KK, Rosen CJ, Lee H, Klibanski A, Misra M (2010) Visceral fat is a negative predictor of bone density measures in obese adolescent girls. J Clin Endocrinol Metab 95:1247–1255PubMedCrossRefGoogle Scholar
  13. 13.
    Motyl KJ, Raetz M, Tekalur SA, Schwartz RC, McCabe LR (2011) CCAAT/enhancer binding protein beta-deficiency enhances type 1 diabetic bone phenotype by increasing marrow adiposity and bone resorption. Am J Physiol Regul Integr Comp Physiol 300:R1250–R1260PubMedCrossRefGoogle Scholar
  14. 14.
    Carmona MC, Hondares E, Rodriguez de la Concepcion ML, Rodriguez-Sureda V, Peinado-Onsurbe J, Poli V, Iglesias R, Villarroya F, Giralt M (2005) Defective thermoregulation, impaired lipid metabolism, but preserved adrenergic induction of gene expression in brown fat of mice lacking C/EBPbeta. Biochem J 389:47–56PubMedCrossRefGoogle Scholar
  15. 15.
    Zanotti S, Stadmeyer L, Smerdel-Ramoya A, Durant D, Canalis E (2009) Misexpression of CCAAT/enhancer binding protein beta causes osteopenia. J Endocrinol 201:263–274PubMedCrossRefGoogle Scholar
  16. 16.
    Motyl KJ, Rosen CJ (2011) Temperatures rising: brown fat and bone. Discov Med 11:179–185PubMedGoogle Scholar
  17. 17.
    Bredella MA, Fazeli PK, Freedman LM, Calder G, Lee H, Rosen CJ, Klibanski A (2012) Young women with cold-activated brown adipose tissue have higher bone mineral density and lower Pref-1 than women without brown adipose tissue: a study in women with anorexia nervosa, women recovered from anorexia nervosa, and normal-weight women. J Clin Endocrinol Metab 97:E584–E590PubMedCrossRefGoogle Scholar
  18. 18.
    Krings A, Rahman S, Huang S, Lu Y, Czernik PJ, Lecka-Czernik B (2012) Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes. Bone 50:546–552PubMedCrossRefGoogle Scholar
  19. 19.
    Olmsted-Davis E, Gannon FH, Ozen M et al (2007) Hypoxic adipocytes pattern early heterotopic bone formation. Am J Pathol 170:620–632PubMedCrossRefGoogle Scholar
  20. 20.
    Zhang H, Schulz TJ, Espinoza DO, Huang TL, Emanuelli B, Kristiansen K, Tseng YH (2010) Cross talk between insulin and bone morphogenetic protein signaling systems in brown adipogenesis. Mol Cell Biol 30:4224–4233PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2012

Authors and Affiliations

  • P. Lee
    • 1
    Email author
  • R. J. Brychta
    • 1
  • M. T. Collins
    • 2
  • J. Linderman
    • 1
  • S. Smith
    • 1
  • P. Herscovitch
    • 3
  • C. Millo
    • 3
  • K. Y. Chen
    • 1
  • F. S. Celi
    • 1
  1. 1.Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA
  2. 2.Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaUSA
  3. 3.PET Department, Clinical CenterNational Institutes of HealthBethesdaUSA

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