Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Mechanisms of Disease: is osteoporosis the obesity of bone?

Nature Clinical Practice Rheumatology volume 2, pages 35–43 (2006)Cite this article

Abstract

Osteoporosis and obesity, two disorders of body composition, are growing in prevalence. Interestingly, these diseases share several features including a genetic predisposition and a common progenitor cell. With aging, the composition of bone marrow shifts to favor the presence of adipocytes, osteoclast activity increases, and osteoblast function declines, resulting in osteoporosis. Secondary causes of osteoporosis, including diabetes mellitus, glucocorticoids and immobility, are associated with bone-marrow adiposity. In this review, we ask a provocative question: does fat infiltration in the bone marrow cause low bone mass or is it a result of bone loss? Unraveling the interface between bone and fat at a molecular and cellular level is likely to lead to a better understanding of several diseases, and to the development of drugs for both osteoporosis and obesity.

Key Points

  • Bone-marrow stromal cells can differentiate into adipocytes or osteoblasts

  • Bone-marrow adiposity increases with age in mammalian species

  • The function of fat in the bone marrow is unknown; it may be protective or detrimental

  • Increased bone-marrow fat as detected by MRI might be associated with greater fracture risk

  • The master controls over stem-cell lineage allocation are still not well defined

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Lineage allocation in the bone-marrow milieu.
Figure 2: (A) MRI of the radius in a 34-year-old healthy woman and (B) in a 64-year-old osteoporotic woman.

Similar content being viewed by others

References

  1. US Department of Health and Human Services (2004) Bone Health and Osteoporosis: A Report of the Surgeon General . Rockville: US Department of Health and Human Services

  2. Rosen CJ et al. (2001) Defining the genetics of osteoporosis: using the mouse to understand man. Osteoporos Int 12: 803–810

    Article  CAS  Google Scholar 

  3. Recker RR and Heaney RP (1993) Peak bone mineral density in young women. JAMA 270: 2926–2927

    Article  CAS  Google Scholar 

  4. Goulding A et al. (2001) Bone mineral density and body composition in boys with distal forearm fractures: a dual-energy X-ray absorptiometry study. J Pediatr 139: 509–515

    Article  CAS  Google Scholar 

  5. Brown S and Rosen CJ (2003) Osteoporosis. Med Clin North Am 87: 1039–1063

    Article  Google Scholar 

  6. Kveiborg M et al. (2000) Changes in the insulin-like growth factor-system may contribute to in vitro age-related impaired osteoblast functions. Exp Gerontol 35: 1061–1074

    Article  CAS  Google Scholar 

  7. Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21: 115–137

    CAS  PubMed  Google Scholar 

  8. Horowitz MC and Lorenzo JA (2004) The origins of osteoclasts. Curr Opin Rheumatol 16: 464–468

    Article  Google Scholar 

  9. Gimble JM et al. (1996) The function of adipocytes in the bone marrow stroma: an update. Bone 19: 421–428

    Article  CAS  Google Scholar 

  10. Cohen PG (2001) Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection. Med Hypotheses 56: 702–708

    Article  CAS  Google Scholar 

  11. Aubin JE (1998) Bone stem cells. J Cell Biochem Suppl 30–31: 73–82

    Article  Google Scholar 

  12. Ducy P et al. (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100: 197–207

    Article  CAS  Google Scholar 

  13. Takeda S et al. (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111: 305–317

    Article  CAS  Google Scholar 

  14. Elefteriou F et al. (2005) Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434: 514–520

    Article  CAS  Google Scholar 

  15. Steppan CM et al. (2000) Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept 92: 73–78

    Article  CAS  Google Scholar 

  16. Cornish J et al. (2002) Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo. J Endocrinol 175: 405–415

    Article  CAS  Google Scholar 

  17. Burguera B. et al. (2001) Leptin reduces ovariectomy-induced bone loss in rats. Endocrinology 142: 3546–3553

    Article  CAS  Google Scholar 

  18. Reid IR (2004) Leptin deficiency—lessons in regional differences in the regulation of bone mass. Bone 34: 369–371

    Article  CAS  Google Scholar 

  19. Hamrick MW et al. (2004) Leptin deficiency produces contrasting phenotypes in bones of the limb and spine. Bone 34: 376–383

    Article  CAS  Google Scholar 

  20. Dhillon H et al. (2004) β-adrenergic receptor KO mice have increased bone mass and strength but are not protected from ovariectomy-induced bone loss [abstract]. J Bone Miner Res 19 (Suppl): S32

    Google Scholar 

  21. Pierroz DD et al. (2004) β1β2 adrenergic receptor KO mice have decreased total body and cortical bone mass despite increased trabecular number [abstract]. J Bone Miner Res 19 (Suppl): S32

    Google Scholar 

  22. Akune T et al. (2004) PPARγ insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 113: 846–855

    Article  CAS  Google Scholar 

  23. Rzonca SO et al. (2004) Bone is a target for the antidiabetic compound rosiglitazone. Endocrinology 145: 401–406

    Article  CAS  Google Scholar 

  24. Moerman EJ et al. (2004) Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: the role of PPAR-γ2 transcription factor and TGF-β/BMP signaling pathways. Aging Cell 3: 379–389

    Article  CAS  Google Scholar 

  25. Uchiyama Y et al. (1994) Adipose conversion is accelerated in bone marrow cells of congenitally osteoporotic SAMP6 mice [abstract]. J Bone Miner Res 9 (Suppl 1): S321

    Google Scholar 

  26. Botolin S. et al. (2005) Increased bone adiposity and peroxisomal proliferator-activated receptor-γ2 expression in type I diabetic mice. Endocrinology 146: 3622–3631

    Article  CAS  Google Scholar 

  27. Rosen CJ et al. (2004) Congenic mice with low serum IGF-I have increased body fat, reduced bone mineral density, and an altered osteoblast differentiation program. Bone 35: 1046–1058

    Article  CAS  Google Scholar 

  28. Rosen CJ et al. (2005) Allelic differences in a quantitative trait locus affecting insulin-like growth factor-I impact skeletal acquisition and body composition. Pediatr Nephrol 20: 255–260

    Article  Google Scholar 

  29. Reid IR (2002) Relationships among body mass, its components, and bone. Bone 31: 547–555

    Article  CAS  Google Scholar 

  30. Wang MC et al. (2005) The relative contributions of lean tissue mass and fat mass to bone density in young women. Bone 37: 474–481

    Article  CAS  Google Scholar 

  31. von Mach MA et al. (2004) Changes in bone mineral content after surgical treatment of morbid obesity. Metabolism 53: 918–921

    Article  CAS  Google Scholar 

  32. Cummings SR et al. (1995) Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 332: 767–773

    Article  CAS  Google Scholar 

  33. Nguyen ND et al. (online 23 February 2005) Abdominal fat and hip fracture risk in the elderly: the Dubbo Osteoporosis Epidemiology Study. [http://www.biomedcentral.com/1471-2474/6/11] (accessed 4 October 2005)

  34. Garnero P et al. (2000) Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res 15: 1526–1536

    Article  CAS  Google Scholar 

  35. Adler RA and Rosen CJ (1994) Glucocorticoids and osteoporosis. Endocrinol Metab Clin North Am 23: 641–654

    Article  CAS  Google Scholar 

  36. Hsu Y et al. (2004) Major determinants of bone mineral density (BMD) at multiple skeletal sites in Chinese [abstract]. J Bone Miner Res 19 (Suppl): S421

    Google Scholar 

  37. Wehrli FW et al. (2000) Cross-sectional study of osteopenia with quantitative MR imaging and bone densitometry. Radiology 217: 527–538

    Article  CAS  Google Scholar 

  38. Meunier P et al. (1971) Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies. Clin Orthop Relat Res 80: 147–154

    Article  CAS  Google Scholar 

  39. Rozman C et al. (1989) Age-related variations of fat tissue fraction in normal human bone marrow depend both on size and number of adipocytes: a stereological study. Exp Hematol 17: 34–37

    CAS  PubMed  Google Scholar 

  40. Justesen J. et al. (2001) Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology 2: 165–171

    Article  CAS  Google Scholar 

  41. Verma S et al. (2002) Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis. J Clin Pathol 55: 693–698

    Article  CAS  Google Scholar 

  42. Schellinger D et al. (2001) Potential value of vertebral proton MR spectroscopy in determining bone weakness. AJNR Am J Neuroradiol 22: 1620–1627

    CAS  PubMed  Google Scholar 

  43. Yeung DK et al. (2005) Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study. J Magn Reson Imaging 22: 279–285

    Article  Google Scholar 

  44. Tuominen JT et al. (1999) Bone mineral density in patients with type 1 and type 2 diabetes. Diabetes Care 22: 1196–1200

    Article  CAS  Google Scholar 

  45. Li X et al. (2005) Steroid effects on osteogenesis through mesenchymal cell gene expression. Osteoporos Int 16: 101–108

    Article  Google Scholar 

  46. Cui Q et al. (2000) Pluripotential marrow cells produce adipocytes when transplanted into steroid-treated mice. Connect Tissue Res 41: 45–56

    Article  CAS  Google Scholar 

  47. van Staa TP et al. (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13: 777–787

    Article  CAS  Google Scholar 

  48. Ahdjoudj S et al. (2002) Transforming growth factor β2 inhibits adipocyte differentiation induced by skeletal unloading in rat bone marrow stroma. J Bone Miner Res 17: 668–677

    Article  CAS  Google Scholar 

  49. Papakitsou EF et al. (2004) Body mass index (BMI) and parameters of bone formation and resorption in postmenopausal women. Maturitas 47: 185–193

    Article  CAS  Google Scholar 

  50. Sekiya I et al. (2004) Adipogenic differentiation of human adult stem cells from bone marrow stroma (MSCs). J Bone Miner Res 19: 256–264

    Article  CAS  Google Scholar 

  51. Rodriguez JP et al. (2000) Mesenchymal stem cells from osteoporotic patients produce a type I collagen-deficient extracellular matrix favoring adipogenic differentiation. J Cell Biochem 79: 557–565

    Article  CAS  Google Scholar 

  52. Weisberg SP et al. (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112: 1796–1808

    Article  CAS  Google Scholar 

  53. Martin RB and Zissimos SL (1991) Relationships between marrow fat and bone turnover in ovariectomized and intact rats. Bone 12: 123–131

    Article  CAS  Google Scholar 

  54. Nuttall ME and Gimble JM (2004) Controlling the balance between osteoblastogenesis and adipogenesis and the consequent therapeutic implications. Curr Opin Pharmacol 4: 290–294

    Article  CAS  Google Scholar 

  55. Lecka-Czernik B et al. (1999) Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARγ2. J Cell Biochem 74: 357–371

    Article  CAS  Google Scholar 

  56. Dorheim MA et al. (1993) Osteoblastic gene expression during adipogenesis in hematopoietic supporting murine bone marrow stromal cells. J Cell Physiol 154: 317–328

    Article  CAS  Google Scholar 

  57. Beresford JN et al. (1992) Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J Cell Sci 102: 341–351

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Author information

Authors and Affiliations

  1. The Jackson Laboratory, Bar Harbor, ME, USA

    Clifford J Rosen

  2. Maine Center for Osteoporosis Research, Bangor, ME, USA

    Clifford J Rosen

  3. Assistant Professor of Orthopedic Surgery at Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, MA, USA

    Mary L Bouxsein

Authors
  1. Clifford J Rosen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mary L Bouxsein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clifford J Rosen.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rosen, C., Bouxsein, M. Mechanisms of Disease: is osteoporosis the obesity of bone?. Nat Rev Rheumatol 2, 35–43 (2006). https://doi.org/10.1038/ncprheum0070

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncprheum0070

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing