The bone-fat interface: Basic and clinical implications of marrow adiposity

The Lancet Diabetes and Endocrinology

Volumn 3, Issue 2, 2015, Pages 141-147

  Devlin, Maureen J ^a   Rosen, Clifford J ^b  

^a UNIVERSITY OF MICHIGAN   (United States)

^b Maine Medical Center Research Institute   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COLLAGEN TYPE 1; FATTY ACID BINDING PROTEIN 4; GHRELIN; GLUCOCORTICOID; INSULIN; INTERLEUKIN 6; LEPTIN; LIPOPROTEIN LIPASE; MESSENGER RNA; OSTEOCALCIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PIOGLITAZONE; PROTEIN ANTIBODY; ROSIGLITAZONE; SCLEROSTIN; SCLEROSTIN ANTIBODY; TRANSCRIPTION FACTOR RUNX2; TRANSFORMING GROWTH FACTOR BETA2; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; ZOLEDRONIC ACID;

ADIPOCYTE; ADIPOSE TISSUE; ANOREXIA NERVOSA; BIOACCUMULATION; BONE DENSITY; BONE MARROW; BONE MASS; BONE METABOLISM; CELL DIFFERENTIATION; DIABETES MELLITUS; DISEASE ASSOCIATION; HEMATOPOIETIC CELL; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; MARROW ADIPOSE TISSUE; MESENCHYMAL STEM CELL; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OSTEOBLAST; OSTEOPOROSIS; REVIEW; ANIMAL; COMPLICATION; FEMALE; MALE; METABOLISM; MOUSE; RAT;

ADIPOCYTES; ADIPOSE TISSUE; ANIMALS; ANOREXIA NERVOSA; BONE MARROW; DIABETES MELLITUS; FEMALE; HUMANS; MALE; MICE; OBESITY; OSTEOPOROSIS; RATS;

EID: 84921358001     PISSN: 22138587     EISSN: 22138595     Source Type: Journal    
DOI: 10.1016/S2213-8587(14)70007-5     Document Type: Review

References (81)

1. Nielson CM, Marshall LM, Adams AL, et al. BMI and fracture risk in older men: the osteoporotic fractures in men study (MrOS). J Bone Miner Res 2011, 26:496-502.
2. Leslie WD, Rubin MR, Schwartz AV, Kanis JA Type 2 diabetes and bone. J Bone Miner Res 2012, 27:2231-2237.
3. McCabe LR Understanding the pathology and mechanisms of type I diabetic bone loss. J Cell Biochem 2007, 102:1343-1357.
4. Bianco P, Robey PG, Saggio I, Riminucci M "Mesenchymal" stem cells in human bone marrow (skeletal stem cells): a critical discussion of their nature, identity, and significance in incurable skeletal disease. Hum Gene Ther 2010, 21:1057-1066.
5. Bianco P, Robey PG, Simmons PJ Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2008, 2:313-319.
6. Muruganandan S, Roman AA, Sinal CJ Adipocyte differentiation of bone marrow-derived mesenchymal stem cells: cross talk with the osteoblastogenic program. Cell Mol Life Sci 2009, 66:236-253.
7. DiGirolamo DJ, Clemens TL, Kousteni S. The skeleton as an endocrine organism. Nat Rev Rheumatol 8: 674-83.
8. Rahman S, Lu Y, Czernik PJ, Rosen CJ, Enerback S, Lecka-Czernik B Inducible brown adipose tissue, or beige fat, is anabolic for the skeleton. Endocrinology 2013, 154:2687-2701.
9. Neumann E The law of distribution of yellow and red marrow in the bones of the extremities. Cent J Med Sci 1882, 20:321-323.
10. Fazeli PK, Horowitz MC, MacDougald OA, et al. Marrow fat and bone-new perspectives. J Clin Endocrinol Metab 2013, 98:935-945.
11. Krings A, Rahman S, Huang S, Lu Y, Czernik PJ, Lecka-Czernik B Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes. Bone 2012, 50:546-552.
12. Sheu Y, Cauley JA The role of bone marrow and visceral fat on bone metabolism. Curr Osteoporos Rep 2011, 9:67-75.
13. Qin W, Bauman WA, Cardozo C Bone and muscle loss after spinal cord injury: organ interactions. Ann N Y Acad Sci 2010, 1211:66-84.
14. Moore SG, Dawson KL Red and yellow marrow in the femur: age-related changes in appearance at MR imaging. Radiology 1990, 175:219-223.
15. Bredella MA, Fazeli PK, Miller KK, et al. Increased bone marrow fat in anorexia nervosa. J Clin Endocrinol Metab 2009, 94:2129-2136.
16. Tuljapurkar SR, McGuire TR, Brusnahan SK, et al. Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging. J Anat 2011, 219:574-581.
17. Ecklund K, Vajapeyam S, Feldman HA, et al. Bone marrow changes in adolescent girls with anorexia nervosa. J Bone Miner Res 2010, 25:298-304.
18. Baum T, Yap SP, Karampinos DC, et al. Does vertebral bone marrow fat content correlate with abdominal adipose tissue, lumbar spine bone mineral density, and blood biomarkers in women with type 2 diabetes mellitus?. J Magn Reson Imaging 2012, 35:117-124.
19. Schwartz AV, Sigurdsson S, Hue TF, et al. Vertebral bone marrow fat associated with lower trabecular BMD and prevalent vertebral fracture in older adults. J Clin Endocrinol Metab 2013, 98:2294-2300.
20. Trudel G, Payne M, Mädler B, et al. Bone marrow fat accumulation after 60 days of bed rest persisted 1 year after activities were resumed along with hemopoietic stimulation: the Women International Space Simulation for Exploration study. J Appl Physiol (1985) 2009, 107:540-548.
21. 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, 22:279-285.
22. Kricun ME Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skeletal Radiol 1985, 14:10-19.
23. Abella E, Feliu E, Granada I, et al. Bone marrow changes in anorexia nervosa are correlated with the amount of weight loss and not with other clinical findings. Am J Clin Pathol 2002, 118:582-588.
24. Fazeli PK, Bredella MA, Freedman L, et al. Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa. J Bone Miner Res 2012, 27:1864-1871.
25. Cohen A, Dempster DW, Stein EM, et al. Increased marrow adiposity in premenopausal women with idiopathic osteoporosis. J Clin Endocrinol Metab 2012, 97:2782-2791.
26. Duque G, Li W, Adams M, Xu S, Phipps R Effects of risedronate on bone marrow adipocytes in postmenopausal women. Osteoporos Int 2011, 22:1547-1553.
27. Dudley-Javoroski S, Shields RK Dose estimation and surveillance of mechanical loading interventions for bone loss after spinal cord injury. Phys Ther 2008, 88:387-396.
28. Minaire P, Edouard C, Arlot M, Meunier PJ Marrow changes in paraplegic patients. Calcif Tissue Int 1984, 36:338-340.
29. Moyer-Mileur LJ, Slater H, Jordan KC, Murray MA IGF-1 and IGF-binding proteins and bone mass, geometry, and strength: relation to metabolic control in adolescent girls with type 1 diabetes. J Bone Miner Res 2008, 23:1884-1891.
30. McCabe L, Zhang J, Raehtz S Understanding the skeletal pathology of type 1 and 2 diabetes mellitus. Crit Rev Eukaryot Gene Expr 2011, 21:187-206.
31. Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature 2009, 460:259-263.
32. Ackert-Bicknell CL, Shockley KR, Horton LG, Lecka-Czernik B, Churchill GA, Rosen CJ Strain-specific effects of rosiglitazone on bone mass, body composition, and serum insulin-like growth factor-I. Endocrinology 2009, 150:1330-1340.
33. Lecka-Czernik B Marrow fat metabolism is linked to the systemic energy metabolism. Bone 2012, 50:534-539.
34. Cao JJ Effects of obesity on bone metabolism. J Orthop Surg 2011, 6:30.
35. Rosen CJ, Klibanski A Bone, fat, and body composition: evolving concepts in the pathogenesis of osteoporosis. Am J Med 2009, 122:409-414.
36. Georgiou KR, Hui SK, Xian CJ Regulatory pathways associated with bone loss and bone marrow adiposity caused by aging, chemotherapy, glucocorticoid therapy and radiotherapy. Am J S Cell 2012, 1:205-224.
37. Zebaze RM, Ghasem-Zadeh A, Bohte A, et al. Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet 2010, 375:1729-1736.
38. Patsch JM, Burghardt AJ, Yap SP, et al. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res 2013, 28:313-324.
39. Newton AL, Hanks LJ, Davis M, Casazza K The relationships among total body fat, bone mineral content and bone marrow adipose tissue in early-pubertal girls. Bonekey Rep 2013, 2:315.
40. Di Iorgi N, Mo AO, Grimm K, Wren TA, Dorey F, Gilsanz V Bone acquisition in healthy young females is reciprocally related to marrow adiposity. J Clin Endocrinol Metab 2010, 95:2977-2982.
41. Di Iorgi N, Rosol M, Mittelman SD, Gilsanz V Reciprocal relation between marrow adiposity and the amount of bone in the axial and appendicular skeleton of young adults. J Clin Endocrinol Metab 2008, 93:2281-2286.
42. Wren TA, Chung SA, Dorey FJ, Bluml S, Adams GB, Gilsanz V Bone marrow fat is inversely related to cortical bone in young and old subjects. J Clin Endocrinol Metab 2011, 96:782-786.
43. Shen W, Chen J, Gantz M, et al. MRI-measured pelvic bone marrow adipose tissue is inversely related to DXA-measured bone mineral in younger and older adults. Eur J Clin Nutr 2012, 66:983-988.
44. Fazeli PK, Bredella MA, Misra M, et al. Preadipocyte factor-1 is associated with marrow adiposity and bone mineral density in women with anorexia nervosa. J Clin Endocrinol Metab 2010, 95:407-413.
45. Tatsumi S, Ito M, Asaba Y, Tsutsumi K, Ikeda K Life-long caloric restriction reveals biphasic and dimorphic effects on bone metabolism in rodents. Endocrinology 2008, 149:634-641.
46. Hamrick MW, Ding KH, Ponnala S, Ferrari SL, Isales CM Caloric restriction decreases cortical bone mass but spares trabecular bone in the mouse skeleton: implications for the regulation of bone mass by body weight. J Bone Miner Res 2008, 23:870-878.
47. Devlin MJ, Cloutier AM, Thomas NA, et al. Caloric restriction leads to high marrow adiposity and low bone mass in growing mice. J Bone Miner Res 2010, 25:2078-2088.
48. Baek K, Bloomfield SA Blocking β-adrenergic signaling attenuates reductions in circulating leptin, cancellous bone mass, and marrow adiposity seen with dietary energy restriction. J Appl Physiol (1985) 2012, 113:1792-1801.
49. Hamrick MW, Della-Fera MA, Choi YH, Pennington C, Hartzell D, Baile CA Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. J Bone Miner Res 2005, 20:994-1001.
50. Hamrick MW, Della Fera MA, Choi YH, Hartzell D, Pennington C, Baile CA Injections of leptin into rat ventromedial hypothalamus increase adipocyte apoptosis in peripheral fat and in bone marrow. Cell Tissue Res 2007, 327:133-141.
51. Schwartz AV, Vittinghoff E, Bauer DC, et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 2011, 305:2184-2192. the Study of Osteoporotic Fractures (SOF) Research Group, the Osteoporotic Fractures in Men (MrOS) Research Groupthe Osteoporotic Fractures in Men (MrOS) Research Group, the Health, Agingthe Health, Aging, Body Composition (Health ABC) Research GroupBody Composition (Health ABC) Research Group.
52. Patsch JM, Li X, Baum T, et al. Bone marrow fat composition as a novel imaging biomarker in postmenopausal women with prevalent fragility fractures. J Bone Miner Res 2013, 28:1721-1728.
53. Botolin S, McCabe LR Bone loss and increased bone adiposity in spontaneous and pharmacologically induced diabetic mice. Endocrinology 2007, 148:198-205.
54. 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, 146:3622-3631.
55. Botolin S, McCabe LR Inhibition of PPARgamma prevents type I diabetic bone marrow adiposity but not bone loss. J Cell Physiol 2006, 209:967-976.
56. Motyl KJ, McCabe LR Leptin treatment prevents type I diabetic marrow adiposity but not bone loss in mice. J Cell Physiol 2009, 218:376-384.
57. Duque G, Li W, Vidal C, Bermeo S, Rivas D, Henderson J Pharmacological inhibition of PPARgamma increases osteoblastogenesis and bone mass in male C57BL/6 mice. J Bone Miner Res 2013, 28:639-648.
58. Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res 2009, 24:702-709.
59. Burghardt AJ, Issever AS, Schwartz AV, et al. High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2010, 95:5045-5055.
60. Rzonca SO, Suva LJ, Gaddy D, Montague DC, Lecka-Czernik B Bone is a target for the antidiabetic compound rosiglitazone. Endocrinology 2004, 145:401-406.
61. Syversen U, Stunes AK, Gustafsson BI, et al. Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)alpha agonist fenofibrate and the PPARgamma agonist pioglitazone. BMC Endocr Disord 2009, 9:10.
62. Lecka-Czernik B, Ackert-Bicknell C, Adamo ML, et al. Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by rosiglitazone suppresses components of the insulin-like growth factor regulatory system in vitro and in vivo. Endocrinology 2007, 148:903-911.
63. Grey A, Beckley V, Doyle A, et al. Pioglitazone increases bone marrow fat in type 2 diabetes: results from a randomized controlled trial. Eur J Endocrinol 2012, 166:1087-1091.
64. Harsløf T, Wamberg L, Møller L, et al. Rosiglitazone decreases bone mass and bone marrow fat. J Clin Endocrinol Metab 2011, 96:1541-1548.
65. Trudel G, Coletta E, Cameron I, et al. Resistive exercises, with or without whole body vibration, prevent vertebral marrow fat accumulation during 60 days of head-down tilt bed rest in men. J Appl Physiol (1985) 2012, 112:1824-1831.
66. Wronski TJ, Morey-Holton E, Jee WS Cosmos 1129: spaceflight and bone changes. Physiologist 1980, 23(suppl 6):79-82.
67. Jee WS, Wronski TJ, Morey ER, Kimmel DB Effects of spaceflight on trabecular bone in rats. Am J Physiol 1983, 244:R310-R314.
68. Wronski TJ, Morey ER Skeletal abnormalities in rats induced by simulated weightlessness. Metab Bone Dis Relat Res 1982, 4:69-75.
69. Wronski TJ, Morey ER Recovery of the rat skeleton from the adverse effects of simulated weightlessness. Metab Bone Dis Relat Res 1983, 4:347-352.
70. Ahdjoudj S, Lasmoles F, Holy X, Zerath E, Marie PJ Transforming growth factor beta2 inhibits adipocyte differentiation induced by skeletal unloading in rat bone marrow stroma. J Bone Miner Res 2002, 17:668-677.
71. Ahdjoudj S, Kaabeche K, Holy X, et al. Transforming growth factor-beta inhibits CCAAT/enhancer-binding protein expression and PPARgamma activity in unloaded bone marrow stromal cells. Exp Cell Res 2005, 303:138-147.
72. 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 biopsies. Clin Orthop Relat Res 1971, 80:147-154.
73. Duque G, Rivas D, Li W, et al. Age-related bone loss in the LOU/c rat model of healthy ageing. Exp Gerontol 2009, 44:183-189.
74. Glatt V, Canalis E, Stadmeyer L, Bouxsein ML Age-related changes in trabecular architecture differ in female and male C57BL/6J mice. J Bone Miner Res 2007, 22:1197-1207.
75. Lazarenko OP, Rzonca SO, Hogue WR, Swain FL, Suva LJ, Lecka-Czernik B Rosiglitazone induces decreases in bone mass and strength that are reminiscent of aged bone. Endocrinology 2007, 148:2669-2680.
76. Li GW, Xu Z, Chen QW, Chang SX, Tian YN, Fan JZ The temporal characterization of marrow lipids and adipocytes in a rabbit model of glucocorticoid-induced osteoporosis. Skeletal Radiol 2013, 42:1235-1244.
77. Li GW, Chang SX, Fan JZ, Tian YN, Xu Z, He YM Marrow adiposity recovery after early zoledronic acid treatment of glucocorticoid-induced bone loss in rabbits assessed by magnetic resonance spectroscopy. Bone 2013, 52:668-675.
78. Hamrick MW Leptin, bone mass, and the thrifty phenotype. J Bone Miner Res 2004, 19:1607-1611.
79. Thompson NM, Gill DA, Davies R, et al. Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology 2004, 145:234-242.
80. Scheller EL, Rosen CJ. What's the matter with MAT? - Marrow adipose tissue, metabolism and skeletal health. Ann N Y Acad Sci (in press).
81. Kang MJ, Lim JS Bone mineral density deficits in childhood cancer survivors: pathophysiology, prevalence, screening, and management. Korean J Pediatr 2013, 56:60-67.