Bone marrow adipose tissue

Bone marrow adipocytes (BMAds){{Cite journal |display-authors=6 |vauthors=Bravenboer N, Bredella MA, Chauveau C, Corsi A, Douni E, Ferris WF, Riminucci M, Robey PG, Rojas-Sutterlin S, Rosen C, Schulz TJ, Cawthorn WP |date=2020 |title=Standardised Nomenclature, Abbreviations, and Units for the Study of Bone Marrow Adiposity: Report of the Nomenclature Working Group of the International Bone Marrow Adiposity Society |journal=Frontiers in Endocrinology |volume=10 |pages=923 |doi=10.3389/fendo.2019.00923 |pmc=6993042 |pmid=32038486 |doi-access=free}} originate from mesenchymal stem cell (MSC) progenitors that also give rise to osteoblasts, among other cell types.{{Cite journal |vauthors=Muruganandan S, Roman AA, Sinal CJ |date=January 2009 |title=Adipocyte differentiation of bone marrow-derived mesenchymal stem cells: cross talk with the osteoblastogenic program |journal=Cellular and Molecular Life Sciences |volume=66 |issue=2 |pages=236–253 |doi=10.1007/s00018-008-8429-z |pmc=11131547 |pmid=18854943 |s2cid=5558912}} Thus, it is thought that BMAT results from preferential MSC differentiation into the adipocyte, rather than osteoblast, lineage in the setting of osteoporosis.{{Cite journal |vauthors=Paccou J, Hardouin P, Cotten A, Penel G, Cortet B |date=October 2015 |title=The Role of Bone Marrow Fat in Skeletal Health: Usefulness and Perspectives for Clinicians |journal=The Journal of Clinical Endocrinology and Metabolism |volume=100 |issue=10 |pages=3613–3621 |doi=10.1210/jc.2015-2338 |pmid=26244490 |doi-access=free}} Since BMAT is increased in the setting of obesity{{Cite journal |display-authors=6 |vauthors=Styner M, Thompson WR, Galior K, Uzer G, Wu X, Kadari S, Case N, Xie Z, Sen B, Romaine A, Pagnotti GM, Rubin CT, Styner MA, Horowitz MC, Rubin J |date=July 2014 |title=Bone marrow fat accumulation accelerated by high fat diet is suppressed by exercise |journal=Bone |volume=64 |pages=39–46 |doi=10.1016/j.bone.2014.03.044 |pmc=4041820 |pmid=24709686}}{{Cite journal |display-authors=6 |vauthors=Scheller EL, Khoury B, Moller KL, Wee NK, Khandaker S, Kozloff KM, Abrishami SH, Zamarron BF, Singer K |date=2016 |title=Changes in Skeletal Integrity and Marrow Adiposity during High-Fat Diet and after Weight Loss |journal=Frontiers in Endocrinology |volume=7 |pages=102 |doi=10.3389/fendo.2016.00102 |pmc=4961699 |pmid=27512386 |doi-access=free}}{{Cite journal |vauthors=Doucette CR, Horowitz MC, Berry R, MacDougald OA, Anunciado-Koza R, Koza RA, Rosen CJ |date=September 2015 |title=A High Fat Diet Increases Bone Marrow Adipose Tissue (MAT) But Does Not Alter Trabecular or Cortical Bone Mass in C57BL/6J Mice |journal=Journal of Cellular Physiology |volume=230 |issue=9 |pages=2032–2037 |doi=10.1002/jcp.24954 |pmc=4580244 |pmid=25663195}} and is suppressed by endurance exercise,{{Cite journal |display-authors=6 |vauthors=Styner M, Pagnotti GM, Galior K, Wu X, Thompson WR, Uzer G, Sen B, Xie Z, Horowitz MC, Styner MA, Rubin C, Rubin J |date=August 2015 |title=Exercise Regulation of Marrow Fat in the Setting of PPARγ Agonist Treatment in Female C57BL/6 Mice |journal=Endocrinology |volume=156 |issue=8 |pages=2753–2761 |doi=10.1210/en.2015-1213 |pmc=4511140 |pmid=26052898}}{{Cite journal |display-authors=6 |vauthors=Styner M, Pagnotti GM, McGrath C, Wu X, Sen B, Uzer G, Xie Z, Zong X, Styner MA, Rubin CT, Rubin J |date=August 2017 |title=Exercise Decreases Marrow Adipose Tissue Through β-Oxidation in Obese Running Mice |journal=Journal of Bone and Mineral Research |volume=32 |issue=8 |pages=1692–1702 |doi=10.1002/jbmr.3159 |pmc=5550355 |pmid=28436105}}{{Cite journal |display-authors=6 |vauthors=Pagnotti GM, Styner M, Uzer G, Patel VS, Wright LE, Ness KK, Guise TA, Rubin J, Rubin CT |date=June 2019 |title=Combating osteoporosis and obesity with exercise: leveraging cell mechanosensitivity |journal=Nature Reviews. Endocrinology |volume=15 |issue=6 |pages=339–355 |doi=10.1038/s41574-019-0170-1 |pmc=6520125 |pmid=30814687}} or vibration,{{Cite journal |vauthors=Luu YK, Pessin JE, Judex S, Rubin J, Rubin CT |date=April 2009 |title=Mechanical Signals As a Non-Invasive Means to Influence Mesenchymal Stem Cell Fate, Promoting Bone and Suppressing the Fat Phenotype |journal=BoneKEy Osteovision |volume=6 |issue=4 |pages=132–149 |doi=10.1138/20090371 |pmc=3255555 |pmid=22241295}} it is likely that BMAT physiology, in the setting of mechanical input/exercise, approximates that of white adipose tissue (WAT).

The first study to demonstrate exercise regulation of BMAT in rodents was published in 2014; Now, exercise regulation of BMAT has been confirmed in a human,{{Cite journal |vauthors=Belavy DL, Quittner MJ, Ridgers ND, Shiekh A, Rantalainen T, Trudel G |date=April 2018 |title=Specific Modulation of Vertebral Marrow Adipose Tissue by Physical Activity |journal=Journal of Bone and Mineral Research |volume=33 |issue=4 |pages=651–657 |doi=10.1002/jbmr.3357 |pmid=29336053 |doi-access=free |hdl-access=free |hdl=10536/DRO/DU:30106029}} adding clinical importance. Several studies demonstrated exercise reduction of BMAT which occurs along with an increase in bone quantity.{{Cite journal |vauthors=Little-Letsinger SE, Pagnotti GM, McGrath C, Styner M |date=December 2020 |title=Exercise and Diet: Uncovering Prospective Mediators of Skeletal Fragility in Bone and Marrow Adipose Tissue |journal=Current Osteoporosis Reports |volume=18 |issue=6 |pages=774–789 |doi=10.1007/s11914-020-00634-y |pmc=7736569 |pmid=33068251}} Since exercise increases bone quantity, reduces BMAT and increases expression of markers of fatty acid oxidation in bone, BMAT is thought to be providing needed fuel for exercise-induced bone formation or anabolism. A notable exception occurs in the setting of caloric restriction: exercise suppression of BMAT does not yield an increase in bone formation and even appears to cause bone loss.{{Cite journal |vauthors=Southmayd EA, Williams NI, Mallinson RJ, De Souza MJ |date=August 2019 |title=Energy Deficiency Suppresses Bone Turnover in Exercising Women With Menstrual Disturbances |journal=The Journal of Clinical Endocrinology and Metabolism |volume=104 |issue=8 |pages=3131–3145 |doi=10.1210/jc.2019-00089 |pmid=30896746 |doi-access=free}} Indeed, energy availability appears to be a factor in the ability of exercise to regulate BMAT. Another exception occurs in lipodystrophy, a condition with reduced overall adipose stores: exercise- induced anabolism is possible, even with minimal BMAT stores.{{Cite journal |display-authors=6 |vauthors=McGrath C, Little-Letsinger SE, Sankaran JS, Sen B, Xie Z, Styner MA, Zong X, Chen W, Rubin J, Klett EL, Coleman RA, Styner M |date=2022-01-25 |title=Exercise Increases Bone in SEIPIN Deficient Lipodystrophy, Despite Low Marrow Adiposity |journal=Frontiers in Endocrinology |volume=12 |pages=782194 |doi=10.3389/fendo.2021.782194 |pmc=8822583 |pmid=35145475 |doi-access=free}}

BMAT has been reported to have qualities of both white and brown fat.{{Cite journal |vauthors=Krings A, Rahman S, Huang S, Lu Y, Czernik PJ, Lecka-Czernik B |date=February 2012 |title=Bone marrow fat has brown adipose tissue characteristics, which are attenuated with aging and diabetes |journal=Bone |volume=50 |issue=2 |pages=546–552 |doi=10.1016/j.bone.2011.06.016 |pmc=3214232 |pmid=21723971}} However, more-recent functional and -omics studies have shown that BMAT is a unique adipose depot that is molecularly and functionally distinct to WAT or BAT.{{Cite journal |display-authors=6 |vauthors=Suchacki KJ, Tavares AA, Mattiucci D, Scheller EL, Papanastasiou G, Gray C, Sinton MC, Ramage LE, McDougald WA, Lovdel A, Sulston RJ, Thomas BJ, Nicholson BM, Drake AJ, Alcaide-Corral CJ, Said D, Poloni A, Cinti S, Macpherson GJ, Dweck MR, Andrews JP, Williams MC, Wallace RJ, van Beek EJ, MacDougald OA, Morton NM, Stimson RH, Cawthorn WP |date=June 2020 |title=Bone marrow adipose tissue is a unique adipose subtype with distinct roles in glucose homeostasis |journal=Nature Communications |volume=11 |issue=1 |pages=3097 |bibcode=2020NatCo..11.3097S |doi=10.1038/s41467-020-16878-2 |pmc=7303125 |pmid=32555194}}{{Cite journal |display-authors=6 |vauthors=Craft CS, Robles H, Lorenz MR, Hilker ED, Magee KL, Andersen TL, Cawthorn WP, MacDougald OA, Harris CA, Scheller EL |date=November 2019 |title=Bone marrow adipose tissue does not express UCP1 during development or adrenergic-induced remodeling |journal=Scientific Reports |volume=9 |issue=1 |pages=17427 |bibcode=2019NatSR...917427C |doi=10.1038/s41598-019-54036-x |pmc=6874537 |pmid=31758074}}{{Cite journal |display-authors=6 |vauthors=Scheller EL, Khandaker S, Learman BS, Cawthorn WP, Anderson LM, Pham HA, Robles H, Wang Z, Li Z, Parlee SD, Simon BR, Mori H, Bree AJ, Craft CS, MacDougald OA |date=January 2019 |title=Bone marrow adipocytes resist lipolysis and remodeling in response to β-adrenergic stimulation |journal=Bone |volume=118 |pages=32–41 |doi=10.1016/j.bone.2018.01.016 |pmc=6062480 |pmid=29360620}}{{Cite journal |display-authors=6 |vauthors=Attané C, Estève D, Chaoui K, Iacovoni JS, Corre J, Moutahir M, Valet P, Schiltz O, Reina N, Muller C |date=January 2020 |title=Human Bone Marrow Is {{sic|Comprised|hide=y|of}} Adipocytes with Specific Lipid Metabolism |journal=Cell Reports |volume=30 |issue=4 |pages=949–958.e6 |doi=10.1016/j.celrep.2019.12.089 |pmid=31995765 |s2cid=210949460 |doi-access=free}} Subcutaneous white fat contain excess energy, indicating a clear evolutionary advantage during times of scarcity. WAT is also the source of adipokines and inflammatory markers which have both positive (e.g., adiponectin){{Cite journal |vauthors=Ye R, Scherer PE |date=April 2013 |title=Adiponectin, driver or passenger on the road to insulin sensitivity? |journal=Molecular Metabolism |volume=2 |issue=3 |pages=133–141 |doi=10.1016/j.molmet.2013.04.001 |pmc=3773837 |pmid=24049728}} and negative{{Cite journal |vauthors=Tilg H, Moschen AR |date=October 2006 |title=Adipocytokines: mediators linking adipose tissue, inflammation and immunity |journal=Nature Reviews. Immunology |volume=6 |issue=10 |pages=772–783 |doi=10.1038/nri1937 |pmid=16998510 |s2cid=29865593}} effects on metabolic and cardiovascular endpoints. Visceral abdominal fat (VAT) is a distinct type of WAT that is "proportionally associated with negative metabolic and cardiovascular morbidity",{{Cite journal |vauthors=Wronska A, Kmiec Z |date=June 2012 |title=Structural and biochemical characteristics of various white adipose tissue depots |journal=Acta Physiologica |volume=205 |issue=2 |pages=194–208 |doi=10.1111/j.1748-1716.2012.02409.x |pmid=22226221 |s2cid=22915022}} regenerates cortisol,{{Cite journal |vauthors=Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS |date=December 2001 |title=A transgenic model of visceral obesity and the metabolic syndrome |journal=Science |volume=294 |issue=5549 |pages=2166–2170 |bibcode=2001Sci...294.2166M |doi=10.1126/science.1066285 |pmid=11739957 |s2cid=768303}} and recently has been tied to decreased bone formation{{Cite journal |display-authors=6 |vauthors=Bredella MA, Lin E, Gerweck AV, Landa MG, Thomas BJ, Torriani M, Bouxsein ML, Miller KK |date=November 2012 |title=Determinants of bone microarchitecture and mechanical properties in obese men |journal=The Journal of Clinical Endocrinology and Metabolism |volume=97 |issue=11 |pages=4115–4122 |doi=10.1210/jc.2012-2246 |pmc=3485587 |pmid=22933540}}{{Cite journal |display-authors=6 |vauthors=Cohen A, Dempster DW, Recker RR, Lappe JM, Zhou H, Zwahlen A, Müller R, Zhao B, Guo X, Lang T, Saeed I, Liu XS, Guo XE, Cremers S, Rosen CJ, Stein EM, Nickolas TL, McMahon DJ, Young P, Shane E |date=June 2013 |title=Abdominal fat is associated with lower bone formation and inferior bone quality in healthy premenopausal women: a transiliac bone biopsy study |journal=The Journal of Clinical Endocrinology and Metabolism |volume=98 |issue=6 |pages=2562–2572 |doi=10.1210/jc.2013-1047 |pmc=3667251 |pmid=23515452}} Both types of WAT substantially differ from brown adipose tissue (BAT) as by a group of proteins that help BAT's thermogenic role.{{Cite journal |vauthors=Wu J, Cohen P, Spiegelman BM |date=February 2013 |title=Adaptive thermogenesis in adipocytes: is beige the new brown? |journal=Genes & Development |volume=27 |issue=3 |pages=234–250 |doi=10.1101/gad.211649.112 |pmc=3576510 |pmid=23388824}} BMAT, by its "specific marrow location, and its adipocyte origin from at least LepR+ marrow MSC is separated from non-bone fat storage by larger expression of bone transcription factors",{{Cite journal |display-authors=6 |vauthors=Al-Nbaheen M, Vishnubalaji R, Ali D, Bouslimi A, Al-Jassir F, Megges M, Prigione A, Adjaye J, Kassem M, Aldahmash A |date=February 2013 |title=Human stromal (mesenchymal) stem cells from bone marrow, adipose tissue and skin exhibit differences in molecular phenotype and differentiation potential |journal=Stem Cell Reviews and Reports |volume=9 |issue=1 |pages=32–43 |doi=10.1007/s12015-012-9365-8 |pmc=3563956 |pmid=22529014}} and likely indicates a different fat phenotype.{{Cite journal |vauthors=Gimble JM, Zvonic S, Floyd ZE, Kassem M, Nuttall ME |date=May 2006 |title=Playing with bone and fat |journal=Journal of Cellular Biochemistry |volume=98 |issue=2 |pages=251–266 |doi=10.1002/jcb.20777 |pmid=16479589 |s2cid=19746472}} Recently, BMAT was noted to "produce a greater proportion of adiponectin – an adipokine associated with improved metabolism – than WAT",{{Cite journal |display-authors=6 |vauthors=Cawthorn WP, Scheller EL, Learman BS, Parlee SD, Simon BR, Mori H, Ning X, Bree AJ, Schell B, Broome DT, Soliman SS, DelProposto JL, Lumeng CN, Mitra A, Pandit SV, Gallagher KA, Miller JD, Krishnan V, Hui SK, Bredella MA, Fazeli PK, Klibanski A, Horowitz MC, Rosen CJ, MacDougald OA |date=August 2014 |title=Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction |journal=Cell Metabolism |volume=20 |issue=2 |pages=368–375 |doi=10.1016/j.cmet.2014.06.003 |pmc=4126847 |pmid=24998914}} suggesting an endocrine function for this depot, akin, but different, from that of WAT.

BMAT increases in states of bone fragility. BMAT is thought to result from preferential MSC differentiation into an adipocyte, rather than osteoblast lineage in osteoporosis based on the inverse relationship between bone and BMAT in bone-fragile osteoporotic states. An increase in BMAT is noted in osteoporosis clinical studies measured by MR spectroscopy.{{Cite journal |vauthors=Duque G, Li W, Adams M, Xu S, Phipps R |date=May 2011 |title=Effects of risedronate on bone marrow adipocytes in postmenopausal women |journal=Osteoporosis International |volume=22 |issue=5 |pages=1547–1553 |doi=10.1007/s00198-010-1353-8 |pmid=20661545 |s2cid=27850362}}{{Cite journal |vauthors=Yeung DK, Griffith JF, Antonio GE, Lee FK, Woo J, Leung PC |date=August 2005 |title=Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: a proton MR spectroscopy study |journal=Journal of Magnetic Resonance Imaging |volume=22 |issue=2 |pages=279–285 |doi=10.1002/jmri.20367 |pmid=16028245 |s2cid=2941430 |doi-access=free}}{{Cite journal |vauthors=Li X, Kuo D, Schafer AL, Porzig A, Link TM, Black D, Schwartz AV |date=April 2011 |title=Quantification of vertebral bone marrow fat content using 3 Tesla MR spectroscopy: reproducibility, vertebral variation, and applications in osteoporosis |journal=Journal of Magnetic Resonance Imaging |volume=33 |issue=4 |pages=974–979 |doi=10.1002/jmri.22489 |pmc=3072841 |pmid=21448966}} Estrogen therapy in postmenopausal osteoporosis reduces BMAT.{{Cite journal |vauthors=Syed FA, Oursler MJ, Hefferanm TE, Peterson JM, Riggs BL, Khosla S |date=September 2008 |title=Effects of estrogen therapy on bone marrow adipocytes in postmenopausal osteoporotic women |journal=Osteoporosis International |volume=19 |issue=9 |pages=1323–1330 |doi=10.1007/s00198-008-0574-6 |pmc=2652842 |pmid=18274695}} Antiresorptive therapies like risedronate or zoledronate also decrease BMAT while increasing bone density, supporting an inverse relationship between bone quantity and BMAT. During aging, bone quantity declines{{Cite journal |display-authors=6 |vauthors=Khosla S, Riggs BL, Atkinson EJ, Oberg AL, McDaniel LJ, Holets M, Peterson JM, Melton LJ |date=January 2006 |title=Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment |journal=Journal of Bone and Mineral Research |volume=21 |issue=1 |pages=124–131 |doi=10.1359/jbmr.050916 |pmc=1352156 |pmid=16355281}}{{Cite journal |vauthors=Glatt V, Canalis E, Stadmeyer L, Bouxsein ML |date=August 2007 |title=Age-related changes in trabecular architecture differ in female and male C57BL/6J mice |journal=Journal of Bone and Mineral Research |volume=22 |issue=8 |pages=1197–1207 |doi=10.1359/jbmr.070507 |pmid=17488199 |doi-access=free}} and fat redistributes from subcutaneous to ectopic sites such as bone marrow, muscle, and liver.{{Cite journal |display-authors=6 |vauthors=Tchkonia T, Morbeck DE, Von Zglinicki T, Van Deursen J, Lustgarten J, Scrable H, Khosla S, Jensen MD, Kirkland JL |date=October 2010 |title=Fat tissue, aging, and cellular senescence |journal=Aging Cell |volume=9 |issue=5 |pages=667–684 |doi=10.1111/j.1474-9726.2010.00608.x |pmc=2941545 |pmid=20701600}} Aging is associated with lower osteogenic and greater adipogenic biasing of MSC.{{Cite journal |vauthors=Kassem M, Marie PJ |date=April 2011 |title=Senescence-associated intrinsic mechanisms of osteoblast dysfunctions |journal=Aging Cell |volume=10 |issue=2 |pages=191–197 |doi=10.1111/j.1474-9726.2011.00669.x |pmid=21210937 |doi-access=free}} This aging-related biasing of MSC away from osteoblast lineage may represent higher basal PPARγ expression{{Cite journal |vauthors=Moerman EJ, Teng K, Lipschitz DA, Lecka-Czernik B |date=December 2004 |title=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 pathways |journal=Aging Cell |volume=3 |issue=6 |pages=379–389 |doi=10.1111/j.1474-9728.2004.00127.x |pmc=1850101 |pmid=15569355}} or decreased Wnt10b.{{Cite journal |vauthors=Stevens JR, Miranda-Carboni GA, Singer MA, Brugger SM, Lyons KM, Lane TF |date=October 2010 |title=Wnt10b deficiency results in age-dependent loss of bone mass and progressive reduction of mesenchymal progenitor cells |journal=Journal of Bone and Mineral Research |volume=25 |issue=10 |pages=2138–2147 |doi=10.1002/jbmr.118 |pmc=3153316 |pmid=20499361}}{{Cite journal |display-authors=6 |vauthors=Bennett CN, Ouyang H, Ma YL, Zeng Q, Gerin I, Sousa KM, Lane TF, Krishnan V, Hankenson KD, MacDougald OA |date=December 2007 |title=Wnt10b increases postnatal bone formation by enhancing osteoblast differentiation |journal=Journal of Bone and Mineral Research |volume=22 |issue=12 |pages=1924–1932 |doi=10.1359/jbmr.070810 |pmid=17708715 |doi-access=free}}{{Cite journal |display-authors=6 |vauthors=Chen Q, Shou P, Zheng C, Jiang M, Cao G, Yang Q, Cao J, Xie N, Velletri T, Zhang X, Xu C, Zhang L, Yang H, Hou J, Wang Y, Shi Y |date=July 2016 |title=Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? |journal=Cell Death and Differentiation |volume=23 |issue=7 |pages=1128–1139 |doi=10.1038/cdd.2015.168 |pmc=4946886 |pmid=26868907}} Thus, bone fragility, osteoporosis, and osteoporotic fractures are thought to be linked to mechanisms which promote BMAT accumulation.{{citation needed|date=August 2021}}

BMAds secrete factors that promote HSC renewal in most bones.{{Cite journal |vauthors=Zhou BO, Yu H, Yue R, Zhao Z, Rios JJ, Naveiras O, Morrison SJ |date=August 2017 |title=Bone marrow adipocytes promote the regeneration of stem cells and haematopoiesis by secreting SCF |journal=Nature Cell Biology |volume=19 |issue=8 |pages=891–903 |doi=10.1038/ncb3570 |pmc=5536858 |pmid=28714970}}

Hematopoietic cells (also known as blood cells) reside in the bone marrow along with BMAds. These hematopoietic cells are derived from hematopoietic stem cells (HSC) which give rise to diverse cells: cells of the blood, immune system, as well as cells that break down bone (osteoclasts). HSC renewal occurs in the marrow stem cell niche, a microenvironment that contains cells and secreted factors that promote appropriate renewal and differentiation of HSC. The study of the stem cell niche is relevant to the field of oncology in order to improve therapy for multiple hematologic cancers. As such cancers are often treated with bone marrow transplantation, there is interest in improving the renewal of HSC.{{citation needed|date=August 2021}}

In order to understand the physiology of BMAT, various analytic methods have been applied. BMAds are difficult to isolate and quantify because they are interspersed with bony and hematopoietic elements. Until recently, qualitative measurements of BMAT have relied on bone histology,{{Cite journal |vauthors=Bielohuby M, Matsuura M, Herbach N, Kienzle E, Slawik M, Hoeflich A, Bidlingmaier M |date=February 2010 |title=Short-term exposure to low-carbohydrate, high-fat diets induces low bone mineral density and reduces bone formation in rats |journal=Journal of Bone and Mineral Research |volume=25 |issue=2 |pages=275–284 |doi=10.1359/jbmr.090813 |pmid=19653818 |doi-access=free}}{{Cite journal |display-authors=6 |vauthors=Spatz JM, Ellman R, Cloutier AM, Louis L, van Vliet M, Suva LJ, Dwyer D, Stolina M, Ke HZ, Bouxsein ML |date=April 2013 |title=Sclerostin antibody inhibits skeletal deterioration due to reduced mechanical loading |journal=Journal of Bone and Mineral Research |volume=28 |issue=4 |pages=865–874 |doi=10.1002/jbmr.1807 |pmc=4076162 |pmid=23109229}} which is subject to site selection bias and cannot adequately quantify the volume of fat in the marrow. Nevertheless, histological techniques and fixation make possible visualization of BMAT, quantification of BMAd size, and BMAT's association with the surrounding endosteum, milieu of cells, and secreted factors.{{Cite journal |display-authors=6 |vauthors=Rosen CJ, Ackert-Bicknell CL, Adamo ML, Shultz KL, Rubin J, Donahue LR, Horton LG, Delahunty KM, Beamer WG, Sipos J, Clemmons D, Nelson T, Bouxsein ML, Horowitz M |date=November 2004 |title=Congenic mice with low serum IGF-I have increased body fat, reduced bone mineral density, and an altered osteoblast differentiation program |journal=Bone |volume=35 |issue=5 |pages=1046–1058 |doi=10.1016/j.bone.2004.07.008 |pmid=15542029}}{{Cite journal |vauthors=Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ |date=July 2009 |title=Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment |journal=Nature |volume=460 |issue=7252 |pages=259–263 |bibcode=2009Natur.460..259N |doi=10.1038/nature08099 |pmc=2831539 |pmid=19516257}}{{Cite journal |display-authors=6 |vauthors=David V, Martin A, Lafage-Proust MH, Malaval L, Peyroche S, Jones DB, Vico L, Guignandon A |date=May 2007 |title=Mechanical loading down-regulates peroxisome proliferator-activated receptor gamma in bone marrow stromal cells and favors osteoblastogenesis at the expense of adipogenesis |journal=Endocrinology |volume=148 |issue=5 |pages=2553–2562 |doi=10.1210/en.2006-1704 |pmid=17317771 |doi-access=free}}

Recent advances in cell surface and intracellular marker identification and single-cell analyses led to greater resolution and high-throughput ex-vivo quantification. Flow cytometric quantification can be used to purify adipocytes from the stromal vascular fraction of most fat depots.{{Cite journal |display-authors=6 |vauthors=Majka SM, Miller HL, Sullivan T, Erickson PF, Kong R, Weiser-Evans M, Nemenoff R, Moldovan R, Morandi SA, Davis JA, Klemm DJ |date=October 2012 |title=Adipose lineage specification of bone marrow-derived myeloid cells |journal=Adipocyte |volume=1 |issue=4 |pages=215–229 |doi=10.4161/adip.21496 |pmc=3609111 |pmid=23700536}} Early research with such machinery cited adipocytes as too large and fragile for cytometer-based purification, rendering them susceptible to lysis; however, recent advances have been made to mitigate this;{{Cite book |title=Methods of Adipose Tissue Biology, Part A |vauthors=Majka SM, Miller HL, Helm KM, Acosta AS, Childs CR, Kong R, Klemm DJ |year=2014 |isbn=9780124116191 |series=Methods in Enzymology |volume=537 |pages=281–96 |chapter=Analysis and Isolation of Adipocytes by Flow Cytometry |doi=10.1016/b978-0-12-411619-1.00015-x |pmc=4143162 |pmid=24480352}} nevertheless, this methodology continues to pose technical challenges{{Cite journal |vauthors=Bernstein RL, Hyun WC, Davis JH, Fulwyler MJ, Pershadsingh HA |date=July 1989 |title=Flow cytometric analysis of mature adipocytes |journal=Cytometry |volume=10 |issue=4 |pages=469–474 |doi=10.1002/cyto.990100416 |pmid=2766892 |doi-access=free}} and is inaccessible to much of the research community.

To improve quantification of BMAT, novel imaging techniques have been developed as a means to visualize and quantify BMAT. Although proton magnetic resonance spectroscopy (1H-MRS) has been used with success to quantify vertebral BMAT in humans,{{Cite journal |display-authors=6 |vauthors=Bredella MA, Torriani M, Ghomi RH, Thomas BJ, Brick DJ, Gerweck AV, Rosen CJ, Klibanski A, Miller KK |date=January 2011 |title=Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women |journal=Obesity |volume=19 |issue=1 |pages=49–53 |doi=10.1038/oby.2010.106 |pmc=3593350 |pmid=20467419}} it is difficult to employ in laboratory animals.{{Cite journal |display-authors=6 |vauthors=de Paula FJ, Dick-de-Paula I, Bornstein S, Rostama B, Le P, Lotinun S, Baron R, Rosen CJ |date=September 2011 |title=VDR haploinsufficiency impacts body composition and skeletal acquisition in a gender-specific manner |journal=Calcified Tissue International |volume=89 |issue=3 |pages=179–191 |doi=10.1007/s00223-011-9505-1 |pmc=3157554 |pmid=21637996}} Magnetic resonance imaging (MRI) provides BMAT assessment in the vertebral skeleton{{Cite journal |display-authors=6 |vauthors=Fazeli PK, Bredella MA, Freedman L, Thomas BJ, Breggia A, Meenaghan E, Rosen CJ, Klibanski A |date=September 2012 |title=Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa |journal=Journal of Bone and Mineral Research |volume=27 |issue=9 |pages=1864–1871 |doi=10.1002/jbmr.1640 |pmc=3415584 |pmid=22508185}} in conjunction with μCT-based marrow density measurements.{{Cite journal |vauthors=Rantalainen T, Nikander R, Heinonen A, Cervinka T, Sievänen H, Daly RM |date=May 2013 |title=Differential effects of exercise on tibial shaft marrow density in young female athletes |journal=The Journal of Clinical Endocrinology and Metabolism |volume=98 |issue=5 |pages=2037–2044 |doi=10.1210/jc.2012-3748 |pmid=23616150 |doi-access=free |hdl-access=free |hdl=10536/DRO/DU:30060423}} A volumetric method to identify, quantify, and localize BMAT in rodent bone has been recently developed, requiring osmium staining of bones and μCT imaging,{{Cite book |title=Methods of Adipose Tissue Biology, Part A |vauthors=Scheller EL, Troiano N, Vanhoutan JN, Bouxsein MA, Fretz JA, Xi Y, Nelson T, Katz G, Berry R, Church CD, Doucette CR, Rodeheffer MS, Macdougald OA, Rosen CJ, Horowitz MC |year=2014 |isbn=9780124116191 |series=Methods in Enzymology |volume=537 |pages=123–39 |chapter=Use of Osmium Tetroxide Staining with Microcomputerized Tomography to Visualize and Quantify Bone Marrow Adipose Tissue in Vivo |doi=10.1016/b978-0-12-411619-1.00007-0 |pmc=4097010 |pmid=24480344 |display-authors=6}} followed by advanced image analysis of osmium-bound lipid volume (in mm³) relative to bone volume. This technique provides reproducible quantification and visualization of BMAT, enabling the ability to consistently quantify changes in BMAT with diet, exercise, and agents that constrain precursor lineage allocation. Although the osmium method is quantitatively precise, osmium is toxic and cannot be compared across batched experiments. Recently, researchers developed and validated a 9.4T MRI scanner technique that allows localization and volumetric (3D) quantification that can be compared across experiments, as in.

Several studies have also analysed BMAT function in vivo using positron emission tomography - computed tomography (PET-CT) combined with the tracer 18F-Fluorodeoxyglucose (FDG). This allows glucose uptake, a measure of metabolic activity, to be quantified in living organisms, including humans. Two recent studies found that, unlike brown adipose tissue, BMAT does not increase glucose uptake in response to cold exposure, demonstrating that BMAT is functionally distinct from BAT.{{Cite journal |display-authors=6 |vauthors=Pham TT, Ivaska KK, Hannukainen JC, Virtanen KA, Lidell ME, Enerbäck S, Mäkelä K, Parkkola R, Piirola S, Oikonen V, Nuutila P, Kiviranta R |date=July 2020 |title=Human Bone Marrow Adipose Tissue is a Metabolically Active and Insulin-Sensitive Distinct Fat Depot |journal=The Journal of Clinical Endocrinology and Metabolism |volume=105 |issue=7 |pages=2300–2310 |doi=10.1210/clinem/dgaa216 |pmc=7247553 |pmid=32311037}} The full extent of BMAT's impact on systemic metabolic homeostasis remains to be determined.{{cn|date=February 2025}}

File:Demonstration of Method- Osmium-μCT with Advanced Image Processing.tif|alt=Demonstration of Osmium-μCT method with Advanced Image Processing|This figure demonstrates the use of the osmium- μCT method with advanced image processing to quantify BMAT. In this figure, running exercise is shown to suppress BMAT despite PPARγ agonist. Fat binder osmium is imaged via μCT (A ) in n =5 per group overlaid images. Quantification of osmium as BMAT/ bone volume in the whole femur is shown. a, significant due to Rosi. b, significant due to exercise. Rosi=rosiglizaone, CTL=control, E=exercise.

File:MRI method copy.tif|This figure demonstrates the use of MRI imaging (9.4T scanner) along with advanced image processing to quantify BMAT. The images and graph demonstrate that BMAT is higher in obese compared with lean mice. B6 mice were fed HFD from age 4 wk until age 16 wk. BMAT was quantified by MRI. A) n=10 superimposed group average images are shown B) BMAT normalized to bone volume in each group.

File:Marrow Adipose Tissue (typical quantity young mouse) .jpg|Representative distal femur histologic section of a 16-week-old healthy C57BL/6 mouse demonstrating a typical quantity of marrow adipocytes.

File:Increased Marrow Adipose Tissue .jpg|Representative distal femur histologic section of a 16-week-old C57BL/6 mouse after 6 weeks of calorie restriction demonstrating an increased quantity of marrow adipocytes.

Because of the increasing interest in BMAT from both researchers and clinicians, in 2018 The International Bone Marrow Adiposity Society (BMAS) was founded.{{Cite web |title=The International Bone Marrow Adiposity Society |url=https://bma-society.org |website=BMAS Website}} Work to build the society began in Lille, France in 2015, when the first International Meeting on Bone Marrow Adiposity (BMA2015) was held. The meeting was a great success and led to a second international meeting (BMA2016) in August 2016 held in Rotterdam, The Netherlands. Both meetings were a success in that they for the first time brought together scientists and physicians from different backgrounds (bone metabolism, cancer, obesity and diabetes) to share ideas and advance research into, and our understanding of, the patho/physiological role of BMAds.{{cn|date=February 2025}}

File:BMAS Logo 2.tif

This success led to a network of researchers discussing the formation of a new society, focusing on bone marrow adiposity (BMA). This network worked together in 2016–2017 to lay the foundations for this society, which was then discussed further during the third international meeting held in Lausanne, Switzerland in 2017 (BMA2017). The statues were then signed at the fourth international meeting, held in 2018 again in Lille (BMA2018). As discussed in the following section, there have since been three further international meetings, held in Odense, Denmark in 2019 (BMA2019), virtually in 2020 (BMA2020), and in Athens, Greece in 2022 (BMA2022). The first BMAS Summer School was held virtually in the summer of 2021.{{cn|date=February 2025}}

Since its foundation, [https://bma-society.org/working-groups/ BMAS working groups] have published three position papers relating to nomenclature, methodologies {{Cite journal |display-authors=6 |vauthors=Tratwal J, Labella R, Bravenboer N, Kerckhofs G, Douni E, Scheller EL, Badr S, Karampinos DC, Beck-Cormier S, Palmisano B, Poloni A, Moreno-Aliaga MJ, Fretz J, Rodeheffer MS, Boroumand P, Rosen CJ, Horowitz MC, van der Eerden BC, Veldhuis-Vlug AG, Naveiras O |date=2020 |title=Reporting Guidelines, Review of Methodological Standards, and Challenges Toward Harmonization in Bone Marrow Adiposity Research. Report of the Methodologies Working Group of the International Bone Marrow Adiposity Society |journal=Frontiers in Endocrinology |volume=11 |pages=65 |doi=10.3389/fendo.2020.00065 |pmc=7059536 |pmid=32180758 |doi-access=free}} and biobanking for BMA research.{{Cite journal |display-authors=6 |vauthors=Lucas S, Tencerova M, von der Weid B, Andersen TL, Attané C, Behler-Janbeck F, Cawthorn WP, Ivaska KK, Naveiras O, Podgorski I, Reagan MR, van der Eerden BC |date=2021 |title=Guidelines for Biobanking of Bone Marrow Adipose Tissue and Related Cell Types: Report of the Biobanking Working Group of the International Bone Marrow Adiposity Society |journal=Frontiers in Endocrinology |volume=12 |pages=744527 |doi=10.3389/fendo.2021.744527 |pmc=8503265 |pmid=34646237 |doi-access=free}} These working groups remain active, with other working groups also focussing on clinical and translational issues, public engagement, and young researchers (Next Generation BMAS)

• BMA2015 (Lille, France){{Cite journal |vauthors=Hardouin P, Marie PJ, Rosen CJ |date=December 2016 |title=New insights into bone marrow adipocytes: Report from the First European Meeting on Bone Marrow Adiposity (BMA 2015) |journal=Bone |volume=93 |pages=212–215 |doi=10.1016/j.bone.2015.11.013 |pmid=26608519}}
• BMA2016 (Rotterdam, Netherlands){{Cite journal |vauthors=van der Eerden B, van Wijnen A |date=October 2017 |title=Meeting report of the 2016 bone marrow adiposity meeting |journal=Adipocyte |volume=6 |issue=4 |pages=304–313 |doi=10.1080/21623945.2017.1313374 |pmc=5736244 |pmid=28410005}}
• BMA2017 (Lausanne, Switzerland){{Cite journal |vauthors=Corsi A, Palmisano B, Tratwal J, Riminucci M, Naveiras O |date=2019 |title=Brief Report From the 3rd International Meeting on Bone Marrow Adiposity (BMA 2017) |journal=Frontiers in Endocrinology |volume=10 |pages=336 |doi=10.3389/fendo.2019.00336 |pmc=6546805 |pmid=31191458 |doi-access=free}}
• BMA2018 (Lille, France){{Cite journal |vauthors=Penel G, Kerckhofs G, Chauveau C |date=2019 |title=Brief Report From the 4th International Meeting on Bone Marrow Adiposity (BMA2018) |journal=Frontiers in Endocrinology |volume=10 |pages=691 |doi=10.3389/fendo.2019.00691 |pmc=6813723 |pmid=31681168 |doi-access=free}}
• [https://bma2019.sciencesconf.org BMA2019] (Odense, Denmark)
• BMA2020 (virtual BMA meeting){{Cite journal |vauthors=Scheller EL, McGee-Lawrence ME, Lecka-Czernik B |date=2021 |title=Report From the 6th International Meeting on Bone Marrow Adiposity (BMA2020) |journal=Frontiers in Endocrinology |volume=12 |pages=712088 |doi=10.3389/fendo.2021.712088 |pmc=8323480 |pmid=34335478 |doi-access=free}}
• BMA Summer School 2021 (virtual){{Cite journal |vauthors=Labella R, Little-Letsinger S, Avilkina V, Sarkis R, Tencerova M, Vlug A, Palmisano B |date=2022 |title=Next Generation Bone Marrow Adiposity Researchers: Report From the 1st BMAS Summer School 2021 |journal=Frontiers in Endocrinology |volume=13 |pages=879588 |doi=10.3389/fendo.2022.879588 |pmc=9043644 |pmid=35498418 |doi-access=free}}
• [https://bma-society.org/welcome-address/ BMA2022] (Athens, Greece)

[https://www.asbmr.org/Default.aspx ASBMR] has published hundreds of presentations and articles on BMAT featured in the ASBMR annual meetings, The [https://www.asbmr.org/Publications/jbmr Journal of Bone and Mineral Research ( JBMR)], [https://www.asbmr.org/publications/jbmr-plus JBMRPlus], and the [https://www.asbmr.org/Publications/Primer Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism].

[https://www.endocrine.org/ Endocrine society] features many presentations and articles on BMAT.

{{CC-notice|cc=by4|url=http://journal.frontiersin.org/article/10.3389/fendo.2016.00094/full|author(s)=Gabriel M. Pagnotti and Maya Styner}}

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• {{Cite web |date=3 July 2014 |title=Bone marrow fat tissue secretes hormone that helps body stay healthy |url=http://www.uofmhealth.org/news/archive/201407/bone-marrow-fat-tissue-secretes-hormone-helps-body-stay |archive-url=https://web.archive.org/web/20150315121850/http://www.uofmhealth.org/news/archive/201407/bone-marrow-fat-tissue-secretes-hormone-helps-body-stay |archive-date=15 March 2015 |publisher=University of Michigan}}
• {{Cite web |date=18 May 2017 |title=Another reason to exercise: Burning bone fat a key to better bone health |url=https://www.sciencedaily.com/releases/2017/05/170518140220.htm |website=Science Daily}}

{{refend}}

• {{Cite web |date=Winter 2017 |title=Why are our bones full of fat? The secrets of bone marrow adipose tissue |url=https://www.endocrinology.org/endocrinologist/126-winter17/features/why-are-our-bones-full-of-fat-the-secrets-of-bone-marrow-adipose-tissue/ |publisher=Society for Endocrinology}}

{{DEFAULTSORT:Bone Marrow Adipose Tissue}}

Category:Bone marrow

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Category:Anatomy

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Category:Mesoderm