Original Research Bone Marrow Fat Content in the Elderly: A Reversal of Sex Difference Seen in Younger Subjects James F. Griffith, MD, 1 * David K.W. Yeung, PhD, 1 Heather Ting Ma, PhD, 2 Jason Chi Shun Leung, MSc, 3 Timothy C.Y. Kwok, MD, 4 and Ping Chung Leung, MD 3 Purpose: To investigate vertebral bone marrow fat content in elderly subjects related to sex, age, and bone mineral density (BMD) and relate these findings to published data in younger subjects. Materials and Methods: A total of 259 healthy subjects (145 females, 114 males; age range, 62–90 years) under- went proton ( 1 H) MR spectroscopy of L3 vertebral body and BMD of the lumbar spine with results stratified according to age. Ninety age- and BMD-matched subjects were selected to determine sex differences in marrow fat content and BMD. Results: In females, vertebral marrow fat content rose sharply between 55 and 65 years of age while in males vertebral marrow fat content rose gradually throughout life. Vertebral marrow fat content in females more than 60 years was approximately 10% higher in females than males, i.e., a reversal of sex difference reported in marrow fat content for subjects less than 60 years. Conclusion: Marrow fat content increases sharply in female subjects between 55 and 65 years of age while male subjects continue to increase marrow fat at a more gradual steady rate. Females older than 60 years have a higher marrow fat content than males. This increased deposition in marrow fat concurs with recognized changes in extraosseous fat distribution in postmenopausal females. Key Words: bone marrow; marrow fat; MR spectroscopy; osteoporosis J. Magn. Reson. Imaging 2012; 000:000–000. V C 2012 Wiley Periodicals, Inc. ALTHOUGH AN INVERSE relationship between increasing marrow fat and trabecular bone loss in se- nile osteoporosis has been recognized for 40 years, marrow fat was until recently considered a metabol- ically inactive tissue which was simply filling the void vacated by trabecular bone (1,2). Several recent find- ings have changed this perception of marrow fat. Mar- row fat, hematopoietic marrow, and trabecular bone mass have been shown to be inextricably linked through differentiation of a pluripotent mesenchymal stem cell, which has the ability to differentiate along adipocytic, hematopoietic, and osteocytic cell lines (3). Marrow adipocytes have also been shown to be both potentially self-promotive and metabolically active with existing adipocytes inducing differentiation of further adipocytes whilst actively suppressing osteo- blastogenesis (4–7). It is conceivable, therefore, that marrow fat may be, at least in part, driving bone loss and contributing to osteoporosis (6,7). Recognizable changes in fat deposition also occur outside of bone particularly in postmenopausal females (8,9). Quantification of marrow fat in vivo, primarily by proton ( 1 H) MR spectroscopy, has become more clini- cally relevant following recognition of this bone: fat connect at a cellular level (10). Previous MR spectros- copy studies addressing lifelong changes in marrow fat content have focused mainly on subjects less than 60 years of age with either little available data on marrow fat content in subjects older than 60 years or else presented normal data in elderly subjects to com- pare with a disease population (11–17). The most comprehensive study to address sex-related changes in marrow fat content was that of Kugel et al (13). Their study clearly shows an age-related increase in marrow fat in both males and females with males pos- sessing approximately 6–10% more fat than females of comparable age between the ages of 20 and 60 years though with relatively little data on subjects aged more than 60 years of age. Such data are of clin- ical relevance as these later years are particularly associated with a high prevalence of senile osteoporo- sis especially though not exclusively in females. This study was designed to investigate sex-related change in lumbar marrow fat content in subjects older than 60 years of age and relate this to age and BMD to bet- ter understand marrow fat accumulation in humans. This in turn would advance knowledge on the 1 Department of Imaging and Interventional Radiology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong. 2 Department of Electronic and Information Engineering, Harbin Institute of Technology Shenzhen Graduate School, Shenzhen, China. 3 Jockey Club Centre for Osteoporosis Care and Control, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong. 4 Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. *Address reprint requests to: J.F.G., Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. E-mail: griffith@cuhk.edu.hk Received July 10, 2011; Accepted January 13, 2012. DOI 10.1002/jmri.23619 View this article online at wileyonlinelibrary.com. JOURNAL OF MAGNETIC RESONANCE IMAGING 000:000–000 (2012) CME V C 2012 Wiley Periodicals, Inc. 1