Red and White Blood Cell Counts Are Associated With Bone Marrow Adipose Tissue, Bone Mineral Density, and Bone Microarchitecture in Premenopausal Women

Overview

Journal J Bone Miner Res

Publisher Oxford University Press

Date 2020 Feb 21

PMID 32078187

Citations 18

Authors

Sai Polineni

Megi Resulaj

Alexander T Faje

Erinne Meenaghan

Miriam A Bredella

Mary Bouxsein

Hang Lee

Ormond A MacDougald

Anne Klibanski

Pouneh K Fazeli

Affiliations

Soon will be listed here.

Abstract

Bone marrow adipose tissue (BMAT) resides within the bone marrow microenvironment where its function remains poorly understood. BMAT is elevated in anorexia nervosa, a disease model of chronic starvation, despite depletion of other fat depots. In addition to BMAT, the marrow microenvironment also consists of osteoblast and hematopoietic progenitors. BMAT is inversely associated with bone mineral density (BMD) in multiple populations including women with anorexia nervosa, and regulates hematopoiesis in animal models. We hypothesized that BMAT would be associated with circulating populations of hematopoietic cells (red and white blood cells) in humans and performed a post hoc analysis of two studies-a cross-sectional study and a longitudinal study-to investigate this hypothesis. We studied 89 premenopausal women cross-sectionally (median age [interquartile range], 27 [24.5, 31.7] years), including 35 with anorexia nervosa. We investigated associations between red blood cell (RBC) and white blood cell (WBC) counts and BMAT assessed by H-magnetic resonance spectroscopy, BMD assessed by DXA, and bone microarchitecture assessed by HR-pQCT. In addition, we analyzed longitudinal data in six premenopausal women with anorexia nervosa treated with transdermal estrogen for 6 months and measured changes in BMAT and blood cell counts during treatment. Cross-sectionally, BMAT was inversely associated with WBC and RBC counts. In contrast, BMD and parameters of bone microarchitecture were positively associated with WBC and RBC. In women with anorexia nervosa treated with transdermal estrogen for 6 months, decreases in BMAT were significantly associated with increases in both RBC and hematocrit (rho = -0.83, p = 0.04 for both). In conclusion, we show that BMAT is inversely associated with WBC and RBC in premenopausal women, and there is a potential association between longitudinal changes in BMAT and changes in RBC. These associations warrant further study and may provide further insight into the role and function of this understudied adipose depot. © 2020 American Society for Bone and Mineral Research.

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References

Calvi L, Adams G, Weibrecht K, Weber J, Olson D, Knight M . Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425(6960):841-6. DOI: 10.1038/nature02040. View

Nakada D, Oguro H, Levi B, Ryan N, Kitano A, Saitoh Y . Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy. Nature. 2014; 505(7484):555-8. PMC: 4015622. DOI: 10.1038/nature12932. View

Shen W, Scherzer R, Gantz M, Chen J, Punyanitya M, Lewis C . Relationship between MRI-measured bone marrow adipose tissue and hip and spine bone mineral density in African-American and Caucasian participants: the CARDIA study. J Clin Endocrinol Metab. 2012; 97(4):1337-46. PMC: 3319176. DOI: 10.1210/jc.2011-2605. View

Leng S, Chaves P, Koenig K, Walston J . Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study. J Am Geriatr Soc. 2002; 50(7):1268-71. DOI: 10.1046/j.1532-5415.2002.50315.x. View

Bredella M, Torriani M, Hosseini Ghomi R, Thomas B, Brick D, Gerweck A . Vertebral bone marrow fat is positively associated with visceral fat and inversely associated with IGF-1 in obese women. Obesity (Silver Spring). 2010; 19(1):49-53. PMC: 3593350. DOI: 10.1038/oby.2010.106. View

Bredella M, Fazeli P, Daley S, Miller K, Rosen C, Klibanski A . Marrow fat composition in anorexia nervosa. Bone. 2014; 66:199-204. PMC: 4125432. DOI: 10.1016/j.bone.2014.06.014. View

Cawthorn W, Scheller E, Learman B, Parlee S, Simon B, Mori H . Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction. Cell Metab. 2014; 20(2):368-375. PMC: 4126847. DOI: 10.1016/j.cmet.2014.06.003. View

Laudisio A, Marzetti E, Pagano F, Bernabei R, Zuccala G . Haemoglobin levels are associated with bone mineral density in the elderly: a population-based study. Clin Rheumatol. 2008; 28(2):145-51. DOI: 10.1007/s10067-008-0998-6. View

Mueller T, Christen D, Sandercott S, Boyd S, van Rietbergen B, Eckstein F . Computational finite element bone mechanics accurately predicts mechanical competence in the human radius of an elderly population. Bone. 2011; 48(6):1232-8. DOI: 10.1016/j.bone.2011.02.022. View

10.

van Staa T, Leufkens H, Cooper C . Utility of medical and drug history in fracture risk prediction among men and women. Bone. 2002; 31(4):508-14. DOI: 10.1016/s8756-3282(02)00848-7. View

11.

Singhal V, Tulsiani S, Campoverde K, Mitchell D, Slattery M, Schorr M . Impaired bone strength estimates at the distal tibia and its determinants in adolescents with anorexia nervosa. Bone. 2017; 106:61-68. PMC: 5694353. DOI: 10.1016/j.bone.2017.07.009. View

12.

Fazeli P, Faje A, Cross E, Lee H, Rosen C, Bouxsein M . Serum FGF-21 levels are associated with worsened radial trabecular bone microarchitecture and decreased radial bone strength in women with anorexia nervosa. Bone. 2015; 77:6-11. PMC: 4447546. DOI: 10.1016/j.bone.2015.04.001. View

13.

Valderrabano R, Lui L, Lee J, Cummings S, Orwoll E, Hoffman A . Bone Density Loss Is Associated With Blood Cell Counts. J Bone Miner Res. 2016; 32(2):212-220. PMC: 5292053. DOI: 10.1002/jbmr.3000. View

14.

Schellinger D, Lin C, Hatipoglu H, Fertikh D . Potential value of vertebral proton MR spectroscopy in determining bone weakness. AJNR Am J Neuroradiol. 2001; 22(8):1620-7. PMC: 7974571. View

15.

Macneil J, Boyd S . Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone. 2008; 42(6):1203-13. DOI: 10.1016/j.bone.2008.01.017. View

16.

Fazeli P, Faje A, Bredella M, Polineni S, Russell S, Resulaj M . Changes in marrow adipose tissue with short-term changes in weight in premenopausal women with anorexia nervosa. Eur J Endocrinol. 2018; 180(3):189-199. PMC: 6545162. DOI: 10.1530/EJE-18-0824. View

17.

Syed F, Oursler M, Hefferanm T, Peterson J, Riggs B, Khosla S . Effects of estrogen therapy on bone marrow adipocytes in postmenopausal osteoporotic women. Osteoporos Int. 2008; 19(9):1323-30. PMC: 2652842. DOI: 10.1007/s00198-008-0574-6. View

18.

Miller K, Grinspoon S, Ciampa J, Hier J, Herzog D, Klibanski A . Medical findings in outpatients with anorexia nervosa. Arch Intern Med. 2005; 165(5):561-6. DOI: 10.1001/archinte.165.5.561. View

19.

Solmi M, Veronese N, Favaro A, Santonastaso P, Manzato E, Sergi G . Inflammatory cytokines and anorexia nervosa: A meta-analysis of cross-sectional and longitudinal studies. Psychoneuroendocrinology. 2014; 51:237-52. DOI: 10.1016/j.psyneuen.2014.09.031. View

20.

Valderrabano R, Lee J, Lui L, Hoffman A, Cummings S, Orwoll E . Older Men With Anemia Have Increased Fracture Risk Independent of Bone Mineral Density. J Clin Endocrinol Metab. 2017; 102(7):2199-2206. PMC: 5505193. DOI: 10.1210/jc.2017-00266. View