Bone marrow fat physiology in relation to skeletal metabolism and cardiometabolic disease risk in children with cerebral palsy

Individuals with cerebral palsy (CP) exhibit neuromuscular complications and low physical activity levels. Adults with CP exhibit a high prevalence of chronic diseases, which is associated with musculoskeletal deficits. Children with CP have poor musculoskeletal accretion accompanied by excess bone marrow fat, which may lead to weaker bones. Mechanistic studies to determine the role of bone marrow fat on skeletal growth and maintenance, and how it relates to systemic energy metabolism among individuals with CP, are lacking. In this review, we highlight the skeletal status in children with CP and analyze the existing literature on the interactions among bone marrow fat, skeletal health, and cardiometabolic disease risk in the general population. Clinically vital questions are proposed, including: (1) Is the bone marrow fat in children with CP metabolically distinct from typically developing children in terms of its lipid and inflammatory composition? (2) Does the bone marrow fat suppress skeletal acquisition? (3) Or, does it accelerate chronic disease development in children with CP? (4) If so, what are the mechanisms? In conclusion, while inadequate mechanical loading may initiate poor skeletal development, subsequent expansion of bone marrow fat may further impede skeletal acquisition and increase cardiometabolic disease risk in those with CP. Address of correspondence: Daniel G. Whitney, PhD, Department of Physical Medicine and Rehabilitation, Michigan Medicine, University of Michigan, Ann Arbor, MI. Phone: 734-936-9474. Fax: 734-615-1770. e-mail: dgwhit@umich.edu All authors declare no conflict of interest. There has been no previous presentation of this work. Daniel G. Whitney is supported by the University of Michigan Advanced Rehabilitation Research Training Program in Community Living and Participation from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) (90AR5020-0200). Mark D. Peterson is funded by the National Institutes of Health (NIH) (1KO1 HD074706) and NIDILRR (90IF0102-01). Christopher M. Modlesky is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the NIH (R01 HD090126). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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