Bone Marrow Fat Physiology in Relation to Skeletal Metabolism and Cardiometabolic Disease Risk in Children With Cerebral Palsy

Abstract

Individuals with cerebral palsy exhibit neuromuscular complications and low physical activity levels. Adults with cerebral palsy exhibit a high prevalence of chronic diseases, which is associated with musculoskeletal deficits. Children with cerebral palsy 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 cerebral palsy are lacking. In this review, we highlight the skeletal status in children with cerebral palsy 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 the following: (1) Is the bone marrow fat in children with cerebral palsy 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 cerebral palsy? (4) If so, what are the mechanisms? In conclusion, although 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 cerebral palsy.

Figure 1

(A) Simple diagram showing mesenchymal stem cell (MSC) and hematopoietic stem cell (HSC) differentiation. In typically developing children, MSCs favor osteogenic differentiation due to adequate loading, nutrition, hormonal milieu, and growth. In children with cerebral palsy, MSCs likely favor adipogenic differentiation due to multiple and complex factors. (B) Diagram showing potential mechanisms of elevated bone marrow fat on skeletal metabolism in children with cerebral palsy. Dashed red line indicates a suppressive role. Solid blue line indicates a stimulating role.