Prospective Analysis of Muscle Adiposity in Children With X-linked Hypophosphatemic Rickets vs Control Children

Virginie Nguyen-Khac; Aurore Bonnet-Lebrun; Agnès Linglart; Marine de Tienda; Jugurtha Berkenou; Inès Mannes; Catherine Adamsbaum; Philippe Wicart; Wafa Skalli


J Endo Soc. 2022;6(12) 

In This Article

Abstract and Introduction


Context: Children with X-linked hypophosphatemic (XLH) rickets have muscle weakness that severely impairs their function. Intermuscular and intramuscular adipose tissue (IMAT and intraMAT, respectively) may contribute to this muscle weakness.

Objective: This work aimed to compare IMAT and intraMAT in XLH children vs typically developing (TD) children.

Methods: A prospective, monocentric cohort study was conducted of XLH (n = 11; aged 10.3 years [6–17]) and TD children (n = 22; aged 10.2 years [5–15.5]). All children underwent magnetic resonance imaging of the lower limbs; IMAT and intraMAT percentages were calculated after manual contouring of each muscle of the thigh and the deep fascia at mid-thigh level.

Results: XLH children were comparable in age but shorter and heavier than TD children (P = .001 and P = .03, respectively). They had smaller muscle length and volume than TD children (P < .001) but there was no statistically significant difference in muscle cross-sectional area between the groups (P = .833). The total percentage of IMAT was higher in XLH children (8.66% vs 3.60% in TD children; P < .0001). In addition, though the total percentage of intraMAT did not differ significantly (12.58% and 10.85% in XLH and TD children, respectively; P = .143) intraMAT was statistically significantly higher in XLH children than TD children in 4 of the 13 muscles studied.

Conclusion: Our results show that IMAT is higher in young children with XLH, independently of obesity and overweight. Further, these results will facilitate both the early prevention of functional and metabolic consequences of the increase in adipose tissue in XLH children.


X-linked hypophosphatemic (XLH) rickets is a rare condition with a prevalence of 3.0 (1.4–6.5) to 8.1 (5.8–11.4) per million in the most recent UK epidemiological study.[1] It is the result of a mutation in the PHEX gene and the main clinical features in children are the combination of bone abnormalities (rickets and lower limb deformities), dental abnormalities, and muscle weakness.[2] While the first 2 of these symptoms have already been the subject of many studies,[3–6] very few have objectively studied the quantitative and qualitative characteristics of muscles in these patients.

In 2012, Veilleux et al[7] described evidence muscle abnormalities in children with XLH on peripheral quantitative computed tomography (CT) scans. A study of muscle composition (via quantitative CT) and function (via jump mechanography) showed lower than normal muscle volume, density, and strength in the leg. Further, studies by Ducher et al[8] and Farr et al[9] suggest that the low muscle density and strength found in these XLH children are related to a high rate of intramuscular fat infiltration, highlighting the need for objective measurement of this type of adipose tissue. In 2020, our group reported on a cohort of 172 children with XLH (113 girls/59 boys) almost a third of whom were overweight or obese at as early as age 5 years and recommended careful monitoring of body mass index (BMI) in these patients.[10]

Over the last decade, there has been growing interest in ectopic adiposity, especially that found in the lower limbs, known as intermuscular (IMAT, ie, beneath the deep fascia and between muscle groups) and intramuscular (intraMAT, ie, within and between muscle fibers). Ectopic fat is known not only to be predictive of metabolic disease such as insulin resistance,[11–15] but also to be associated with decreased strength[16–19] and mobility impairment[20–23] and to have a direct role in muscle weakness.[24,25]

We describe a prospective analysis to quantify and compare muscle composition (IMAT and intraMAT) in XLH children vs typically developing (TD) children using magnetic resonance imaging (MRI). We hypothesize that IMAT and/or intraMAT are higher in XLH children than in TD children and that this may help explain muscle weakness.