Osteogenesis Imperfecta: The Impact of Genotype and Clinical Phenotype on Adiposity and Resting Energy Expenditure

Abstract

Context: Mutations in type I collagen or collagen-related proteins cause osteogenesis imperfecta (OI). Energy expenditure and body composition in OI could reflect reduced mobility or intrinsic defects in osteoblast differentiation increasing adipocyte development.

Objective: This study compares adiposity and resting energy expenditure (REE) in OI and healthy controls (HC), for OI genotype- and Type-associated differences.

Methods: We studied 90 participants, 30 with OI (11 COL1A1 Gly, 8 COL1A2 Gly, 4 COL1A1 non-Gly, 1 COL1A2 non-Gly, 6 non-COL; 8 Type III, 16 Type IV, 4 Type VI, 1 Type VII, 1 Type XIV) and 60 HC with sociodemographic characteristics/BMI/BMIz similar to the OI group. Participants underwent dual-energy x-ray absorptiometry to determine lean mass and fat mass percentage (FM%) and REE. FM% and REE were compared, adjusting for covariates, to examine the relationship of OI genotypes and phenotypic Types.

Results: FM% did not differ significantly in all patients with OI vs HC (OI: 36.6% ± 1.9%; HC: 32.7% ± 1.2%; P = 0.088). FM% was, however, greater than HC for those with non-COL variants (P = 0.016). FM% did not differ from HC among OI Types (P values > 0.05).Overall, covariate-adjusted REE did not differ significantly between OI and HC (OI: 1376.5 ± 44.7 kcal/d; HC: 1377.0 ± 96 kcal/d; P = 0.345). However, those with non-COL variants (P = 0.016) and Type VI OI (P = 0.04) had significantly lower REE than HC.

Conclusion: Overall, patients with OI did not significantly differ in either extra-marrow adiposity or REE from BMI-similar HC. However, reduced REE among those with non-COL variants may contribute to greater adiposity.

Trial registration: ClinicalTrials.gov NCT03575221 NCT00459992 NCT00001522.

Keywords: adiposity; osteogenesis imperfecta; resting energy expenditure.

Published by Oxford University Press on behalf of the Endocrine Society 2021.

Figures

Figure 1.

Mean ± SEM percentage total body fat mass (A) and resting energy expenditure (REE) adjusted for covariates including total lean body mass (B) in the entire cohort of individuals with OI (n = 30) and healthy controls (n = 60).

Figure 2.

Mean ± SEM percentage total body fat mass in individuals with OI and healthy controls. (A) Grouped according to genotype. Gly: genetic variants altering the coding for glycine in COL1A1 (n = 11) or COL1A2 (n = 8); Non-Gly: genetic variants altering the coding for other amino acids in COL1A1 (n = 4) or COL1A2 (n = 1); Non-Col (n = 6): function-altering variants in genes that cause OI and do not code for collagen proteins; HC (n = 60): healthy controls. (B) Grouped by type of protein defect. COL Gly (n = 19): genetic variants altering the coding for glycine in COL1A1 or COL1A2; COL Non-Gly (n = 5): genetic variants altering the coding for other amino acids in COL1A1 or COL1A2 and HC (n = 60). (C): Grouped by Sillence Type: Type III (n = 8), Type IV (n = 16), Type VI (n = 4) and HC (n = 60). *P < 0.05, **P < 0.01, ***P = 0.001.

Figure 3.

Mean ± SEM resting energy expenditure (REE) adjusted for covariates including total lean body mass in individuals with OI grouped according to genotype and in healthy controls. (A) Mean ± SEM REE adjusted for covariates including total lean body mass in individuals with OI grouped by glycine-specific defect. Gly: genetic variants altering the coding for glycine in COL1A1 (n = 11) or COL1A2 (n = 8); Non-Gly: genetic variants altering the coding for other amino acids in COL1A1 (n = 4) or COL1A2 (n = 1); Non-Col (n = 6): function-altering variants in genes that cause OI and do not code for collagen proteins; HC (n = 60): healthy controls. (B) Mean ± SEM REE adjusted for covariates including total lean body mass in individuals with OI grouped by type of protein defect. COL Gly (n = 19): genetic variants altering the coding for glycine in COL1A1 or COL1A2; COL Non-Gly (n = 5): genetic variants altering the coding for other amino acids in COL1A1 or COL1A2 and HC (n = 60). (C) Mean ± SEM REE adjusted for covariates including total lean body mass in individuals with OI grouped by Sillence Type: Type III (n = 8), Type IV (n = 16), Type VI (n = 4) and HC (n = 60). *P < 0.05, **P < 0.01, ***P = 0.001.

Figure 4.

Individual resting energy expenditure (REE) measurements. (A) REE versus total lean body mass in healthy controls and in individuals with OI according to genotype. Gly: genetic variants altering the coding for glycine in COL1A1 (n = 11) or COL1A2 (n = 8); Non-Gly: genetic variants altering the coding for other amino acids in COL1A1 (n = 4) or COL1A2 (n = 1); Non-Col (n = 6): function-altering variants in genes that cause OI and do not code for collagen proteins; HC (n = 60): healthy controls. The graphed regression line is for the relationship between total lean body mass and REE in healthy control participants. (B) REE (adjusted for covariates) versus age among Controls (n = 60), Type III OI (n = 8), and Type IV OI (n = 4). REE was adjusted for sex, race, lean mass, and fat mass percentage. Lines show linear fits for each group. The slopes for each line had a negative coefficient for all 3 groups and was significantly different from 0 only for controls (-8.35, P = 0.02), but not for Type III (-16.74, P = 0.09) or Type IV (-12.54, P = 0.067) OI. Comparisons among the groups found no significant differences for slopes (P = 0.65) or intercepts (P = 0.99).