Exploring The Relationship Between Morphology And Metabolism In People With Achondroplasia: An Interim Analysis

PURPOSE: Achondroplasia is the most common form of skeletal dysplasia; a genetic condition affecting bone and cartilage development. This results in disproportionate short stature due to restricted growth of the long bones in the upper and lower limbs. Obesity and some associated health outcomes are common and can be particularly problematic for individuals with this condition. No previous study has examined the relationship between anthropometric and metabolic parameters in individuals with achondroplasia. Here we report an interim analysis of an ongoing study. METHODS: Five female and 6 male adults with achondroplasia completed a whole-body dual-energy X-ray absorptiometric (DXA) scan, a peripheral quantitative computed tomography (pQCT) scan of their dominant leg (66% of the tibia from distal end), basic anthropometric measures, and an assessment of resting metabolic rate (RMR) via indirect calorimetry. RESULTS: Participants’ mean ± standard deviation (range) age was 33 ± 14 y (18-61), height 1.27 ± 0.07 m (1.15-1.38), body mass 62.1 ± 14.0 kg (47.3-91.6), waist-to-hip ratio 0.82 ± 0.08 (0.71-0.96), sagittal abdominal diameter (SAD) 21.4 ± 4.3 cm (15.2-29.8), and sitting height 82.3 ± 3.2 cm (76.8-85.8). DXA-derived whole-body fat mass was 24.4 ± 11.3 kg (9.7-48.5), bone mineral content 1.7 ± 2.7 kg (1.3-2.1), and lean soft tissue mass 34.8 ± 7.2 kg (24.3-45.2). Participants’ pQCT-derived lower-leg muscle density was 73.4 ± 3.7 mg/cm (64.8-78.5), muscle cross-sectional area was 63.5 ± 19.8 cm (29.5-84.3), and total fat cross-sectional area was 58.5 ± 27.4 cm (15.0-100.3). Resting metabolic rate was 1594 ± 219 kcal·d-1 (1154-1840). From these data, the best correlates with RMR were bone mineral content from DXA (r = 0.78, p = 0.02), whole-body lean soft tissue mass (r = 0.70, p = 0.05), and total body mass (r = 0.70, p = 0.02) – although stature was not correlated with RMR in this population (r = 0.42, p = 0.20). CONCLUSION: Despite the disproportionate anatomical morphology that occurs in individuals with achondroplasia, resting metabolic requirements remain broadly proportionate to body tissue masses in this population irrespective of height. Further research is needed to examine how metabolic responses may scale according to specific regional tissue distribution. Supported by funding from BBSRC (SWBio DTP) and University of Bath