Low bone mass in Noonan syndrome children correlates with decreased muscle mass and low IGF-1 levels

Although musculoskeletal abnormalities have long been described in patients with Noonan syndrome (NS), only a few studies have investigated the bone status of these patients. The aim of this retrospective observational study was to describe the bone health of children with NS. Thirty-five patients with a genetically confirmed diagnosis of NS were enrolled. We analyzed the axial skeleton (lumbar spine) using dual energy X-ray absorptiometry and the appendicular skeleton (hand) with the BoneXpert system. Bone metabolism markers, including mineral homeostasis parameters, serum 25-hydroxy vitamin D (25-OHD) levels and markers of bone formation and resorption were also reported. Compared to the general population, axial and appendicular bone mass was significantly decreased in children with NS (p 0.0001). Serum 25-OHD levels were low in about half of the patients and were negatively correlated with age (r = -0.52; p 0.0001). Patients with NS exhibited reduced bone formation marker levels and increased bone resorption marker levels (p 0.0001). No gender difference or genotype-phenotype correlations were found for the different bone parameters. Muscle mass and, to a lesser extent, serum insulin-like growth factor 1 (IGF-1) levels were independent predictors of whole-body bone mineral content (p 0.0001 for both parameters; adjusted R