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

Bone. 2021 Dec:153:116170. doi: 10.1016/j.bone.2021.116170. Epub 2021 Sep 4.


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 R2 = 0.97). In conclusion, bone mass is reduced in children with NS and correlates with decreased muscle mass and low serum IGF-1 levels. These data justify addressing all potential threats to bone health including sufficient calcium and vitamin D intake, regular physical exercise, and hormone replacement therapy.

Keywords: Bone mass; Insulin-like growth factor 1; Muscle mass; Noonan syndrome; RAS/ERK signaling pathway; RASopathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Bone Density
  • Child
  • Humans
  • Insulin-Like Growth Factor I*
  • Lumbar Vertebrae
  • Muscles
  • Noonan Syndrome*
  • Retrospective Studies


  • Insulin-Like Growth Factor I