Assessment of bone mineral status in children with Marfan syndrome

Am J Med Genet A. 2012 Sep;158A(9):2221-4. doi: 10.1002/ajmg.a.35540. Epub 2012 Aug 7.

Abstract

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder with skeletal involvement. It is caused by mutations in fibrillin1 (FBN1) gene resulting in activation of TGF-β, which developmentally regulates bone mass and matrix properties. There is no consensus regarding bone mineralization in children with MFS. Using dual-energy X-ray absorptiometry (DXA), we evaluated bone mineralization in 20 children with MFS unselected for bone problems. z-Scores were calculated based on age, gender, height, and ethnicity matched controls. Mean whole body bone mineral content (BMC) z-score was 0.26±1.42 (P=0.41). Mean bone mineral density (BMD) z-score for whole body was -0.34±1.4 (P=0.29) and lumbar spine was reduced at -0.55±1.34 (P=0.017). On further adjusting for stature, which is usually higher in MFS, mean BMC z-score was reduced at -0.677±1.37 (P=0.04), mean BMD z-score for whole body was -0.82±1.55 (P=0.002) and for lumbar spine was -0.83±1.32 (P=0.001). An increased risk of osteoporosis in MFS is controversial. DXA has limitations in large skeletons because it tends to overestimate BMD and BMC. By adjusting results for height, age, gender, and ethnicity, we found that MFS patients have significantly lower BMC and BMD in whole body and lumbar spine. Evaluation of diet, exercise, vitamin D status, and bone turnover markers will help gain insight into pathogenesis of the reduced bone mass. Further, larger longitudinal studies are required to evaluate the natural history, incidence of fractures, and effects of pharmacological therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Bone Density*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Fibrillin-1
  • Fibrillins
  • Humans
  • Male
  • Marfan Syndrome / genetics
  • Marfan Syndrome / physiopathology*
  • Microfilament Proteins / genetics

Substances

  • FBN1 protein, human
  • Fibrillin-1
  • Fibrillins
  • Microfilament Proteins