title: Calcium homeostasis and skeletal integrity in individuals with familial hypercholesterolemia and aortic calcification.
abstract: BACKGROUND
  Familial hypercholesterolemia (FH) due to mutations in the low-density lipoprotein receptor (LDLR) gene exhibit severe, premature aortic calcification in a gene-dosage, age-dependent fashion. We sought to determine potential associations with mineral and skeletal indices.
  
  
  METHODS
  We obtained computed tomography (CT) scan aortic calcium scores (AoCSs) in 19 (age 49 [SD 14] years) FH patients heterozygous for the 15-kb deletion at the LDLR gene and examined associations with various indices of mineral and skeletal homeostasis.
  
  
  RESULTS
  We found that mean bone mineral density (BMD) at the femoral neck in these patients did not differ from age-, sex-, and province-matched mean BMD, and we observed no association of AoCS with any marker of bone resorption. However, there were negative correlations between AoCS and serum concentrations of osteocalcin, a marker of bone formation (r = -0.64, P = 0.0034), urinary calcium (r = -0.59, P = 0.0085), and estimated glomerular filtration rate (r = -0.67, P = 0.0019).
  
  
  CONCLUSIONS
  We found that LDLR-deficient FH was not associated with obvious bone loss or a major disturbance in calcium homeostasis. The lack of LDLR, however, may modify osteoblast function or extracellular calcium distribution, manifesting as lower bone formation, and reduced calcium excretion, resulting in increased deposition in calcifying vascular tissue.
authors: Cardiovascular Research Laboratories, McGill University Health Centre and McGill University, Montreal, Quebec, Canada.
authors: Zuhier
authors: Z
authors: Awan
authors: Khalid
authors: K
authors: Alwaili
authors: Ali
authors: A
authors: Alshahrani
authors: Lisa
authors: L
authors: Langsetmo
authors: David
authors: D
authors: Goltzman
authors: Jacques
authors: J
authors: Genest
mesh_terms: D001018:Aortic Diseases / Q000097:blood / Q000503:physiopathology* / Q000517:prevention & control; D001027:Aortography; D015519:Bone Density; D001842:Bone and Bones / Q000503:physiopathology*; D002114:Calcinosis / Q000097:blood / Q000503:physiopathology* / Q000517:prevention & control; D002118:Calcium / Q000097:blood*; D005260:Female; D006706:Homeostasis; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000503:physiopathology* / Q000517:prevention & control; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015675:Osteocalcin / Q000097:blood; D011973:Receptors, LDL / Q000235:genetics; D014057:Tomography, X-Ray Computed
chemical_list: D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D015675:Osteocalcin; D002118:Calcium