Calcium homeostasis and skeletal integrity in individuals with familial hypercholesterolemia and aortic calcification.
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.
Awan
Zuhier
Z
Cardiovascular Research Laboratories, McGill University Health Centre and McGill University, Montreal, Quebec, Canada.
Alwaili
Khalid
K
Alshahrani
Ali
A
Langsetmo
Lisa
L
Goltzman
David
D
Genest
Jacques
J
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
D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D015675:Osteocalcin; D002118:Calcium