Progression of aortic valve stenosis is associated with bone remodelling and secondary hyperparathyroidism in elderly patientsuthe COFRASA study

There is currently no medical therapy that can prevent the progression of aortic valve stenosis (AS). Recent data highlight a possible relationship between bone metabolism and AS progression but prospective data are lacking. Serum levels of calcium, phosphorus, creatinine, 25-OH vitamin D, intact parathyroid hormon (iPTH), C-terminal-telopeptide of type-1-collagen (CTX) and osteocalcin were assessed at baseline in 110 elderly patients (age 70 years) with at least mild AS. CTX/osteocalcin ratio was calculated as a marker of bone remodelling balance. AS severity was assessed at baseline and 1-year based on the mean gradient. Two-thirds of patients had low 25-OH vitamin D and 20 had secondary hyperparathyroidism. AS progression was not associated with age, glomerular filtration rate (GFR), calcium and phosphorus levels, calciumphosphorus product, but significantly with iPTH, CTX/osteocalcin and vitamin D status (all P 0.01). There was no correlation between iPTH and CTX/osteocalcin (R 0.04, P 0.70) and AS progression was associated with CTX/osteocalcin (R 0.42, P 0.009), but not with iPTH (R 0.10, P 0.55) in patients with normal vitamin D levels, whereas it was associated with iPTH (R 0.47, P 0.001) and not with CTX/osteocalcin (R 0.04, P 0.73) in those with low vitamin D levels, especially if mild renal insufficiency was present (R 0.61, P 0.001). In elderly patients with AS, we observed an association between AS progression and vitamin D, iPTH and CTX/osteocalcin ratio and their respective influence varied according to the vitamin D status. In patients with normal vitamin D levels, AS progression was associated with a bone resorptive balance, whereas in patients with low vitamin D levels, AS progression was associated with iPTH and secondary hyperparathyroidism, especially if mild renal insufficiency was present. These findings may have important prognostic and therapeutic implications. Trial registration information: Clinicaltrials.gov identifier number: NCT00338676, funded by AP-HP, the COFRASA study.