Effects of statins on biomarkers of bone metabolism: a randomised trial.
OBJECTIVE
Recently, several studies have indicated there may be differences among statins regarding a possible association between therapy and a reduction in risk of fractures. No data from prospective randomised clinical trials designed to assess either biochemical or clinical effects on bone metabolism are yet available. We assayed levels of biochemical markers of bone formation in stored serum samples from a recently completed randomised clinical trial conducted to compare the effects of simvastatin and atorvastatin on the lipid profile of patients with hypercholesterolaemia.


RESULTS
This 12-week, randomised, multicenter, open-label study was designed to compare the safety and lipid-lowering efficacy of simvastatin 40 mg or 80 mg with that of atorvastatin 20 mg or 40 mg in 846 hypercholesterolaemic patients. Stored serum samples from this study were analysed to compare the effects of simvastatin and atorvastatin on 2 biomarkers of bone turnover, bone-specific alkaline phosphatase (BSAP), a marker of bone formation, and C-teleopeptide of type 1 collagen (CTx), a marker of bone resorption. Treatment with simvastatin 40 and 80 mg/day, but not atorvastatin 20 and 40 mg/day, led to significant (p < 0.05) reductions in BSAP in both men (4.1-5.4% reduction) and women (4.2-7.4% reduction). In addition, there appeared to be a dose-dependent effect with greater reductions in BSAP seen with the 80 mg dose of simvastatin. Treatment with either 20 mg or 40 mg of atorvastatin had no significant effect on BSAP levels on the groups as a whole or in the gender-specific subgroups. CTx showed a small, but not statistically significant, decrease with simvastatin, again with an apparent dose-related trend. Atorvastatin treatment generally resulted in small, non significant increases in CTx.


CONCLUSIONS
The present serum bone biomarker results show that treatment with simvastatin, but not atorvastatin, decreases BSAP and suggest that simvastatin may have a beneficial effect on bone turnover.
Stein
E A
EA
Medical Research Laboratories, 2 Tesseneer Drive, Highland Heights, KY 41076, USA.
Farnier
M
M
Waldstreicher
J
J
Mercuri
M
M
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D001846:Bone Development / Q000187:drug effects; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D015415:Biomarkers; D024042:Collagen Type I; D006538:Heptanoic Acids; D010455:Peptides; D011758:Pyrroles; C052929:collagen type I trimeric cross-linked peptide; D003094:Collagen; D000069059:Atorvastatin; D019821:Simvastatin; D000469:Alkaline Phosphatase