Age-dependent effects of atorvastatin on biochemical bone turnover markers: a randomized controlled trial in postmenopausal women.
The use of HMG-CoA-reductase inhibitors (statins) has been associated with decreased risk of bone fractures in epidemiological studies. In vitro evidence suggests that statins may stimulate bone formation, but the data are still preliminary. We assessed the effects of the HMG-CoA-reductase inhibitor atorvastatin on biochemical parameters of bone metabolism in a multicenter, randomized, double-blind, placebo-controlled trial conducted between October 2001 and October 2002 in three hospital-based outpatient metabolism clinics. Forty-nine postmenopausal women, mean age 61 +/- 5 years, mean time postmenopause 12.6 +/- 8.8 years, were treated with atorvastatin, 20 mg per day ( n=24) or matching placebos ( n=25) for 8 weeks. Comparing the differences to baseline between the groups, there were no statistically significant effects of atorvastatin either on the bone formation markers intact osteocalcin and bone-specific alkaline phosphatase or on the bone resorption markers C-telopeptide and intact parathyroid hormone. The marker of bone fractures, undercarboxylated osteocalcin, was also unchanged. When analyzed in dependence of age, atorvastatin increased C-telopeptide and osteocalcin in the younger subjects, while it decreased them in older subjects. Most interestingly, in older subjects, atorvastatin caused a significant decrease in the ratio of C-telopeptide to osteocalcin, an indicator of bone remodeling, while the ratio was increased in younger subjects, suggesting beneficial effects on bone turnover exclusively in older individuals (approx. >63 years). In summary, the present data suggest that short-term treatment with atorvastatin may have age-dependent effects on biochemical markers of bone turnover in postmenopausal women.
Berthold
Heiner K
HK
Institute for Clinical Research and Department Clinical Pharmacology, Center for Cardiovascular Diseases, Rotenburg an der Fulda, Germany. heiner.berthold@dgn.de
Unverdorben
Susanne
S
Zittermann
Armin
A
Degenhardt
Ralf
R
Baumeister
Bernhard
B
Unverdorben
Martin
M
Krone
Wilhelm
W
Vetter
Hans
H
Gouni-Berthold
Ioanna
I
D000368:Aged; D000375:Aging / Q000502:physiology*; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000097:blood; D017698:Postmenopause / Q000378:metabolism*; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D012307:Risk Factors
D015415:Biomarkers; D024042:Collagen Type I; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010455:Peptides; D011758:Pyrroles; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D003094:Collagen; D000069059:Atorvastatin