Effects of simvastatin on bone turnover and BMD: a 1-year randomized controlled trial in postmenopausal osteopenic women.
To study effects of statins on human bone, 82 postmenopausal women were randomized to 1-year treatment with simvastatin 40 mg/day or placebo. The study showed no effect of simvastatin on biochemical bone markers or on BMD at the hip or spine. Thus, our results do not support a general beneficial effect of simvastatin on bone.


BACKGROUND
Statins have been reported to cause bone anabolic as well as antiresorptive effects, and therefore statins have been suggested as potential agents in treatment of osteoporosis.


METHODS
In a double-blinded design, 82 healthy postmenopausal women with osteopenia were randomized to 1-year simvastatin treatment 40 mg/day or placebo. BMD and plasma levels of cholesterol, parathyroid hormone (PTH), and biochemical bone markers were measured at baseline, after 1 year of treatment (week 52), and 26 weeks after withdrawal of treatment (week 78). Calcium supplements (400 mg/day) were administrated during the entire 1.5-year study period.


RESULTS
Seventy-eight women completed the 1-year treatment. After 1 year, simvastatin but not placebo caused reduced plasma cholesterol (-27% versus +1%, p < 0.001) and low-density lipoprotein (LDL) levels (-43% versus +1%, p < 0.001). After withdrawal of treatment, cholesterol and LDL levels returned to baseline levels and no longer differed from the placebo group. However, plasma levels of PTH and biochemical bone markers did not differ between groups at week 52 or 78. Compared with placebo, simvastatin caused no changes in BMD at the lumbar spine, total hip, femoral neck, or whole body at week 52 or 78. However, a significant increase in BMD was found in response to simvastatin at the forearm. Within the simvastatin group, changes in cholesterol levels did not correlate to BMD changes at any site.


CONCLUSIONS
Our results do not support a general beneficial effect of simvastatin on bone.
Rejnmark
Lars
L
Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital, Aarhus, Denmark. rejnmark@post6.tele.dk
Buus
Niels Henrik
NH
Vestergaard
Peter
P
Heickendorff
Lene
L
Andreasen
Frederik
F
Larsen
Mogens Lytken
ML
Mosekilde
Leif
L
D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008137:Longitudinal Studies; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D019821:Simvastatin / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D015415:Biomarkers; D024042:Collagen Type I; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010281:Parathyroid Hormone; D010455:Peptides; D014280:Triglycerides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D003094:Collagen; D002784:Cholesterol; D019821:Simvastatin; D000469:Alkaline Phosphatase