Effects of simvastatin on bone mineral density and remodeling parameters in postmenopausal osteopenic subjects: 1-year follow-up study.
Observational studies suggest that statin use may be associated with lower incidence of fracture. However, there are conflicting data for their effects on bone remodeling parameters and bone mineral density (BMD). In the present study, we aimed to investigate the effects of simvastatin on bone metabolism and BMD in subjects with hypercholesterolemia (>240 mg/dl). For this purpose, 32 postmenopausal osteopenic subjects who were given simvastatin treatment (20 mg/day) and not on osteoporosis treatment were included in the study. During the 1-year follow-up period, the total cholesterol level decreased from 262.1+/-30.9 to 202.2+/-30.1 mg/dl (p<0.0001). At a period as early as the 3rd month, levels of the anabolic markers, e.g., bone-specific alkaline phosphatase (BSAP) and osteocalcin (OCL), were found to be significantly increased (from 120.8+/-56.6 to 149.5+/-57.6 IU/l, p=0.008, and from 20.8+/-12.6 to 34.7+/-18.4 microg/l, p=0.015, respectively) while no significant change was observed in the resorptive marker of serum N-telopeptide of type I collagen (CTX). At the 6th and 12th month, BSAP and OCL were both found to be decreased below the pretreatment values. While a significant reduction was found in BSAP levels (from 120.8+/-56.6 to 55.9+/-18.8 IU/l, p<0.001), no significant change was observed in CTX levels after the 6-month treatment period. Parathyroid hormone showed a gradual profound increase during the follow-up period (from 62.7+/-41.5 to 108.4+/-51.7 pg/ml, p<0.001). No significant change was found in BMD levels at the spine, femoral neck, Ward's triangle, and trochanter at the end of the 1-year follow-up period. In conclusion, simvastatin treatment showed a short-lasting anabolic effect on bone metabolism. However, this effect was lost by prolongation of therapy. The decrease in both anabolic and resorptive markers at the 6th and 12th month suggests that simvastatin affects bone metabolism mostly in favor of inhibition of the bone turnover in a long-term observation period although this inhibitory effect was not reflected in BMD.
Tikiz
Canan
C
Department of Physical Medicine and Rehabilitation, Faculty of Medicine, University of Celal Bayar, Manisa, Turkey. canan.tikiz@bayar.edu.tr
Tikiz
Hakan
H
Taneli
Fatma
F
Gümüşer
Gül
G
Tüzün
Ciğdem
C
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000097:blood; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010281:Parathyroid Hormone; D015675:Osteocalcin; D019821:Simvastatin; D000469:Alkaline Phosphatase
J Clin Endocrinol Metab. 2001 Sep;86(9):4556-9
11549708
J Clin Endocrinol Metab. 2000 Mar;85(3):1137-42
10720052
Clin Chim Acta. 2001 Jun;308(1-2):133-7
11412825
Osteoporos Int. 2001;12(5):380-4
11444086
Arch Intern Med. 2002 Mar 11;162(5):537-40
11871921
JAMA. 2001 Apr 11;285(14):1850-5
11308398
Lancet. 2001 Feb 17;357(9255):509-12
11229669
Lancet. 2000 Jun 24;355(9222):2185-8
10881890
Ann Intern Med. 2003 Jul 15;139(2):97-104
12859159
J Bone Miner Res. 1992 Jan;7(1):65-72
1532281
Osteoporos Int. 2002 Jul;13(7):537-41
12111013
Biochem Biophys Res Commun. 2001 Jan 26;280(3):874-7
11162604
J Bone Miner Res. 2001 Oct;16(10):1846-53
11585349
World Health Organ Tech Rep Ser. 1994;843:1-129
7941614
Eur J Clin Invest. 2002 Aug;32(8):581-9
12190958
Endocr Rev. 1993 Aug;14(4):424-42
8223340
Am J Med. 2001 May;110(7):584-7
11343673
JAMA. 2000 Jun 28;283(24):3211-6
10866868
Nutr Metab Cardiovasc Dis. 2001 Apr;11(2):84-7
11434192
Science. 1999 Dec 3;286(5446):1946-9
10583956
Lancet. 1996 Jan 13;347(8994):102-3
8538301
Arch Intern Med. 2004 Jan 26;164(2):146-52
14744837
J Bone Miner Res. 2003 Jan;18(1):88-96
12510809
JAMA. 2000 Jun 28;283(24):3205-10
10866867
Osteoporos Int. 2003 Jun;14(4):273-82
12736772
Arterioscler Thromb Vasc Biol. 2001 Nov;21(11):1712-9
11701455
JAMA. 1998 Dec 23-30;280(24):2077-82
9875874
N Engl J Med. 2001 Feb 1;344(5):333-40
11172164
Arch Intern Med. 2000 Oct 9;160(18):2865
11025797
N Engl J Med. 2003 Sep 25;349(13):1277-9
14500803
Lancet. 2000 Jun 24;355(9222):2218-9
10881898