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Effect of statins on bone mineral density and bone histomorphometry in rodents.
Arterioscler Thromb Vasc Biol. 2001 Oct; 21(10):1636-41.AT

Abstract

Statins have been postulated to affect bone metabolism. We investigated the effects of different doses of simvastatin (1, 5, 10, and 20 mg. kg(-1). d(-1)), atorvastatin (2.5 mg. kg(-1). d(-1)), and pravastatin (10 mg. kg(-1). d(-1)) administered orally for 12 weeks to intact female Sprague-Dawley rats and the effect of 20 mg. kg(-1). d(-1) simvastatin in sham-operated and ovariectomized rats on femoral bone mineral density (BMD) and quantitative bone histomorphometry (QBH) and compared them with controls. BMD was decreased by 1 mg. kg(-1). d(-1) simvastatin (P=0.042), atorvastatin (P=0.0002), and pravastatin (P=0.002). The effect on QBH parameters differed with different doses of simvastatin (ANOVA, P=0.00012). QBH parameters of both bone formation and resorption were equivalently and markedly increased by 20 mg. kg(-1). d(-1) simvastatin in 2 separate groups of intact rats and were reflected by a relatively unchanged BMD. At lower doses, 1 mg. kg(-1). d(-1) simvastatin decreased bone formation while increasing bone resorption, as reflected by a marked decrease in BMD. Ovariectomized animals receiving 20 mg. kg(-1). d(-1) simvastatin showed no change in BMD relative to the untreated, ovariectomized controls; their increase in bone formation was smaller than in sham-operated rats receiving simvastatin, and there was no change in bone resorption. Dose-response curves of simvastatin for bone formation and resorption differed. These studies indicate that (1) statins decrease BMD in rodents, (2) high-dose simvastatin increases bone formation and resorption, (3) low-dose simvastatin decreases bone formation and increases bone resorption, (4) the effects of simvastatin on QBH differ at different dosages, (5) the effects of simvastatin seen in intact rats are not observed in ovariectomized rats, and (6) simvastatin is unable to prevent bone loss caused by ovariectomy.

Authors+Show Affiliations

Endocrinology and Metabolism Unit, Department of Internal Medicine, University of Stellenbosch and Tygerberg Hospital, Tygerberg, South Africa. maritz@mweb.co.za.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11597938

Citation

Maritz, F J., et al. "Effect of Statins On Bone Mineral Density and Bone Histomorphometry in Rodents." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 21, no. 10, 2001, pp. 1636-41.
Maritz FJ, Conradie MM, Hulley PA, et al. Effect of statins on bone mineral density and bone histomorphometry in rodents. Arterioscler Thromb Vasc Biol. 2001;21(10):1636-41.
Maritz, F. J., Conradie, M. M., Hulley, P. A., Gopal, R., & Hough, S. (2001). Effect of statins on bone mineral density and bone histomorphometry in rodents. Arteriosclerosis, Thrombosis, and Vascular Biology, 21(10), 1636-41.
Maritz FJ, et al. Effect of Statins On Bone Mineral Density and Bone Histomorphometry in Rodents. Arterioscler Thromb Vasc Biol. 2001;21(10):1636-41. PubMed PMID: 11597938.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of statins on bone mineral density and bone histomorphometry in rodents. AU - Maritz,F J, AU - Conradie,M M, AU - Hulley,P A, AU - Gopal,R, AU - Hough,S, PY - 2001/10/13/pubmed PY - 2002/1/5/medline PY - 2001/10/13/entrez SP - 1636 EP - 41 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 21 IS - 10 N2 - Statins have been postulated to affect bone metabolism. We investigated the effects of different doses of simvastatin (1, 5, 10, and 20 mg. kg(-1). d(-1)), atorvastatin (2.5 mg. kg(-1). d(-1)), and pravastatin (10 mg. kg(-1). d(-1)) administered orally for 12 weeks to intact female Sprague-Dawley rats and the effect of 20 mg. kg(-1). d(-1) simvastatin in sham-operated and ovariectomized rats on femoral bone mineral density (BMD) and quantitative bone histomorphometry (QBH) and compared them with controls. BMD was decreased by 1 mg. kg(-1). d(-1) simvastatin (P=0.042), atorvastatin (P=0.0002), and pravastatin (P=0.002). The effect on QBH parameters differed with different doses of simvastatin (ANOVA, P=0.00012). QBH parameters of both bone formation and resorption were equivalently and markedly increased by 20 mg. kg(-1). d(-1) simvastatin in 2 separate groups of intact rats and were reflected by a relatively unchanged BMD. At lower doses, 1 mg. kg(-1). d(-1) simvastatin decreased bone formation while increasing bone resorption, as reflected by a marked decrease in BMD. Ovariectomized animals receiving 20 mg. kg(-1). d(-1) simvastatin showed no change in BMD relative to the untreated, ovariectomized controls; their increase in bone formation was smaller than in sham-operated rats receiving simvastatin, and there was no change in bone resorption. Dose-response curves of simvastatin for bone formation and resorption differed. These studies indicate that (1) statins decrease BMD in rodents, (2) high-dose simvastatin increases bone formation and resorption, (3) low-dose simvastatin decreases bone formation and increases bone resorption, (4) the effects of simvastatin on QBH differ at different dosages, (5) the effects of simvastatin seen in intact rats are not observed in ovariectomized rats, and (6) simvastatin is unable to prevent bone loss caused by ovariectomy. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/11597938/Effect_of_statins_on_bone_mineral_density_and_bone_histomorphometry_in_rodents_ L2 - https://www.ahajournals.org/doi/10.1161/hq1001.097781?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -