The Effect of Tamoxifen and Fluoride on Bone Mineral Density, Biomechanical Properties and Blood Lipids in Ovariectomized Rats

Abstract

Abstract:The most important aspect of therapy with fluoride and tamoxifen concerns its influence on bone tissue and lipid metabolism. The aim of the study was to evaluate the effect of tamoxifen and natrium fluoride (NaF) on bone metabolism, biochemical properties and blood lipids levels in ovariectomized rats. The study was performed in Wistar rats divided into 5 subgroups: ovariectomized controls, rats treated with NaF 20 mg/kg/24 hr, rats treated with NaF 20 mg/kg/24 hrπtamoxifen 2 mg/kg/24 hr, rats treated with NaF 20 mg/kg/24 hr plus tamoxifen 4 mg/kg/24 hr, and shamoperated controls. In ovariectomized rats the increase of total cholesterol, low-density lipoproteins cholesterol (LDLcholesterol) as well as the decrease of bone mineral content, bone mineral density and biomechanical properties was observed. The therapy with NaF increased the level of total cholesterol, LDL-cholesterol, triglycerides, bone mineral density, bone mineral content. In this group the decrease of bone strength and stiffness was observed. The administration of tamoxifen reduced the changes in plasma lipid levels, but did not improve the biomechanical properties of bone tissue.Natrium fluoride (NaF) is used experimentally and in clinical trials for treatment of osteoporosis. However several studies have shown structural abnormalities or mineralization defect in the bone formed during fluoride administration (Kleerekoper et al. 1991).In contrast to oestrogen suppression of bone turn-over, fluoride stimulates bone formation. The controversy revolves around the issue of whether this new bone is biomechanical sound enough to reduce fractural risk. The use of relatively higher doses of fluoride in man unfortunately resulted in the increase of fractures as well as other sideeffects (Boivin et al. 1993). Animal studies have shown that therapy with high doses of fluoride induces disturbances in lipid metabolism (Chinoy et al. 1994;Wang et al. 2000). Riggs et al. (1990) hypothesized that the combination of fluoride with oestrogens may reduce the side effects of fluoride. The aim of present study was to evaluate whether the administration of tamoxifen reduce the changes in lipid metabolism induced by high doses of NaF as well as the possibility of a positive effect on bone mass and biomechanical properties. Materials and MethodsFemale Wistar rats were used in this experiment. They were allowed to acclimatize for a minimum of 10 days prior to the study. The Author for correspondence: Andrzej Pawlik, Department of Pharmacokinetics and Therapeutic Drug Monitoring Pomeranian Medical University, Powstań ców Wielkopolskich 72, PL 70-111 Szczecin, Poland (fax π48 91 4661600, e-mail pawand/poczta. onet.pl).rats were housed in a room maintained of 21∫1 ae with 12 hr light:-dark cycle with the light cycle on at 6:00 a.m. At 3 months of age 50 female rats (body weight 238.3∫10.4 g) were anaesthetized with a combination of ketamin (Ketalar, Warner-Lamert, Schweiz) and xylazin (Rompun, Bayer, Germany) and were ovariectomized (40 individuals) or sham-operate...

Comparing the effects of atamestane, toremifene and tamoxifen alone and in combination, on bone, serum lipids and uterus in ovariectomized rats

“…As monotherapy TOR has a significant and equivalent stimulatory effect on uterine epithelium as TAM. These monotherapy findings are consistent with published studies in this rat model [24][25][26][27][28][29][30].…”

Lipid metabolism disorders and bone dysfunction-interrelated and mutually regulated (Review)

“…OP and AS are often present in the same individual and a number of clinical studies support a role for lipid metabolism in the development of OP ( 8 ), although this is not a universal finding. The data on the impact of lipid metabolism disorders on bone status were obtained from clinical reports ( 5 , 9 – 18 ) as well as from animal studies ( 19 – 22 ).…”

“…In experimental animal models, TC and LDL-C levels were significantly increased, while the BMC and BMD of femurs were significantly decreased in ovariectomized (OVX) rats ( 19 ). Liu et al ( 20 ) investigated the prophylactic and therapeutic action of the Gengnianchun medicinal preparation on OVX-induced OP and hyperlipidemia.…”

Tocotrienol Supplementation Improves Late-Phase Fracture Healing Compared to Alpha-Tocopherol in a Rat Model of Postmenopausal Osteoporosis: A Biomechanical Evaluation

“…This assumption may not always be accurate as discovered with the fluoride treatment of osteoporosis. The bone density appeared to be improved with fluoride treatment but in actual fact there was no improvement in strength as the new bones formed were fragile [18–21]. …”