The Effect of Zonisamide on Rat Bone Mass, Structure, and Metabolism.

INTRODUCTION: Our study aimed to investigate the effect of zonisamide (ZNS) on bone metabolism in the rat model. METHODS: Eight-week-old rats were divided into four groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+ZNS) and the sham-operated control group (SHAM+ZNS) received SLD enriched with ZNS for 12 weeks. Bone marker concentrations in serum of receptor activator of nuclear factor kappa B ligand, PINP, and osteoprotegerin, and the levels of sclerostin and bone alkaline phosphatase in bone homogenate, were measured using an enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. The femurs were used for biomechanical testing. RESULTS: We found a statistically significant reduction in BMD and biomechanical strength 12 weeks after orchidectomy of the rats (ORX). After ZNS administration to orchidectomized rats (ORX+ZNS) and the sham-operated control rats (SHAM+ZNS), there were no statistically significant changes in BMD, bone turnover markers, or biomechanical properties as compared with the ORX group and SHAM group. CONCLUSIONS: The results suggest that administration of ZNS to rats exerts no negative effect on BMD, bone metabolism markers, or biomechanical properties.

Effects of Amlodipine on Bone Metabolism in Orchidectomised Spontaneously Hypertensive Rats.

Spontaneously hypertensive rats (SHR) represent a model of essential hypertension. We studied the effect of amlodipine (AML) on bone markers, bone mineral density (BMD), and biomechanical properties of osteopenic bone induced by orchidectomy in male SHR. Rats were allocated to 3 groups and were sacrificed after 12 weeks: sham-operated control; orchidectomised control; and orchidectomised receiving a diet supplemented with AML. Indicators of bone turnover were assessed in bone homogenate, BMD was measured by dual energy X-ray absorptiometry, and the femurs were subjected to biomechanical testing. Long-term AML administration does not have a negative impact on bone metabolism and density in male SHR.

Modulation of Rat Liver Regeneration after Partial Hepatectomy by Dietary Cholesterol.

INTRODUCTION: The aim of study was to evaluate impact of long-term dietary cholesterol overload on the cholesterol homeostasis and liver regeneration. MATERIAL AND METHODS: Serum lipid parameters, 14C-cholesterol incorporation, liver DNA synthesis and protein expression was determined in partially hepatectomized (PH) rats fed with a standard (SLD) or hypercholesterolemic (CHOL) diet. RESULTS: 29-day intake of CHOL diet before PH produced increase in serum total cholesterol, LDL lipoprotein, and triglyceride concentration. PH provoked decrease in serum total cholesterol and triglyceride concentration in both groups. PH was associated with increase in serum ALT activity more pronounced in CHOL animals. Hepatic DNA synthesis was increased after PH in both groups, but lower in CHOL. Hypercholesterolemic diet reduced the absorption of radiolabelled cholesterol in intestine and then activity in blood and liver. The 14C-cholesterol hepatic activities tend to increase after PH in both groups. CHOL diet produced up-regulation of Acyl-CoA:cholesterol acyltransferase-2 protein expression. PH was associated with increase of LDL receptor and Acyl-CoA:cholesterol acyltransferase-2 protein expression in both dietary groups. DISCUSSION: Liver regeneration after PH is negatively influenced by CHOL diet. The increased uptake of cholesterol in the liver after PH associated with up-regulation of LDL receptor protein expression suggests preferential use of extrahepatic cholesterol by the liver.

Inactivation of dermatophyte infection by nonthermal plasma on animal model.

Superficial fungal infections are a major epidemiological issue with increasing prevalence and are a common global problem. This article describes experimental therapy of superficial fungal skin infection using low-temperature plasma. Groups of guinea pigs were artificially infected with Trichophyton mentagrophytes SK 3286 dermatophyte and treated with plasma produced by a DC cometary discharge with an inserted grid. The course of infection was a week shorter and milder in animals treated by plasma than that in nontreated animals, the significant lowering of dermatophytic germs also occurred in the treated group. The exposure to plasma causes no harm to experimental animals. The results allow for the development of a new dermatophytoses therapy by low temperature plasma treatment.

Effect of mirtazapine on rat bone tissue after orchidectomy.

OBJECTIVE: Our study aimed to investigate the effect of mirtazapine on bone metabolism in the orchidectomized rat model. METHODS: Rats were divided into three groups. A sham-operated control group (SHAM group) and a control group after orchidectomy (ORX group) received the standard laboratory diet (SLD). An experimental group after orchidectomy (ORX MIRTA group) received SLD enriched with mirtazapine for 12 weeks. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Bone marker concentrations of osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I, bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 were examined in bone homogenate. The femurs were used for biomechanical testing. RESULTS: Compared with the control ORX group, we found a lower BMD in the ORX MIRTA group. The differences were statistically significant, although not in the lumbar vertebrae. BMD was lower in the MIRTA group, suggesting a preferential effect on cortical bone. However, although the thickness of the diaphyseal cortical bone was not different, the fragility in the femoral neck area was statistically significantly different between the groups in biomechanical testing. Regarding the bone metabolism markers, there was a significant decrease in OPG and BALP levels, suggesting a reduction in osteoid synthesis. CONCLUSIONS: The results suggest that prolonged use of mirtazapine may have a negative effect on the synthesis of bone and on its mechanical strength, especially in the femoral neck. Further studies are warranted to establish whether mirtazapine may have a clinically significant adverse effect on bone exclusively in the model of gonadectomized rats, or whether the effect occurs also in the model of gonadally intact animals and in respective human models.

Protective effect of amlodipine on rat bone tissue after orchidectomy.

AIM: Our study aimed to investigate the effect of amlodipine on bone metabolism in orchidectomized rats. METHODS: Eight-week-old rats were divided into three groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+AML) received SLD enriched with amlodipine for 12 weeks. Bone marker concentrations in serum of PINP, OPG and IGF-1, and the levels of CTX-I, BAP and BMP-2 in a bone homogenate were measured using enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. The femurs were used for biomechanical testing. RESULTS: Bone markers (CTX-I, BAP, BMP-2) in ORX were higher versus SHAM. In ORX+AML there was a decrease in PINP, CTX-I, BAP, BMP-2 and OPG versus ORX. IGF-1 was decreased in ORX versus SHAM. In ORX+AML it was increased versus ORX. In ORX, a decrease was demonstrated versus SHAM in BMD of the whole body, in the lumbar vertebrae and in both femurs. In ORX+AML there was an increase in BMD of the whole body versus ORX. Three-point bending test revealed a decrease in maximal load values in ORX versus SHAM. After amlodipine administration there was an increase in the left femur versus ORX. CONCLUSIONS: Amlodipine is capable of mitigating the negative effects of orchidectomy and could be a good prevention of osteoporosis.

The effect of mud-bath therapy on bone status in rats during adjuvant subchronic arthritis.

INTRODUCTION: We studied influence of mud-bath on bone status in male Wistar rats with subchronic arthritis. METHODS: Arthritis was induced by 2 subplantar injections of Freund's adjuvans with heat-killed Streptoccocus pyogenes into paw. Groups: intact (int) on chippings; (con) arthritis on chippings; (san38) arthritis on hot sand; (mu38) arthritis on hot mud; (mu21) arthritis on mild mud. Bone mineral density (BMD, g/cm2) was measured by dual energy X-ray absorptiometry and femurs were tested biomechanically. Bone markers osteocalcin (OC), PINP and CTX were analysed in bone. RESULTS: BMD of right femur decreased vs. left in san38 (p = 0.030) and mu38 (p = 0.047). Fracture load of right/left femur (N) decreased in experimental groups, significantly in san38 (p = 0.05). Fracture threshold of neck decreased in right vs. left in experimental groups, but significantly in san38 (p = 0.05). OC decreased in mu38 vs. con (1.84 +/- 0.14/2.62 +/- 0.23). PINP decreased in int vs. san38 (p = 0.005) and mu21 (p < 0.001). CTX decreased in int vs. mu38 (p = 0.006) and mu21 (p = 0.005). CONCLUSION: The hot bath appears indifferent in relation to osteoporosis, while cold mud-bath shows good effect on bone metabolism. The cold mud-baths help to reduce arthritic inflammation and pain and thereby lead to higher mobility with positive consequence on bone.

The influence of simvastatin, atorvastatin and high-cholesterol diet on acetylcholinesterase activity, amyloid beta and cholesterol synthesis in rat brain.

OBJECTIVE: There is evidence to suppose that cholesterol-lowering medicine might confer protection against dementia, probably via modulation of cholesterol synthesis in the brain. The aim of the present study was to investigate the potential influence of statins and cholesterol diet on selected parameters relevant to Alzheimer's disease pathophysiology. METHODS: For 15 days, rats were orally administered simvastatin (10 or 20mg/kg b.wt.), atorvastatin (10 or 20mg/kg b.wt.), or aqua (control group); and one group was fed high-cholesterol (2%) diet. At the end of experiments brain (and plasma) cholesterol, lathosterol, hydroxymethylglutaryl-coenzyme A reductase protein, acetylcholinesterase activity, amyloid beta (40 and 42) and cholesterol synthesis rate (using the incorporation of deuterium from deuterated water) were determined and statistically compared to those of aqua. RESULTS: Both statins were able to lower cholesterol in the plasma, but none elicited an effect on total brain cholesterol. Significant reductions of brain lathosterol and cholesterol synthesis rate were observed after simvastatin and atorvastatin treatment. Acetylcholinesterase activity, amyloid beta and hydroxymethylglutaryl-coenzyme A reductase levels remained unaffected by the two drugs. CONCLUSIONS: This study brings additional evidence of a role for statins in cholesterol synthesis in the brain. Our data question the relationship between amyloid beta, acetylcholinesterase activity and cholesterol synthesis in the rat brain as well as the assumption about no exchange between peripheral and brain cholesterol pools.

Various surgical techniques for the repair of injured vas deferens in rat experiments.

OBJECTIVE: The aim of this study was to evaluate whether the different vasovasostomy techniques can be performed using only the operating loupe in a rat model. The secondary aims were to evaluate the patency rate and inflammation of the vas deferens (VD) after contusion and the different vasovasostomy repair techniques. METHODS: A total of 40 male rats were divided into 4 groups based on the type of surgery: 1. contusion of the VD; 2. cutting of the VD and vasovasostomy with absorbable sutures; 3. cutting and joining of the VD using absorbable sutures with an intraluminally situated lead fibre; and 4. cutting and joining of the VD using non-absorbable sutures with an intraluminally situated lead fibre. Ninety days after the surgery the VD was resected, patency and histopathological signs of inflammation in the VD were evaluated. RESULTS: All vasovasostomy techniques were successfully performed in all animals using only the operating loupe. The patency rate was 100% in the subgroup with contusion. Differences in the patency rates were found among the subgroups with vasovasostomy (P=0.007). The patency rate was higher in the subgroup that underwent group 3. Compared with vasovasostomies, contusion was associated with lower rates of inflammation (P=0.02) and severe inflammation (P=0.003). No differences were found among the subgroups of vasovasostomy techniques. CONCLUSION: Contusion of the VD was not related to impairment in terms of patency. Vasovasostomy with an intraluminally situated lead fibre resulted in the highest patency rate among the standard vasovasostomy techniques.

The effect of gabapentin and pregabalin on bone turnover and bone strength: A prospective study in Wistar rats.

BACKGROUND: There are limited data on the effects of GBP on bone and no data for PGB. Some data suggest that there is a significant influence of sex hormone balance on the susceptibility of bone to antiepileptic drug-induced bone loss. METHODS: Forty-eight male Wistar rats were divided into six groups that were subjected to two surgeries, sham (noORX) or real orchidectomy (ORX), and were fed three diets, a SLD, a SLD enriched with GBP or a SLD enriched with PGB. Dual energy X-ray absorptiometry was used to measure the bone mineral density. The concentrations of bone turnover markers were assayed. The femurs were biomechanically tested. RESULTS: Significant reductions in bone mineral density, weight and biomechanical strength were observed in ORX animals. GBP or PGB exposure did not cause significant alterations in bone mineral density or biomechanical strength. No changes in bone turnover markers were observed, except for RANKL. A significant increase was found in the ORX GBP and ORX PGB groups. Within the orchidectomized animal group, RANKL levels were significantly higher in the ORX PGB group than in the ORX GBP group. CONCLUSIONS: Because neither GBP nor PGB affected bone mineral density or mechanical bone strength, both of these antiepileptic drugs could be considered drugs with lower risks to bone health. A shift in RANKL levels indicates that the effects of GBP and PGB on osteoclast activity may be dependent on the hormonal status of animals.

The effect of levetiracetam on rat bone mineral density, bone structure and biochemical markers of bone metabolism.

Some data suggest that exposure to levetiracetam (LEV) might be associated with a risk for bone health in the model of orchidectomized rats. The aim of this study was to investigate if there is any significant risk of LEV for bone health in the model of gonadally intact animals. Wistar rats were divided into a control group and a test group, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed SLD enriched with LEV for 12 weeks. Dual energy X-ray absorptiometry was used to measure BMD of the whole body, femur and lumbar vertebrae. The concentrations of bone markers were examined in bone homogenate. Both femurs and tibiae were used for biomechanical testing. We found in the LEV group significantly decreased absolute and relative values of adipose tissue, higher whole-body BMD, higher right tibia cortical thickness, and a significantly increased concentration of Bone Alkaline Phosphatase (BALP) and cross-linked C-telopeptide of type I collagen (CTX-I) compared with the control group. The results suggest that the long-term administration of LEV in the model of gonadally intact rats does not have a negative effect on bone. Significant increase in BMD and cortical thickness of the right tibia may indicate even a positive influence on the properties of bone. Further studies will be necessary in animals and humans to confirm these findings.

The influence of repeated blood withdrawals before surgery on clinical outcome.

UNLABELLED: The aim of this study was to find the influence of blood withdrawals and diet iron on elective surgery. Male Wistar rats (n=24) were divided: 1. group (SLD) ate standard laboratory diet (SLD), 2. group (FE) an iron enriched diet (FE) with one blood withdrawal after 9 weeks. 3. group (SLD-w) SLD and 4. group (FE-w) ate the FE diet; with 9 withdrawals once a week. The rats were sacrificed 18 hour after partial hepatectomy (PH) in the 10th week. Liver DNA synthesis (3H-thymidin - kBq/mg DNA) was performed. Serum hepcidin (pg/ml), iron concentration, respiratory burst of polymorfonucleares (RB, spontaneous; stimulated, %), count of blood cells were determined. FE-w had a higher (2.36+/-0.36) liver DNA synthesis after PH vs. SLD (1.21+/-0.49). Higher hemoglobin in erythrocytes (pg) was in FE-w and SLD-w vs. FE and SLD. PMN count in SLD-w, FE-w increased vs. SLD, FE. Hepcidin after PH decreased in SLD (78.0), FE (68.0), FE-w (97.0), but increased in SLD-w (217). Serum iron increased in SLD-w. RB after PH increased in FE-w (4.5; 47.6) vs. SLD (1.15; 29.1), FE (3.20;17.8), SLD-w (3.30;13.7). CONCLUSIONS: The iron diet with stimulation of haematopoesis by withdrawals improves an organism's condition expressed as better response to elective surgery and better PMN functions.

The effect of lamotrigine and phenytoin on bone turnover and bone strength: A prospective study in Wistar rats.

OBJECTIVE: Some data suggest that exposure to lamotrigine (LTG) might be associated with impaired bone health in an orchidectomized rat model. The aim of this study was to determine if LTG poses any significant risk for bone in a gonadally intact animals and to compare the effect of LTG with that of phenytoin (PHT). METHOD: Twenty-four rats were divided into control and test groups, (n=8 per group). Control rats received a standard laboratory diet (SDL), while rats in the test groups were fed a SLD enriched with LTG or PHT for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density (BMD). The concentrations of bone turnover markers (BTM) were assayed in bone homogenates. The femurs were measured and biomechanically tested. RESULTS: Treatment with either LTG or PHT had no significant effect on BMD or on the biomechanical strength of the bones. In contrast to the effect of LTG, we did find significant changes in BTM in the PHT group: a highly significant decrease in the osteoprotegerin/receptor activator of nuclear factor kappa B ratio (p<0.01) and highly significant increases in bone alkaline phosphatase and amino-terminal propeptide of procollagen type I (p<0.001, p˂0.01, respectively). In the LTG group, the only significant change was a decrease in sclerostin (p˂0.05). The PHT level was 19.0 (15.6-19.5) µmol/l, which represents the lower end of the therapeutic range used in humans. The level of LTG was 60.7 (58.5-61.8) µmol/l. CONCLUSIONS: LTG has no effect on the BMD, BTM or mechanical strength in gonadally intact animals. Although a low dose of PHT was associated with enhanced BTM, it did not affect BMD or the biomechanical properties of the bones, similar to the results observed for LTG.

Negative effect of serotonin-norepinephrine reuptake inhibitor therapy on rat bone tissue after orchidectomy.

Our goal was to determine if venlafaxine has a negative effect on bone metabolism. Rats were divided into three groups. The sham-operated control group (SHAM), the control group after orchidectomy (ORX), and the experimental group after orchidectomy received venlafaxine (VEN ORX) in standard laboratory diet (SLD) for 12 weeks. Bone mineral content (BMC) was measured by dual energy X-ray absorptiometry (DXA). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I (P1NP), bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 (BMP-2) were examined in bone homogenate. The femurs were used for biomechanical testing. Compared to the ORX group we found lower BMD in the diaphysis area of the femur in the VEN ORX group, suggesting a preferential effect on cortical bone. Of the bone metabolism markers, there was significant decrease (ORX control group versus VEN ORX experimental group) in BALP levels and increase in sclerostin and CTX-I levels, suggesting a decrease in osteoid synthesis and increased bone resorption. The results suggest that the prolonged use of venlafaxine may have a negative effect on bone metabolism. Further studies are warranted to establish whether venlafaxine may have a clinically significant adverse effect on bone.

The effect of lacosamide on bone tissue in orchidectomised male albino Wistar rats.

AIMS: While most antiepileptic drugs (AEDs) have been associated with various adverse effects on bone health, for the recently introduced lacosamide (LCM) no corresponding data have been published. The present study evaluates the effect of LCM on bone mineral density, bone turnover markers, and bone mechanical strength in a rat model. METHODS: 16 orchidectomized Wistar rats were divided into control and experimental groups, 8 rats each. Dual energy X-ray absorptiometry was used to measure bone mineral density (BMD). As bone metabolism markers, the concentrations of bone markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. RESULTS: Compared to the control group, we found lower BMD in the experimental group in the area of the left (8%) as well as the right femur (12%), all differences being statistically significant. In both femur diaphyses, but not in lumbar vertebrae, BMD was lower in the LCM group, suggesting a preferential effect on cortical bone. However, neither the thickness of the diaphyseal cortical bone nor the fragility in biomechanical testing was different between the groups. Of the bone metabolism markers, the significant decline was in procollagen type I N-terminal peptide (PINP) levels (37.4%), suggesting a decrease in osteoid synthesis. CONCLUSION: We assume then that long-lasting exposure to LCM can represent a certain risk to the health of bone in the setting of gonadal insufficiency. Further studies will be needed to confirm these findings and to determine how high the risk will be in comparison to the other AEDs.

Serum leptin concentrations after surgery in young rats.

OBJECTIVES: We describe changes in serum leptin concentrations after surgery (laparotomy, partial hepatectomy, splenectomy, and unilateral nephrectomy) in young male rats. Because we presumed that pain and inflammation would influence food intake and subsequent leptin release, laparotomized and partially hepatectomized rats were treated with ibuprofen. METHODS: Preoperative blood samples were taken from the retroorbital sinuses, and postoperative blood samples were taken from the aorta, vena portae, and vena cava 18 h after surgery. Serum leptin concentrations were estimated by radioimmunoassay. RESULTS: Pre- and postoperative serum leptin concentrations did not differ significantly in rats with partial hepatectomy (5.1 +/- 0.4 versus 4.2 +/- 1.1 microg/L), splenectomy (6.1 +/- 0.4 versus 5.0 +/- 0.6 microg/L), or unilateral nephrectomy (4.1 +/- 0.7 versus 5.0 +/- 1.3 microg/L). Significant decreases in serum leptin were observed after laparotomy (8.1 +/- 0.9 versus 3.7 +/- 0.5 microg/L), laparotomy plus ibuprofen treatment (8.9 +/- 1.6 versus 3.1 +/- 0.4 microg/L), and partial hepatectomy plus ibuprofen treatment (5.4 +/- 0.6 versus 3.2 +/- 0.3 microg/L). We observed no significant differences in serum leptin concentrations measured in different regions of the body. CONCLUSIONS: Surgical interventions in young rats are accompanied by decreases in serum leptin. The liver, spleen, and kidney may participate in leptin clearance. Ibuprofen treatment leads to additional decreases in serum leptin concentrations.

Influence of high cholesterol diet and pravastatin sodium on the initiation of liver regeneration in rats after partial hepatectomy.

OBJECTIVES: Liver regeneration is influenced by cholesterol and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-reductase). HMG-CoA-reductase is a key enzyme for cholesterol synthesis. Recent studies have shown that inhibitors of HMG-CoA-reductase improve liver functions after 67% partial hepatectomy (PH). METHODS: Male Wistar rats (W) and Prague hereditary hypercholesterolemic rats (PHHC) were used. Aqua pro injectione (AI) or pravastatin (prava; 1 mg/kg) was administered orally once daily. Group 1: W, standard diet (SD) + AI; group 2: W, SD + prava; group 3: W, cholesterol-enriched diet (chol) + AI; group 4: PHHC, chol + AI; group 5: PHHC, chol + prava. After 27 d, PH was performed in all groups. RESULTS: Groups fed chol before PH had significantly higher liver triacylglycerol content (group 3: 25.8 +/- 2.6 mg/g of liver weight; group 4: 16.0 +/- 1.0 of liver weight; group 5: 22.0 +/- 1.0 of liver weight) than did the groups fed SD (group 1: 6.1 +/- 0.5; group 2: 5.9 +/- 0.7). Liver DNA synthesis after PH was significantly lower in chol-fed groups (group 3: 561 +/- 78; group 4: 472 +/- 92) than in SD-fed groups (group 1: 1645 +/- 574; group 2: 2935 +/- 1298), except the chol-fed PHHC given prava (group 5: 3230 +/- 527). CONCLUSIONS: In prava-treated rats, the induction of HMG-CoA activity overcame the inhibitory capability of pravastatin. The induction of HMG-CoA-reductase activity had a stimulatory effect on the initiation of liver regeneration.

The effect of topiramate and lamotrigine on rat bone mass, structure and metabolism.

There is only limited data concerning the effect of the newer antiepileptic drugs on bone. The objective of this study was to determine the effect of topiramate (TPM) and lamotrigine (LTG) monotherapy on bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomized (ORX) rat model. 24 orchidectomized Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LTG or TPM for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density. The concentrations of bone metabolism markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Compared to the control group, both test groups had significantly lower weight, fat mass, whole body and femur BMD, BMC and reduced mechanical strength of bone. All of these changes were more pronounced in rats exposed to LTG. In conclusion, both LTG and TPM significantly reduce BMD and body weight and impair mechanical strength of bone. A question arises as to the degree of dependence of the effect on the dose. Further studies are warranted to establish whether LTG and TPM may have a clinically significant effect on BMD exclusively in the model of gonadectomized rats, or whether the effect applies also in the model of gonadally intact animals, and in the respective human models.

The effect of levetiracetam on rat bone mass, structure and metabolism.

OBJECTIVE: To determine the effect of levetiracetam (LEV) Lon bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomised (ORX) rat model. METHOD: 16 orchidectomised Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LEV for 12 weeks. BMD was measured by dual energy X-ray absorptiometry at the whole body, lumbar spine and femur. Bone marker concentrations were examined of osteoprotegerin (OPG) and insulin-like growth factor 1 (IGF-1) in serum, and amino-terminal propeptide of procollagen type I (PINP), carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), bone alkaline phosphatase (ALPL), and bone morphogenetic protein 2 (BMP-2) in bone homogenate. The femurs were used for biomechanical testing. RESULTS: Compared to the control group we found lower fat mass, lower BMD in the area of the left femur, lower BMC in both femurs, a reduced concentration of OPG, and an increased concentration of CTX-I of borderline statistical significance (p=0.0661). Biomechanical parameters did not differ between groups. CONCLUSIONS: Significant loss of BMD or BMC was seen at the left and right femur area in the LEV group. Administration of LEV in the ORX-rat model significantly decreased levels of OPG (marker of bone formation) in serum and increased levels of CTX-I (marker of bone resorption) in bone homogenate, but results in this study did not reveal any change in biomechanical bone strength. Administration of LEV in the ORX-rat model may reduce adipose tissue. Further studies in animals and humans will be needed to confirm these findings.

Protective effect of atorvastatin on bone tissue in orchidectomised male albino Wistar rats.

Recent studies have shown that atorvastatin influences bone metabolism. We investigated its bone protective effect in orchidectomised rats after 12 weeks of treatment. Eight-week-old rats were divided into 3 groups: sham-operated group, control group after orchidectomy and experimental group after orchidectomy with atorvastatin administration (12 mg/kg/day). Bone mineral density and bone marker concentrations of aminoterminal propeptide of procollagen type I (PINP), osteoprotegerin (OPG), insulin-like growth factor 1 (IGF-1) in serum, and carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), bone alkaline phosphatase (BALP), bone morphogenetic protein 2 (BMP-2) in bone homogenate were measured. Total serum calcium and tibial calcium content was determined. Femurs were used for three-point bending test of the shaft and compression testing of the femoral neck. Bone markers (CTX-I, BALP, BMP-2) in control rats were higher vs. sham-operated rats. Atorvastatin reduced CTX-I, BMP-2 and OPG compared to controls. IGF-1 was decreased in control rats vs. sham-operated rats; atorvastatin increased IGF-1 vs. control rats. Atorvastatin exerts a positive effect on bone metabolism by increasing bone mineral density of the whole body, which had decreased under the effects of orchidectomy. Three-point bending test revealed an increase in maximal load values of the left femurs after atorvastatin administration compared to controls. The diameter of the left femur and length of both femurs were increased after atorvastatin administration compared to controls. Our findings suggest that atorvastatin has a beneficial effect on bone metabolism in orchidectomised rats by decreasing bone turnover, with resulting improvement in bone mineral density and bone biomechanical properties.