Browsing by Subject "Bone Density Conservation Agents"

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    Comparison of the effects of alendronate and risedronate on bone mineral density and bone turnover markers in postmenopausal osteoporosis
    (2006) Sarioglu M.; Tuzun C.; Unlu Z.; Tikiz C.; Taneli F.; Uyanik B.S.
    The aim of the study was to compare the effects of once-weekly alendronate sodium and daily risedronate sodium treatment on bone mineral density (BMD) and bone turnover markers in postmenopausal osteoporotic subjects. For this purpose, 50 patients were included in this study and randomly classified into two groups. Group I (n = 25) received risedronate (5 mg/day) and group II (n = 25) received alendronate Na (70 mg/ week). The study duration was limited to 12 months. The efficacy of the treatment was evaluated by BMD measurements at spine and hip at 6th and 12th months of the treatment, as well as by the measurement of bone turnover markers such as serum osteocalcin (OC), bone-specific alkaline phosphatase (BASP), urine deoxypyridinoline (DPD) and calcium/creatine ratio in 24-h urine at 1st, 3rd, 6th and 12th months. The evaluation of the changes in BMD in all regions revealed a significant increase in BMD in both groups compared to baseline values except for spine (L2-L4) in alendronate group at 6th and 12th month and femoral neck in risedronate group at 6th month. However, the difference in percentage increase in BMD measurements was not statistically significant between the two groups at 6th and 12th months. In both groups, serum OC, BSAP and urine DPD were found to be significantly attenuated at 1st month of the treatment period, and continued to be lowered throughout the 3rd, 6th and 12th months (P < 0.05). However, there was no statistically-significant difference between both groups of patients (P > 0.05). In conclusion, our results suggest that both treatment protocols provide treatment options of similar efficiency for postmenopausal osteoporosis, and have almost-similar effects in enhancing the BMD and in slowing the bone turnover. Risedronate seems to havea more potent effect in the spinal region than that of alendronate, although this potency was not statistically significant. © Springer-Verlag 2004.
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    The effect of clomiphene citrate on osteoporosis in ovariectomized rats
    (2008) Uyar Y.; Koltan S.O.; Pögün Ş.; Vatansever S.; Çaglar H.
    Objective: The aim of this study was to investigate whether clomiphene citrate (CC) administration could be a new therapeutic agent in case of contraindication of estrogen therapy for hormone-dependent osteoporosis and to show the changes in bone structure by histomorphometric analysis in ovariectomized rats administered CC. Study design: This study was carried out in the Experimental Surgery Laboratory of the Brain Research Centre of the Medical Faculty of Ege University. Four-month-old Sprague-Dawley rats were used for the experiment. The study was carried out on six groups of animals each consisted of eight rats. Four groups of rats were ovariectomized and 2 groups of rats were used as control group. For 6 weeks every day, rats were injected physiological saline solution (1 ml/kg), clomiphene citrate (1 or 10 mg/1 ml/kg, Organon), 17β-estradiol (50 μg/1 ml/kg, within susame oil, Sigma) or susame oil (1 ml/kg, Sigma). Drug administrations were carried out according to the weekly weight measurements. Group 1(PSS), n = 8, non-ovariectomized, were injected with physiological saline solution. Group 2(CC-1), n = 7, non-ovariectomized, were injected with CC (1 mg/1 ml/kg). Group 3(OVX + CC-1), n = 7, ovariectomized, were injected with CC (1 mg/1 ml/kg). Group 4(OVX + CC-10), n = 6, ovariectomized, were injected with CC (10 mg/1 ml/kg). Group 5(OVX + E), n = 8, ovariectomized, were injected with 17β-estradiol (50 μg/1 ml/kg). Group 6(OVX), n = 8, ovariectomized, were injected with susame oil (1 ml/kg) Bone-specific serum alkaline phosphatase (ALP) levels were measured and statistical analyses were made by Kruskal Wallis test. Left femur bone histomorphometric studies were done. The uteri were dissected out to measure their weight and ANOVA was used to show the intergroup differences. Results: The level of ALP in group 3 was significantly higher than the other five groups. Bone histomorphometric examination showed that total bone volume in group 3, 4, and 5 was higher than group 6, and group 4 had the highest level of bone volume compared to the rest of the groups. Uterus weights in group 1 were significantly higher than group 3 and 6 (P = 0.02, P = 0.01) and uterus weights in group 5 were significantly higher than group 3 and 4 (P = 0.00, P = 0.01) Conclusions: In ovariectomized rats, treatment with CC is seen as effective as estrogen treatment in preventing osteoporosis, without causing uterin hyperstimulation. Nevertheless, further investigations on more rats are needed to assess whether it is an alternative treatment method to estrogen. © 2007 Springer-Verlag.
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    Comparative effects of risedronate, atorvastatin, estrogen and SERMs on bone mass and strength in ovariectomized rats
    (2009) Uyar Y.; Baytur Y.; Inceboz U.; Demir B.C.; Gumuser G.; Ozbilgin K.
    Objective: The aim of this study was to investigate bone protective effects of risedronate, atorvastatin, raloxifene and clomiphene citrate in ovariectomized rats. Methods: Our study was conducted on 63 rats at Experimental Research Center of Celal Bayar University. Six-month-old rats were divided into seven groups. There were five drug administered ovariectomized groups, one ovariectomized control group without drug administration and one non-ovariectomized control group without drug administration. Eight weeks postovariectomy, rats were treated with the bisphosphonate risedronate sodium, the statin atorvastatin, the estrogen 17β-estradiol and the selective estrogen receptor modulators (SERMs) raloxifene hydrochloride and clomiphene citrate by gavage daily for 8 weeks. At the end of the study, rats were killed under anesthesia. For densitometric evaluation, left femurs and tibiae were removed. Left femurs were also used to measure bone volume. Right femurs were used for three-point bending test. Results: Compared to ovariectomized group, femur cortex volume increased significantly in non-ovariectomized group (p = 0.016). Compared to non-ovariectomized group, distal femoral metaphyseal and femur midshaft bone mineral density values were significantly lower in ovariectomized group (p = 0.047). In ovariectomy + atorvastatin group, whole femur and femur midshaft bone mineral density and three-point bending test maximal load values were significantly higher than ovariectomized group (p = 0.049, 0.05, and 0.018). When compared to the ovariectomized group, no significant difference was found with respect to femoral maximum load values in groups treated with risedronate, estrogen, raloxifene and clomiphene (p = 0.602, 0.602, 0.75, and 0.927). In ovariectomy + risedronate group, femur midshaft bone mineral density values were significantly higher than the values in ovariectomized group (p = 0.023). When compared to ovariectomized group, no significant difference was found with respect to femur midshaft bone mineral density values in groups treated with estrogen, raloxifene and clomiphene (p = 0.306, 0.808, and 0.095). Conclusions: While risedronate sodium prevented the decrease in bone mineral density in ovariectomized rats, atorvastatin maintained mechanical characteristics of bone and also prevented the decrease in bone mineral density as risedronate sodium. © 2009 Elsevier Ireland Ltd. All rights reserved.
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    Effects of bisphosphonates on sutural bone formation and relapse: A histologic and immunohistochemical study
    (2011) Öztürk F.; Babacan H.; Nan S.; Gümüş C.
    Introduction: The aim of this experimental study was to evaluate the effects of systemically applied zoledronic acid on bone regeneration in response to expansion of the sagittal suture and relapse in rats. Methods: Thirty-six male Wistar rats were divided into 3 groups. In the first and second groups, saline solution was given subcutaneously after expansion, and the retention periods lasted 14 and 7 days, respectively. In the third group, 0.1 mg of zoledronic acid was diluted with saline solution and given subcutaneously after expansion; the retention period lasted for 7 days. Expansion and relapse amounts were measured by using computed tomography. After the retention period, 6 rats from each group were killed for histologic and immunohistochemical assessments. The other 6 rats from each group were used for observation of the relapse. Results: The histologic evaluation showed that, in groups 1 and 2, the numbers of osteoblasts were less than observed in group 3. When scores of staining intensity were compared, immunoreactivities were statistically significantly increased in group 3 compared with groups 2 and 1. Statistically significant differences were found when the relapse percentages were compared between the groups (P <0.05). The smallest relapse occurred in group 3. Conclusions: Zoledronic acid has positive effects on bone formation in the sagittal suture in response to expansion and decreases the relapse ratio after expansion in rats. Copyright © 2011 by the American Association of Orthodontists.
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    Zoledronic acid in combination with serine/threonine phosphatase inhibitors induces enhanced cytotoxicity and apoptosis in hormone-refractory prostate cancer cell lines by decreasing the activities of PP1 and PP2A
    (2012) Cirak Y.; Varol U.; Atmaca H.; Kisim A.; Sezgin C.; Karabulut B.; Uzunoglu S.; Uslu R.; Karaca B.
    OBJECTIVES • To investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the serine/threonine protein phosphatase inhibitors calyculin A (CA) and okadaic acid (OA) in hormone and drug refractory prostate cancer cells, PC-3 and DU-145. • To discover the effect of these combination treatments on phosphatase 1 (PP1) and PP2A protein expression levels in prostate cancer cells. MATERIALS AND METHODS • An XTT cell viability assay was used to determine cytotoxicity. • Apoptosis was evaluated by enzymelinked immunosorbent assay (ELISA) using a Cell Death Detection ELISA Plus Kit and verifi ed by measuring caspase 3/7 enzyme activity. • The PP1 and PP2A enzyme activities were evaluated by serine/threonine phosphatase ELISA and expression levels of PP1 and PP2A proteins were then re-assessed by Western blot RESULTS • Combination of ZA with either CA or OA showed synergistic cytotoxicity and apoptosis compared with any agent alone in both PC-3 and DU-145 prostate cancer cells. • The combination of ZA with phosphatase inhibitors resulted in enhanced suppression of both PP1 and PP2A enzyme activity andprotein levels, which was more overt with the ZA/CA combination. CONCLUSION • Results from our study increase the translational potential of our in vitro fi ndings and offer the basic rationale for the design of new combinatory strategies with ZA and phosphatase inhibitors for the treatment of prostate cancer, which may become resistant to conventional therapy. © 2012 B J U I N T E R N A T I O N A L.
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    Prospective evaluation of free radicals and antioxidant activity following 6-month risedronate treatment in patients with postmenopausal osteoporosis
    (2012) Zinnuroglu M.; Dincel A.S.; Kosova F.; Sepici V.; Karatas G.K.
    In addition to the well-described implications of estrogen deficiency in postmenopausal osteoporosis (PMO), free radicals are also effective on bone metabolism. The antioxidant vitamins C and E play an important role in the production of collagen, mesenchymal cell differentiation into osteoblasts, and bone mineralization. Therefore, the incidence of osteoporosis and the risk of fractures were decreased with vitamin C and E. It was proposed that free oxygen radicals are responsible for biological aging, atherosclerosis, carcinogenesis, and osteoclastic activity via their negative effects on the cell and DNA. In this study, we aimed to investigate and compare the levels of free radicals and serum antioxidant activity in patients with PMO and healthy subjects before and after six-month treatment with risedronate, which is an inhibitor of bone resorption. Twenty-three postmenopausal patients aged between 52-83 (mean [± standard deviation] 67.6 ± 8.17) with T scores below -2.5 in femur neck or L1-L4, and 23 postmenopausal healthy subjects were enrolled into the study. Patients who had received any medications within the last 6 months that could alter bone metabolism were excluded. Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were analyzed in both groups. The patients with PMO were commenced on 5 mg of risedronate, 1,200 mg of calcium, and 800 IU of vitamin D daily. The patients were reevaluated at the end of the sixth month. MDA and SOD levels were similar in patients with PMO when compared to the healthy group before the treatment, while the GPx levels were lower in patients with PMO (P = 0.014). GPx (P = 0.028) and MDA (P = 0.04) levels were increased in patients with PMO after the treatment. In contrast, SOD levels were decreased when compared to the initial levels (P = 0.006). There may be an insufficiency in different steps of the enzymatic antioxidant systems in patients with PMO without treatment. We observed an increment in lipid peroxidation levels and GPx levels with risedronate. We think that the decrement in SOD levels may be related with the utilized antioxidants due to the increased free radicals and the compensatory increment in the other steps of the antioxidant system. © Springer-Verlag 2011.