• Title/Summary/Keyword: Inhibiting Effect

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APOPTOTIC EFFECT IN COMBINATION OF CYCLOSPORIN A AND TAXOL ON ORAL SQUAMOUS CELL CARCINOMA CELL LINE THROUGH THE PI-3 KINASE/AKT1 PATHWAY (구강 편평세포암종 세포주에서 Cyclosporin A와 Taxol 투여시 PI-3 kinase/Akt1 Pathway에 의한 세포사멸 병용효과)

  • Kim, Kyu-Young;Lee, Jae-Hoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.5
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    • pp.426-436
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    • 2007
  • Oral cancer take up 2-6% of all carcinomas and squamous cell carcinoma, which is the most common type in oral cancer, has a poor prognosis due to its high metastasis and recurrence rates. In treating oral cancer, chemotherapy to the primary, metastasized and recurrent lesion is a very important and useful treatment, even though its widespread usage is limited due to high general toxicity and local toxicity to other organs. Taxol, a microtubule stabilizing agent, is an anticancer drug that induces cell apoptosis by inhibiting depolymerization of microtubules in between the metaphase and anaphase of the cell mitosis. Recently, its effectiveness and mechanism on various tumor has been reported. However, not much research has been done on the application of Taxol to oral squamous cell carcinoma. Cyclosporin A, which is an immunosuppressant, is being used on cancers and when co-administered with Taxol, effectiveness of Taxol is enhanced by inhibition of Taxol induced multidrug resistance. In this study, Cyclosporin A with different concentration of Taxol was co-administered to HN22, the oral squamous cell carcinomacell line. To observe the cell apoptosis and the mechanisms that take part in this process, mortality evaluation of tumor cell using wortmannin, c-DNA microarray, RT-PCR analysis, cytometry analysis and western blotting were used, and based upon the observation on the effect and mechanism of the agent, the following results were obtained: 1. The HN22 cell line viability was lowest when $100{\mu}M$ of Wortmannin and $5{\mu}g/ml$ of Taxol were co-administered, showing that Taxol participates in P13K-AKT1 pathway. 2. In c-DNA microarray, where $1{\mu}g/ml$ of cyclosporine A and 3mg/ml of Taxol were co-administered, no up regulation of AKT1, PTEN and BAD c-DNA that participate in cell apoptosis was observed. 3. When $1{\mu}g/ml$ of Cyclosporin A was applied alone to HN22 cell line, no difference was found in AKT1, PTEN and BAD mRNA expression. 4. Increased AKT1, mRNA expression was observed when $3{\mu}g/ml$ of Taxol was applied alone to HN22 cell line. 5. When $1{\mu}g/ml$ of Cyclosporin A and Taxol($3{\mu}g/ml\;and\;5{\mu}g/ml$) were co-administered to HN22 cell line, PTEN mRNA expression increased, whereas AKT1 and BAD mRNA decreased. 6. As a result of cytometry analysis, in the group of Cyclosporin A($1{\mu}g/ml$) and Taxol($3{\mu}g/ml$) co-administration, increased Annxin V was observed, which shows that apoptosis occurred by deformation of plasma membrane. However, no significant difference was observed with vary ing concentration. 7. In western blot analysis, no caspase 3 was observed in the group of Cyclosporin A($1{\mu}g/ml$) and Taxol($3{\mu}g/ml$) co-administration. From the results of this study, it can be concluded that synergistic effect can be observed in combination therapy of Taxol and Cyclosporin A on oral squamous cell carcinoma cell line, where decreased activity of the cell line was observed. This resulted in decreased AKT1 and BAD mRNA and increased PTEN mRNA expression and when wortmannin and Taxol were co-administered, the viability decreased which confirms that Taxol decreases the viability of tumor cell line. Hence, when Taxol and cyclosporine A are co-administered, it can be assumed that cell apoptosis occurs through AKt1 pathway.

Influence of $TiO_2$ Concentrations and Irradiation Lights on the Photocatalytic Reaction for Inhibiting Growth of Streptococcus mutans ($TiO_2$ 농도 및 여기광에 따른 광촉매 반응이 Streptococcus mutans의 생장에 미치는 영향)

  • Kang, Si-Mook;Lee, Hae-Na;Kim, Hee-Eun;Kim, Baek-Il
    • Journal of dental hygiene science
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    • v.14 no.3
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    • pp.319-324
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    • 2014
  • The aim of this study was to evaluate influences of titanium dioxide ($TiO_2$) concentrations and irradiation times on growth of Streptococcus mutans when irradiated by visible light (405 nm wavelength) and by ultraviolet light (254 nm wavelength). To find the optimal antibacterial concentration of $TiO_2$, 0.01, 0.1, 1.0, and 10.0 mg/ml $TiO_2$ suspension was prepared with sterilized distilled water. S. mutans cultured media was added to $TiO_2$ solution to set the final cell count to $10^4CFU/ml$. The photocatalytic reaction was induced by irradiating 254 nm and 405 nm lights for 10 minutes. To compare the bactericidal activities according to irradiation times, all photocatalytic reaction was carried out with 0.1 mg/ml $TiO_2$ for 0, 10, 20, 30, and 40 minutes with both lights. After the photocatalytic reaction, $100{\mu}m$ of the reaction mixture was immediately plated on brain heart infusion agar. These plates were placed at 5% $CO_2$, $37^{\circ}C$, for 24 hours and the bacterial colonies were counted. All experiments were performed in quintuplicate. One-way ANOVA was used to determine whether there were any significant differences between the $TiO_2$ concentrations or the irradiation times. The most effective concentration of $TiO_2$ for its photocatalytic bactericidal effect on S. mutans was 0.1 mg/ml when irradiated with 254 nm and 405 nm lights. The longer the irradiation time, the bigger the bactericidal effect for both wavelengths. Over 99% of bacteria in the inoculum were killed after irradiation with 254 nm for 20 minutes and with 405 nm for 40 minutes. In conclusion, a photocatalytic reaction of $TiO_2$ induced by visible light of 405 nm constitutes the bactericidal effect on S. mutans.

Effect of buchu (Allium tuberosum) on lipid peroxidation and antioxidative defense system in streptozotocin-induced diabetic rats (부추가 Streptozotocin 유발 당뇨쥐의 지질과산화와 항산화방어체계에 미치는 영향)

  • 송영선;정현실;노경희;조혜연;박지영;최춘연;권태완
    • Journal of Life Science
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    • v.13 no.3
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    • pp.333-342
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    • 2003
  • The pathogenic effort of high glucose, possibly in concert with fatty acids, is mediated to vascular complications of diabetes via increased production of reactive oxygen species(ROS), reactive nitrogen species(RNS), and subsequent oxidative stress. This study was carried out to investigate the suppressive effect of buchu(Allium tuberosum) on oxidative stress in streptozotocin(STZ)-induced diabetes in Sprague Dawley male rats. The effect of buchu supplementation (10%) on lipid peroxidation, and antioxidative defense system in blood and liver was compared among normal rats fed basal diet(normal) and diabetic rats fed basal diet(DM-control) or 10% buchu-supplemented diet(DM-buchu). Diabetes was experimentally induced by the femoral muscle injection of 50 mg STZ per kg of body weight. Animals were sacrificed after 4 wks of experimental diets feeding. The induction of diabetes by STZ elevated the level of lipid peroxidation represented by thiobarbituric acid-reactive substances(TBARS) and conjugated dienes in plasma, LDL, liver, and erythrocytes. 10% buchu-supplemented diet significantly reduced the levels of conjugated dienes in erythrocytes(p<0.05) and lowered TBARS in liver and LDL to the levels of control. Induction of diabetes by STZ elevated Mn-superoxide dismutase(Mn-SOD) activity and lowered activities of glutathionine reductase(GSH-red) and glutathionine peroxidase(GSH-px). Catalase activity was not affected by the induction of diabetes by STZ. However, buchu supplementation to diabetic rats significantly elevated catalase activity(p<0.05) and slightly elevated GSH-px and GSH-red activities in liver. GSH levels of blood and liver were lowered or not changed by induction of diabetes by STZ, respectively, while buchu supplementation to diabetic rats significantly elevated hepatic GSH level (p<0.05). In conclusion, it can be concluded that buchu might be a food source to attenuate oxidative stress in diabetic patients by inhibiting lipid peroxidation, by increasing hepatic GSH level, and by inducing anti-oxidative enzyme systems.

Selection and Treatment Effect of Plant Growth Retardants on Potted Spathiphyllum Grown in a Recirculating Subirrigation System (순환식 저면관수 시스템을 이용한 스파티필럼의 생장조절제 선발과 처리효과)

  • Won, Eun Jeong;Park, Yoo Gyeong;Jeong, Byoung Ryong
    • FLOWER RESEARCH JOURNAL
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    • v.19 no.2
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    • pp.81-88
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    • 2011
  • Effect of concentrations of different plant growth retardants (PGRs) supplied to a recirculated nutrient solution in an ebb and flow system on the growth and development of potted Spathiphyllum 'Top-Pin' and 'Mini' was examined. Plants were planted in 10 cm diameter plastic pots filled with a mixture of peat moss and perlite (1 : 1, v/v) on 30 June 2005 and grown until 23 Sep. 2005. In a closed ebb and flow system, 50, 200, 350, $500mg{\cdot}L^{-1}$ daminozide (B-9), 10, 40, 70, $100mg{\cdot}L^{-1}$ paclobutrazol (Boundy), 5, 15, 25, $35mg{\cdot}L^{-1}$ ethephon (Florel), and 1, 4, 7, $10mg{\cdot}L^{-1}$ uniconazole (Sumagic) were supplemented to a nutrient solution at the initiation of experiment. On every irrigation, the nutrient solution containing PGRs was supplied at a 2 cm depth and kept for 15-20 minutes. The surplus nutrient solution was drained back into the tank for next irrigations. Paclobutrazol gave the most pronounced effect in inhibition of stretchiness. The greatest reduction of leaf length, fresh and dry weights of shoot, and elevated chlorophyll content were recorded in Spathiphyllum, with increasing paclobutrazol concentration. Daminozide concentration greater than $200mg{\cdot}L^{-1}$ resulted in minor stunting. The lowest concentration ($1mg{\cdot}L^{-1}$) of uniconazole showed greater leaf length, leaf width, and leaf petiole length than the control ($0mg{\cdot}L^{-1}$). Uniconazole concentration greater than $1mg{\cdot}L^{-1}$ resulted in similar plant growth as the plant in the control ($0mg{\cdot}L^{-1}$). High concentration ($35mg{\cdot}L^{-1}$) of ethephon resulted in the shortest leaf length, and the greatest chlorophyll content. Inhibition of stretchiness was observed even in the lowest concentration treatments. Among the PGRs, paclobutrazol was most effective in suppressing plant stretchiness. In both cultivars, ethephon and paclobutrazol, but not daminozide and uniconazole, significantly inhibited stretchiness. The results suggested that plant growth retardants (ethephon or paclobutrazol) selected in this study may be used as the most effective agents for inhibition of stretchiness in Spathiphyllum.

Effect of amendments and their causes of rice yield increase in ill drained paddy soil (습답(濕沓)에 대(對)한 개량제(改良劑)의 효과(效果)와 유효개량제(有效改良劑)의 수도증수원인(水稻增收原因)에 관(關)한 연구(硏究))

  • Park, Chon Suh;Song, Jae Ha;Kim, Yung Sup;Lee, Chung Young;Choh, Young Sun
    • Korean Journal of Soil Science and Fertilizer
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    • v.4 no.1
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    • pp.13-19
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    • 1971
  • In order to establish the method of improving ill drained paddy soil where the accumulation of absorption inhibitor is worried in the earlier stages of rice growth, proper soil is selected and an field experiment is designed having treatments such as lime materials, none sulfate fertilizers, boron and straw etc. The data of yield and plant analysis in different stages of rice growth is eveluated and discussed to obtain following summaries. (1) Significant yield increase was made by the treatment of lime materials such as slacked lime or wollastonite powder, materials inhibiting the activity of microorganisms such as boron and of none sulfate fertilizers lacking inhibitor producing sources. (2) The crop scientifice causes of decreasing yield are the decreasing the number of panicles per hill, grains per panicle and the weight of grains. (3) The plant nutritional causes of decreasing yield are the lowering of nitrogen content throughout the life, phosphate content since young premodia formation stage of plant and the decreased content of magnesium, calcium and silicate in straw at harvesting stage. (4) The causes of lowering the content of various elements in rice plant grown in ill drained paddy soil are suggested as root damage by producing and accumulating absorption inhibitors such as organic acids and hydrogen sulfide etc, from the following observed facts; (a) In young premodia formation stage, attaining to the maximum production and accumulation of absorption inhibitor, the phosphate accumulation in plant was smaller in the phosphate plots than without phosphate plots and much higher in the neutralized plots by adding lime materials. (b) In the plots of straw addition, the potassium content in plant at the young premodia formation stage is very low probabley due to root damage by absorption inhibitor produced from the process of straw decomposition but higher at the stage of harvesting probably due to the immetabolic negative absorption of damaged roots. (c) The effect of boron, known as the inhibitor of microorganism activity to decompose organic matter, is apparent. (d) The effect of nonsulfate fertilizer treatment, having no source of producing inhibitor such as hydrogen sulfide, was significant. (e) All the yield components, decided around the young premodia formation stage attaining to the maximum inhibitor concentration in soil and minimum root activity, are significantly decreased.

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Effects of Schisandrae Fructus and Corni Fructus Extracts on the Proliferation and Expression of Prostatic Hyperplasia-inducing Factors in Dihydrotestosterone-stimulated LNCaP Human Prostate Carcinoma Cells (오미자와 산수유 추출물이 dihydrotestosterone가 처리된 LNCaP 인간 전립선 암세포의 증식 및 전립선 비대 유발 인자 발현에 미치는 영향)

  • Kim, Min Yeung;Ji, Seon Yeong;Hwangbo, Hyun;Lee, Hyesook;Kim, Tae Hee;Yoon, Seonhye;Kim, Hyun Jin;Kim, Sung Yeon;Kim, Tae Jung;Kim, Min Ji;Jung, Ha Eun;Choi, Yung Hyun
    • Journal of Life Science
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    • v.31 no.10
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    • pp.885-897
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    • 2021
  • Schisandrae Fructus (SF) and Corni Fructus (CF) have been used for a long time for the prevention and treatment of various diseases. Although reports have highlighted the possibility of inhibiting the onset and progression of benign prostatic hyperplasia (BPH), studies on related mechanisms are still lacking. In this study, we investigated the potential of SF and CF in improving BPH by using a dihydrotestosterone (DHT)-induced in vitro BPH model using LNCaP prostate carcinoma cells. According to our results, water and ethanol extracts of SF and CF significantly inhibited the proliferation of LNCaP cells by DHT treatment and markedly downregulated the expression of DHT-induced BPH biomarkers and growth factors. They also regulated the expression of apoptosis regulatory factors and significantly reduced DHT-mediated oxidative stress. In addition, the protective effect on major factors involved in the pathogenesis of BPH was more effective in the ethanol extract treatment group than in the water extract group. Furthermore, the improvement effect on BPH was higher in the 1:1 combined treatment group than in the ethanol extract alone treatment group of SF and CF, and 60% ethanol extracts showed a better effect than 40% ethanol extracts. Therefore, our findings demonstrate that SF and CF can protect against BPH by preventing the hyperproliferation of prostate cells through the inhibition of the androgen signaling pathway, which was correlated with their antioxidant activities. Therefore, SF and CF extracts may be useful in the clinical treatment of BPH, and the combination of these two extracts can be synergistic.

Effect of Fractions From Stachys sieboldii Miq. Root on Antioxidant, Anti-inflammation and Smad Signaling (초석잠 뿌리 분획물의 항산화 및 항염증 효과와 smad 신호 전달에 미치는 효과)

  • Jung Woo Lee;Myungwon Choi;Sun Young Lim
    • Journal of Life Science
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    • v.34 no.4
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    • pp.245-253
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    • 2024
  • We investigated to analyze total flavonoid content and fatty acid composition of Stachys sieboldii Miq root. In order to determine antioxidant and anti-inflammatory effects of fractions from S. sieboldii Miq. root, we conducted 1.1-Diphenyl-2-picryhydrazyl (DPPH) and 2,2'-Azino-bis (3-ethylbenothiazoline-6-sulfonic acid) diammonium salt radical cation (ABTS) assays for antioxidant and measured nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 cells. In addition, we examined an inhibitory effect of fractions from S. sieboldii Miq. root on smad signaling induced by transforming growth factor (TGF) β. Among the fractions, n-butanol (n-BuOH) fraction showed the highest flavonoid content (16.67 mg/g), followed by n-Hexane, water and 85% aqueous methanol (85% aq. MeOH) fractions. The fatty acid composition of S. sieboldii Miq. root was in the following order : n-6 fatty acids (54.3%) > n-3 fatty acids (21.2%) > saturated fatty acids (19.7%) > n-9 fatty acids (3.6%). As a result of the antioxidant efficacy, the DPPH and ABTS assays showed that n-BuOH fraction had higher scavenging activity compared to other fractions. Inhibitory effect on NO production showed that all fractions decreased LPS-induced NO production, indicating an anti-inflammatory activity of S. sieboldii Miq. root. 85% aq. MeOH and water fractions showed a higher efficacy in inhibiting transforming growth factor (TGF) β induced smad signaling. From the results, it suggests that food processing products using S. sieboldii Miq. root will be developed as a functional food for promoting health.

Changes of Refractive Correction Value with Different Age Group: A Case for Myopia Control Lens, Single Vision Lens and Reverse Geometry Contact Lens (Myopia Control Lens, Single Vision Lens, Reverse Geometry Contact Lens의 연령에 따른 굴절교정상태 변화에 대한 추적 연구)

  • Yoon, Min-Hwa
    • Journal of Korean Ophthalmic Optics Society
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    • v.18 no.1
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    • pp.75-84
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    • 2013
  • Purpose: Changes of refractive correction value in different age group were investigated. Regarding the inhibitive effects against myopia progression after wearing reverse geometry contact lenses and myopia control lenses (MC lenses), the effects after wearing single vision lenses were compared. Methods: We organized children between the ages of six and fifteen into three groups by age, and distributed fifty-seven reverse geometry contact lenses, fifty-six MC lenses and seventy-eight single vision lenses among them to be worn. Group 1 consisted of children aged ten and under, Group 2 consisted of children between the ages of eleven and fifteen, and Group 3 represents all of the study participants. The aim of this study was to learn the inhibitive effects against myopia progression attained by changes of refractive correction value and to verify their statistical significance at twelve months and under, thirteen to twenty-four months and twenty-five to thirty-six months. Results: Changes of refractive correction value by each length of use in Group 3 were as follows. For the age group of under twelve months, participants using the reverse geometric contact lens showed no change, while those using the MC or single vision lens had significant changes (P<0.05) of $-0.36{\pm}0.10$ D and $-0.67{\pm}0.52$ D, respectively. Users of all three lens types displayed significant change (P<0.05), in the age group of between thirteen and twenty-four months, of $0.18{\pm}0.49$ D, $0.60{\pm}0.42$ D and $1.37{\pm}0.72$ D for users of the reverse geometry contact lens, the MC lens and the single vision lens, respectively. There were significant changes (P<0.05) of $0.29{\pm}0.61$ D, $0.93{\pm}0.57$ D and $1.72{\pm}0.78$ in the same respective order as the above in the age group of twenty-five to thirty-six months. Refractive correction value showed changes with different age group. Group 1 displayed significant changes (P<0.05) of $0.29{\pm}0.73$ D, $1.07{\pm}0.59$ D and $1.75{\pm}0.74$ D for users of the reverse geometry contact lens, MC lens and single vision lens, respectively, up to thirty-six months of lens wearing; Group 2, also up to thirty-six months, displayed significant changes (P<0.05) of $0.28{\pm}0.42$ D, $0.75{\pm}0.49$ D and $1.70{\pm}0.84$ D in the same respective order, and changes in refractive correction for the age group under ten years was significantly greater (P<0.05) for the age group of eleven and older. Conclusions: The results found in this study demonstrate that there were no changes of refractive correction value for the case of wearing reversing geometry contact lens up to twelve month or less. MC lens showed less changes in variations of visual acuity for all users which might be resulted in inhibiting progression of myoptia. When both reverse geometry contact lens and the MC lens are wearing for the period from 13 to 36 month, both lens showed less changes in variation of visual acuity for all users. The results suggested that the less changes in variation of visual acuity of both lens had an effect on inhibiting progression of myopia.

The effect of chitosan/ACS on bone regeneration in rat calvarial defects (백서두개골 결손부에서 키토산/흡수성 콜라겐 전달체의 골재생)

  • Kim, Soo-Kyoung;Suk, Hun-Joo;Kim, Chang-Sung;Cho, Kyoo-Sung;Chai, Jung-Kiu;Kim, Chong-Kwan;Choi, Seong-Ho
    • Journal of Periodontal and Implant Science
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    • v.33 no.3
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    • pp.457-474
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    • 2003
  • The ultimate objective of periodontal treatment is to get rid of an on-going periodontal disease and further regenerate the supporting tissue, which is already destroyed, functionally. Currently, the bone grafting operation using various kinds of bone grafting materials and the operation for induced regeneration of periodontal tissue using the blocking membrane are performed for regeneration of the destroyed periodontal tissue. However, there are respective limitations Galenical preparations, which are used for regeneration of periodontal of tissue, has less risk of rejective reaction or toxicity that may be incidental to degradation and their effect is sustainable. Thus, in case they are applicable to a clinic, they can he used economically. Chitosan has such compatibility, biological actions including antibacterial activity, acceleration of wound treatment, etc., and excellent mechanical characteristics, which has recently aroused more interest in it. Also, it has been reported that it promotes osteogenesis directly or indirectly by functioning as a matrix to promote migration and differentiation of a specific precussor cell (for example, osteoblast) and further inhibiting the function of such a cell as fibroblast to prevent osteogenesis. In this study, the pure chitosan solution, which was obtained by purifying chitosan, was used. However, since this chitosan is of a liquiform, it is difficult to sustain it in a defective region. It is, therefore, essential to use a carrier for delivering chitosan to, and sustaining it gradually in the defective region. In the calvarial defect model of the Sprague-Dawley rat, it is relatively easy to maintain a space. Therefore, in this study, the chitosan solution with which ACS was wetted was grafted onto the defective region, For an experimental model, a calvarial defect of rat m s selected, and a critical size of the defective region was a circular defect with a diameter of 8 mm. A group in which no treatment was conducted for the calvarial defect was set as a negative control group. Another group in which treatment was conducted with ACS only was set as a positive control group (ACS group). And another group in which treatment was conducted was conducted with by grafting the pure chitosan solution onto the defective region through ACS which was wetted with the chitosan solution was set an experimental group (Chitosan/ACS group). Chitosan was applied to the Sprague-Dawley rat's calvarial bone by applying ACS which was wetted with the chitosan solution, and each Sprague-Dawley rat was sacrificed respectively 2 weeks and 8 weeks after the operation for such application. Then, the treatment results were compared and observed histologically and his tometrically. Thereby, the following conclusions were obtained. 1. In the experimental group, a pattern was shown that from 2 weeks after the operation, vascular proliferation proceeded and osteogenesis proceeded through osteoblast infiltration, and at 8 week after the operation, ACS was almost absorbed, the amount of osteogensis was increased and many osteoid tissue layers were observed. 2. At 2 weeks after the operation, each amount of osteogenesis appeared to be 8.70.8 %, 13.62.3 % and 4.80.7 % respectively in the experimental group, the positive control group and the negative control group. Accordingly, it appeared to be higher in the Experimental group and the positive control group than in the negative control group, but there was no significant difference statistically (p<0.01). 3. At 8 weeks after the operation, each amount of osteogenesis appeared to be 62.26.1%, 17.42.5 % and 8.21.4 % respectively in the experimental group, the positive control group and the negative control group. Accordingly, it appeared to be substantially higher in the experimental group than in the positive control group and the negative control group, and there was a significant difference statistically (p<0.01). As a result of conducting the experiment, when ACS was used as a carrier for chitosan, chitosan showed effective osteogenesis in the perforated defective region of the Sprague-Dawley rat's calvarial bone.

Efficacy of Statins on BMB or Fracture Risk in Postmenopausal Women (스타틴이 폐경기 여성의 골밀도 혹은 골절위험에 미치는 효과 -보고된 임상연구결과 분석을 중심으로-)

  • Bang, Joon-Seok
    • Korean Journal of Clinical Pharmacy
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    • v.16 no.2
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    • pp.86-91
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    • 2006
  • There are 3 different hypotheses on how statins may affect bones, through promoting bone formation, inhibiting bone resorption or through anti-inflammatory effect. In the 3 cross-sectional studies above, one showed increase BMD at hip and spine, one showed increase BMD only at mid-forearm and one showed that the risk reduction in fractures is not explained by the changes in BMD however, all 3 studies showed a decrease in risk of fracture associated with statins. In the 2 prospective cohort studies, one showed the use of statins was not associated with BMD at any skeletal site or decreasing the risk of fracture, and the other showed statins except pravastatin decreased in risk of vertebrate fracture but not affecting lumbar spine BMD. All of case-control studies indicated reduction in fracture risk but did not provide any data regarding BMD. 2 of the randomized, controlled studies showed no significant reduction in fracture risk as well as statins' effects on BMD. Finally, one longitudinal study showed statin use reduced fracture risk and increased BMD. Among the conflicting results shown above, even when statin use was shown to increase BMD, it does not seem to account for the reduction in fracture risk. There may be different ways that statins affect bone other than those hypotheses proposed above. Many studies seem to agree that pravastatin does not have any effect on bone. Some studies suggested that the reason statins did not achieve clinically significant increases in BMD in some studies, is due to the low affinity of statins on bone; statins are designed to act in the liver therefore their effective concentration in extrahepatic tissue is low. The limitations to those studies discussed above. Many studies did not account for the change of lifestyle while subjects' were on statins. Increases in weight bearing exercise and changes in diet might affect BMD and thus reduce risk of fractures. Mental alertness and vision acuity might prevent falls from occurring; many statin-users in the studies were young so the risk of fractures from falls would be decreased. Almost all of the studies failed exclude patients with neurological problems. During study periods, many subjects may have been started on drugs for diseases that usually occur with aging which could cause drowsiness and lead to falls. The sample sizes used in some of the trials were small and the duration of treatment and follow up might not have been long enough to see clinically relevant results.

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