A Comprehensive Analysis of Volumetric 68Ga-PSMA PET/CT Parameters, Clinical and Histopathologic Features: Evaluation of the Predictive Role.

Objectives: To evaluate the relationships between volumetric 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) parameters, Gleason score (GS), prostate-specific antigen (PSA) levels, histopathological data, and metastatic status in newly diagnosed prostate cancer (PCa) patients and to assess the predictive factors for progression despite treatment. Methods: A total of 78 newly diagnosed patients with PCa who had 68Ga-PSMA PET/CT scans were included. Clinical parameters, histopathological data, and metastatic status were documented, and volumetric parameters of primary prostate lesions were measured. All obtained data were compared statistically. Results: Primary prostate tumor maximum standardized uptake value (SUVmax) and GS were significantly related to serum PSA levels (p<0.05). PSA levels and SUVmax values were significantly higher in patients with lymph node metastases than in those without. GS was found to be significantly increased in metastatic patients. PSMA-derived tumor volume (PSMA-TV) and total lesion PSMA of the primary lesion had a significant relationship with PSA value, GS, and regional lymph node metastases. Receiver operating characteristic analysis, conducted in patients with metastatic and localized disease, identified the cutoff value for SUVmax as 10.85. According to the results of the logistic regression analysis, PSMA-TV was found to be a predictive factor for progression despite treatment. Conclusion: 68Ga-PSMA PET/CT remains an invaluable imaging modality that should be considered first in PCa staging because of its superior compatibility with clinical and histopathologic data. The importance of this method goes beyond diagnostic accuracy; it also extends into the predictive domain, where the PSMA-TV value of primary prostate lesions is a potential predictor of treatment efficacy. This information is valuable for personalizing patient treatment, improving prognostic accuracy, and predicting clinical outcomes.

EFFECTIVE HALF-LIFE, EXCRETION AND RADIATION EXPOSURE OF 177LU-PSMA.

The study aims to evaluate the radiation safety conditions by detecting the patient's urine excretion rate, calculating the effective half-life, and determining the retention of 177Lu-PSMA in the body. Urine samples of patients were collected for 24 hours (6, 12, 18, and 24 hours) following the infusion, excretion rate and retention of 177Lu-PSMA in the body of patients were calculated. The measurements of dose rate were performed. Effective half-life calculated from dose rate measurements was found as 18.5 ± 11 h within the first 24 h and 48.1 ± 22.8 h between 24 and 72 h. Excreted activity in urine was found as 33.8 ± 20.7, 40.4 ± 20.3, 46.1 ± 22.4, and 53.3 ± 21.5% of total doses at 6, 12, 18, and 24 h after administration, respectively. External dose rates for 4 h and 24 h were 24.51 µSv/h, 16.14 µSv/h, respectively. Our results showed that 177Lu-PSMA treatment was suitable for outpatient treatment in terms of radiation safety.

Inguinoscrotal Bladder Hernia Mimicking Testicle Tumor.

Bladder hernias usually begin asymptomatically and are discovered incidentally at the time of discovery. Preoperative diagnosis of bladder hernias is important to reduce the risk of bladder injury during surgery. Although F-18 FDG PET/CT is applied for oncological purposes, benign conditions should also be taken into account when evaluating the implants. In this article, a case of bladder hernia, which can be confused with pathological cancer involvement, with the diagnosis of F-18 FDG PET/CT performed in a 73-year-old male patient with renal cell carcinoma is presented.

Contribution of Open Mouth Technique in 18F-FDG PET/CT Imaging in Patients with Malignant Lip Neoplasm.

Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays an important role in evaluating head and neck cancers. However, localization and size evaluation in this region can be rough due to the multitude of the anatomic structures and physiologic uptakes. The aim of this study was to evaluate malignant lip lesions with the contribution of open mouth (OM) imaging technique at PET/CT. Methods: Fifty-six patients with malignant lip neoplasm underwent 18F-FDG PET/CT imaging. Each patient was imaged twice as whole-body PET/CT with routine closed mouth (CM) position; and OM head and neck image, standardized with a special device. Lesion maximum standard uptake value (SUVmax), localization, size, and involvement of lymph nodes were evaluated. Results: Lesion localization was correctly detected in 100% of the OM images. Lesion size in PET/CT was compared with clinical, radiological (magnetic resonance imaging and CT) and/or histopathological results and the size measurement was coherent at 47.1% and 95.6% for CM and OM images, respectively. It was observed that OM acquisition did not contribute additionally in detecting regional lymph node metastasis. Forty-one PET/CT scans with CT artifacts due to dental amalgams were evaluated and 46.3% dimensional and 53.7% localization errors were detected in the CM position. There was no statistically significant difference between OM and CM SUVmax (p>0.05). Conclusion: We concluded that additional OM head and neck imaging is useful and necessary to accurately determine the localization and size of the tumor, thus enhancing the value of PET/CT in staging, treatment response assessment, and restaging of patients with malignant lip cancer with or without dental amalgam.

Unexpected Metastatic Localizations of Prostate Cancer Determined by 68Ga PSMA PET/CT: Series of Four Cases.

Prostate-specific membrane antigen (PSMA) is a transmembrane protein with overexpression in most prostate cancer cells. Gallium-68-(68Ga) PSMA positron emission tomography/computed tomography (PET/CT) imaging is a game-changer in the management of prostate cancer. 68Ga PSMA PET/CT scan is advanced and a promising radioligand has high sensitivity in determining lesions of prostate cancer with a high tumor to background ratio. The most common areas of metastasis are the bone and pelvic lymph nodes. The prognosis of prostate cancer is mainly determined by the status of metastases. The presence and the localization of metastases affects treatment planning. In our cases, we presented some examples of uncommon sites of metastases such as the brain, adrenal glands, penis and orbit. Improvements in imaging techniques, such as 68Ga PSMA PET/CT have led to the possibility to make more determi nation of rare metastase sites in prostate cancer patients.

Bone mineral density, vitamin D status, and calcium intake in healthy female university students from different socioeconomic groups in Turkey.

Peak bone mass is reached in late adolescence. Low peak bone mass is a well recognized risk factor for osteoporosis later in life. Our data do not support a link between vitamin D status, bone mineral density (BMD), and socioeconomic status (SES). However, there was a marked inadequacy of daily calcium intake and a high presence of osteopenia in females with low SES. PURPOSE: Our aims were to (1) examine the effects of different SES on BMD, vitamin D status, and daily calcium intake and (2) investigate any association between vitamin D status and BMD in female university students. SUBJECTS AND METHODS: A questionnaire was used to obtain information about SES, daily calcium intake, and physical activity in 138 healthy, female university students (age range 18-22 years). Subjects were stratified into lower, middle, and higher SES according to the educational and occupational levels of their parents. All serum samples were collected in spring for 25-hydroxyvitamin D concentration (25OHD). Lumbar spine and total body BMD was obtained by dual-energy X-ray absorptiometry (DXA) scan (Lunar DPX series). Osteopenia was defined as a BMD between - 1.0 and - 2.5 standard deviations (SDs) below the mean for healthy young adults on lumbar spine DXA. RESULTS: No significant difference was found between the three socioeconomic groups in terms of serum 25OHD concentration, BMD levels, or BMD Z scores (p > 0.05). Both the daily intake of calcium was significantly lower (p = 0.02), and the frequency of osteopenia was significantly higher in girls with low SES (p = 0.02). There was no correlation between serum 25OHD concentration and calcium intake and BMD values and BMD Z scores (p > 0.05). The most important factor affecting BMD was weight (ß = 0.38, p < 0.001). CONCLUSIONS: Low SES may be associated with sub-optimal bone health and predispose to osteopenia in later life, even in female university students.

Evaluation of abnormal radiological findings in children aged 2 to 36 months followed by recurrent urinary tract infection: a retrospective study.

Our aim is to determine the rational usage of imaging techniques in order to prevent or minimize permanent renal damage in recurrent urinary tract infections (UTIs). This study was enrolled children aged between 2 and 36 months, following-up with the diagnosis of recurrent UTI. All children had ultrasonography (USG) and dimercaptosuccinic acid scanning, 39 of them had underwent on voiding cystourethrography. There were 133 children (87 girls, 46 boys) with the mean age of 32.82 ± 38.10 months included into the study. Forty-three kidney units were normal in ultrasonogram of which seven units had reflux whereas among 35 units with hydronephrosis 22 units had reflux. Sensitivity and specificity presence of hydronephrosis in ultrasonogram for prediction of reflux was 75.9% and 73.5%, respectively. There were 19 dilated ureters in ultrasonogram, and among them 14 had reflux. Sensitivity and specificity of presence with ureteral dilatation in ultrasonogram for prediction of reflux was found as 48.3% and 89.8%, respectively. The sensitivity of parenchymal thinning seen in ultrasonogram for the evaluation of renal parenchyma was 15.9%, whereas specificity was 98.2% .Sensitivity and specificity of dimercaptosuccinic acid for prediction of reflux was 51.6% and 72.3%, respectively. The normal ultrasonogram findings cannot rule out neither possibility of reflux presence nor development of renal scarring. Therefore, DMSA scanning has major role both in determination of parenchymal damage and prevention of scarring. Also we get an important result as ureteral dilatation seen in USG, related to presence of reflux.

Samarium-153 therapy for prostate cancer: the evaluation of urine activity, staff exposure and dose rate from patients.

The aim of this study was to determine the excretion of Samarium-153-ethylenediaminetetramethylphosphonic acid ((153)Sm-EDTMP) in urine and to calculate the dose rate of its retention in the body as a function of time and the dose received by the skin of laboratory staff's finger. Urine samples were collected from 11 patients after intravenous injection of (153)Sm-EDTMP. The measurements of dose rate were performed. Thermoluminescent dosemeters were used for absorbed dose measurements. Effective half-lives that were calculated from urine sample measurements were found as 7.1±3 h within the first 24 h. Whole body dose rates before collecting urine of patients were 60.0 ± 15.7 µSv h(-1) for within 1 h following (153)Sm-EDTMP administration. The highest finger radiation dose is to the right-hand thumb (3.8 ± 2 mGy). The results of the study imply that patients who recieved (153)Sm-EDTMP therapy should be kept a minumum of 8 h in an isolated room at hospital and that one staff should give therapy at most two patients per week.

The effects of lornoxicam on brain edema and blood brain barrier following diffuse traumatic brain injury in rats.

BACKGROUND: In this experiment, the effects of lornoxicam on brain edema and the blood brain barrier (BBB) following diffuse traumatic brain injury (TBI) were studied. METHODS: Twenty adult male Wistar albino rats were anesthetized, and experimental closed head trauma was induced by the Marmarou method. After head injury, the rats were randomly divided into two groups: Group I was the control group, to which 2 ml saline was administered intraperitoneally, and Group II was the lornoxicam group, to which 2 ml 1.3 mg kg-1 lornoxicam was administered intraperitoneally. Twenty-four hours after head trauma, 99 mTc pentetate (DTPA) was injected at a dose of 37 MBq, and posterior planar images of each rat were obtained using an Infinia gamma camera. After imaging of BBB permeability, brain tissues were dissected from the cranium. The brain water content (BWC) of each sample was calculated using the wet-dry method. RESULTS: The lesion/background (L/b) ratio of Group I was 3.76±0.46 and 3.02±0.66 for early (5th min) and late (60th min) imaging, respectively. In Group II, the L/b ratios were 3.52±0.96 and 2.63±0.63 for early and late imaging, respectively (p>0.05). BWC was 79.6±2.5% and 77.5±1.1% for Groups I and II, respectively (p<0.05). CONCLUSION: In this rat model of TBI, lornoxicam reduced brain edema but did not affect BBB permeability.

The evaluation of urine activity and external dose rate from patients receiving radioiodine therapy for thyroid cancer.

The aim of this study was to determine the external dose rate of iodine retention as a function of time in the bodies of thyroid cancer patients during their isolation period in the hospital. Urine samples were collected at 6th, 12th, 18th, 24th h and 2nd, 3rd, 4th, 5th d from 83 patients after oral administration of (131)I and counted. The external dose rates were also simultaneously determined at the same time points. Then, it was expressed as retained radioiodine body activity versus dose rate. Effective half life calculated from urine sample measurements was found as 18.4±1.8 h within the first 24 h and 64±2.7 h between 48 and 120 h. According to this results, the external dose rate (<20 µSv h(-1)), which patients could be discharged, was achieved after 48 h for 3700 and 5550 MBq, and after 72 h for 7400 MBq of (131)I treatments.

Technetium-99m-hexamethylpropylene amine oxime lung scintigraphy findings in patients with Behçet's disease.

AIM: Behçet's disease (BD) is a multisystem disorder that is characterized by vasculitis, and consists of a triad of recurrent ulcers of the oral and genital mucosa with relapsing uveitis. The prevalence of pulmonary involvement varies in the range of 1-10% in various studies, and its complications are severe and life threatening. To objectively assess the degree of pulmonary vascular endothelial damage in BD, the lung uptake, and the clearance rate of technetium-99m-hexamethylpropylene amine oxime (Tc-99m-HMPAO) were determined. METHODS: Twenty-three nonsmoking patients with BD (10 female, 13 male) and 11 (six female, five male) healthy nonsmoking controls underwent Tc-99m-HMPAO lung scanning, pulmonary function tests (PFT), chest radiograph examination, contrast-enhanced spiral chest computed tomography scanning, and high-resolution computed tomography examinations. Immediately after the bolus injection of 740 MBq of Tc-99m-HMPAO posterior sequential images were obtained at 1-s intervals for 150 s and subsequent images were obtained at one frame per minute (min) over a 10-min period, using a double-headed gamma camera equipped with a low-energy all-purpose parallel hole collimator. Dynamic images were used to calculate the Tc-99m-HMPAO lung clearance rate (T1/2). Simultaneously, a static anterior image, including a large part of the liver, was obtained of 5-min duration at 10 min after the injection. Regular regions of interests were drawn over the midportion of the right lung and the highest activity area of the liver parenchyma was selected and lung/liver (L/Li) uptake ratios were calculated to represent the degree of pulmonary vascular endothelial damage. RESULTS: Chest radiograph, high-resolution computed tomography, and computed tomography findings in patients with BD were nonspecific for BD. There was also a statistically significant difference between patients with BD (30.26 ± 10.55 s) and normal controls (19.53 ± 6.24 s) on their T1/2 values (P = 0.0004). The results show that the L/Li ratios on the Tc-99m-HMPAO lung scan were significantly higher in patients with BD (0.60 ± 0.19) than those in normal controls (0.39 ± 0.07) (P = 0.0021). Using a cutoff value of 0.50, 15 of 23 (65%) patients with BD had increased L/Li ratios. No correlation was found between the mean T1/2 values of Tc-99m-HMPAO clearance and the PFT in patients with BD. The L/Li ratios were not correlated with PFT in patients with BD. CONCLUSION: The degree of pulmonary vascular endothelial damage was represented as increased L/Li ratios and decreased lung clearance rate measured on the Tc-99m-HMPAO lung scan in patients with BD. Our results indicated that determining the T1/2 values and the L/Li ratios on Tc-99m-HMPAO lung imaging should be an objective method to assess subclinical pulmonary damage even in the early stages of BD in the patients.

Assessment of alveolar epithelial permeability with Tc-99m DTPA aerosol scintigraphy in patients with Sjogren syndrome.

Sjögren's syndrome (SjS) is a systemic autoimmune disease that mainly affects the exocrine glands and usually presents as persistent dryness of the mouth and eyes. Lung disease in SjS has been reported to occur early following clinical presentation of the disease. In this study, technetium-99m diethylene triamine penta-acetic acid (Tc-99m DTPA) aerosol inhalation scintigraphy was used to assess the pulmonary membrane permeability in patients with primary SjS. A total of 18 patients with primary SjS and 13 healthy controls were investigated. Clinical evaluation, chest X-ray examination, pulmonary function tests, Tc-99m DTPA aerosol scintigraphy were performed in all the cases. The presence of respiratory symptoms (dyspnea and cough), duration of sicca symptoms were recorded. The clearance half time of Tc-99m DTPA radioaerosols in patients with SjS (20.49 +/- 2.56 min) was faster when compared to normal controls (42.32 +/- 13.28 min) (P = 0.000) which means that there is a significant increase in lung permeability in patients with SjS compared to the controls. There is also a significant difference between PI of patients with SjS (0.34 +/- 0.09) and that of controls (0.42 +/- 0.07) (P = 0.012). According to the results of our preliminary study, one can detect pulmonary involvement by Tc-99m DTPA aerosol inhalation scintigraphy in patients with primary SjS.

Effects of 99mTc-MIBI and 99mTc-MDP administration on dual-energy X-ray absorptiometry bone mineral density measurements.

OBJECTIVE: Nuclear medicine procedures are often performed in close-time proximity to bone densitometry studies. The purpose of this study was to determine the effects of Tc-hexakis-2-methoxyisobutyl isonitrile (MIBI) and Tc-methylene diphosphonate (MDP) on the accuracy of bone mineral density (BMD) measurements performed using dual-energy X-ray density. METHODS: The effect of a diagnostic dose of Tc-MIBI on BMD estimations in the lumbar spine and the left total hip was assessed in 30 patients (19 female, 11 male; mean age: 55.5+/-10.5 years) by using a Lunar DPX-NT scanner. Thirty patients, admitted to the nuclear medicine department for bone scintigraphy (15 female, 15 male; mean age: 56+/-15.92 years), were included into the study. Each patient underwent dual-energy X-ray density assessment for which a Lunar DPX-NT scanner was used before and 2 h after intravenous injection of Tc-MDP (925 MBq) and Tc-MIBI (1110 MBq). BMD measurements were calculated from lumbar spine (including L2-4) and left hip (including femoral neck, trochanter, and total hip). For statistical analysis, the Wilcoxon test was used and a P value of less than 0.05 was accepted as statistically significant. RESULTS: According to Wilcoxon's statistical test, we found extremely significant changes on the measured BMD, T-score, before and 2 h after the injection of Tc-MIBI for lumbar spine and left hip in 30 patients. We found statistically significant decrement on measured BMD from lumbar spine and trochanter before and 2 h after the injection of Tc-MDP. Although MDP BMD values in femoral neck and total hip were decreased after the injection of Tc-99m, they did not reach a statistically significant value. The comparison of pre-T-score and post-T-score values showed a statistically significant decrease after the injection for only L2-4 lumbar spine (P = 0.002), but left hip of pre-T-score and post-T-score values did not reach a statistically significant value. CONCLUSION: In this study, it was determined that measured BMD values are decreased in lumbar spine for all patients. The magnitude of the effect is dependent on the location of the activity. We assume that some radioactivity from Tc is counted by the densitometer's detector, thus resulting in a decrease in the measured BMD. Scintigraphy and bone densitometry should be performed on different days to avoid artifactual reduction in BMD measurements.

Comparative effects of risedronate, atorvastatin, estrogen and SERMs on bone mass and strength in ovariectomized rats.

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 17beta-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.

Early renal parenchymal histological changes in an experimental model of vesico-ureteral reflux and the role of apoptosis.

OBJECTIVES: To observe early renal parenchymal cellular changes in an experimental model of vesico-ureteral reflux (VUR) and to show whether the apoptotic pathway plays a role in these cellular changes. MATERIAL AND METHODS: Fourteen New Zealand breed rabbits were used and were divided into two equal groups (control and experimental groups). Urine samples were obtained in a sterile manner and cultured. In the study group, reflux was created in the right kidneys surgically. Renal scintigraphy and voiding cystourethrography (VCUG) were performed in both groups on Day 17. The kidneys were examined in terms of histology, apoptotic activity and caspase activity. RESULTS: No growth was observed in urine cultures in either group. VUR was manifested in only two rabbits in the experimental group on VCUG. On renal scintigraphy, no renal scarring was observed in either of the groups and renal uptake values were in the normal range. There was a greater increase in collagen in the right kidneys in the experimental group than in the control group and apoptotic activity was significantly increased in the study group: 0% in the control group, 10.8%+/-0.7% in the experimental group (p<0.001). Caspase-6 activity was strongly positive and caspase-8 and -9 activities were moderately positive in the right kidneys of the experimental group. Caspase-6 activity was moderately positive, and caspase-8 and -9 activities were weakly positive in the contralateral kidneys of the experimental group. Caspase activities in the control group were negative (p<0.001). CONCLUSIONS: In this experimental model of VUR, apoptotic activity was initiated via the caspase-8 and -9 pathway and collagen tissue increased in the renal parenchyma where reflux occurred. The balance of apoptotic activity may play a key role in the occurrence of reflux nephropathy.

Bone mineral density in girls and boys at different pubertal stages: relation with gonadal steroids, bone formation markers, and growth parameters.

Puberty has a key role in bone development. During puberty, several nutritional and hormonal factors play a major role in this process. The aim of this study was to determine the changes in areal bone mineral density (BMD), gonadal steroids, bone formation markers, and growth parameters in healthy Turkish pubertal girls and boys at different pubertal stages. In additional, we aimed to detect the relationship between BMD, sex steroids, and growth parameters, and to reveal the most important determinant of BMD in the pubertal period. BMD of the lumbar spine and total body was performed by dual-energy X-ray absorptiometry (Lunar DPX series) in 174 healthy pubertal children (91 girls, 83 boys), aged 11-15 years. Height and weight were measured. Pubertal stages were assesed. Bone formation markers and gonadal steroids were measured. BMD values significantly increased until stage IV in girls. In boys, BMD values also increased during puberty (P < 0.05), but it was significantly higher in stage IV compared with that in other pubertal stages (P < 0.01). Testosterone levels increased until stage IV in both sexes, particularly in boys. Estrogen levels significantly increased during puberty in girls, whereas it was significantly higher at stage IV in boys (P < 0.001). Bone-specific alkaline phosphatase (BAP) level was higher in early and midpuberty, and decreased in late puberty in girls (P < 0.001). BAP level was higher in stage IV in boys. Osteocalcin level was shown not to change significantly in pubertal stages. There was a modest correlation between BMD values and estrogen and testosterone levels in boys. In girls, there was a correlation between BMD values and estrogen levels only (P < 0.05). Weight was significantly associated with BMD in both sexes (P < 0.05). Estrogen had a significant influence on BMD in boys and girls. In conclusion, bone mass increased throughout puberty in both sexes. Peak bone mass was not achieved in girls, but was obtained at stage IV in boys. Bone formation markers were good predictors of bone mass in girls, but not in boys. Estrogen level made the greatest contribution to bone mineral acquisition in boys and girls. The achievement of peak bone mass was sustained by estrogen in boys. The major independent determinant of BMD in both sexes was weight.

Effects of simvastatin on bone mineral density and remodeling parameters in postmenopausal osteopenic subjects: 1-year follow-up study.

Observational studies suggest that statin use may be associated with lower incidence of fracture. However, there are conflicting data for their effects on bone remodeling parameters and bone mineral density (BMD). In the present study, we aimed to investigate the effects of simvastatin on bone metabolism and BMD in subjects with hypercholesterolemia (>240 mg/dl). For this purpose, 32 postmenopausal osteopenic subjects who were given simvastatin treatment (20 mg/day) and not on osteoporosis treatment were included in the study. During the 1-year follow-up period, the total cholesterol level decreased from 262.1+/-30.9 to 202.2+/-30.1 mg/dl (p<0.0001). At a period as early as the 3rd month, levels of the anabolic markers, e.g., bone-specific alkaline phosphatase (BSAP) and osteocalcin (OCL), were found to be significantly increased (from 120.8+/-56.6 to 149.5+/-57.6 IU/l, p=0.008, and from 20.8+/-12.6 to 34.7+/-18.4 microg/l, p=0.015, respectively) while no significant change was observed in the resorptive marker of serum N-telopeptide of type I collagen (CTX). At the 6th and 12th month, BSAP and OCL were both found to be decreased below the pretreatment values. While a significant reduction was found in BSAP levels (from 120.8+/-56.6 to 55.9+/-18.8 IU/l, p<0.001), no significant change was observed in CTX levels after the 6-month treatment period. Parathyroid hormone showed a gradual profound increase during the follow-up period (from 62.7+/-41.5 to 108.4+/-51.7 pg/ml, p<0.001). No significant change was found in BMD levels at the spine, femoral neck, Ward's triangle, and trochanter at the end of the 1-year follow-up period. In conclusion, simvastatin treatment showed a short-lasting anabolic effect on bone metabolism. However, this effect was lost by prolongation of therapy. The decrease in both anabolic and resorptive markers at the 6th and 12th month suggests that simvastatin affects bone metabolism mostly in favor of inhibition of the bone turnover in a long-term observation period although this inhibitory effect was not reflected in BMD.