Explore the vast range of titles available.

Summary Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n  = 45) and risedronate (35 mg/week, n  = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.

Summary The level of increased bone formation after 24 months of treatment with teriparatide (rhPTH (1-34), TPTD) is similar in patients who were either treatment-naïve (TN) or had lower bone turnover initially due to previous alendronate (ALN) therapy. Introduction Bone anabolic effects of TPTD in postmenopausal women with osteoporosis may be blunted during the initial phase after switching from ALN to TPTD. To explore the long-term implications, we examined histomorphometric and biochemical markers of bone turnover of patients on TPTD therapy after long-term ALN treatment. Methods Paired biopsies were obtained after tetracycline double labeling at baseline and after 24 months of TPTD treatment from 29 ALN-pretreated (64.5 ± 16.4 months) and 16 TN patients. Biochemical markers were measured at baseline, during the treatment, or at study end. Results Compared with the baseline, after 24-month TPTD, activation frequency (Ac.F.) and osteoid surface (OS) increased in both groups: 0.11-0.34 cycles per year, 3.96-9.8% in the ALN-pretreated group and 0.19-0.33 cycles per year, 6.2-11.3% (p < 0.05) in the TN group, respectively. Biochemical and histomorphometric markers correlated positively both at baseline and endpoint. Serum amino terminal propeptide of type I procollagen (PINP) correlated with Ac.F. (r = 0.57, p < 0.001 and r = 0.48, p < 0.01) and OS (r = 0.51, p < 0.01 and r = 0.56, p < 0.01) at baseline and endpoint, respectively. Following 3 months of treatment, increases in biochemical markers like PINP predicted the increase in Ac.F. (r = 0.52, p < 0.01) and OS (r = 0.54, p < 0.01) after 24 months. Conclusions The increased level of formation is similar in patients who were either TN or had lower bone turnover initially due to previous ALN therapy. Elevated bone formation in postmenopausal women with osteoporosis was sustained over a 24-month period by TPTD. Biochemical markers of bone formation are a good surrogate for the assessment of TPTD effects.

Summary The results of the present study, involving analysis of biopsies from patients who received teriparatide for 2 years and were previously either treatment-naïve or on long-term alendronate therapy, suggest that prior alendronate use does not blunt the favorable effects of teriparatide on bone quality. Introduction Examine the effect of 2 years of teriparatide (TPTD) treatment on mineral and organic matrix properties of the newest formed bone in patients who were previously treatment-naïve (TN) or on long-term alendronate (ALN) therapy. Methods Raman and Fourier transform infrared microspectroscopic analyses were used to determine the mineral/matrix (M/M) ratio, the relative proteoglycan (PG) content, and the mineral maturity/crystallinity (MMC; determined by three methods: carbonate content, full width at half height of the v 1 PO 4 band [FWHH], and wavelength at maxima of the v 1 PO 4 band), as well as collagen maturity (ratio of pyridinoline/divalent cross-links), in paired iliac crest biopsies at trabecular, endosteal, and osteonal surfaces of newly formed bone in postmenopausal osteoporotic women who were previously either TN ( n  = 16) or receiving long-term ALN treatment ( n  = 24). Results Trabecular M/M ratio increased and matrix content decreased significantly in the ALN pretreated group. Collagen maturity decreased in both patient groups. Endosteal M/M ratio increased significantly in the TN group. Trabecular M/M ratio was higher at endpoint in the ALN pretreated group than in the TN group. Overall, no changes from baseline were observed in PG content, except that PG content was higher in the ALN pretreated group than in the TN group at endosteal surfaces at endpoint. The ability of TPTD treatment to reduce MMC in both patient groups and at the different bone surfaces depended on the measurement tool (relative carbonate content or wavelength at maxima of the v 1 PO 4 band). None of the changes in MMC were different between the two patient groups. Conclusions The results suggest some favorable impact of TPTD on bone mineral and organic matrix properties of in situ forming bone in terms of increased initial mineralization and decreased MMC and collagen maturity. Moreover, prior long-term ALN administration may have only limited influence on these properties in bone newly formed after 2 years of TPTD treatment.

Background The ISSO was an Italian, 24-month, observational, prospective study that evaluated the effectiveness of anti-osteoporotic treatments available in normal clinical practice for severe multi-fractured osteoporotic patients defined according to reimbursement criteria set out by the Italian Health National Service (Note 79, second part). Objectives The primary objective of the study was to estimate the proportion of patients experiencing one or more new clinical vertebral and non-vertebral fragility fractures in the first 24 months from the initiation of anti-osteoporosis medication. The evaluation of back pain and Health-Related Quality of Life (HRQOL) at 18 and 24 months were important secondary endpoints of the study and results are herein presented. Methods Back pain was evaluated by using a 0-10 visual analogue scale ([VAS]; 0 = no pain, 10 = worst possible pain), whereas the HRQOL was evaluated by using the European Quality of Life 5-Dimensions questionnaire (EQ-5D), which includes 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), and with a 0-100 mm VAS (0 = worst imaginable health state, 100 = best imaginable health state). Results Of the 769 patients (mean age ± SD 72.8±8.8 years; 689 [90.7%] women) enrolled between April 2008 and February 2009, 663 (87.2%) started a therapy and 438 (57.6%) completed the 24 months of observation. Teriparatide (572/663 patients, 86.3%) was the drug most commonly used during the study: 420/663 (63.3%) patients received only teriparatide (OT), 38/663 (5.7%) only bisphosphonates, 19/663 (2.9%) only parathyroid hormone, and 18/663 (2.7%) only strontium ranelate, while 168/663 patients (25.3%) took more than one drug. The rate of patients with back pain decreased from baseline to 18 and 24 months both in the total population (TP) (94.1%, 79.5% and 76.2%, respectively) and in those treated with OT (95.0%, 77.1% and 75.9%). The mean decreases in pain VAS from baseline to 18 and 24 months were -1.93 (95% CI: -2.21 to -1.65) and -2.05 (95% CI: -2.37 to -1.73) in TP, and were -2.31 (95% CI: -2.65 to -1.97) and -2.64 (95% CI: -3.04 to -2.23) in OT, respectively. The mean changes in EQ-5D score from baseline to 18 and 24 months were 0.125 (95% CI: 0.103 to 0.148) and 0.116 (95% CI: 0.093 to 0.138) in TP, and were 0.138 (95% CI: 0.108 to 0.167) and 0.121 (95% CI: 0.093 to 0.149) in OT, respectively. Changes in EQ-5D VAS were consistent with those of score. Conclusions The results at 18 and 24 months of the ISSO study show that the prescribed treatment was associated with improvements in back pain and HRQOL, which were sustained up to the end of the 24-month observational period. Patients treated with teriparatide as monotherapy improved at least as markedly as did the TP. Disclosure of Interest F. Bertoldo: None Declared, O. Di Munno: None Declared, L. Pietrogrande: None Declared, R. Del Fiacco Employee of: Eli Lilly Italy, H. Petto Employee of: Eli Lilly austria, P. Marchi Employee of: Eli Lilly Italy, S. Silvestri Shareholder of: Eli Lilly italy (minority shareholder), Employee of: Eli Lilly Italy

ABSTRACT Objectives: The aim was to investigate patient compliance with different osteoporosis medications commonly prescribed in clinical practice, to determine risk factors associated with discontinuation and to evaluate quality of life changes. Research design and methods: We conducted a 1-year observational study of patients of age ≥ 60 years in a clinical setting at 917 sites in 10 European countries (Germany, Greece, UK, Sweden, Netherlands, Romania, Norway, Finland, Denmark, Estonia), Lebanon and South Africa. Demographic data, concomitant diseases, the reasons for intervention, educational, socio-economical status and disease knowledge were captured at baseline. Self-reported compliance, discontinuation data and health status were collected. Main outcome measures: Out of 5198 patients, 3490 (67.1%) patients received 60 mg daily raloxifene (RAL), 452 (8.7%) 10 mg daily alendronate (AQD), 769 (14.8%) 70 mg once weekly alendronate (AQW) and 487 (9.4%) 5 mg daily risedronate (RIS). Among patients completing the study (4231, 81%), the percentage of patients with high compliance was 80% (RAL), 79% (AQD), 65% (AQW) and 76% (RIS). The discontinuation due to side effects was highest on AQW (7.0%), followed by AQD (6.4%), RAL (3.8%) and RIS (3.4%). The discontinuation-rate was higher for patients with a history of surgical menopause, increased age, lack of knowledge about medical prevention of osteoporosis and thin frame as a reason for intervention. The EQ-5D weighted index showed the highest improvement for RIS (0.13), followed by RAL (0.11), AQD (0.08) and AQW (0.07). Conclusions: Data from this non-interventional observational study indicate moderate overall compliance and discontinuation rate with the prescribed osteoporosis medications.

Introduction Changes to Treatment and Outcomes in Patients with Type 2 Diabetes Initiating Injectable Therapy (CHOICE) is a European prospective, observational cohort study assessing time to, and factors associated with, a significant change in therapy after type 2 diabetes patients initiate their first injectable glucose-lowering therapy, and these patients’ clinical outcomes over 24 months. The authors report baseline data and factors associated with the injectable treatment regimen. Methods Demographic, clinical, and healthcare resource-use data were collected at initiation of injectable therapy and analyzed using univariate tests between cohorts and multivariate logistic regression analysis for treatment. Results Overall, 1,177 patients initiated exenatide twice daily (b.i.d.) and 1,315 initiated insulin. Most patients were recruited by secondary-care physicians. Univariate analyses revealed statistically significant differences between the characteristics of patients who initiated exenatide b.i.d. and patients who initiated insulin. On multivariate analysis, higher body mass index [BMI; 5 kg/m 2 higher: odds ratio (OR) 2.10, 95% confidence intervals (CI) 1.84–2.40], lower glycated hemoglobin (HbA 1c ; 1% higher: OR 0.77, 95% CI 0.69–0.86), and lower age (5 years older: OR 0.82, 95% CI 0.76–0.88) were the variables most strongly associated with increased probability of receiving exenatide b.i.d. ( P  < 0.0001). Patients initiating exenatide b.i.d. had a mean BMI of 35.3 ± 6.5 kg/m 2 , HbA 1c of 8.4 ± 1.4%, and age of 58 ± 10 years, compared with 29.7 ± 5.4 kg/m 2 , 9.2 ± 1.9%, and 64 ± 11 years, respectively, in patients initiating insulin ( P  < 0.0001). Other characteristics significantly associated with exenatide b.i.d. initiation were “disinhibited eating” (Diabetes Health Profile-18), lower random blood glucose, less blood glucose self-monitoring, lower low-density lipoprotein cholesterol, and receipt of diet/exercise advice. Conclusions Patients who initiated exenatide b.i.d. were on average younger and more obese with lower HbA 1c than those initiating insulin.

OBJECTIVE: Hypoglycemia causes recurrent morbidity in patients with type 2 diabetes. This study evaluated if exenatide twice daily (BID) was noninferior to premixed insulin aspart 70/30 BID (PIA) for glycemic control and associated with less hypoglycemia. RESEARCH DESIGN AND METHODS: In this open-label study, metformin-treated adults with type 2 diabetes were randomized to 26-week treatment with exenatide BID (4 weeks 5 μg, then 10 μg) or PIA. RESULTS: Exenatide BID (n = 181) was noninferior to PIA (n = 173) for A1C control (least squares [LS] mean change -1.0 vs. -1.14%; difference [95% CI] 0.14 [-0.003 to 0.291]) and associated with a lower risk for hypoglycemia (8.0 vs. 20.5%, P < 0.05). LS mean weight decreased by 4.1 kg and increased by 1.0 kg with PIA (P < 0.001). A total of 39.2 vs. 20.8% of patients reached the composite end point of A1C <7.0%, no weight gain, and no hypoglycemia (P < 0.001; post hoc analysis). CONCLUSIONS: In metformin-treated patients, exenatide BID was noninferior to PIA for glycemic control but superior for hypoglycemia and weight control.

Purpose Prostate-specific membrane antigen (PSMA)-targeted PET/CT has become increasingly important in the management of prostate cancer, especially in localization of biochemical recurrence (BCR). PSMA-targeted PET/CT imaging with long-lived radionuclides as 89 Zr (T 1/2  = 78.4 h) may improve diagnostics by allowing data acquisition on later time points. In this study, we present our first clinical experience including preliminary biodistribution and dosimetry data of [ 89 Zr]Zr-PSMA-617 PET/CT in patients with BCR of prostate cancer. Methods Seven patients with BCR of prostate cancer who revealed no ( n  = 4) or undetermined ( n  = 3) findings on [ 68 Ga]Ga-PSMA-11 PET/CT imaging were referred to [ 89 Zr]Zr-PSMA-617 PET/CT. PET/CT imaging was performed 1 h, 24 h, 48 h, and 72 h post injection (p.i.) of 111 ± 11 MBq [ 89 Zr]Zr-PSMA-617 (mean ± standard deviation). Normal organ distribution and dosimetry were determined. Lesions visually considered as suggestive of prostate cancer were quantitatively analyzed. Results Intense physiological uptake was observed in the salivary and lacrimal glands, liver, spleen, kidneys, intestine and urinary tract. The parotid gland received the highest absorbed dose (0.601 ± 0.185 mGy/MBq), followed by the kidneys (0.517 ± 0.125 mGy/MBq). The estimated overall effective dose for the administration of 111 MBq was 10.1 mSv (0.0913 ± 0.0118 mSv/MBq). In 6 patients, and in particular in 3 of 4 patients with negative [ 68 Ga]Ga-PSMA-11 PET/CT, at least one prostate cancer lesion was detected in [ 89 Zr]Zr-PSMA-617 PET/CT imaging at later time points. The majority of tumor lesions were first visible at 24 h p.i. with continuously increasing tumor-to-background ratio over time. All tumor lesions were detectable at 48 h and 72 h p.i. Conclusion [ 89 Zr]Zr-PSMA-617 PET/CT imaging is a promising new diagnostic tool with acceptable radiation exposure for patients with prostate cancer especially when [ 68 Ga]Ga-PSMA-11 PET/CT imaging fails detecting recurrent disease. The long half-life of 89 Zr enables late time point imaging (up to 72 h in our study) with increased tracer uptake in tumor lesions and higher tumor-to-background ratios allowing identification of lesions non-visible on [ 68 Ga]Ga-PSMA-11 PET/CT imaging.

Prostate-specific membrane antigen (PSMA)-targeted PET/CT has become increasingly important in the management of prostate cancer, especially in localization of biochemical recurrence (BCR). PSMA-targeted PET/CT imaging with long-lived radionuclides as 89Zr (T1/2 = 78.4 h) may improve diagnostics by allowing data acquisition on later time points. In this study, we present our first clinical experience including preliminary biodistribution and dosimetry data of [89Zr]Zr-PSMA-617 PET/CT in patients with BCR of prostate cancer.PURPOSEProstate-specific membrane antigen (PSMA)-targeted PET/CT has become increasingly important in the management of prostate cancer, especially in localization of biochemical recurrence (BCR). PSMA-targeted PET/CT imaging with long-lived radionuclides as 89Zr (T1/2 = 78.4 h) may improve diagnostics by allowing data acquisition on later time points. In this study, we present our first clinical experience including preliminary biodistribution and dosimetry data of [89Zr]Zr-PSMA-617 PET/CT in patients with BCR of prostate cancer.Seven patients with BCR of prostate cancer who revealed no (n = 4) or undetermined (n = 3) findings on [68Ga]Ga-PSMA-11 PET/CT imaging were referred to [89Zr]Zr-PSMA-617 PET/CT. PET/CT imaging was performed 1 h, 24 h, 48 h, and 72 h post injection (p.i.) of 111 ± 11 MBq [89Zr]Zr-PSMA-617 (mean ± standard deviation). Normal organ distribution and dosimetry were determined. Lesions visually considered as suggestive of prostate cancer were quantitatively analyzed.METHODSSeven patients with BCR of prostate cancer who revealed no (n = 4) or undetermined (n = 3) findings on [68Ga]Ga-PSMA-11 PET/CT imaging were referred to [89Zr]Zr-PSMA-617 PET/CT. PET/CT imaging was performed 1 h, 24 h, 48 h, and 72 h post injection (p.i.) of 111 ± 11 MBq [89Zr]Zr-PSMA-617 (mean ± standard deviation). Normal organ distribution and dosimetry were determined. Lesions visually considered as suggestive of prostate cancer were quantitatively analyzed.Intense physiological uptake was observed in the salivary and lacrimal glands, liver, spleen, kidneys, intestine and urinary tract. The parotid gland received the highest absorbed dose (0.601 ± 0.185 mGy/MBq), followed by the kidneys (0.517 ± 0.125 mGy/MBq). The estimated overall effective dose for the administration of 111 MBq was 10.1 mSv (0.0913 ± 0.0118 mSv/MBq). In 6 patients, and in particular in 3 of 4 patients with negative [68Ga]Ga-PSMA-11 PET/CT, at least one prostate cancer lesion was detected in [89Zr]Zr-PSMA-617 PET/CT imaging at later time points. The majority of tumor lesions were first visible at 24 h p.i. with continuously increasing tumor-to-background ratio over time. All tumor lesions were detectable at 48 h and 72 h p.i.RESULTSIntense physiological uptake was observed in the salivary and lacrimal glands, liver, spleen, kidneys, intestine and urinary tract. The parotid gland received the highest absorbed dose (0.601 ± 0.185 mGy/MBq), followed by the kidneys (0.517 ± 0.125 mGy/MBq). The estimated overall effective dose for the administration of 111 MBq was 10.1 mSv (0.0913 ± 0.0118 mSv/MBq). In 6 patients, and in particular in 3 of 4 patients with negative [68Ga]Ga-PSMA-11 PET/CT, at least one prostate cancer lesion was detected in [89Zr]Zr-PSMA-617 PET/CT imaging at later time points. The majority of tumor lesions were first visible at 24 h p.i. with continuously increasing tumor-to-background ratio over time. All tumor lesions were detectable at 48 h and 72 h p.i.[89Zr]Zr-PSMA-617 PET/CT imaging is a promising new diagnostic tool with acceptable radiation exposure for patients with prostate cancer especially when [68Ga]Ga-PSMA-11 PET/CT imaging fails detecting recurrent disease. The long half-life of 89Zr enables late time point imaging (up to 72 h in our study) with increased tracer uptake in tumor lesions and higher tumor-to-background ratios allowing identification of lesions non-visible on [68Ga]Ga-PSMA-11 PET/CT imaging.CONCLUSION[89Zr]Zr-PSMA-617 PET/CT imaging is a promising new diagnostic tool with acceptable radiation exposure for patients with prostate cancer especially when [68Ga]Ga-PSMA-11 PET/CT imaging fails detecting recurrent disease. The long half-life of 89Zr enables late time point imaging (up to 72 h in our study) with increased tracer uptake in tumor lesions and higher tumor-to-background ratios allowing identification of lesions non-visible on [68Ga]Ga-PSMA-11 PET/CT imaging.