No abstract

We investigated the effects of 18 months of treatment with teriparatide in patients previously treated with long-term antiresorptive therapy using bone turnover markers and bone densitometry. Previous raloxifene treatment allowed for teriparatide-induced early bone marker and BMD increases comparable with previously published results for treatment-naïve patients. Conversely, previous alendronate treatment reduced the bone marker and BMD response.Introduction: ] has been shown to increase BMD and reduce the risk of fracture in postmenopausal women with osteoporosis. Our objective was to investigate the skeletal effects of 18 months of treatment with teriparatide in women whose osteoporosis was previously treated with either alendronate or raloxifene. Materials and Methods: Daily subcutaneous injections of 20 g teriparatide were administered for 18 months to 59 postmenopausal women, 60 -87 years of age, with BMD T-scores Յ Ϫ2.0 who had previously received either alendronate (ALN) or raloxifene (RLX) therapy for 18 -36 months. All patients received daily calcium (1000 mg) and vitamin D (400 IU) supplementation. The primary study outcome was change in lumbar spine BMD measured by DXA. Secondary outcomes included changes in bone turnover markers, total hip BMD, and safety. Results: Median baseline bone turnover marker levels in prior ALN patients were about one-half those of prior RLX patients. During teriparatide treatment, bone markers in prior ALN patients increased later and peaked at about one-third lower levels compared with prior RLX patients. During the first 6 months, there were statistically significant (p Ͻ 0.05) group differences in BMD change at the hip (prior ALN Ϫ1.8% versus prior RLX ϩ0.5%) and at the spine (prior ALN ϩ0.5% versus prior RLX ϩ5.2%). The positive slopes in hip and lumbar spine BMD were similar in both groups between 6 and 18 months. After 18 months, mean lumbar spine BMD increased 10.2% in prior RLX compared with 4.1% in prior ALN (p Ͻ 0.05) patients. Furthermore, at 18 months, mean total hip BMD had significantly increased (1.8%, p Ͻ 0.05) in prior RLX patients but was not different from baseline in prior ALN patients. Conclusions: Teriparatide treatment stimulates bone turnover in patients pretreated with both RLX and ALN. Prior treatment with RLX allows for the expected teriparatide-induced BMD increases comparable with those previously reported for treatment-naïve patients. In contrast, prior treatment with ALN prevents increases in BMD, particularly in the first 6 months.

Objective: This randomized, double-blind, placebo-controlled, dose-ranging phase 2 study explored safety, efficacy, and biomarker effects of ELND005 (an oral amyloid anti-aggregation agent) in mild to moderate Alzheimer disease (AD). Methods:A total of 353 patients were randomized to ELND005 (250, 1,000, or 2,000 mg) or placebo twice daily for 78 weeks. Coprimary endpoints were the Neuropsychological Test Battery (NTB) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. The primary analysis compared 250 mg (n ϭ 84) to placebo (n ϭ 82) after an imbalance of infections and deaths led to early discontinuation of the 2 higher dose groups. Results:The 250 mg dose demonstrated acceptable safety. The primary efficacy analysis at 78 weeks revealed no significant differences between the treatment groups on the NTB or ADCS-ADL. Brain ventricular volume showed a small but significant increase in the overall 250 mg group (p ϭ 0.049). At the 250 mg dose, scyllo-inositol concentrations increased in CSF and brain and CSF A␤x-42 was decreased significantly compared to placebo (p ϭ 0.009). Conclusions:Primary clinical efficacy outcomes were not significant. The safety and CSF biomarker results will guide selection of the optimal dose for future studies, which will target earlier stages of AD.

Background & Aims: Tenofovir disoproxil fumarate (TDF) is a first-line treatment for chronic hepatitis B (CHB). We aimed to describe the efficacy and safety profiles of TDF treatment for up to 10 years in a well-described cohort of CHB patients. Methods: Hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients from two randomised, double-blind trials (ClinicalTrials.gov: NCT00117676 and NCT00116805) completed 48 weeks of randomised treatment with TDF or adefovir dipivoxil. A subset of these patients was then eligible to receive open-label TDF treatment for up to 10 years. At Year 10, patients were assessed for virological suppression, alanine aminotransferase (ALT) normalisation, serological response, safety and tolerability. Results: Of 641 randomised and treated patients, 585 (91%) entered the open-label extension phase with 203 (32%) patients completing Year 10 of the study. At Year 10, 118/118 (100%) of HBeAg-negative patients and 78/80 (98%) of HBeAg-positive | 1869 MARCELLIN Et AL.

The change in BMD is a poor predictor of vertebral fracture risk after raloxifene treatment. One-year percent change in bone turnover and BMD was used to predict vertebral fracture risk. The percent change in osteocalcin was determined to be a better predictor of vertebral fracture risk than BMD. Introduction:The association between baseline BMD and fracture risk is well understood. However, the relationship between changes in BMD and fracture risk is not well defined. It has previously been demonstrated that BMD change was a poor predictor of vertebral fracture risk in raloxifene-treated women, whereas bone turnover markers were significantly associated with fracture risk. In the current analysis, we explore the prediction of vertebral fracture risk using changes in both BMD and bone turnover. Materials and Methods:The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a randomized, placebo-controlled trial of 7705 women with osteoporosis treated with raloxifene 60 or 120 mg/day for 3 years. Markers of bone turnover were measured in one-third of the study population (n ϭ 2503), and the present analyses include these women. Logistic regression models were constructed using one-year percent changes in BMD and bone turnover and relevant baseline demographics to predict the risk of vertebral fracture with pooled raloxifene therapy at 3 years. All covariates were standardized before modeling to facilitate direct comparisons between changes in BMD and bone turnover. Results and Conclusion: Prevalent vertebral fracture status (p Ͻ 0.0001), baseline lumbar spine BMD (p Ͻ 0.0001), and number of years postmenopausal (p ϭ 0.0005) were independent predictors of fracture risk in raloxifene-treated patients. Therapy-by-change in femoral neck BMD (p ϭ 0.02) and therapy-by-change in osteocalcin (OC; p ϭ 0.01) were also significant for all treatment groups, indicating that changes in BMD and OC have different effects on fracture risk for the placebo and pooled raloxifene groups. The final model included significant baseline variables and change in OC (p ϭ 0.01), whereas change in femoral neck BMD was not significant. After adjustment of each significant baseline variable, the percent change in OC was better able to predict the reduction in vertebral fracture risk than the percent change in femoral neck BMD in patients treated with raloxifene.