Bone turnover markers to explain changes in lumbar spine BMD with abaloparatide and teriparatide: results from ACTIVE.

Summary Early PINP changes correlate with 18-month lumbar spine BMD changes and the correlation was greater with abaloparatide versus teriparatide. The uncoupling index was similar between the two agents. Introduction We evaluated the relationship between early PINP changes and subsequent changes in spine BMD following abaloparatide and teriparatide treatments. We also explored the use of an “uncoupling index” (UI), the balance between bone formation and bone resorption, which we hypothesised would be similar in response to these treatment groups. Methods Blood samples were taken for measurement of bone turnover markers (BTMs) s-PINP and s-CTX at baseline, 1, 3, 6, 12, and 18 months from 189 abaloparatide patients and 227 teriparatide patients randomly selected from all participants who completed the study. BMD was measured by DXA at baseline, 6, 12, and 18 months. Correlations were calculated between log ratio of BTMs from baseline to 3 months and percent change from baseline in BMD at 18 months. A UI was calculated using log transformation and subtraction of the standard deviate for s-CTX from the standard deviate for s-PINP for each patient. Results Early BTM changes were associated with subsequent BMD changes for both treatments. Pearson correlations for the log ratio of PINP over baseline at 3 months and BMD percent change from baseline at 18 months were larger (P < 0.0001) with abaloparatide (r = 0.561) than teriparatide (r = 0.198). The mean UI at 1 month was greater for abaloparatide versus teriparatide (1.743 and 1.493, respectively; P = 0.03) but was similar at 3 months or later time points. Conclusions Early s-PINP changes correlate with percentage change in lumbar spine BMD 18 months after treatment with both abaloparatide and teriparatide, though the correlation with abaloparatide was greater. The UI was similar between abaloparatide and teriparatide suggesting that the balance between formation and resorption markers was similar

Recommendations for the conduct of clinical trials for drugs to treat or prevent sarcopenia

PURPOSE: Sarcopenia is an age-related muscle condition which is frequently a precursor of frailty, mobility disability and premature death. It has a high prevalence in older populations and presents a considerable social and economic burden. Potential treatments are under development but, as yet, no guidelines support regulatory studies for new drugs to manage sarcopenia. The objective of this position paper is therefore to suggest a set of potential endpoints and target population definitions to stimulate debate and progress within the medico-scientific and regulatory communities. METHODS: A multidisciplinary expert working group was hosted by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, which reviewed and discussed the recent literature from a perspective of clinical experience and guideline development. Relevant parallels were drawn from the development of definition of osteoporosis as a disease and clinical assessment of pharmaceutical treatments for that indication. RESULTS: A case-finding decision tree is briefly reviewed with a discussion of recent prevalence estimations of different relevant threshold values. The selection criteria for patients in regulatory studies are discussed according to the aims of the investigation (sarcopenia prevention or treatment) and the stage of project development. The possible endpoints of such studies are reviewed and a plea is made for the establishment of a core outcome set to be used in all clinical trials of sarcopenia. CONCLUSIONS: The current lack of guidelines for the assessment of new therapeutic treatments for sarcopenia could potentially hinder the delivery of effective medicines to patients at risk

Rural Youth’s Perceptions of Information Sources and Rural Library Services

It has been recognized that youth populations are the capital for nation building. According to the Malaysian National Census (2000) about 60% of Malaysian youth (age 15-29) are concentrated in the rural areas. This population as already known is a valuable asset for the successor of country development. They are believed to be the agents of change for economic and social growth of the society. They can play an active role for the development of themselves and their environment. They should be actively involved in giving their expertise and assistance in various fields such as education, business, rural industries and human development. The true development must mean the development of man, the creativity of improving their material conditions of living through the use of information available to them. The United Nation describes one of the more significant characteristics of young people is to live under conditions that encourage their imagination, ideals, energy and vision to flourish on the benefit of their societies (United Nation, 2007). They need to be imaginative, energetic and visionary for the benefit of their societies. As information and youth represent two of the largest in country development, it is important to understand the rural youth’s perception towards information sources and usage. They are expected to use the information for several reasons such as to complete a task, to solve a problem as well as to decide. In seeking information, rural youth is likely to depend on a variety of sources. Among valuable sources, library service is recognized, in many studies of human information seeking behavior, as a major source of information. For instance, T.D. Wilson (2000) had reported that the origin studies of information seeking behavior are found related to the library use. However, the characteristics of being rural, especially those who lived in the underserved areas often make it hard for them to access information and translate that information into useful knowledge. In many discussions on the rural development, rural communities are often described as disadvantage communities. For people living in these underserved areas, it is crucial to have access to information in printed or online materials. Concern has been raised by several relevant studies about the poor services of rural libraries. Studies such as conducted by Momodu (2002) showed that rural populations in Nigeria are lack of access to information, which is a vital necessity for their developmental process. For this reason, it is important for the government to examine and, where necessary, improved and expanded services related to the information delivery. However, for library services to become more effective and meet the needs of groups, it is vital to identify the rural youths’ information needs and gaining an understanding of how and where rural youths seek information. As proposed by Israel and Ilvento (1995), community needs assessment is importance for rural development. Over the past 20 years, little evidence has been found into youth’s information need. Shenton (2004) provided in depth analysis of the research of young people’s information seeking showing the limited nature of research on this area. In her analysis, she reported that much of the researches were difficult to synthesize a coherent and comprehensive knowledge base relating to what is known about youngster’s information seeking. Since research in this area is limited, this study should be conducted to examine youth’s information need as well as the perceptions they make of rural library services. This study enables librarian to plan an effective information service and meet the youth’s information needs. To achieve that goal, the study focused on the following research questions: a) What kind of information sources do the rural youths use? b) Do they satisfy with these sources? c) What problems can be identified while seeking information? d) How effective do the library services in meeting rural youth’s information needs

Abaloparatide in patients with mild or moderate renal impairment: results from the ACTIVE phase 3 trial

Objective: To evaluate, post hoc, the efficacy and safety of abaloparatide by degree of renal impairment. Methods: ACTIVE was a phase 3, 18-month, randomized, double-blind, active-comparator, placebo-controlled study of postmenopausal women with osteoporosis who received subcutaneous abaloparatide 80 mu g, placebo, or open-label teriparatide 20 mu g daily. Patients with serum creatinine >2.0 mg/dL or 1.5-2.0 mg/dL with an estimated glomerular filtration rate (eGFR) = 90 mL/min, 1276 had 60 to <90 mL/min, and 527 had <60 mL/min. Older age and lower T-scores were associated with greater renal impairment. Among renal-function subgroups, there were no meaningful changes in bone mineral density, fracture risk reduction, or overall incidence of treatment-emergent adverse events in the active-treatment arms. Anemia, nausea, hypercalcemia, and upper-respiratory-tract infection tended to be more frequent with increasing renal impairment. Hypercalcemia measured by albumin-adjusted serum calcium occurred significantly less frequently with abaloparatide than teriparatide in patients with eGFR <60 mL/min (3.6% versus 10.9%; p = .008) and in the overall ACTIVE safety population (3.4% versus 6.4%; p = .006). Computed tomography scans in 376 patients revealed no evidence of increased renal calcification. Conclusion: Increased exposure to abaloparatide and teriparatide in patients with renal impairment led to no meaningful differences in efficacy or safety. These results support the use of abaloparatide without dosage adjustment in patients with renal impairment, provided those with severe renal impairments are monitored for adverse events.Bone and mineral researc

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene

Context: Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known. Objective: To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures. Design: The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial. Setting and Participants: A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events. Interventions: Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol. Main Outcome Measures: Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry. Results: At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4- 0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1% (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer. Conclusions: In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture

Recommendations for an update of 2003 European regulatory requirements for registration of drugs to be used in the treatment of RA.

Since 2003, the European Medicines Agency (EMA) document, 'Points to consider on clinical investigation of medicinal products other than NSAIDs (nonsteroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis' has provided guidance for the clinical development of both biologic and non-biologic disease-modifying antirheumatic drugs (DMARDs). In the last few years, several new products have been developed or are in development for the treatment of RA, which offer significant efficacy with regard to disease control, including prevention of structural damage and disability. Concurrently, novel insights have been gained with respect to the assessment of disease activity, joint damage and disability. New treatment strategies have been established which relate to early therapy, tight control and rapid switching of medication. Accordingly, several new EULAR/ACR recommendations have been or are being developed. Several important additions and changes are needed in the 2003 guidance to incorporate the current scientific knowledge into clinical trial design for the development of future products. Under the auspices of the Group for the Respect of Ethics and Excellence in Science (GREES), a group of experts in the field of RA and clinical trial design met to provide a consensus recommendation for an update to the 2003 EMA guidance document