Biomechanical Computed Tomography analysis (BCT) for clinical assessment of osteoporosis.

The surgeon general of the USA defines osteoporosis as "a skeletal disorder characterized by compromised bone strength, predisposing to an increased risk of fracture." Measuring bone strength, Biomechanical Computed Tomography analysis (BCT), namely, finite element analysis of a patient's clinical-resolution computed tomography (CT) scan, is now available in the USA as a Medicare screening benefit for osteoporosis diagnostic testing. Helping to address under-diagnosis of osteoporosis, BCT can be applied "opportunistically" to most existing CT scans that include the spine or hip regions and were previously obtained for an unrelated medical indication. For the BCT test, no modifications are required to standard clinical CT imaging protocols. The analysis provides measurements of bone strength as well as a dual-energy X-ray absorptiometry (DXA)-equivalent bone mineral density (BMD) T-score at the hip and a volumetric BMD of trabecular bone at the spine. Based on both the bone strength and BMD measurements, a physician can identify osteoporosis and assess fracture risk (high, increased, not increased), without needing confirmation by DXA. To help introduce BCT to clinicians and health care professionals, we describe in this review the currently available clinical implementation of the test (VirtuOst), its application for managing patients, and the underlying supporting evidence; we also discuss its main limitations and how its results can be interpreted clinically. Together, this body of evidence supports BCT as an accurate and convenient diagnostic test for osteoporosis in both sexes, particularly when used opportunistically for patients already with CT. Biomechanical Computed Tomography analysis (BCT) uses a patient's CT scan to measure both bone strength and bone mineral density at the hip or spine. Performing at least as well as DXA for both diagnosing osteoporosis and assessing fracture risk, BCT is particularly well-suited to "opportunistic" use for the patient without a recent DXA who is undergoing or has previously undergone CT testing (including hip or spine regions) for an unrelated medical condition

Association between gastrointestinal events and compliance with osteoporosis therapy

AbstractPurposeThe aim of this study was to estimate the rate of gastrointestinal (GI) events, and association between GI events and compliance with osteoporosis therapy among osteoporotic women.MethodsA retrospective cohort study using a large administrative claims database in the United States from 2001 through 2010 was conducted. We studied women ≥55years old who were continuously enrolled in a health plan for at least 2years, a baseline year before and a follow-up year after the date of the first prescription of oral bisphosphonate as the first oral osteoporosis treatment. Compliance with osteoporosis therapy was measured using the medication possession ratio (MPR), with compliance defined as MPR ≥0.8. Multivariate logistic regression was used to assess the association between occurrence of GI events and compliance with osteoporosis therapy after controlling for demographic and clinical characteristics.ResultsA sample consisting of 75,593 women taking at least one oral bisphosphonate with mean (SD) age of 64 (8) years was identified. A total of 21,142 (28%) patients experienced at least one GI event during the follow-up period. Only 31,306 (41%) patients were compliant with osteoporosis therapy. Patients who experienced GI events after initiation of oral bisphosphonates were 29% less likely to adhere to osteoporosis therapy as compared to patients who did not experience GI events (odds ratio [95% CI], 0.71 [0.69–0.74]; P<.001).ConclusionsLess than half of the patients were compliant with osteoporosis therapy within one year after initiating oral bisphosphonates, and the likelihood of compliance was significantly lower by 29% among women with GI events

Five-year follow-up of Japanese patients with Paget's disease of the bone after treatment with low-dose oral alendronate: a case series

<p>Abstract</p> <p>Introduction</p> <p>Paget's disease of the bone is characterized by focal abnormalities of increased bone turnover affecting one or more sites throughout the skeleton. Although this disease is rare in Japan, it is common in western and southern Europe, and among British migrants in Australia and New Zealand. Bisphosphonates have been widely used for the treatment of Paget's disease of the bone and are considered to be the treatment of choice. However, there have been few reports on the long-term follow-up examination of patients after their treatment with bisphosphonates.</p> <p>Case presentation</p> <p>We report the treatment with a low dose of oral alendronate (5 mg per day) which was effective in reducing bone turnover and pain over the five-year follow-up period in two Japanese patients, a 66-year-old man and a 68-year-old woman, with Paget's disease of the bone. Furthermore, in one patient, no clinical symptoms, such as bone pain or increases in serum total alkaline phosphatase and urinary N-terminal telopeptide of type I collagen as markers of bone turnover, were observed over the patient's five-year follow-up period.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first report of a long-term follow-up of patients with Paget's disease of the bone after a six-month treatment with low-dose oral alendronate (5 mg per day).</p

Bacterial vaccine antigen discovery in the reverse vaccinology 2.0 era: progress and challenges

The ongoing, and very serious, threat from antimicrobial resistance necessitates the development and use of preventative measures, predominantly vaccination. Polysaccharide-based vaccines have provided a degree of success in limiting morbidity from disseminated bacterial infections, including those caused by the major human obligate pathogens, Neisseria meningitidis and Streptococcus pneumoniae. Limitations of these polysaccharide vaccines, such as partial coverage and induced escape leading to persistence of disease, provide a compelling argument for the development of protein vaccines. In this review, we briefly chronicle approaches that have yielded licensed vaccines before highlighting reverse vaccinology 2.0 and its potential application in the discovery of novel bacterial protein vaccine candidates. Technical challenges and research gaps are also discussed

Genetic association study of UCMA/GRP and OPTN genes (PDB6 locus) with Paget's disease of bone

We performed a genetic association study of rare variants and single nucleotide polymorphisms (SNPs) of UCMA/GRP and OPTN genes, in French-Canadian patients with Paget's disease of bone (PDB) and in healthy controls from the same population. We reproduced the variant found in the UCMA/GRP basal promoter and tested its functionality using in vitro transient transfection assays. Interestingly, this SNP rs17152980 appears to affect the transcription level of UCMA/GRP. In addition, we have identified five rare genetic variants in UCMA/GRP gene, four of them being population-specific, although none were found to be associated with PDB. Six Tag SNPs of UCMA/GRP gene were associated with PDB, particularly the SNP rs17152980 (uncorrected P = 3.8 x 10(-3)), although not significant after Bonferroni's correction. More importantly, we replicated the strong and statistically significant genetic association of two SNPs of the OPTN gene, the rs1561570 (uncorrected P = 5.7 x 10(-7)) and the rs2095388 (uncorrected P = 4.9 x 10(-3)), With PDB. In addition, we identified a very rare variant found to be located close to the basal promoter of the OPTN gene, at -232 bp from its distal transcription start site. Furthermore, depending on the type of allele present (G or A), the binding of several important nuclear factors such as the vitamin D or the retinoic acid receptors is predicted to be altered at this position, suggesting a significant effect in the regulation of transcription of the OPTN gene. In conclusion, we identified a functional SNP located in the basal promoter of the UCMA/GRP gene which provided a weak genetic association with PDB. In addition, we replicated the strong genetic association of two already known SNPs of the OPTN gene, with PDB in a founder effect population. We also identified a very rare variant in the promoter of OPTN, and through bioinformatic analysis, identified putative transcription factor binding sites likely to affect OPTN gene transcription. (C) 2012 Elsevier Inc. All rights reserved.Fonds de la Recherche du Quebec - Sante (FRQS), Canada; Portuguese Science and Technology Foundation, Portugal [SFRH/BPD/48206/2008]; Catalyst Grant (Bone Health) from the Canadian Institutes of Health Research (Canada); CHUQ Foundation (Canada); Groupe de Recherche en Maladies Osseuses (Canada); Canadian Foundation for Innovation (Canada); FRSQ (Canada); Laval University (Canada); CHUQ (CHUL) Research Centre (Canada); Centre of Marine Sciences (CCMAR) (Portugal)info:eu-repo/semantics/publishedVersio

Bone mineral density enhances use of clinical risk factors in predicting ten-year risk of osteoporotic fractures in Chinese men: the Hong Kong Osteoporosis Study

This prospective study aimed to determine the risk factors and the 10-year probability of osteoporotic fracture in Southern Chinese men. The findings show substantial population differences in fracture incidence and risk prediction compared to the FRAX TM model, and the addition of BMD information to clinical risk factor assessment improved fracture risk prediction in Chinese men. Introduction: Clinical risk factors with or without bone mineral density (BMD) measurements are increasingly recognized as reliable predictors of fracture risk. Prospective data on fracture incidence in Asian men remain sparse. This prospective study aimed to determine the risk factors and the 10-year absolute fracture risk in Southern Chinese men. Methods: This is a part of the Hong Kong Osteoporosis Study. One thousand eight hundred ten (1,810) community-dwelling, treatment-naive men aged 50 years or above were evaluated. Baseline demographic characteristics, clinical risk factors and BMD were recorded. Ten-year risk of osteoporotic fracture was calculated using Cox proportional hazards models. Results: The mean age of subjects was 68.0 ± 10.3 years. After a mean follow-up period of 3.5±2.9 years (range 1 to 14 years), 37 incident low-trauma fractures were recorded. The incidence for all osteoporotic fractures and hip fractures was 635/100,000 and 123/100,000 person-years, respectively. The most significant predictors of osteoporotic fracture were history of fall (RR 14.5), femoral neck BMD T-score < -2.5 (RR 13.8) and history of fracture (RR 4.4). Each SD reduction in BMD was associated with a 1.8 to 2.6-fold increase in fracture risk. Subjects with seven clinical risk factors and BMD T-score of -1 had an absolute 10-year risk of osteoporotic fracture of 8.9%, but this increased to 22.7% if they also had a femoral neck BMD T-score of -2.5. Conclusions: These findings show substantial population differences in fracture incidence and risk prediction. The addition of BMD information to clinical risk factor assessment improved fracture risk prediction in Chinese men. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201