Arcus senilis corneae-its relationship to serum lipids in the South African bantu

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Discordance in diagnosis of osteoporosis using spine and hip bone densitometry

BACKGROUND: Diagnostic discordance for osteoporosis is the observation that the T-score of an individual patient varies from one key measurement site to another, falling into two different diagnostic categories identified by the World Health Organization (WHO) classification system. This study was conducted to evaluate the presence and risk factors for this phenomenon in a large sample of Iranian population. METHODS: Demographic data, anthropometric measurements, and risk factors for osteoporosis were derived from a database on 4229 patients referred to a community-based outpatient osteoporosis testing center from 2000 to 2003. Dual-energy X-ray absorptiometry (DXA) was performed on L1–L4 lumbar spine and total hip for all cases. Minor discordance was defined as present when the difference between two sites was no more than one WHO diagnostic class. Major discordance was present when one site is osteoporotic and the other is normal. Subjects with incomplete data were excluded. RESULTS: In 4188 participants (3848 female, mean age 53.4 ± 11.8 years), major discordance, minor discordance, and concordance of T-scores were seen in 2.7%, 38.9% and 58.3%, respectively. In multivariate logistic regression analysis, older age, menopause, obesity, and belated menopause were recognized as risk factors and hormone replacement therapy as a protective factor against T-score discordance. CONCLUSION: The high prevalence of T-score discordance may lead to problems in interpretation of the densitometry results for some patients. This phenomenon should be regarded as a real and prevalent finding and physicians should develop a particular strategy approaching to these patients

The effect of postexercise carbohydrate and protein ingestion on bone metabolism

Purpose To investigate the effect of feeding carbohydrate and protein (CHO+PRO), immediately or 2 h after an exhaustive run, on the bone turnover response in endurance runners. Methods 10 men (age 28±5 y, height 1.74±0.05 m, body mass 69.7±6.3 kg) performed treadmill running at 75%VO2max, until exhaustion, on three occasions. Blood was collected before and immediately, 1, 2, 3, 4 and 24 h post-exercise, for measurement of β-CTX, P1NP, PTH, PO4, ACa and Ca2+. This was a randomised, counterbalanced, placebo-controlled, single-blinded, cross-over study. The three trials were; i) placebo (PLA), PLA solution was ingested immediately and 2 h post-exercise, ii) immediate feeding (IF), CHO+PRO (1.5 g.kgBM-1 dextrose and 0.5 g.kgBM-1 whey) were ingested immediately post-exercise and PLA 2 h post-exercise, and iii) delayed feeding (DF), PLA was ingested immediately post-exercise and CHO+PRO solution 2 h post-exercise. Data were analysed using repeated measures ANOVA and post-hoc Tukey’s HSD. Results At 1 and 2 h post-exercise, β-CTX concentrations were lower in the IF trial than the DF and PLA trials (P≤0.001). At 3 h post-exercise, β-CTX concentrations were higher in the PLA trial than the IF (P≤0.001) and DF trials (P=0.026). At 4 h post-exercise, β-CTX concentrations were lower in the DF trial than the IF (P=0.003) and PLA trials (P≤0.001). At 4 h post-exercise, P1NP was higher in the IF trial than in DF (P=0.026) and PLA trials (P=0.001). At 3 h post-exercise, PTH was higher in the IF trial than the DF trial (P≤0.001). Conclusions Following exhaustive running, immediate ingestion of CHO+PRO may be beneficial, as it decreases bone resorption marker concentrations and increases bone formation marker concentrations; creating a more positive bone turnover balance

Assessment of bone response to systemic therapy in an EORTC trial: preliminary experience with the use of collagen cross-link excretion

This study was designed to evaluate new bone resorption and tumour markers as possible alternatives to serial plain radiographs for the assessment of response to treatment. Thirty-seven patients with newly diagnosed bone metastases from breast cancer, randomized to receive oral pamidronate or placebo tablets in addition to anticancer treatment within the context of a multicentre EORTC trial, who were both assessable for radiographic response in bone and had serum and urine samples collected for more than 1 month were studied. The markers of bone metabolism measured included urinary calcium (uCa), hydroxyproline (hyp), the N-telopeptide cross-links of type I collagen (NTx) and total alkaline phosphatase. The tumour markers measured were CA15-3 and cancer-associated serum antigen (CASA). Before treatment, levels of Ntx, uCa and Hyp were elevated in 41%, 24% and 28% respectively, and CA15-3 and CASA increased in 69% and 50%. For assessment of response and identification of progression, Ntx was the most useful bone marker. All markers behaved similarly in no change (NC) and partial response (PR) patients. There was a significant difference (P ≤ 0.05) in Ntx levels (compared to baseline) at 1 and 4 months and in CA15-3/CASA at 4 months between patients with PR or NC and those with progressive disease (PD), and at 4 months between those with time to progression (TP) > 7 and those with TP ≤ 7 months. The diagnostic efficiency (DE) for prediction of PD following a > 50% increase in Ntx or CA15-3 was 78% and 62% respectively. An algorithm to predict response to therapy has been developed for future prospective evaluation

The impact of inflammation on bone mass in children

Bone is a dynamic tissue. Skeletal bone integrity is maintained through bone modeling and remodeling. The mechanisms underlying this bone mass regulation are complex and interrelated. An imbalance in the regulation of bone remodeling through bone resorption and bone formation results in bone loss. Chronic inflammation influences bone mass regulation. Inflammation-related bone disorders share many common mechanisms of bone loss. These mechanisms are ultimately mediated through the uncoupling of bone remodeling. Cachexia, physical inactivity, pro-inflammatory cytokines, as well as iatrogenic factors related to effects of immunosuppression are some of the common mechanisms. Recently, cytokine signaling through the central nervous system has been investigated for its potential role in bone mass dysregulation in inflammatory conditions. Growing research on the molecular mechanisms involved in inflammation-induced bone loss may lead to more selective therapeutic targeting of these pathological signaling pathways

Reporting bias in medical research - a narrative review

Reporting bias represents a major problem in the assessment of health care interventions. Several prominent cases have been described in the literature, for example, in the reporting of trials of antidepressants, Class I anti-arrhythmic drugs, and selective COX-2 inhibitors. The aim of this narrative review is to gain an overview of reporting bias in the medical literature, focussing on publication bias and selective outcome reporting. We explore whether these types of bias have been shown in areas beyond the well-known cases noted above, in order to gain an impression of how widespread the problem is. For this purpose, we screened relevant articles on reporting bias that had previously been obtained by the German Institute for Quality and Efficiency in Health Care in the context of its health technology assessment reports and other research work, together with the reference lists of these articles

Morning vs evening dosing of the cathepsin K inhibitor ONO-5334: effects on bone resorption in postmenopausal women in a randomized, phase 1 trial

SUMMARY: The cathepsin K inhibitor, ONO-5334, improves bone mineral density in postmenopausal women with osteoporosis. The effects of morning versus evening administration of ONO-5334 were investigated by measuring bone turnover marker levels in healthy postmenopausal women. Morning administration of ONO-5334 showed a more consistent suppressive effect on bone resorption than evening administration. INTRODUCTION: Bone turnover is thought to be subject to circadian variation, and the efficacy of osteoporosis treatments may be optimized by regulating the time of dosing. This study assessed whether evening administration of the cathepsin K inhibitor, ONO-5334, had a differential effect on the bone turnover marker, C-terminal telopeptide of type I collagen (CTX-I), compared with morning administration. METHODS: This was a single-center, single blind crossover study. Fourteen healthy postmenopausal women were assigned to receive ONO-5334 150 mg once daily for 5 days in each period; they were randomized to receive either evening doses in the first period and morning doses in the second or vice versa. Serum and urinary levels of CTX-I were measured throughout the study. RESULTS: Both regimens showed similar patterns of reduction in serum and urinary CTX-I; however, CTX-I suppression was more consistently >60% over 24 h following morning administration. Morning administration led to 6% greater suppression of 24-h serum CTX-I area under the effect curve (AUE; 69 vs 63%; P < .05) and 7% greater suppression of urinary CTX-I/creatinine AUE (93 vs 86%; P < .01) than evening administration. Higher plasma ONO-5334 concentrations were observed between 12 and 24 h postdose following morning administration, with mean trough concentrations for the morning and evening regimens at 9.4 and 4.0 ng/mL, respectively. There were no safety findings of concern. CONCLUSION: Morning dosing of ONO-5334 is more efficacious at reducing markers of bone turnover in healthy postmenopausal women than evening dosing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01384188, registered on June 27, 2011 EudraCT: 2008-006284-37 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00198-015-3342-4) contains supplementary material, which is available to authorized users