Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

<p>Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.</p> <p>Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.</p> <p>Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.</p> <p>Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.</p> <p>Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.</p> <p>Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.</p&gt

Active vitamin D (1,25-dihydroxyvitamin D) and bone health in middle-aged and elderly men: the European male aging study (EMAS)

<p>Context: There is little information on the potential impact of serum 1,25-dihydroxyvitamin D [1,25(OH)2D] on bone health including turnover.</p> <p>Objective: The objective of the study was to determine the influence of 1,25(OH)2D and 25-hydroxyvitamin D [25(OH)D] on bone health in middle-aged and older European men.</p> <p>Design, Setting, and Participants: Men aged 40–79 years were recruited from population registers in 8 European centers. Subjects completed questionnaires that included questions concerning lifestyle and were invited to attend for quantitative ultrasound (QUS) of the heel, assessment of height and weight, and a fasting blood sample from which 1,25(OH)2D, 25(OH)D, and PTH were measured. 1,25(OH)2D was measured using liquid chromatography tandem mass spectrometry. Bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (β-cTX) were also measured. Dual-energy x-ray absorptiometry (DXA) of the hip and lumbar spine was performed in 2 centers.</p> <p>Main Outcome Measure(s): QUS of the heel, bone markers P1NP and β-cTX, and DXA of the hip and lumbar spine were measured.</p> <p>Results: A total of 2783 men, mean age 60.0 years (SD 11.0) were included in the analysis. After adjustment for age and center, 1,25(OH)2D was positively associated with 25(OH)D but not with PTH. 25(OH)D was negatively associated with PTH. After adjustment for age, center, height, weight, lifestyle factors, and season, 1,25(OH)2D was associated negatively with QUS and DXA parameters and associated positively with β-cTX. 1,25(OH)2D was not correlated with P1NP. 25(OH)D was positively associated with the QUS and DXA parameters but not related to either bone turnover marker. Subjects with both high 1,25(OH)2D (upper tertile) and low 25(OH)D (lower tertile) had the lowest QUS and DXA parameters and the highest β-cTX levels.</p> <p>Conclusions: Serum 1,25(OH)2D is associated with higher bone turnover and poorer bone health despite being positively related to 25(OH)D. A combination of high 1,25(OH)2D and low 25(OH)D is associated with the poorest bone health.</p&gt

Interpretation of DAS28 and its components in the assessment of inflammatory and non-inflammatory aspects of rheumatoid arthritis

Background: DAS28 is interpreted as the inflammatory disease activity of RA. Non-inflammatory pain mechanisms can confound assessment. We aimed to examine the use of DAS28 components or DAS28-derived measures that have been published as indices of non-inflammatory pain mechanisms, to inform interpretation of disease activity. Methods: Data were used from multiple observational epidemiology studies of people with RA. Statistical characteristics of DAS28 components and derived indices were assessed using baseline and follow up data from British Society for Rheumatology Biologics Registry participants [1] commencing anti-TNF therapy (n = 10813), or [2] changing between non-biologic DMARDs (n=2992), [3] Early Rheumatoid Arthritis Network participants (n=813), and [4] participants in a cross-sectional study exploring fibromyalgia and pain thresholds (n=45). Repeatability was tested in 34 patients with active RA. Derived indices were the proportion of DAS28 attributable to patient-reported components (DAS28-P), tender-swollen difference and tender:swollen ratio. Pressure pain detection threshold (PPT) was used as an index of pain sensitisation. Results: DAS28, tender joint count, visual analogue scale, DAS28-P, tender-swollen difference and tender:swollen ratio were more strongly associated with pain, PPT and fibromyalgia status than were swollen joint count or erythrocyte sedimentation rate. DAS28-P, tender-swollen difference and tender:swollen ratio better predicted pain over 1 year than did DAS28 or its individual components. Conclusions: DAS28 is strongly associated both with inflammation and with patient-reported outcomes. DAS28-derived indices such as tender-swollen difference are associated with non-inflammatory pain mechanisms, can predict future pain and should inform how DAS28 is interpreted as an index of inflammatory disease activity in RA

Idiopathic toe-walking in children, adolescents and young adults: a matter of local or generalised stiffness?

<p>Abstract</p> <p>Background</p> <p>Idiopathic Toe Walking (ITW) is present in children older than 3 years of age still walking on their toes without signs of neurological, orthopaedic or psychiatric diseases. ITW has been estimated to occur in 7% to 24% of the childhood population. To study associations between Idiopathic Toe Walking (ITW) and decrease in range of joint motion of the ankle joint. To study associations between ITW (with stiff ankles) and stiffness in other joints, muscle strength and bone density.</p> <p>Methods</p> <p>In a cross-sectional study, 362 healthy children, adolescents and young adults (mean age (sd): 14.2 (3.9) years) participated. Range of joint motion (ROM), muscle strength, anthropometrics sport activities and bone density were measured.</p> <p>Results</p> <p>A prevalence of 12% of ITW was found. Nine percent had ITW and severely restricted ROM of the ankle joint. Children with ITW had three times higher chance of severe ROM restriction of the ankle joint. Participants with ITW and stiff ankle joints had a decreased ROM in other joints, whereas bone density and muscle strength were comparable.</p> <p>Conclusion</p> <p>ITW and a decrease in ankle joint ROM might be due to local stiffness. Differential etiological diagnosis should be considered.</p

Absence of polysialylated NCAM is an unfavorable prognostic phenotype for advanced stage neuroblastoma

<p>Abstract</p> <p>Background</p> <p>The expression of a neural crest stem cell marker, polysialic acid (polySia), and its main carrier, neural cell adhesion molecule (NCAM), have been detected in some malignant tumors with high metastatic activity and unfavorable prognosis, but the diagnostic and prognostic value of polySia-NCAM in neuroblastoma is unclear.</p> <p>Methods</p> <p>A tumor tissue microarray (TMA) of 36 paraffin-embedded neuroblastoma samples was utilized to detect polySia-NCAM expression with a polySia-binding fluorescent fusion protein, and polySia-NCAM expression was compared with clinical stage, age, <it>MYCN </it>amplification status, histology (INPC), and proliferation index (PI).</p> <p>Results</p> <p>PolySia-NCAM-positive neuroblastoma patients had more often metastases at diagnosis, and polySia-NCAM expression associated with advanced disease (<it>P </it>= 0.047). Most interestingly, absence of polySia-NCAM-expressing tumor cells in TMA samples, however, was a strong unfavorable prognostic factor for overall survival in advanced disease (<it>P </it>= 0.0004), especially when <it>MYCN </it>was not amplified. PolySia-NCAM-expressing bone marrow metastases were easily detected in smears, aspirates and biopsies.</p> <p>Conclusion</p> <p>PolySia-NCAM appears to be a new clinically significant molecular marker in neuroblastoma, hopefully with additional value in neuroblastoma risk stratification.</p

Assessment of cartilage-dedicated sequences at ultra-high-field MRI: comparison of imaging performance and diagnostic confidence between 3.0 and 7.0 T with respect to osteoarthritis-induced changes at the knee joint

The objectives of the study were to optimize three cartilage-dedicated sequences for in vivo knee imaging at 7.0 T ultra-high-field (UHF) magnetic resonance imaging (MRI) and to compare imaging performance and diagnostic confidence concerning osteoarthritis (OA)-induced changes at 7.0 and 3.0 T MRI. Optimized MRI sequences for cartilage imaging at 3.0 T were tailored for 7.0 T: an intermediate-weighted fast spin-echo (IM-w FSE), a fast imaging employing steady-state acquisition (FIESTA) and a T1-weighted 3D high-spatial-resolution volumetric fat-suppressed spoiled gradient-echo (SPGR) sequence. Three healthy subjects and seven patients with mild OA were examined. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), diagnostic confidence in assessing cartilage abnormalities, and image quality were determined. Abnormalities were assessed with the whole organ magnetic resonance imaging score (WORMS). Focal cartilage lesions and bone marrow edema pattern (BMEP) were also quantified. At 7.0 T, SNR was increased (p &lt; 0.05) for all sequences. For the IM-w FSE sequence, limitations with the specific absorption rate (SAR) required modifications of the scan parameters yielding an incomplete coverage of the knee joint, extensive artifacts, and a less effective fat saturation. CNR and image quality were increased (p &lt; 0.05) for SPGR and FIESTA and decreased for IM-w FSE. Diagnostic confidence for cartilage lesions was highest (p &lt; 0.05) for FIESTA at 7.0 T. Evaluation of BMEP was decreased (p &lt; 0.05) at 7.0 T due to limited performance of IM-w FSE. Gradient echo-based pulse sequences like SPGR and FIESTA are well suited for imaging at UHF which may improve early detection of cartilage lesions. However, UHF IM-w FSE sequences are less feasible for clinical use

Developmental variations in plasma leptin, leptin soluble receptor and their molar ratio in healthy infants

<p>Abstract</p> <p>Background</p> <p>Leptin and its soluble receptor (sOB-R) are important to regulation of body composition but there are no data on the developmental variations in these plasma variables and their relationship with body composition measurements,</p> <p>Methods</p> <p>Weight, length, and body composition (bone, fat and lean mass) by dual energy absorptiometry, and plasma variables were measured in healthy infants at 2, 4, 8 and 12 months.</p> <p>Results</p> <p>15 whites and 29 African Americans (21 males and 23 females) with mean birth weight 3357 +/- 45 (SEM) g and gestation of 39.3 +/- 0.17 weeks were studied. The overall Z score for weight, length and weight for length during the study were 0.00 +/- 0.15, -0.08 +/- 0.11 and 0.12 +/- 0.14 respectively. With increasing age, plasma leptin (1.0 to 18.2, median 5.5 ng/mL) and sOB-R:leptin molar ratio (10.1 to 247.4, median 59.9) were lowered (r = -0.47, p < 0.01; and r = -0.37, p < 0.05 respectively), best predicted by weight Z score and percentage of fat mass, and higher in African American and female. Presence of body composition measurements eliminated the race and gender effect on the plasma variables. Plasma sOB-R (49.5 to 173.9, median 81.3 ng/mL) did not change significantly with age and was correlated and predicted only by body composition measurements.</p> <p>Conclusion</p> <p>In healthy growing infants, plasma leptin but not sOB-R decreases with age. Gender, race and anthropometric measurements are additional physiological determinants predictive of plasma leptin and the receptor:ligand ratio. However, body composition is the only variable that can predict plasma leptin and its soluble receptor and the receptor: ligand ratio; and body composition measurements eliminated the race and gender effect on these plasma variables.</p

Screening for low bone mass with quantitative ultrasonography in a community without dual-energy X-ray absorptiometry: population-based survey

BACKGROUND: Dual-energy x-ray absorptiometry (DXA) is the criterion standard to identify low bone mineral density (BMD), but access to axial DXA may be limited or cost prohibitive. We screened for low bone mass with quantitative ultrasonography (QUS) in a community without DXA, analyzed its reliability and obtained reference values and estimated the prevalence of low QUS values. METHODS: We enrolled 6493 residents of Kinmen, Taiwan, and a reference group (96 men and 70 women aged 20–29 years) for this cross-sectional, community-based study. All participants completed a questionnaire and underwent ultrasonographic measurements. Reliability and validity of QUS measurements were evaluated. Broadband ultrasound attenuation (BUA) values were obtained and statistically analyzed by age, sex and weight. Annual loss of BUA was determined. Trends in the prevalence of QUS scores were evaluated. RESULTS: Two QUS were used and had a correlation coefficient of 0.90 (p < 0.001). Calcaneal BUA was significantly correlated with BMD in the femoral neck (r = 0.67, p < 0.001) and BMD of the total lumbar spine (r = 0.59, p < 0.001). BUAs in the reference group were 92.72 ± 13.36 and 87.90 ± 10.68 dB/MHz for men and women, respectively. Estimated annual losses of calcaneal BUA were 0.83% per year for women, 0.27% per year for men, and 0.51% per year for the total population. The prevalence of severely low QUS values (T-score = -2.5) tended to increase with aging in both sexes (p < 0.001). Across age strata, moderately low QUS values (-2.5 < T-score < -1.0) were 31.6–41.0% in men and 23.7–38.1% in women; a significant trend with age was observed in men (p < 0.001). CONCLUSION: Age-related decreases in calcaneal ultrasonometry, which reflected the prevalence of low bone mass, were more obvious in women than in men