OBJECTIVE: Osteopenia is a common complication of juvenile idiopathic arthritis (JIA). In adults, low bone density and increased fracture risk are associated with low vitamin K status of bone. The vitamin K-dependent protein osteocalcin plays an important role in bone metabolism. Its activity depends upon post-translational carboxylation in which vitamin K is an essential co-factor. Hence, vitamin K deficiency leads to under-carboxylated (i.e., inactive) osteocalcin (ucOC). Little is known about the vitamin K status and bone health in children with juvenile idiopathic arthritis (JIA). We studied the vitamin K status of bone and its association with bone mass properties in children with JIA compared to healthy children.METHODS: We performed a cross sectional study in 55 children with JIA and 54 healthy controls between 6-18 years of age. Bone markers, ultrasound bone mass properties and vitamin K status of bone were determined.RESULTS: Overall, no differences in vitamin K status of bone were found between the study groups. Among children with JIA, a high ratio of ucOC/cOC indicating low vitamin K status was associated with low bone ultrasound parameters, whereas children with a high vitamin K status had markedly higher bone properties. This association was independent of physical activity, age, gender and BMI.CONCLUSION: These results suggest that vitamin K may be one of multiple risk factors for low bone mass in children with JIA, in addition to other recognized determinants of bone mass. The question remains whether JIA patients would benefit from increased dietary vitamin K intake.
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At this moment, no method is available to objectively estimate the temperature to which skeletal remains have been exposed during a fire. Estimating this temperature can provide crucial information in a legal investigation. Exposure of bone to heat results in observable and measurable changes, including a change in colour. To determine the exposure temperature of experimental bone samples, heat related changes in colour were systemically studied by means of image analysis. In total 1138 samples of fresh human long bone diaphysis and epiphysis, varying in size, were subjected to heat ranging from room temperature to 900 °C for various durations and in different media. The samples were scanned with a calibrated flatbed scanner and photographed with a Digital Single Lens Reflex camera. Red, Green, Blue values and Lightness, A-, and B-coordinates were collected for statistical analysis. Cluster analysis showed that discriminating thresholds for Lightness and B-coordinate could be defined and used to construct a model of decision rules. This model enables the user to differentiate between seven different temperature clusters with relatively high precision and accuracy. The proposed decision model provides an objective, robust and non-destructive method for estimating the exposure temperature of heated bone samples.
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Rationale: The number of obese older adults with diabetes type 2 is increasing worldwide. Weight loss treatment in this group seems beneficial for cardio-metabolic and other health outcomes, but it might reduce muscle mass and bone mineral density (BMD). The association between obesity and BMD is controversial, and the role of muscle mass and dietary protein intake is not fully clear. This study explores the association between body weight, muscle mass, dietary protein intake, and physical activity level on BMD in obese older adults with diabetes type 2. Methods: For this cross-sectional analysis we used baseline data of a 13-week randomized trial evaluating the effect of a multi-modal intervention on muscle preservation and insulin sensitivity during a weight loss program in obese older adults (55-80y) with diabetes type 2 (PROBE). Body weight was measured using a calibrated scale (Life Measurement), appendicular lean mass (ALM) was used as a proxy for muscle mass and was measured by dual-energy X-ray absorptiometry (DXA, Hologic Discovery A), dietary protein intake was estimated by a 3-day food record, Physical Activity Level (PAL) was estimated by a 3-day activity record, and hip BMD was assessed by DXA. After determination of Pearson’s correlation coefficients for body weight, ALM, protein intake, and PAL with BMD, linear regression analysis was performed with significantly correlating determinants (body weight [kg], ALM [kg], protein intake [g/kg/d], and/or PAL [-]) and hip BMD (g/cm2) as outcome variable. Results: Mean age of the 122 included subjects was 67±6y, with a BMI of 33±4kg/m2. 65% of subjects were male. Body weight and ALM correlated significantly with BMD (r=0.34, p<0.001; r=0.43, p<0.001) whereas protein intake and PAL did not (r=0.02, p=0.84; r=0.005, p=0.95). Linear regression analysis with the two determinants body weight and ALM identified ALM as being significantly associated with BMD, whereas body weight was not. Beta for ALM was +0.011 g/cm2 (95% CI: 0.004 – 0.017; p<0.01), meaning that a 1 kg increase in ALM is associated with a +0.011 g/cm2 increase in BMD. Conclusion: In this explorative cross-sectional analysis appendicular muscle mass is positively associated with BMD, rather than body weight, protein intake, and physical activity level.
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OBJECTIVE: Evaluate clinical outcome of early cyclic intravenous pamidronate treatment in children with moderate-to-severe osteogenesis imperfecta (OI), commenced before three years of age.METHODS: A retrospective review of 17 patients with moderate-to-severe OI. Development, anthropometry, fracture history, bone mineral density (BMD) and biochemistry were collected at baseline, 12 and 24 months.RESULTS: Four had OI type I, eleven had type III, one OI-FKBP10 type and one OI type V. Mean age at start of pamidronate was 14 ± 11 months. Pamidronate ranged from 6 to 12 mg/kg/year. No adverse reaction apart from fever and vomiting was noted. Long bone fracture decreased from a mean of 10.4/year to 1.2/year after 12 months and 1.4/year after 24 months (p = 0.02). Lumbar spine age- and height-matched BMD Z-scores increased (p < 0.005). Sixteen with vertebral compression fractures at baseline all showed improved vertebral shape (p < 0.001). Concavity index, likewise, improved (p < 0.005). Motor milestones compared to historical data show earlier attainment in rolling over, crawling, pulling to stand and walking independently but not sitting.CONCLUSION: Cyclic intravenous pamidronate, started under 3 years of age in children with moderate-to-severe OI, was well tolerated and associated with an increase in lumbar spine BMD, reduced fracture frequency, vertebral remodelling and attainment of motor milestones at an earlier age.
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BackgroundIdiopathic 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.MethodsIn 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.ResultsA 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.ConclusionITW and a decrease in ankle joint ROM might be due to local stiffness. Differential etiological diagnosis should be considered.
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Background: The objective of this study was to derive evidence-based physical activity guidelines for the general Dutch population. Methods: Two systematic reviews were conducted of English language meta-analyses in PubMed summarizing separately randomized controlled trials and prospective cohort studies on the relation between physical activity and sedentary behaviour on the one hand and the risk of all-cause mortality and incidence of 15 major chronic diseases and conditions on the other hand. Other outcome measures were risk factors for cardiovascular disease and type 2 diabetes, physical functioning, and fitness. On the basis of these reviews, an expert committee derived physical activity guidelines. In deriving the guidelines, the committee first selected only experimental and observational prospective findings with a strong level of evidence and then integrated both lines of evidence. Results: The evidence found for beneficial effects on a large number of the outcome measures was sufficiently strong to draw up guidelines to increase physical activity and reduce sedentary behaviour, respectively. At the same time, the current evidence did not provide a sufficient basis for quantifying how much physical activity is minimally needed to achieve beneficial health effects, or at what amount sedentary behaviour becomes detrimental. A general tenet was that at every level of current activity, further increases in physical activity provide additional health benefits, with relatively larger effects among those who are currently not active or active only at light intensity. Three specific guidelines on (1) moderate- and vigorous-intensity physical activity, (2) bone- and musclestrengthening activities, and (3) sedentary behaviour were formulated separately for adults and children. Conclusions: There is an unabated need for evidence-based physical activity guidelines that can guide public health policies. Research in which physical activity is measured both objectively (quantity) and subjectively (type and quality) is needed to provide better estimates of the type and actual amount of physical activity required for health.
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ObjectiveThe Plants for Joints (PFJ) intervention significantly improved pain, stiffness, and physical function, and metabolic outcomes, in people with metabolic syndrome-associated osteoarthritis (MSOA). This secondary analysis investigated its effects on body composition.MethodIn the randomized PFJ study, people with MSOA followed a 16-week intervention based on a whole-food plant-based diet, physical activity, and stress management, or usual care. For this secondary analysis, fat mass, muscle mass, and bone mineral density were measured using dual-energy X-ray absorptiometry (DEXA) for all participants. Additionally, in a subgroup (n = 32), hepatocellular lipid (HCL) content and composition of visceral adipose tissue (VAT) were measured using magnetic resonance spectroscopy (MRS). An intention-to-treat analysis with a linear-mixed model adjusted for baseline values was used to analyse between-group differences.ResultsOf 66 people randomized, 64 (97%) completed the study. The PFJ group experienced significant weight loss (−5.2 kg; 95% CI –6.9, −3.6) compared to controls, primarily from fat mass reduction (−3.9 kg; 95% CI –5.3 to −2.5). No significant differences were found in lean mass, muscle strength, or bone mineral density between groups. In the subgroup who underwent MRI scans, the PFJ group had a greater reduction in HCL (−6.5%; 95% CI –9.9, 3.0) compared to controls, with no observed differences in VAT composition.ConclusionThe PFJ multidisciplinary intervention positively impacted clinical and metabolic outcomes, and appears to significantly reduce body fat, including liver fat, while preserving muscle mass and strength.
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Klotho knock-out mice are an important model for vascular calcification, which is associated with chronic kidney disease. In chronic kidney disease, serum magnesium inversely correlates with vascular calcification. Here we determine the effects of serum magnesium on aortic calcification in Klotho knock-out mice treated with a minimal or a high magnesium diet from birth. After eight weeks, serum biochemistry and aorta and bone tissues were studied. Protective effects of magnesium were characterized by RNA-sequencing of the aorta and micro-CT analysis was performed to study bone integrity. A high magnesium diet prevented vascular calcification and aortic gene expression of Runx2 and matrix Gla protein found in such mice on the minimal magnesium diet. Differential expression of inflammation and extracellular matrix remodeling genes accompanied the beneficial effects of magnesium on calcification. High dietary magnesium did not affect serum parathyroid hormone, 1,25-dihydroxyvitamin D3 or calcium. High magnesium intake prevented vascular calcification despite increased fibroblast growth factor-23 and phosphate concentration in the knock-out mice. Compared to mice on the minimal magnesium diet, the high magnesium diet reduced femoral bone mineral density by 20% and caused excessive osteoid formation indicating osteomalacia. Osteoclast activity was unaffected by the high magnesium diet. In Saos-2 osteoblasts, magnesium supplementation reduced mineralization independent of osteoblast function. Thus, high dietary magnesium prevents calcification in Klotho knock-out mice. These effects are potentially mediated by reduction of inflammatory and extracellular matrix remodeling pathways within the aorta. Hence magnesium treatment may be promising to prevent vascular calcification, but the risk for osteomalacia should be considered.
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Older, more vulnerable individuals are increasingly often described in the literature as being frail. Because frailty is often perceived as being undesirable and associated with high health risks, it is important to establish how we can predict, recognize, and treat frailty. Frailty is predisposed by advancing age in combination with physiological deterioration, especially a loss of muscle mass and bone density. Although the symptoms of frailty are diverse, the most common symptoms are a deterioration of activities of daily living (ADL), mobility, nutritional status, cognition, and endurance. The consequences of frailty are institutionalization, morbidity, and mortality. The main determinants of frailty are limitations in ADL, weight loss, diminished mobility or patterns of activity, lowered serum cholesterol level, and sensitivity to change. There is no gold standard for the measurement of frailty, and often studies use a combination of instruments. Although a couple of multidimensional instruments have been developed to measure frailty in its totality, the reliability and validity of these instruments have yet to be established. Successful interventions against frailty include increasing muscle strength through training and individualized recommendations made on the basis of an extensive geriatric assessment.
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By applying Axiomatic Design, a Smart Medical Cast was developed to provide patients, who are suffering from forearm fractures, with a personalized healing process. The device monitors the overall healing status and three complications, which are: Muscle Atrophy, Compartment Syndrome, and Deep Vein Thrombosis. In the conceptual phase, desk research has been performed to find biomarkers that correlate with the monitored processes. Per biomarker, a measuring principle has been designed and these combined formed the design of the smart medical cast. Following the design phase, two tests were performed on healthy individuals to measure the robustness in a real application. The first test focused on correctly measuring the biomarkers and further specifying the sensor specifications. For the second test, a new prototype was used to determine correlations between the measured data and the monitored process and the impact of application during the casting process. The test results show that the measuring system can measure the biomarkers within the expected range, except for bone density. No significant impact on the casting process was measured. The Smart Medical Cast has only been evaluated in situations without a fracture, the next step will be to test the measurables in an environment with a fracture
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