Stefan Goemaere

There is an increasing awareness of sarcopenia in older people. We applied machine learning principles to predict mortality and incident immobility in older Belgian men through sarcopenia and frailty characteristics. Mortality could be predicted with good accuracy. Serum 25-hydroxyvitamin D and bone mineral density scores were the most important predictors.

In this work, we report a microfluidic platform that can be easily translated into a biomarker diagnostic. This platform integrates microfluidic technology with electrochemical sensing and embodies a reaction/detection chamber to measure serum levels of different biomarkers. Microfabricated Au electrodes encased in a microfluidic chamber are functionalized to immobilize the antibodies, which can selectively capture the corresponding antigen. An oxidative peak is obtained using the chronoamperometry technique at room temperature. The magnitude of the response current varies linearly with the logarithmic concentration of the relative biomarker and, thus, is used to quantify the concentration of the relative biomarker in serum samples. We demonstrated the implementation, feasibility and specificity of this platform (Osteokit) in assaying serum levels of bone turnover markers (BTMs) using osteocalcin (limits of detection (LOD) = 1.94 ng/mL) and collagen type 1 cross-linked C-telopeptide (CTX) (LOD = 1.39 pg/mL). To our knowledge, this is the first such device fabricated to measure BTMs. Our results also showed that the sensitivity of Osteokit is comparable with the current states of art, electrochemiluminescence (ECLIA).

Objective: In type 2 diabetes mellitus, fracture risk is increased despite preserved BMD. This might in part be due to insulin resistance affecting bone geometry; however, studies investigating the associations of insulin sensitivity with bone geometry are lacking. We aimed to explore this relationship in a cohort of healthy, young adult men. Methods: In 1001 healthy men aged 25–45 years, cortical bone geometry was assessed using pQCT (radius and tibia, 66% from distal end point). Insulin and glucose were measured from fasting serum samples; insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). Results: In age and BMI-adjusted analyses, HOMA-IR and insulin levels correlated inversely with periosteal circumference (PC), endosteal circumference (EC) and polar strength-strain index (SSIp) at both the radius (PC: both ß=−0.13, PP≤0.031; SSIp: ß=−0.14 and ß=−0.16, PPP≤0.007; SSIp: ß=−0.10, P≤0.003). Moreover, insulin levels but not HOMA-IR correlated inversely with cortical thickness at the radius (ß=−0.07, P=0.048). After adjustment for DXA-derived body composition (total fat and lean body mass) instead of BMI, the associations of HOMA-IR and insulin with PC and SSIp at both the radius and tibia and with EC at the tibia remained significant (ß≥−0.11, P≤0.019), whereas the associations of HOMA-IR and insulin with EC and the association of insulin with cortical thickness at the radius lost significance. Conclusion: In this cohort of healthy young men, insulin sensitivity correlates with cortical bone size at least in part independently of body composition. Given the important contribution of bone geometry to overall bone strength, this might contribute to the paradoxically increased fracture risk in patients with type 2 diabetes mellitus. Whether this association is a direct consequence of impaired insulin signaling in bone tissue or reflects indirect effects through modulation of the muscle-bone relationship remains to be established.

Background: Impaired bone geometry and/or aberrant bone matrix formation may underlie the increased fracture risk observed in patients with type 1 diabetes mellitus (T1DM). Although reduced areal and volumetric bone mineral density (aBMD, vBMD) have been observed in pediatric and adolescent T1DM patients, few studies have confirmed these observations in adults. Moreover, data on bone geometry in T1DM remain scarce. Objective: To compare areal and volumetric bone parameters and cortical bone geometry in adult T1DM patients and gender- and age-matched controls. Methods: In 64 adult T1DM patients (39 men, 41.1±8.1 years) and 63 controls, areal and volumetric bone parameters and bone geometry were assessed using DXA and pQCT (radius: 4% and 66% regions). Results: Median diabetes duration was 23.1 years, with a mean HbA1c of 63±5 mmol/mol over the last 10 years. In age-, height-, weight- and gender-adjusted analyses, T1DM was associated with lower aBMD and bone mineral content at the total hip (−5.14%, P=0.011 and −6.72%, P=0.013) and femoral neck (−7.43%, P=0.003 and −9.04%, PP=0.014). Cortical vBMD was higher in T1DM patients as compared to controls (+2.06%, P=0.004), but total vBMD was lower (−5.19%, P=0.020) and T1DM patients showed a cortical bone size deficit with smaller cortical thickness (−6.21%, P=0.035) and trends towards lower cortical area (−4.64%, P=0.060) and increased endosteal circumference (+5.29%, P=0.074). Furthermore, T1DM was associated with lower trabecular vBMD and higher trabecular area (−9.00% and +7.62%, P=0.013). Except for trabecular area, which was higher in male but not female T1DM patients as compared to controls, no major interactions between health status and gender were observed. Conclusion: Besides decreased aBMD and trabecular vBMD, adult T1DM patients present with a cortical bone size deficit characterized by lower cortical thickness and higher endosteal circumference. This might contribute to the higher fracture risk observed in diabetic patients.

Background: Ehlers–Danlos syndrome (EDS) comprises a group of inherited connective tissue disorders, caused by various defects in the biosynthesis or secretion of fibrillar collagens. As collagen represents a major constituent of the bone matrix as well as of tendons and muscle, bone strength in EDS patients might be impaired both via direct and indirect pathways. Although decreased muscle strength, decreased areal bone mineral density (BMD) and increased fracture risk have been reported, no studies have investigated volumetric bone parameters in these patients. Objective: We aimed to compare volumetric BMD (vBMD) and cortical bone geometry in patients with EDS hypermobility type (EDS-HT) and age- and sex-matched controls. Methods: Forty-two female EDS-HT patients (mean age 40.0±10.8 years) and 42 controls were included in a cross-sectional study. vBMD and bone geometry at the tibia (4 and 66% region) as well as lower leg muscle cross-sectional area (CSA, 66% region) were measured using pQCT. Results: Although EDS-HT patients did not differ from controls with regard to trabecular or cortical vBMD, they presented with about 6.3% smaller trabecular bone area (P=0.014), 8.9% smaller cortical bone area (P=0.005), 6.6% smaller cortical thickness (P=0.021), and, albeit non-significant, 2.9% smaller periosteal circumference (P=0.101). As a result, strength-strain index was 9.8% lower in EDS-HT patients as compared with controls (P=0.039). Furthermore, EDS-HT was associated with a 10.8% decreased muscle CSA (P=0.004) without differences in muscle density. Bone/muscle CSA ratio was within the normal range and did not differ between groups. Conclusions: EDS-HT patients present with both a trabecular and cortical tibial bone size deficit as compared with controls, which might contribute to their increased fracture risk. As indicated by the decreased muscle CSA and normal bone/muscle CSA ratio, this bone size deficit is probably secondary to decreased mechanical loading in these patients with known muscle dysfunction.

Background: Advancing maternal age at childbirth has been associated with a higher risk of pregnancy complications and with adverse short-term and long-term offspring health outcomes, but little is known about the effects of increasing maternal age on offspring bone acquisition. Objective: To investigate associations of maternal age at childbirth with offspring bone parameters in healthy men at the age of peak bone mass. Methods: We used cross-sectional data from 689 subjects participating in a population-based sibling pair study including healthy men aged 25–45 years. Data include maternal age at childbirth, offspring birth weight, adult weight and height, and offspring DXA and pQCT-derived areal and volumetric bone parameters and cortical bone geometry. Cross-sectional associations were investigated using linear mixed-effects modeling with adjustment for offspring age, height and weight. Results: Maternal age at childbirth was 27.0±4.7 years and correlated inversely with areal bone mineral density (aBMD) and bone mineral content (BMC) at the lumbar spine (ß=-0.09, P= 0.011 and ß=-0.01, P= 0.017), as well as with trabecular volumetric BMD (vBMD) at the distal radius (ß=-0.10, P= 0.014). No associations of maternal age were found with aBMD or BMC at the total hip or femoral neck, nor with cortical vBMD at the proximal radius or tibia. However, increasing maternal age was associated with smaller cortical thickness (ß=-0.13, P= 0.002), cortical area (ß=-0.08, P= 0.024), and cortical over total bone area ratio (ß=-0.11, P= 0.010) as well as with larger endosteal circumference (ß=0.10, P= 0.010) at the tibia. No associations of maternal age with cortical bone geometry were observed at the radius. Conclusions: Advancing maternal age at childbirth might adversely affect the acquisition of peak bone mass and geometry in male offspring, with in particular less favourable trabecular bone mineral density and tibial cortical bone geometry. Whether this results from altered placental function or from epigenetic changes due to lifestyle factors remains to be established.

Therapy-induced mucositis and dysphagia puts head and neck (H&N) cancer patients at increased risk for developing cachexia. Omega-3 fatty acids (n-3 FA) have been suggested to protect against cachexia. We aimed to examine if echium oil, a plant source of n-3 FA, could reduce weight loss in H&N cancer patients undergoing radio(chemo)therapy with curative intent. In a double-blind trial, patients were randomly assigned to echium oil (intervention (I) group; 7.5 ml bis in die (b.i.d.), 235 mg/ml α-linolenic acid (ALA) + 95 mg/ml stearidonic acid (SDA) + 79 mg/ml γ-linolenic acid (GLA)) or n-3 FA deficient sunflower oil high oleic (control (C) group; 7.5 ml b.i.d.) additional to standard nutritional support during treatment. Differences in percentage weight loss between both groups were analysed according to the intention-to-treat principle. Erythrocyte FA profile, body composition, nutritional status and quality of life were collected. Ninety-one eligible patients were randomised, of whom 83 were evaluable. Dietary supplement adherence was comparable in both groups (median, I: 87%, C: 81%). At week 4, the I group showed significantly increased values of erythrocyte n-3 eicosapentanoic acid (EPA, 14% vs −5%) and n-6 GLA (42% vs −20%) compared to the C group, without a significant change in n-6 arachidonic acid (AA, 2% vs −1%). Intention-to-treat analysis could not reveal a significant reduction in weight loss related to echium oil consumption (median weight loss, I: 8.9%, C: 7.6%). Also, no significant improvement was observed in the other evaluated anthropometric parameters. Echium oil effectively increased erythrocyte EPA and GLA FAs in H&N cancer patients. It failed however to protect against weight loss, or improve nutritional parameters. ClinicalTrials.gov Identifier NCT01596933 .