Genetic and environmental determinants of bone quality: a cross-sectional analysis of the Hungarian Twin Registry.

There is abundant evidence that bone mineral content is highly heritable, while the heritability of bone quality (i.e. trabecular bone score [TBS] and quantitative ultrasound index [QUI]) is rarely investigated. We aimed to disentangle the role of genetic, shared and unique environmental factors on TBS and QUI among Hungarian twins. Our study includes 82 twin (48 monozygotic, 33 same-sex dizygotic) pairs from the Hungarian Twin Registry. TBS was determined by DXA, QUI by calcaneal bone ultrasound. To estimate the genetic and environmental effects, we utilized ACE-variance decomposition. For the unadjusted model of TBS, an AE model provided the best fit with > 80% additive genetic heritability. Adjustment for age, sex, BMI and smoking status improved model fit with 48.0% of total variance explained by independent variables. Furthermore, there was a strong dominant genetic effect (73.7%). In contrast, unadjusted and adjusted models for QUI showed an AE structure. Adjustments improved model fit and 25.7% of the total variance was explained by independent variables. Altogether 70-90% of the variance in QUI was related to additive genetic influences. We found a strong genetic heritability of bone quality in unadjusted models. Half of the variance of TBS was explained by age, sex and BMI. Furthermore, the adjusted model suggested that the genetic component of TBS could be dominant or an epistasis could be present. In contrast, independent variables explained only a quarter of the variance of QUI and the additive heritability explained more than half of all the variance.

The effect of COVID-19 vaccination status on all-cause mortality in patients hospitalised with COVID-19 in Hungary during the delta wave of the pandemic.

The high mortality of patients with coronavirus disease 2019 (COVID-19) is effectively reduced by vaccination. However, the effect of vaccination on mortality among hospitalised patients is under-researched. Thus, we investigated the effect of a full primary or an additional booster vaccination on in-hospital mortality among patients hospitalised with COVID-19 during the delta wave of the pandemic. This retrospective cohort included all patients (n = 430) admitted with COVID-19 at Semmelweis University Department of Medicine and Oncology in 01/OCT/2021-15/DEC/2021. Logistic regression models were built with COVID-19-associated in-hospital/30 day-mortality as outcome with hierarchical entry of predictors of vaccination, vaccination status, measures of disease severity, and chronic comorbidities. Deceased COVID-19 patients were older and presented more frequently with cardiac complications, chronic kidney disease, and active malignancy, as well as higher levels of inflammatory markers, serum creatinine, and lower albumin compared to surviving patients (all p < 0.05). However, the rates of vaccination were similar (52-55%) in both groups. Based on the fully adjusted model, there was a linear decrease of mortality from no/incomplete vaccination (ref) through full primary (OR 0.69, 95% CI: 0.39-1.23) to booster vaccination (OR 0.31, 95% CI 0.13-0.72, p = 0.006). Although unadjusted mortality was similar among vaccinated and unvaccinated patients, this was explained by differences in comorbidities and disease severity. In adjusted models, a full primary and especially a booster vaccination improved survival of patients hospitalised with COVID-19 during the delta wave of the pandemic. Our findings may improve the quality of patient provider discussions at the time of admission.

Strong Genetic Effects on Bone Mineral Density in Multiple Locations with Two Different Techniques: Results from a Cross-Sectional Twin Study.

Background and Objectives: Previous studies have demonstrated that risk of hip fracture is at least partly heritable. The aim of this study was to determine the magnitude of the genetic component of bone mineral density (BMD), using both X-ray and ultrasound assessment at multiple sites. Materials and Methods: 216 adult, healthy Hungarian twins (124 monozygotic, MZ, 92 dizygotic, DZ; mean age 54.2 ± 14.3 years), recruited from the Hungarian Twin Registry with no history of oncologic disease underwent cross-sectional BMD studies. We measured BMD, T- and Z-scores with dual energy X-ray absorptiometry (DEXA) at multiple sites (lumbar spine, femoral neck, total hip and radius). Quantitative bone ultrasound (QUS) was also performed, resulting in a calculated value of estimated bone mineral density (eBMD) in the heel bone. Heritability was calculated using the univariate ACE model. Results: Bone density had a strong genetic component at all sites with estimates of heritability ranging from 0.613 to 0.838 in the total sample. Lumbar BMD and calcaneus eBMD had major genetic components with estimates of 0.828 and 0.838 respectively, and least heritable (0.653) at the total hip. BMD of the radius had also a strong genetic component with an estimate of 0.806. No common environmental effect was found. The remaining variance was influenced by unique environment (0.162 to 0.387). In females only, slightly higher additive genetic estimates were found, especially in the case of the femoral neck and total hip. Conclusion: Bone mineral density is strongly heritable, especially in females at all locations using both DEXA and QUS, which may explain the importance of family history as a risk factor for bone fractures. Unshared environmental effects account for the rest of the variance with slight differences in magnitude across various bone regions, supporting the role of lifestyle in preventing osteoporotic fractures with various efficacy in different bone regions.

Influence of local exposure to static magnetic field on pain perception and bone turnover of osteoporotic patients with vertebral deformity - a randomized controlled trial.

PURPOSE: Static magnetic field (SMF) could improve pain sensation and bone turnover. In a single-center randomized double-blind placebo-controlled study we investigated the effects of SMF exposure on subjective pain and bone turnover. MATERIALS AND METHODS: Postmenopausal osteoporotic women (aged 50-70 years) with bone deformity and back pain were randomized to 10 weekly visits of 30-min SMF (n = 6) or treatment with non-magnetized pads (n = 5) on the back. Primary and secondary outcomes were changes in pain sensation on a visual analogue scale (VAS) during each visit and over 10 weeks, respectively. Tertiary outcomes were changes in osteocalcin and ß-crosslaps. SMF was inhomogeneous with 192 millitesla peak-to-peak value by 19 tesla/meter gradient of the magnetic flux density at 3 mm. RESULTS: Participants randomized to sham had higher VAS at baseline (mean difference: 2.8, 95% confidence interval (CI) 0.47-5.2 cm). Both SMF and sham similarly reduced short term pain (sham-SMF: 0.59, 95% CI - 0.31-1.49 cm, p = 0.195). VAS did not change in SMF, while it decreased in the sham group (between-group difference 0.27, 95% CI 0.04-0.50 cm/visit). Bone turnover markers remained stable. CONCLUSIONS: SMF as used in this investigation is not recommended for pain relief in postmenopausal women with vertebral deformity. The finding on long-term pain relief may relate to unbalanced randomization.

[Effect of cigarette smoking on bone quality parameters in women]. / A dohányzás hatása a nok csontjának minoségi jellemzoire.

INTRODUCTION: Smoking is a risk factor for osteoporosis. In a previous study, the authors showed lower bone density among smokers in a group of postmenopausal women. AIMS: After this finding, the primary goal of current research was to investigate how smoking could influence bone quality. METHODS: Forty-five (age range: 25-72 ys) smoker women were compared with 45 nonsmoker women adjusted for age and anthropometric parameters. Quantitative ultrasound method was used to determine the speed of ultrasound and the ultrasound attenuation transmitting the left heel (Achilles In Sight, GE Lunar). Dual photon absorptiometry method was applied to investigate the bone mineral density of lumbar spine and left femoral neck (Prodigy, GE Lunar) and single photon absorptiometry was used to determine the bone mineral content of radius at the non dominant side (NK-364, Gamma). RESULTS: No difference was found between smokers and non-smokers among the premenopausal group, however, postmenopausal smoker women had slightly lower speed of ultrasound and ultrasound attenuation values than non-smoker women. Postmenopausal smoker women suffering from bone fracture had significantly lower speed of ultrasound than postmenopausal non-smoker women (1508.9 vs. 1525.3 m/s, respectively), despite their bone density did not differ from each other. CONCLUSION: These data augment the knowledge about the injurious effect of smoking. The increased risk for bone fracture among smokers could be explained not only with the decrease of bone mass, which was previously described, but also with a decreased bone elasticity.

Bone disorders in experimentally induced liver disease in growing rats.

AIM: To investigate the change of bone parameters in a new model of experimentally induced liver cirrhosis and hepatocellular carcinoma (HCC) in growing rats. METHODS: Fischer-344 rats (n = 55) were used. Carbon tetrachloride (CCl(4)), phenobarbital (PB), and a single diethylnitrosamine (DEN) injection were used. Animals were killed at wk 8 and 16. Bone mineral content, femoral length, cortical index (quotient of cortical thickness and whole diameter) and ultimate bending load (F(max)) of the femora were determined. The results in animals treated with DEN+PB+CCl(4) (DPC, n = 21) were compared to those in untreated animals (UNT, n = 14) and in control group treated only with DEN+PB (DP, n = 20). RESULTS: Fatty liver and cirrhosis developed in each DPC-treated rat at wk 8 and HCC was presented at wk 16. No skeletal changes were found in this group at wk 8, but each parameter was lower (P<0.05 for each) at wk 16 in comparison to the control group. Neither fatty liver nor cirrhosis was observed in DP-treated animals at any time point. Femoral length and F(max) values were higher (P<0.05 for both) in DP-treated animals at wk 8 compared to the UNT controls. However, no difference was found at wk 16. CONCLUSION: Experimental liver cirrhosis and HCC are accompanied with inhibited skeletal growth, reduced bone mass, and decreased mechanical resistance in growing rats. Our results are in concordance with the data of other studies using different animal models. A novel finding is the transiently accelerated skeletal growth and bone strength after a 8-wk long phenobarbital treatment following diethylnitrosamine injection.