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Objectives: X-linked hypophosphatemia (XLH, OMIM 307800) is a rare genetic disorder that affects phosphate metabolism. While lower limb deformity represents a hallmark symptom of patients with XLH, the effect on the foot has not been investigated. This study aimed to characterise foot pathologies and assess related outcome scores in adolescents and adults with XLH. Methods: Patients aged ≥ 16 years with genetically verified XLH were included in this study. Physical examination was performed, and foot scores as well as foot X-rays were assessed. Radiographic analysis included the assessment of osteoarthritis, enthesopathies, and alignment abnormalities. Results: Twenty-six participants (51 limbs) with a mean age of 33.9 ± 15.4 years were eligible for the study. Patients with XLH presented with flatfoot deformity (reduced Meary angles > −4° in 84.3%), elevated first and fifth metatarsal angles > 30° (IM 1–5, 53.5%) and hallux valgus angles > 15° (36.0%). Moderate-to-severe joint space narrowing was observed in the talonavicular (49%) and cuneonavicular joints (41.2%). The American Orthopedic Foot and Ankle Society (AOFAS) score was associated with mildly reduced midfoot function. Conclusions: A high rate of bony deformity, joint degeneration, and decreased foot scores indicated the impact of forefoot and midfoot disorders in patients with XLH. [ABSTRACT FROM AUTHOR]

Objective: Anorexia Nervosa (AN) is characterized by a distortion of body image, very low body weight, malnutrition and hormonal dysregulations, resulting in reduced bone mineral density (BMD) and impaired bone microarchitecture. The updated Trabecular Bone Score (TBS) algorithm accounts for soft tissue thickness (TBSTT) instead of BMI (TBSBMI). The aim of the study was to assess both TBS algorithms in adult AN patients compared to normal-weight controls(CTRL). Method: This retrospective cross-sectional study investigated 34 adult female anorexia nervosa (AN) patients and 26 healthy normal-weighted age- and sex-matched controls (CTRL). Bone texture analysis was assessed by TBSTT and TBSBMI (TBS iNsight® V4.0 and V3.1), bone mineral density (BMD; lumbar spine LS, femoral neck, total hip) and body composition by DXA (GE Lunar iDXATM). Laboratory analyses included bone turnover markers (CTX; P1NP; sclerostin). Data analysis was performed using parametric (t-test) or non-parametric test (Mann-Whitney-U-Test) depending on normality, one-way ANCOVA and correlation analysis (Perason's or Spearman's). Results: AN patients (BMI 14.7(1.6)) and CTRL (BMI 22.4(4.0)) were of comparable age (22.8(7.1) vs.25.0(4.0)years, p = 0.145). TBSTT(1.319±0.09 vs.1.502±0.07, p<0.001) and TBSBMI(1.317±0.10 vs.1.548±0.09, p<0.001) were significantly lower in AN patients compared to CTRL. Soft tissue thickness was lower in AN (p<0.001). Within the CTRL group, but not in AN, TBSTT and TBSBMI were significantly different (p<0.001). BMD was lower at all sites in AN patients (p<0.001 for all), being lowest at LS. Bone Mineral Content, Lean Body mass and Fat Mass were lower in AN (p<0.001). AN patients had lower P1NP (p = 0.05), but higher CTX (p = 0.001) and sclerostin (p = 0.003) levels. Conclusion: Adult AN patients have lower TBSTT and TBSBMI, reduced BMD and an uncoupling of bone turnover. In AN both TBS algorithms show similar reduced trabecular bone microarchitecture. The observed difference of TBSTT and TBSBMI in CTRL with normal body composition highlight the importance of the new algorithm. [ABSTRACT FROM AUTHOR]

Hypophosphatasia (HPP) is characterized by low activity of tissue nonspecific alkaline phosphatase (TNSALP). The enzyme replacement therapy asfotase alfa has been approved for childhood-onset forms of HPP. MicroRNAs (miRNAs) have emerged as a novel disease biomarker, with potential application in therapy monitoring. Circulating miRNAs were analyzed at baseline, months 1, 2, 4, and 16 in a 49-yr-old woman with childhood-onset HPP, chronic musculoskeletal pain, and non-traumatic fractures prior to enzyme replacement therapy. Serum RNA was extracted and sequenced using miRNeasy Mini Kit (Qiagen, Germany), RealSeq Biosciences Kit (Santa Cruz, US) together with miND spike-in control kit (TAmiRNA, Austria) and Illumina NovaSeq 6000 SP1 flow cell (San Diego, US). Brief Pain Inventory Severity and Interference scores (BPI-S/BPI-I), fatigue severity scale (FSS), Patient Global Impression of Improvement (PGI-I), Western Ontario and McMaster university hip disability and osteoarthritis outcome score (WOMAC), fibromyalgia impact questionnaire (FIQ), 6-Minute Walking Test (6-MWT), chair-rise-test (CRT), and handgrip dynamometry (HD) were performed at baseline and different timepoints during the therapy. Out of >800 screened, 84 miRNAs were selected based on differences in expression profiles between 24 HPP patients and 24 healthy controls. Six miRNAs showed a clear graphic trend and were up- or downregulated by ≥50% reads per million (rpm). These included hsa-let-7i-5p (+50%), hsa-miR-1-3p (−66.66%), hsa-miR-1294 (+63.63%), hsa-miR-206 (−85.57%), hsa-miR-375-3p (−71.43%), and hsa-miR-624-5p (+69.44%). hsa-miR-1-3p and hsa-miR-206 were identified as muscle-specific miRNAs. hsa-mir-375-3p, which negatively regulates osteogenesis, was significantly downregulated. In terms of patient-reported outcomes, BPI-S, BPI-I, FSS, PGI-I, WOMAC, and FIQ showed a reduction by −58.62%, −68.29%, −33.33%, −75.00%, −63.29%, and −43.02%, respectively. 6-MWT improved by +33.89% and CRT by −44.46%. Mean hand grip strength of the right/left hand measured by HD improved by +12.50% and + 23.53%, respectively. miRNA profile changes during the therapy with asfotase alfa, accompanying improvements in functionality tests and quality of life scores. Lay Summary: Hypophosphatasia (HPP) is a rare genetic bone disease characterized by low activity of an enzyme involved in mineralization of bony tissues, the nonspecific alkaline phosphatase (TNSALP). The enzyme replacement therapy with recombinant asfotase alfa has been approved recently. MicroRNAs (miRNAs) are small signaling molecules, which are involved in the regulation of gene expression and signaling pathways. They emerged as a novel disease biomarker, with potential application in therapy monitoring. We analyzed the levels of miRNAs of a 49-yr-old woman with childhood-onset HPP during the therapy. The patient suffered from musculoskeletal pain and non-traumatic fractures before the begin of enzyme replacement therapy. miRNAs in blood and clinical tests were performed at baseline and different timepoints. Blood levels of 6 miRNAs showed a clear graphic trend and were elevated or lowered by ≥50% units (reads per million) during the therapy. Patient-reported questionnaires showed a reduction of at least a third, reflecting clinical improvement of symptoms during the therapy. The scores of 6-MWT and CRT and hand grip also improved, signaling improvements in muscle functionality under asfotase alfa. miRNA profile changes during the therapy with asfotase alfa, accompanying improvements in functionality tests and quality of life scores. [ABSTRACT FROM AUTHOR]

Background: A balanced diet rich in calcium and protein is recommended for bone-healthy people and osteoporosis patients, but it may also be important for rare bone disease (RBD). Little data is available on RBD and diet. Therefore, the aim of this study was to evaluate the nutritional behavior of patients with RBD. Methods: This single-center, cross-sectional, questionnaire-based study assessed the nutritional behavior of RBD patients (X-linked hypophosphatemia (XLH), osteogenesis imperfecta (OI), hypophosphatasia (HPP)), osteoporosis (OPO) patients and healthy controls (CTRL). The nutritional questionnaire comprised 25 questions from seven nutritional areas. The associations between socioeconomic factors and BMI were assessed by age-adjusted univariate analysis of covariance (ANCOVA). Results: Fifty patients with RBD (17 OI, 17 HPP, 16 XLH; mean age of 48.8 ± 15.9, 26.0% male, mean BMI 26.2 ± 5.6), 51 with OPO (mean age 66.6 ± 10.0, 9.8% male, mean BMI 24.2 ± 3.9) and 52 CTRL (mean age 50.8 ± 16.3, 26.9% male, mean BMI 26.4 ± 4.7) participated. Twenty-six (52.0%) RBD, 17 (33.4%) OPO and 24 (46.1%) CTRL were overweight or obese according to BMI. Only a minority of RBD, OPO and CTRL had a daily intake of at least three portions of milk or milk products (17.3% RBD, 15.6% OPO, 11.6% CTRL, p = 0.453). In general, similar nutritional behavior was observed between the three subgroups. However, significant differences were found in caffeine consumption (p = 0.016), fruit/vegetable juice consumption (p = 0.034), portions of fish per week (p = 0.044), high-fat meals per week (p = 0.015) and consumption of salty snacks (p = 0.001). Conclusion: Nutritional counseling, controlling BMI and ensuring sufficient calcium and protein intake are crucial in patients with osteoporosis as well as in rare bone diseases. Vitamin D does not appear to be sufficiently supplied by the diet, and therefore supplementation should be considered in patients with bone diseases. [ABSTRACT FROM AUTHOR]

Osteoporosis is a widespread disease and affects over 500,000 people in Austria. Fragility fractures are associated with it and represent not only an individual problem for the patients, but also an enormous burden for the healthcare system. While trauma surgery care is well provided in Vienna, there is an enormous treatment gap in secondary prevention after osteoporotic fracture. Systematic approaches such as the Fracture Liaison Service (FLS) aim to identify patients with osteoporosis after fracture, to clarify diagnostically, to initiate specific therapy, and to check therapy adherence. The aim of this article is to describe the practical implementation and operational flow of an already established FLS in Vienna. This includes the identification of potential FLS inpatients, the diagnostic workup, and recommendations for an IT solution for baseline assessment and follow-up of FLS patients. We summarize the concept, benefits, and limitations of FLS and provide prospective as well as clinical and economic considerations for a city-wide FLS, managed from a central location. Future concepts of FLS should include artificial intelligence for vertebral fracture detection and simple IT tools for the implementation of FLS in the outpatient sector. [ABSTRACT FROM AUTHOR]

Objective miRNAs are small non-coding RNAs that control gene expression. Specific intra- and extracellular miRNA signatures have been identified in various diseases. Whether certain miRNA signatures are associated with psoriasis (PsO) and PsA is currently unknown. We aimed to search for circulating miRNA signatures associated with PsO and PsA patients. Methods Expression of miRNAs was analysed by reverse transcription quantitative real-time PCR (RT-qPCR) in the serum of PsA, PsO patients and healthy controls. Demographic and disease-specific characteristics and imaging data from hand MRI were recorded. In the discovery phase, 192 miRNA assays were analysed in 48 samples (PsA, PsO, controls: each N  = 16). For validation, 17 selected miRNAs were measured in the total population. Results A total of 141 patients and controls were analysed (51 PsA, 40 PsO, 50 controls). In the discovery phase 51 miRNAs in PsO and 64 miRNAs in PsA were down- or upregulated compared with controls, with 33 miRNAs being changed in both (adj. P  < 0.05). The 17 top candidates from discovery were assessed in the validation phase, 9 of them discriminated PsA and PsO from controls [area under the curve (AUC) ≥0.70, all P  < 0.05]. Four miRNAs (miR-19b-3p, miR-21-5p, miR-92a-3p and let-7b-5p) were significantly differently regulated between PsO and PsA. A combination of these miRNAs increased the AUC to 0.92 in multivariate regression model to discriminate PsO and PsA. Conclusion miRNA signatures in PsA and PsO patients differ from controls. Nine miRNAs were differentially regulated in PsA and PsO patients, five of them previously reported to be involved in bone and cartilage metabolism, indicating an intimate association of psoriatic inflammation and bone/cartilage changes. [ABSTRACT FROM AUTHOR]