Circulating miRNAs in bone health and disease

microRNAs have evolved as important regulators of multiple biological pathways essential for bone homeostasis, and microRNA research has furthered our understanding of the mechanisms underlying bone health and disease. This knowledge, together with the finding that active or passive release of microRNAs from cells into the extracellular space enables minimal-invasive detection in biofluids (circulating miRNAs), motivated researchers to explore microRNAs as biomarkers in several pathologic conditions, including bone diseases. Thus, exploratory studies in cohorts representing different types of bone diseases have been performed. In this review, we first summarize important molecular basics of microRNA function and release and provide recommendations for best (pre-)analytical practices and documentation standards for circulating microRNA research required for generating high quality data and ensuring reproducibility of results. Secondly, we review how the genesis of bone-derived circulating microRNAs via release from osteoblasts and osteoclasts could contribute to the communication between these cells. Lastly, we summarize evidence from clinical research studies that have investigated the clinical utility of microRNAs as biomarkers in musculoskeletal disorders. While previous reviews have mainly focused on diagnosis of primary osteoporosis, we have also included studies exploring the utility of circulating microRNAs in monitoring anti-osteoporotic treatment and for diagnosis of other types of bone diseases, such as diabetic osteopathy, bone degradation in inflammatory diseases, and monogenetic bone diseases.Peer reviewe

Metabolic Bone Diseases—A Topic of Great Diversity

The progress in research has improved the understanding of the epidemiology and pathogenesis of osteoporosis and bone disorders in general [...

Bone microarchitecture deteriorations and a fragility fracture in a patient with beta and alpha heterozygous thalassemia : a case report

To date there are few studies that have investigated bone mineral density (BMD) and markers of bone metabolism in patients with thalassemia minor form. None of the previous trials presented bone structure analysis in the patient populations. We present the case of a 24-year-old Turkish woman with heterozygous beta and alpha thalassemia who sustained a low-trauma fracture of the inferior pubic ramus. Despite normal markers of bone metabolism, the dual Xray absorptiometry (DXA) showed decreased areal bone mineral density. Furthermore, severely reduced bone structure parameters and reduced volumetric bone mineral density was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Due to these diagnostic findings at time of peak bone mass, an osteoanabolic therapy with teriparatide for 24 months was initiated. The findings concerning BMD and bone structure in this patient can be seen as caused by the beta and alpha thalassemia.(VLID)352460

Differences in bone structure between rheumatoid arthritis and psoriatic arthritis patients relative to autoantibody positivity

Objective: To investigate whether trabecular and cortical bone structure differ between patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). So far, no study has performed a detailed comparative analysis of bone structure in patients with RA and PsA. Methods: 110 patients (60 RA, 50 PsA) received high-resolution peripheral quantitative CT of the distal radius. Demographic and disease-specific parameters including anti-rheumatic treatment, bone erosion status and previous fractures were recorded. Results: RA and PsA patients were comparable in age, gender, body mass index, disease duration, disease activity, functional status, antirheumatic treatment and bone erosion status. No significant differences were found for volumetric bone mineral density (BMD), including total BMD (300±77 vs 316±62 mgHA/cm3), trabecular BMD (152±46 vs 165±40 mgHA/cm3) and cortical BMD (787±113 vs 818±76 mgHA/cm3) when comparing RA patients to PsA patients, respectively. However, in contrast to seronegative RA, seropositive RA showed significantly reduced trabecular BMD (p=0.007), bone volume per tissue volume (p=0.007) and trabecular number (p=0.044), as well as a strong trend towards higher trabecular inhomogeneity compared to PsA patients. In the regression analysis, higher age, female gender and presence of autoantibodies were independently associated with trabecular bone loss. Conclusions: Seropositive RA exhibits more profound changes in trabecular bone architecture than seronegative RA or PsA. The data support the concept that seropositive RA is a disease entity that is distinct from seronegative RA and PsA

Hipofosfatemia sprzężona z chromosomem X. Postępowanie ortopedyczne w środowisku multidyscyplinarnym

X-linked hypophosphatemia is a rare disorder of bone metabolism caused by inactivating mutations in the PHEX. Conservative therapies such as treatment with phosphate salts or FGF23-inhibiting antibodies can improve symptoms, the latter being superior to the healing of rickets. Recent studies show a high burden of disease of children and adults with XLH. Orthopedic surgeons should be aware that lower limb deformity in early childhood can present as the first symptom of XLH and should prompt further diagnostics and treatment. Treatment needs to be coordinated with pediatric endocrinologists. The optimal and adequate planning of orthopedic interventions seem to be key factors which may lead to a satisfactory result.Hipofosfatemia sprzężona z chromosomem X (XLH) jest rzadkim zaburzeniem metabolizmu kości powodowanym przez mutacje inaktywujące gen PHEX. Leczenie zachowawcze, np. leczenie solami fosforanowymi lub przeciwciałami hamującymi FGF23, może złagodzić objawy, przy czym te ostatnie są lepsze pod kątem leczenia krzywicy. Ostatnie badania wskazują na duże obciążenie chorobą dzieci i dorosłych z XLH. Chirurdzy ortopedzi powinni być świadomi, że deformacja kończyn dolnych we wczesnym dzieciństwie może być pierwszym objawem XLH i powinna skłaniać do dalszej diagnostyki i leczenia. Leczenie musi być prowadzone we współpracy z endokrynologami dziecięcymi. Optymalne i adekwatne zaplanowanie interwencji ortopedycznych wydaje się stanowić kluczowy czynnik, który może prowadzić do osiągnięcia satysfakcjonującego wyniku

Pelvic Fractures—An Underestimated Problem? Incidence and Mortality Risk after Pelvic Fracture in Austria, 2010–2018

(1) Background: Pelvic fractures (PFs) are related to osteoporosis, and represent a serious individual and socioeconomic burden. (2) Methods: We examined age- and sex-standardised incidence rates (SIRs) of PF, along with rates of all-cause overall and one-year mortality among patients with PF. We compared the mortality rates between PF patients and a matched fracture-free cohort. Patients ≥50 years old in Austria hospitalised with PF in 2010–2018, along with their dates of death, were recorded. (3) Results: We identified 54,975 patients with PF, of whom 70.9% were women. Between 2010 and 2018 the SIR of PF increased in men by 10.0%—from 125.3 (95% Confidence Interval 118.9–132.0) to 137.8 (95% CI 131.8–144.0) per 100,000—and in women by 2.7%—from 218.7 (95% CI 212.0–225.6) to 224.7 (95% CI 218.3–231.3) per 100,000. The one-year post-PF mortality rate was higher in men than in women (13.0% and 11.1%, respectively; p < 0.001). Pelvic fracture patients aged ≥65 had an elevated mortality risk (Hazard Ratio 1.75, 95% CI 1.71–1.79, p < 0.001) compared to controls. (4) Conclusions: There is a clear increase in the incidence of PF in the elderly population, with a greater increase in men over time. Pelvic fracture itself contributes to increased mortality in individuals aged 65 and above

Impact of Tenofovir Disoproxil‐Induced Fanconi Syndrome on Bone Material Quality: A Case Report

ABSTRACT Tenofovir is a nucleotide analog reverse‐transcriptase inhibitor (NtARTI) used for treatment of chronic hepatitis B and human immunodeficiency virus (HIV). Fanconi syndrome (FS) is a condition affecting the proximal tubules of the kidney, leading to increased passage and impaired reabsorption of various small molecules such as glucose, phosphate, bicarbonate, and amino acids. Tenofovir disoproxil fumarate (TDF) is one of two pro‐drugs of tenofovir associated with a greater nephrotoxicity and renal complications such as FS with subsequent osteomalacia, acute kidney injury, and reduction of glomerular filtration rate (GFR) compared with tenofovir alafenamide (TAF). We present the case of a 33‐year‐old white woman treated with TDF because of chronic hepatitis B infection suffering four atraumatic fractures over the period of 2 years. The patient was taken off the TDF regimen 3 months before presentation. Initial blood and urine samples suggested the presence of TDF‐induced osteomalacia, which was confirmed by transiliac bone biopsy and histomorphometry. Moreover, bone mineral density distribution (BMDD) by quantitative backscattered electron imaging (qBEI) analysis showed that approximately 56% of the bone surface was normally mineralized and 44% showed a reduced mineralization consistent with the presence of osteomalacia. The patient made a significant recovery upon cessation of the causative agent. This case report emphasizes the use of bone biopsy, histomorphometry and qBEI in confirming the diagnosis of drug‐induced Fanconi syndrome and associated osteomalacia. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research