Journal of Bone and Mineral Research

Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junctions, resulting in muscle weakness and fatigue. Muscle weakness, restricted mobility, and frequent use of corticosteroids in patients with MG may predispose them to a higher risk of fractures. However, studies on the impact of MG on bone health and the associated fracture risk are scarce. Utilizing claim database of the Korean National Health Insurance Service collected between 2002 and 2020, we compared the risk of major osteoporotic fracture between 23 118 patients with MG and 115 590 individuals as an age- and sex-matched control group using multivariable Cox proportional hazard models...

Osteoporosis is characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-related bone formation, particularly increased osteoclastogenesis. However, the mechanisms by which epigenetic factors regulate osteoclast precursor differentiation during osteoclastogenesis remain poorly understood. Here, we show that the specific knockout of the chromatin remodeling factor Arid1a in bone marrow-derived macrophages (BMDMs) results in increased bone mass. The loss of Arid1a in BMDM inhibits cell-cell fusion and maturation of osteoclast precursors, thereby suppressing osteoclast differentiation...

Population-based epidemiological studies on post-acute phase COVID-19-related fractures in older adults are lacking. This study aims to examine the risk of incident major osteoporotic fractures following COVID-19 infection among individuals aged ≥50, compared to individuals without COVID-19. It was a retrospective, propensity-score matched, population-based cohort study of COVID-19 patients and non-COVID individuals identified from the electronic database of the Hong Kong Hospital Authority from January 2020 to March 2022...

Lipid metabolism plays a crucial role in maintaining bone homeostasis, particularly in osteoclasts (OCs) formation. Here, we found the expression level of FATP2, a transporter for long-chain and very-long-chain fatty acids, was significantly upregulated during OC differentiation and in the bone marrow of mice fed a high-fat diet (HFD). Notably, the use of FATP2 siRNA or a specific inhibitor (Lipofermata) resulted in significant inhibition of OC differentiation while only slightly affecting osteoblasts (OBs)...

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Two months after her first pregnancy, a 35-year-old exclusively breastfeeding woman bent to move her baby in the car seat and experienced sudden, severe pain from five spontaneous vertebral compression fractures. Genomic screen was negative but she had mild ankylosing spondylitis previously well controlled on Etanercept. She was vegetarian with a high phytate intake. A lactation consultant had advised her to pump and discard milk between feeds, such that she believed she produced twice as much milk as her baby ingested...

Ablation of Cyp27b1 eliminates calcitriol but does not disturb fetal mineral homeostasis or skeletal development. However, independent of fetal genotypes, maternal loss of Cyp27b1 altered fetal mineral and hormonal levels compared to offspring of WT dams. We hypothesized that these maternal influences would alter postnatal skeletal development. Cyp27b1 null and WT females were mated to bear only Cyp27b1+/- offspring. 48 hrs after birth, pups were cross-fostered to dams of the same or opposite genotype that bore them...

INTRODUCTION: The continued development of high-resolution peripheral quantitative computed tomography (HR-pQCT) has led to a second-generation scanner with higher resolution and longer scan region. However, large multi-center prospective cohorts were collected with first-generation HR-pQCT and have been used to develop bone phenotyping and fracture risk prediction (μFRAC) models. This study establishes whether there is sufficient universality of these first-generation trained models for use with second-generation scan data...

Healthy alveolar bone is the cornerstone of oral function and oral treatment. Alveolar bone is highly dynamic during the entire lifespan and is affected by both systemic and local factors. Importantly, alveolar bone is subjected to unique occlusal force in daily life, and mechanical force is a powerful trigger of bone remodeling, but the effect of occlusal force in maintaining alveolar bone mass remains ambiguous. In this study, the Piezo1 channel is identified as an occlusal force sensor. Activation of Piezo1 rescues alveolar bone loss caused by a loss of occlusal force...

Fracture risk increases with lower areal BMD (aBMD); however, aBMD-related estimate of risk may decrease with age. This may depend on technical limitations of 2-dimensional (2D) DXA which are reduced with 3D high-resolution peripheral quantitative computed tomography (HR-pQCT). Our aim was to examine whether the predictive utility of HR-pQCT measures with fracture varies with age. We analyzed associations of HR-pQCT measures at the distal radius and distal tibia with two outcomes: incident fractures and major osteoporotic fractures...

Osteoporosis is the most common metabolic bone disease in the world, which increases the healthcare service burden. Recent studies have linked higher white matter hyperintensities (WMH) to reduced bone mineral density (BMD), increasing the risk of fractures and falls in older adults. However, limited evidence exists regarding the dose-response relationship between WMH and bone health in a larger and younger population. Our study aimed to examine the association of WMH volume with BMD, incident fractures and falls, with a particular focus on dose-response relationship with varying levels of WMH volume...

Single case studies of extraordinary disease resilience may provide therapeutic insight into conditions for which no definitive treatments exist. An otherwise healthy 35-year-old man (patient-R) with the canonical pathogenic ACVR1R206H variant and the classic congenital great toe malformation of fibrodysplasia ossificans progressiva (FOP) had extreme paucity of post-natal heterotopic ossification (HO) and nearly normal mobility. We hypothesized that patient-R lacked a sufficient post-natal inflammatory trigger for HO...

Romosozumab treatment in women with postmenopausal osteoporosis increases bone formation while decreasing bone resorption, resulting in large BMD gains to reduce fracture risk within 1 year. DXA-based 3D modeling of the hip was used to assess estimated changes in cortical and trabecular bone parameters and map the distribution of 3D changes in bone parameters over time in patients from two randomized controlled clinical trials: FRAME (romosozumab vs placebo followed by denosumab) and ARCH (romosozumab vs alendronate followed by alendronate)...

The purpose of this study was to investigate the prevalence of three sarcopenia definitions and their associations with fracture risk in a population of older Swedish women when adjusted for FRAX-based risk factors. 2883 women 77.8 years (mean) old were included. Sarcopenia was defined based on the Sarcopenia Definitions and Outcomes Consortium (SDOC; low handgrip strength and gait speed), revised European Working Group on Sarcopenia in Older People (EWGSOP2; low appendicular lean mass index (ALM, appendicular lean mass/height (kg/m2)), and hand grip strength (kg)) and Asian Working Group for Sarcopenia (AWGS; low ALM, and hand grip strength (kg)) definition...

Bone histomorphometric endpoints in transilial biopsies may be associated with increased risk of atypical femoral fracture (AFF) in patients with osteoporosis who take antiresorptives, including bisphosphonates (BP). One way to test this hypothesis is to evaluate bone histomorphometric endpoints in age-, gender-, and treatment time matched patients who either had AFF or did not have AFF. In this study, we performed trans-iliac bone biopsies in 52 white postmenopausal women with (n = 20) and without (n = 32) AFFs, all of whom had been treated for osteoporosis continuously with alendronate for 4 to 17 years...

Rebound bone loss following denosumab discontinuation is an important clinical challenge. Current treatment strategies to prevent this fail to suppress the rise and overshoot in osteoclast-mediated bone resorption. In this present study, we use a murine model of denosumab treatment and discontinuation to show the temporal changes in osteoclast formation and activity during RANKL inhibition and withdrawal. We show that the cellular processes that drive the formation of osteoclasts and subsequent bone resorption following withdrawal of RANKL inhibition precede the rebound bone loss...

Fracture risk is high in chronic kidney disease (CKD) and underlying pathophysiology and risk factors may differ from the general population. In a cohort study of 3939 participants in the Chronic Renal Insufficiency Cohort (CRIC), we used Cox regression to test associations of putative risk factors with the composite of first hip or vertebral fracture assessed using hospital discharge codes. Mean age was 58 years, 45% were female, 42% were Black, and 13% were Hispanic. There were 82 hip and 24 vertebral fractures over a mean (SD) 11...

Mutations in the Chromodomain helicase DNA-binding protein 7 - coding gene (CHD7) cause CHARGE syndrome (CS). Although craniofacial and skeletal abnormalities are major features of CS patients, the role of CHD7 in bone and cartilage development remain largely unexplored. Here, using a zebrafish (Danio rerio) CS model, we show that chd7-/- larvae display abnormal craniofacial cartilage development and spinal deformities. The craniofacial and spine defects are accompanied by a marked reduction of bone mineralization...

Observational studies have reported inconsistent associations between bone mineral density (BMD) and coronary artery calcification (CAC). We examined the observational association of BMD with CAC in two large population-based studies and evaluated the evidence for a potential causal relation between BMD and CAC using polygenic risk scores (PRS), 1- and 2-sample Mendelian randomization (MR) approaches. Our study populations comprised 1414 individuals (mean age 69.9 years, 52.0% women) from the Rotterdam Study and 2233 individuals (mean age 56...

This study aimed to enhance the fracture risk prediction accuracy in major osteoporotic fractures (MOF) and hip fractures (HF) by integrating genetic profiles, machine learning (ML) techniques, and Bayesian optimization. The Genetic Risk Score (GRS), derived from 1103 risk single nucleotide polymorphisms (SNPs) from GWAS, was formulated for 25 772 postmenopausal women from the Women's Health Initiative dataset. We developed four ML models: Support Vector Machine (SVM), Random Forest, XGBoost, and Artificial Neural Network (ANN) for binary fracture outcome and ten-year fracture risk prediction...