Bone

The low vertebral bone computed tomography (CT) Hounsfield unit values measured on CT scans reflect low bone mineral density (BMD) and are known as diagnostic indicators for osteoporosis. The potential prognostic significance of low BMD defined by vertebral bone CT values for the coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to assess the impact of BMD on the clinical outcome in Japanese patients with COVID-19 and evaluate the association between BMD and critical outcomes, such as high-flow nasal cannula, non-invasive and invasive positive pressure ventilation, extracorporeal membrane oxygenation, or death...

The present study aimed to establish and evaluate a preclinical model of steroid-associated osteonecrosis (SAON) in mice. Sixteen 24-week-old male C57BL/6 mice were used to establish SAON by two intraperitoneal injections of lipopolysaccharide (LPS), followed by three subcutaneous injections of methylprednisolone (MPS). Each injection was conducted on working day, with an interval of 24 h. Six cycles of injections were conducted. Additional twelve mice (age- and gender-matched) were used as normal controls...

BACKGROUND: Clinical concerns about preventing and managing fractures after spinal cord injury (SCI) have been growing. OBJECTIVE: This study investigates the risk of fractures among SCI patients according to the presence of disability, disease severity, and level of injury. METHODS: We performed a retrospective cohort study using the Korean National Health Insurance Service (KNHIS 2010-2018) database. We included 5190 SCI patients and 1:3 age- and sex-matched control participants...

Mechanical properties are becoming fundamental for advancing the comprehension of cellular processes. This study addresses the relationship between viscoelastic properties and the cellular mineralization process. Osteoblast-like cells treated with an osteogenic medium were employed for this purpose. Additionally, the study explores the impact of hydroxyapatite (HA) and hydroxyapatite/silver (HA/Ag) composite on this process. AFM relaxation experiments were conducted to extract viscoelastic parameters using the Fractional Zener (FZ) and Fractional Kelvin (FK) models...

INTRODUCTION: Patients with chronic kidney disease (CKD) are at an alarming risk of fracture compared to age and sex-matched non-CKD individuals. Clinical and preclinical data highlight two key factors in CKD-induced skeletal fragility: cortical porosity and reduced matrix-level properties including bone hydration. Thus, strategies are needed to address these concerns to improve mechanical properties and ultimately lower fracture risk in CKD. We sought to evaluate the singular and combined effects of mechanical and pharmacological interventions on modulating porosity, bone hydration, and mechanical properties in CKD...

PURPOSE: Bone is susceptible to fluctuations in iron homeostasis, as both iron deficiency and overload are linked to poor bone strength in humans. In mice, however, inconsistent results have been reported, likely due to different diet setups or genetic backgrounds. Here, we assessed the effect of different high and low iron diets on bone in six inbred mouse strains (C57BL/6J, A/J, BALB/cJ, AKR/J, C3H/HeJ, and DBA/2J). METHODS: Mice received a high (20,000 ppm) or low-iron diet (~10 ppm) after weaning for 6-8 weeks...

The healing of bone fractures can become aberrant and lead to nonunions which in turn have a negative impact on patient health. Understanding why a bone fails to normally heal will enable us to make a positive impact in a patient's life. While we have a wealth of molecular data on rodent models of fracture repair, it is not the same with humans. As such, there is still a lack of information regarding the molecular differences between normal physiological repair and nonunions. This study was designed to address this gap in our molecular knowledge of the human repair process by comparing differentially expressed genes (DEGs) between physiological fracture callus and two different nonunion types, hypertrophic (HNU) and oligotrophic (ONU)...

PURPOSE: Mitofusin 2 (Mfn2) is one of two mitofusins involved in regulating mitochondrial size, shape and function, including mitophagy, an important cellular mechanism to limit oxidative stress. Reduced expression of Mfn2 has been associated with impaired osteoblast differentiation and function and a reduction in the number of viable osteocytes in bone. We hypothesized that the genetic absence of Mfn2 in these cells would increase their susceptibility to aging-associated metabolic stress, leading to a progressive impairment in skeletal homeostasis over time...

Overgrowth and intellectual disability disorders in humans are typified by length/height and/or head circumference ≥ 2 standard deviations above the mean as well as intellectual disability and behavioral comorbidities, including autism and anxiety. Tatton-Brown-Rahman Syndrome is one type of overgrowth and intellectual disability disorder caused by heterozygous missense mutations in the DNA methyltransferase 3A (DNMT3A) gene. Numerous DNMT3A mutations have been identified in Tatton-Brown-Rahman Syndrome patients and may be associated with varying phenotype severities of clinical presentation...

The skeleton serves as a supportive and protective organ for the body. As individuals age, their bone tissue undergoes structural, cellular and molecular changes, including the accumulation of senescent cells. Extracellular vesicles (EVs) play a crucial role in aging through the cellular secretome and have been found to induce or accelerate age-related dysfunction in bones and to contribute further via the circulatory system to the aging of phenotypes of other bodily systems. However, the extent of these effects and their underlying mechanisms remain unclear...

PURPOSE: Human evidence on the association between oxidative stress and osteoporosis is inconsistent. Fluorescent Oxidation Products (FlOPs) are global biomarkers of oxidative stress. We examined the associations of FlOPs (excitation/emission wavelengths 320/420 nm for FlOP_320, 360/420 nm for FlOP_360, and 400/475 nm for FlOP_400) with osteoporosis, bone microstructure, and bone turnover markers in humans and rats. METHODS: In humans, we conducted a 1:2 age, sex, hospital, and specimen-matched case-control study to test the association between FlOPs and osteoporosis diagnosed from dual-energy X-ray absorptiometry...

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent and incapacitating condition that affects the hip joint. Unfortunately, early diagnostic and treatment measures are limited. METHODS: Our study employed Tandem Mass Tag (TMT) labeling mass spectrometry (MS)-based quantitative proteome to compare the proteins of femoral head tissues in patients with SONFH with those of patients who sustained femoral neck fracture (FNF). We investigated the level and effects of glucose transporter member 1 (GLUT1) in SONFH patients and MC3T3-E1 cells and examined the function and molecular mechanism of GLUT1 in the context of SONFH using in vivo and in vitro approaches...

Hydroxyapatite [HA, Ca10 (PO4 )6 (OH)2 ], with its robust biocompatibility and bioactivity, has found extensive utility in bone grafting, replacement therapies, and supplemental medical materials. HA is highly regarded for its osteoconductive properties because it boasts hydrophilicity, nontoxicity, non-allergenicity, and non-mutagenicity. Nevertheless, HA's intrinsic mechanical weakness has spurred efforts to enhance its properties. This enhancement is achieved through ion incorporation, with elements such as magnesium, zinc, lithium, strontium, boron, and others being integrated into the HA structure...

INTRODUCTION: Massive bone allografts enable the reconstruction of critical bone defects in numerous conditions (e.g. tumoral, infection or trauma). Unfortunately, their biological integration remains insufficient and the reconstruction may suffer from several postoperative complications. Perfusion-decellularization emerges as a tissue engineering potential solution to enhance osseointegration. Therefore, an intrinsic vascular study of this novel tissue engineering tool becomes essential to understand its efficacy and applicability...

Most postmenopausal women who sustain fragility fracture (Fx) have their areal bone mineral density (aBMD) above the osteoporosis threshold. A sizeable proportion of them have normal aBMD. The aim of this study was to prospectively investigate the association of fragility Fx with bone microarchitecture (MA) assessed by high resolution peripheral computed tomography (HR-pQCT) in postmenopausal women without low BMD. At the 14th annual follow-up of the OFELY study, we have measured bone MA at the distal radius and tibia with HR-pQCT in addition to areal BMD with DXA, in 586 postmenopausal women...

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Bone Health Index (BHI) has been proposed as a useful instrument for assessing bone health in children. However, its relationship with fracture risk remains unknown. We aimed to investigate whether BHI is associated with bone mineral density (BMD) and prevalent fracture odds in children from the Generation R Study. We also implemented genome-wide association study (GWAS) and polygenic score (PGS) approaches to improve our understanding of BHI and its potential. In total, 4150 children (49.4 % boys; aged 9...

INTRODUCTION: Osteogenesis imperfecta (OI) is a congenital disease comprising a heterogeneous group of inherited connective tissue disorders. The main treatment in children is bisphosphonate therapy. Previous animal studies have shown that bisphosphonates delay tooth eruption. The aim of this study is to determine whether patients with OI treated with pamidronate and/or zoledronic acid have a delayed eruption age compared to a control group of healthy children. METHODS: An ambispective longitudinal cohort study evaluating the age of eruption of the first stage mixed dentition in a group of children with OI (n = 37) all treated with intravenous bisphosphonates compared with a group of healthy children (n = 89)...

The high occurrence of distal fibula fractures among older women suggests a potential link to impaired bone health. Here we used a multiscale imaging approach to investigate the microarchitecture, mineralization, and biomechanics of the human distal fibula in relation to age and sex. Microcomputed tomography was performed to analyze the local volumetric bone mineral density and various microstructural parameters of the trabecular and the cortical compartment. Bone mineral density distribution and osteocyte lacunar parameters were quantified using quantitative backscattered electron imaging in periosteal, endocortical and trabecular regions...

BACKGROUND: The use of proton pump inhibitors (PPIs) has been associated with an increased fracture risk in observational studies. However, the reported association between PPI use and bone mineral density (BMD), bone microarchitecture, and bone strength is inconsistent. This study aims to assess the association between PPI use and bone microarchitecture and strength using high-resolution peripheral quantitative CT (HR-pQCT) in a three-year follow-up study in patients with a recent fracture visiting the Fracture Liaison Service (FLS)...