Calcified Tissue International最新文献

Excessive phosphate used as flavor enhancers and preservatives in processed foods can exacerbate cardiovascular and kidney diseases. In clinical and pre-clinical studies, chronic (over 52 weeks) high-phosphate diet (HPD) negatively affects bone health. We previously demonstrated that 12-week-HPD decreases exercise capacity and skeletal muscle metabolism in adult male mice; however, alteration of bone characteristics associated with HPD independent of disease complications is not well-characterized. Thus, we determined the effects of shorter-term-HPD on characteristics of mouse femurs and mandibles. Adult male mice were fed a normal phosphate diet (NPD) or HPD for 18 weeks, serum markers of mineral metabolism and bone formation and resorption were quantified in femurs, and histological analysis was performed on tibias. Volumetric, mineral density, and morphology parameters of femurs and mandibles were determined using micro-computed tomography, and dynamic mechanical analysis and fracture testing of the femur were conducted. Our studies revealed that 18-week-HPD significantly reduced bone quality (tissue mineral density (TMD) and cortical thickness) without changing bone quantity (total mineral content and volume) of both femurs and mandibles, and femur mechanical properties were aggravated increasing the risk of fracture. Serum markers of osteoclastic resorption and osteoblastic formation were increased with HPD, indicating active osteoclastic bone resorption and osteoblastic new bone formation. These findings provide detailed information on how excessive dietary phosphate substantially alters characteristics of bone, resulting in bone weakening.

Rheumatoid arthritis (RA) has a higher risk of fractures that is often neglected. We determined the prevalence and risk factors for fractures in women with longstanding RA. Consecutive women with RA from a tertiary hospital underwent bone densitometry (DXA) and spine radiography with morphometric analysis. Disease characteristics, activity, and medication use were assessed. Logistic and linear regression analyses identified risk factors for osteoporosis and fractures. The study included 179 women with RA aged 65.1 ± 9.7 years with a median disease duration of 21 (12.5) years (72% positive for rheumatoid factor). Glucocorticoid (GC), csDMARDs, b/tsDMARDs use, and current moderate-to-high disease activity were observed in 26.3%, 92.7%, 58.6%, and 45.3% of the patients, respectively. Densitometric osteoporosis and fractures were found in 43.6% and 28.5% of the patients, respectively. Fractures were observed in 51 patients (28.5%), primarily occurring at the spine (N = 43) and forearm (N = 10). Almost half of the patients with fractures (N = 24) had a BMD T-score greater than - 2.5. BMI (OR 0.916; 95%CI 0.854-0.983; P = 0.015) and smoking load (OR 1.023; 95%CI 1.002-1.044; P = 0.032) were predictors for osteoporosis, while cumulative 5-year disease activity (OR 3.474; 95%CI 1.557-7.751; P = 0.002) and total femur T-score (OR 0.646; 95%CI 0.436-0.956; P = 0.029) were predictors of fractures. Current GC dose and femoral neck T-score were predictors of spinal deformity index (R² = 0.108; P < 0.001). Almost half of the women with longstanding RA presenting with fractures had BMD values above the osteoporotic range. Moderate-to-high cumulative 5-year disease activity, GC use, and lower BMD at the proximal femur were risk factors for fractures.

Bone fractures, especially in the elderly, are increasing, posing challenges to healthcare systems. Traditional treatment often focuses merely on bone repair and overlooks the overall healing environment. Peripheral magnetic stimulation (PMS), a non-invasive method, shows promise for bone regeneration. In our murine femoral fracture model study, male C57BL6/J mice were divided into a control group and three PMS treatment groups (10, 50, and 100 Hz). After a fracture, the mice received 30-min daily PMS sessions. The pain was monitored weekly using the von Frey test. Micro-computed tomography (μCT), biomechanics, and histology evaluated bone healing. Our results have shown that 10 and 100 Hz PMS significantly reduced pain and promoted early callus formation by speeding up early mineralized callus. After 4 weeks, the 10 Hz PMS improved mechanical strength, and the 10 and 100 Hz PMS increased bone mineral density. Histology revealed more cartilage, new bone formation, and enhanced osteoblast activity. PMS also decreased fibrous tissue, indicating better bone remodeling. The staining results confirmed that PMS promoted early cartilage formation, endochondral ossification, and increased vascular density. These findings suggest that PMS at 10 and 100 Hz accelerates endochondral ossification, enhances bone formation, and improves biomechanical strength, demonstrating its potential application value in fracture treatment.

Persistent low serum alkaline phosphatase (ALP) levels are crucial in identifying genetic disorders such as hypophosphatasia (HPP). This study investigates the causes of low ALP levels in children, aiming to evaluate the demographic and clinical characteristics of those diagnosed with HPP.We evaluated 2243 children and adolescents, ranging from 0 to 19 years old between September 2019 and July 2024, who exhibited at least two ALP levels below the age- and gender-specific lower limit.In the patient group, 95.4% (2140 patients) exhibited transient low ALP levels, while 4.6% (103 patients) showed persistently low levels. In the persistent group, eleven additional medical conditions were identified, excluding HPP, with calorie depletion (anorexia, malnutrition) being the most common cause. The study identified 16 HPP patients (10 females, 6 males) with high phenotypic variability even within the same variants, comprising 0.71% of the whole group. Genetic testing identified 13 pathogenic/likely pathogenic ALPL gene variants (10 heterozygous, 3 homozygous), two of which were novel. Among HPP patients, 56.2% presented with HPP-related symptoms, most commonly short stature. We found a significant negative correlation between total ALP and serum pyridoxal phosphate (PLP) levels (Rho = - 0.55, p = 0.039), but no correlation with urine phosphoethanolamine.Persistently low ALP levels are a vital clinical indicator for a wide range of disorders, especially HPP. This study expands the phenotypic and genotypic profiles of HPP while improving our understanding of the disease in children. Increasing disease awareness, particularly for milder forms, is essential to avoid delayed diagnosis.

The changes in bone mineral density (BMD), bone structure, and bone size at the proximal humerus with aging, which can lead to fragile fractures in men, are not well understood. This study aimed to investigate age-related changes in the skeletal properties of the surgical neck of the humerus in men. We conducted a cross-sectional cohort study involving 193 Chinese men, divided into three age groups: Group I (20-50 years), Group II (51-64 years), and Group III (≥ 65 years). Bone mass, structure, and geometric properties were evaluated using quantitative computed tomography (QCT). Bone mineral density at the surgical neck showed the strongest negative correlation with age. However, cortical thickness did not significantly correlate with age. Medullary diameter, perimeter, and area increased by 2.68%, 2.72%, and 5.68% per decade, respectively. Periosteal expansion was evidenced by a 2.77%, 2.80%, and 5.57% per decade increase in periosteal diameter, perimeter, and total area. Significant differences in periosteal and medullary parameters were observed between age groups. Section modulus and second moments of area exhibited significant linear associations with age. Notably, these indices did not differ significantly between men aged 20-30 years and those over 80 years. Cortical thickness and periosteal diameter were most strongly associated with section modulus and second moments of area. The study demonstrated that periosteal expansion progresses with aging, paralleling the decline in BMD. Importantly, geometry-related bending and torsion resistance of the surgical neck were not significantly diminished in older men.

Physical activity (PA) and sedentary behavior (SB) are two key lifestyle factors with profound implications for bone health across the lifespan. While PA is recognized for its positive effects on bone mineral density (BMD) and fracture prevention, emerging evidence highlights the detrimental consequences of prolonged sedentary time, independent of PA levels. This review synthesizes current knowledge on the impact of PA and SB on bone health outcomes, focusing on BMD and fracture risk in children, adolescents, adults, and older populations. A selection of epidemiological studies, systematic reviews, and meta-analyses was analyzed to explore the associations between movement behaviors and bone health indicators across different life stages. Particular attention was given to studies objectively measuring SB and PA and to the substitution effects of sedentary time with light or moderate-to-vigorous PA. In children and adolescents, higher levels of SB are associated with lower BMD, particularly at weight-bearing sites, while participation in weight-bearing and impact-loading PA positively influences bone mass accrual. In adults and older individuals, regular PA, including moderate-to-vigorous intensity weight-bearing PA and resistance training activities, is consistently linked to greater BMD and reduced fracture risk. Conversely, high sedentary time is associated with lower BMD and increased fracture incidence, particularly among frail or pre-frail individuals. Importantly, replacing sedentary time with even light-intensity PA yields measurable benefits for bone health, particularly among older adults and postmenopausal women, and may contribute to a reduced risk of fractures, although evidence remains limited. Promoting PA while minimizing SB should be central to clinical practice and public health policies aimed at maximizing and preserving skeletal health and preventing osteoporotic fractures, across the lifespan. Early intervention, continuous promotion across life stages, and adherence to WHO guidelines offer an effective, evidence-based framework for lifelong bone health maintenance.

Alterations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been associated with primary osteoporosis, leading to recurrent low-trauma fractures. Heterozygous carriers typically show a milder phenotype, with reduced bone mass starting in early childhood. In this paper, we described the clinical features and therapeutic outcomes of a cohort of 7 children (5 males) harboring different variants in the LPR5 gene. Eight heterozygous variants of the LRP5 gene were identified (6 missense, 2 nonsense), two of which were likely pathogenic. One male patient was compound heterozygous, carrying two different variants, including p.(Arg570Gln), previously reported as pathogenic in homozygous form, and exhibited a more severe phenotype consistent with Osteoporosis-Pseudoglioma Syndrome, including vitreoretinal abnormalities. At initial presentation, most patients had a history of low-trauma long bone fractures, or spontaneous vertebral fractures, and bone/joint pain. Five of them received bisphosphonate therapy and one patient also received denosumab. No new fractures occurred during follow-up (9 months-4 years). Bone mineral density (BMD) increased in all patients (3-103%, mean: 55%), and partial vertebral reshaping was described. No adverse effects were reported. This pediatric case series highlights the phenotypic variability of LRP5 gene variants, and underscores the efficacy of bisphosphonate therapy in improving BMD and reducing fracture risk. However, while bisphosphonates remain the standard of care, further research is needed on precision therapies that target Wnt signaling and other pathways affected by LRP5 gene alterations.

Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by low parathyroid hormone (PTH) levels, hypocalcemia, hyperphosphatemia, reduced active vitamin D (1,25-OH2 vitamin D), and hypercalciuria. Due to its rarity, non-specialized physicians often lack experience managing HypoPT. To address this, expert consensus statements were developed for the DACH region (Germany, Austria, Switzerland), considering regional differences and high HypoPT incidence. These statements aim to enhance adherence to guideline recommendations and improve non-specialist knowledge. From December 2023 to April 2024, three rounds of a Delphi consensus survey were conducted with seven DACH-region clinical experts. Consensus was defined as agreement among at least 6 of 7 participants (85%). Experts agreed surgery accounts for 90% of chronic HypoPT cases. Common symptoms include paresthesia, muscle cramps, and fatigue. Albumin-adjusted serum calcium should be measured 12-24 h post-surgically, within 2 weeks, and every 3-6 months thereafter. Key treatment goals are maintaining albumin-adjusted serum calcium in the lower normal range, symptom control, and quality of life. Long-term objectives include avoiding hypo- and hypercalcemia phases and disease-related complications. Failure of calcium and active vitamin D therapy is defined by persistent symptoms, hospitalization, laboratory values outside of the normal range, or medication intolerance. Experts emphasized using HypoPT-specific, validated quality-of-life questionnaires. This consensus provides practical guidance for non-specialists in diagnosing, treating, and monitoring HypoPT, improving care in German-speaking regions.

Heterotopic ossification (HO) frequently occurs after procedures such as hip replacements, acetabular fractures, and elbow fractures. While radiotherapy (RT) has been a longstanding preventive measure against HO, its efficacy remains controversial, with some studies questioning its effectiveness and noting potential side effects. Previous research has predominantly focused on total hip arthroplasty (THA), leading to a gap in comprehensive evaluation of RT's efficacy and safety across other conditions. This systematic review and meta-analysis were conducted strictly adhering to PRISMA guidelines, utilizing the PICO framework to critically assess randomized clinical trials. A thorough literature search was executed across PubMed, Embase, Cochrane Library, and Web of Science). Methodological integrity was ensured through structured data extraction and quality assessment using validated criteria. The protocol was prospectively registered with INPLASY, ensuring full methodological transparency. A total of seven studies with 933 patients were included in the analysis, comprising 594 patients receiving RT and 339 patients in the control condition. Subgroup analyses included 784 patients undergoing THA and 149 patients receiving other surgical interventions. Overall findings supported RT's efficacy in significantly reducing severe HO formation. Notably, subgroup analysis of patients who underwent non-THA procedures indicated no statistically meaningful reduction in the incidence of mild-to-moderate HO (Brooker I-II) after RT treatment compared to controls. Conversely, an increased risk of nonunion was specifically noted among patients receiving elbow RT. Our meta-analysis strongly supports the preventive effect of RT on HO, especially for high-risk patients and in cases that other treatments, like NSAIDs, are contraindicated or avoided. However, the risk of nonunion in elbow treatments warrants caution. Further prospective randomized controlled trials, particularly focusing on non-hip joints, are necessary to validate these findings.

Obesity, type 2 diabetes, and therapeutic weight loss are all associated with impaired bone quantity and microarchitecture. Glucagon-like peptide receptor analogs (GLP1RAs) have direct beneficial effects on bone microarchitecture, in preclinical settings. This study aimed to evaluate the net impact of GLP1RA on microarchitecture in overweight/obese type 2 diabetes individuals. It was an interventional, paired-sample cohort study with oral semaglutide in consecutive type 2 diabetes patients with overweight/obesity and metabolic-dysfunction associated steatotic liver disease. Oral semaglutide was initiated at 3 mg daily, with escalation to 14 mg at the end of 12 weeks. Bone turnover markers (P1NP, β-CTX) were estimated by electrochemiluminescence and body composition by DXA. Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed using HRpQCT (XtremeCT II, Scanco Medical). There were 36 patients (44% males) with a mean (± SD) age of 50.8 ± 10.1 years, mean BMI of 34.3 ± 6.2 kg/m² and median duration of diabetes being 7 (IQR 2-13) years. At 52 weeks, there was an increase in tibial total vBMD (317.4 ± 47.4 vs. 331.6 ± 52.7 mg HA/cm³, p = 0.06) and cortical vBMD at both radius and tibia (trend towards significance). Trabecular vBMD and trabecular bone volume fraction at radius were also increased. Males showed significantly increased tibial total and cortical vBMD, and trabecular bone volume fraction, but there was no significant change in females. There were no significant differences in bone microarchitecture based on steatosis or fibrosis reduction. Oral semaglutide improves vBMD in overweight/obese type 2 diabetes, despite a significant reduction in body weight.