Calcified Tissue International最新文献

KFP-1, a kefir-fermented peptide, promotes osteoblast differentiation and bone formation while inhibiting osteoclast differentiation and bone resorption. We also confirmed the bioaccessibility of KFP-1 in bone tissue and its overall benefits for bone health. Kefir is a dairy beverage rich in bioactive peptides with diverse health benefits. We identified a kefir-fermented peptide, KFP-1 (TEVPAINTIASAEPTVH), which enhances intestinal calcium absorption and may modulate bone remodeling. This study investigated the effects of KFP-1 on osteoblast and osteoclast gene expression and differentiation in BMMSCs, MC3T3-E1, BMMs, and Raw264.7 cells. Using iodine-125 labeling, we tracked KFP-1 distribution in mice following oral and intravenous administration, and evaluated its osteoprotective effects in AKR1A1 knockout (AKR1A1-KO) osteoporotic mice. KFP-1 upregulated osteogenic markers (ALP, Col1a1, OCN, OPG, RUNX2, OSX, BMP-2, β-catenin) and promoted osteoblast differentiation and mineralization, while downregulating osteoclastic markers (CTK, CTR, DC-STAMP, TRAP, c-Fos, c-Src, NFATc1) and inhibiting osteoclast differentiation and resorption via the inhibition of NFATc1, c-Fos, and c-Jun nuclear translocation and attenuation of RANKL-induced p38 MAPK, JNK, ERK, and NF-κB signaling. Biodistribution analysis showed KFP-1 reached femur and tibia at approximately 0.4% (oral) and 1% (intravenous) of the administered dose. In AKR1A1-KO mice, oral KFP-1 prevented bone loss, with additional calcium supplementation further improving cortical bone mechanical properties. These findings highlight KFP-1's dual action in promoting bone formation and inhibiting bone resorption, supporting its potential as a therapeutic adjuvant or functional food ingredient for osteoporosis prevention and bone health.

This study aims to investigate the effects of tacrolimus (TAC) on the osseointegration of titanium rods in ovariectomized (OVX) and Sham-operated (Sham) rats. Additionally, it seeks to explore the role of TAC in the differentiation of osteoblasts and osteoclasts under high Oxidative Stress. Firstly, the effect of TAC on osseointegration in both OVX and sham-operated rats was examined. Subsequently, TAC was utilized to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under H₂O₂ conditions. In animal experiments, we could observe that TAC had a positive effect on bone integration and bone mass in OVX rats through Micro-CT, histological and biomechanical evaluations. Specifically, significantly higher values were observed for BAR, BIC, BMD, BMC, BV/TV, Tb.Th, Conn.D, Tb.N, fixation strength, failure energy, and interface stiffness, while Tb.Sp was significantly lower (P < 0.05) in the OVX + TAC group compared with the OVX group. Serum and immunofluorescence analyses revealed that levels of P1NP, CTX-1, GSH, TNF-α, and IL-6 were reduced in the OVX + TAC group (P < 0.05), whereas MDA and SOD2 levels were significantly elevated (P < 0.05) relative to the OVX group. However, the rats from Sham + TAC group showed adverse effects on the above mentioned parameters (P < 0.05), compared with the Sham group. In vitro experiments showed that TAC could protect the osteogenic activity of MC3T3-E1 cells by inhibiting H₂O₂-induced oxidative stress, as evaluated by alkaline phosphatase staining and alizarin red staining, and inhibit the H₂O₂-enhanced osteoclast differentiation of RAW264.7 cells, as evaluated by TRAP staining. These results suggest that TAC can improve osseointegration and bone mass under osteoporosis, but inhibit osseointegration and reduce bone mass under normal BMD. The mechanism may be related to the regulation of TAC on bone metabolism under high oxidative stress.

During pregnancy and lactation, changes in mineral metabolism provide fetuses with sufficient calcium. Eith a reported instance of 4-400 per 1 million pregnancies, the decrease in bone mineral density causes pregnancy and lactation associated osteoporosis (PLO). This the first systematic review conducted on this condition affecting the hip. A comprehensive literature search of the databases Embase, PubMed, and Web of Science was conducted. The articles included for review were case studies or case series that consisted of pregnant patients with PLO of the hip. Data extraction was performed on the resulting 64 studies, totaling 149 patient cases. The average age reported was 33.5 years, with an average BMI of 26.5 kg/m² and an average height of 165.8 cm. Symptom onset was reported in 50% of cases, 69% in the 3rd trimester, 25% in the 2nd trimester, and 4% in the postpartum period. The route of delivery was a cesarean section in 44% of cases, vaginal delivery in 33%, and unreported in 23%. Treatment included modified weight-bearing (40%), vitamin D and/or calcitriol (26%), and surgery (26%). Cesarean section in patients with PLO occurred at a greater percentage (44%) when compared to the rate of cesarean section in the United States in 2023 (32.1%). This could have implications for the health of the mother and the fetus. The majority of cases occurred during pregnancy. This may complicate the diagnosis and care of the patient. The absence of metabolic disease workup details in these cases is an area for future research and clinical focus.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer management, leading to unprecedented improvements in clinical outcomes. Several adverse events from ICIs have been documented, but the risk and clinical relevance of bone adverse events (BAEs) remain uncertain. Sporadic reports describe inflammatory cytokine upregulation, osteoporosis onset during ICI treatment, and increased risk of fragility fractures. In this review, original articles written in English and published up to June 2025, were identified in PubMed, Scopus, and WOS databases by using pre-selected keywords. Based on pre-defined inclusion/exclusion criteria, 23 articles were included in the final analysis. As BAEs, we considered the following conditions: fractures, osteoporosis, osteopenia, bone pain, altered bone metabolism markers. Overall, we found 1610 cancer patients developing at least one BAE, whose percentage was highly variable among studies (range 0.3-88.9%), reflecting the differences in study design, patient enrollment, and BAE recording. Median age was > 55 years, and BAEs were reported in patients with various primary solid tumors, most commonly lung cancer patients (10/23 studies), mainly treated with programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors. However, several limitations of the studies emerged from the analysis and are highlighted in the manuscript. In conclusion, BAEs may occur more frequently among patients treated with ICIs but are likely to be underreported in most studies. Further investigation is needed to estimate and mitigate the risk of such events, since diagnostic techniques and anti-osteoporotic drugs are widely available in the clinical practice. A research agenda focusing on higher-quality reporting of BAEs from ICIs is warranted.

This retrospective cross-sectional study investigated the diagnostic performance of four magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) scoring methods for identifying osteoporosis in postmenopausal women and explored the impact of MRI system variability, using quantitative computed tomography (QCT) as the reference standard. A total of 181 women who underwent lumbar spine QCT and MRI within a six-month interval were included. VBQ scores were calculated from routine sagittal T1-weighted images. Diagnostic performance was assessed using receiver operating characteristic curve analysis, correlations with QCT-derived bone mineral density (BMD) were evaluated using Spearman's correlation, and agreement and inter-method variability were analyzed using appropriate comparative and agreement analyses. All four VBQ scoring methods demonstrated moderate diagnostic performance, with areas under the curve ranging from 0.739-0.783, and showed moderate negative correlations with BMD (R = - 0.488 to - 0.549). Significant differences were observed among VBQ scoring methods (p = 0.018) and across MRI systems from different vendors (p < 0.001). An optimal cutoff value of VBQ > 4.0 was identified using the Youden index. These findings suggest that MRI-derived VBQ scoring may serve as a useful, radiation-free, opportunistic adjunct for osteoporosis assessment in postmenopausal women undergoing lumbar MRI for other clinical indications. However, the observed inter-method and inter-scanner variability highlights the need for further standardization of VBQ scoring approaches and MRI acquisition protocols before broader clinical implementation.