Search Results (1,154)

Hypophosphatasia (HPP) is a rare inherited disorder caused by deficient tissue-nonspecific alkaline phosphatase (TNSALP) activity and classically characterized by impaired mineralization processes, although growing evidence suggests broader systemic involvement beyond bone. This cross-sectional study aimed to characterize circulating levels of osteoglycin and sclerostin in patients with HPP and to explore their relationships with TNSALP activity and systemic clinical–biochemical profiles. This cross-sectional study included 25 genetically confirmed HPP patients and 25 age- and sex-matched controls without cardiovascular disease. Circulating osteoglycin and sclerostin were measured by ELISA, and clinical, metabolic, renal, inflammatory, cardiovascular, and bone-related variables were assessed. HPP patients showed lower osteoglycin and higher sclerostin levels compared with controls. Osteoglycin was mainly associated with ALP activity and mineral-related variables, while sclerostin showed broader associations involving glycemic, inflammatory, renal, and cardiovascular domains. In multivariable analyses, osteoglycin was linked to ALP, renal and inflammatory markers, whereas sclerostin was associated with glycemic, mineral, inflammation, and circulatory markers. Overall, osteoglycin variability appeared mainly driven by mineral-related factors, while sclerostin was more influenced by metabolic and inflammatory domains. In conclusion, HPP is associated with an imbalance in circulating bone-derived proteins, characterized by reduced osteoglycin and increased sclerostin, suggesting systemic alterations in bone-related signaling beyond impaired mineralization. Full article

Aflatoxin B₁ (AFB₁) is a prevalent mycotoxin contaminating food and environmental matrices that can induce hepatic injury, thereby posing a substantial threat to livestock production. Portulaca oleracea L. polysaccharide (POP) possesses diverse biological activities, including antioxidant and anti-inflammatory properties. However, the protective effects of POP against AFB₁-induced hepatic injury have not been fully elucidated. In the present study, a rabbit model of AFB₁-induced hepatic injury was established to investigate the hepatoprotective mechanisms of POP. Histopathological examination and liver function assessments demonstrated that POP markedly ameliorated hepatic histopathological alterations and decreased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Molecular analyses further demonstrated that POP attenuated AFB₁-induced oxidative stress and hepatocyte apoptosis, effects that were associated with activation of the PI3K/AKT signaling pathway and suppression of the mitochondria-mediated apoptotic pathway. Furthermore, microbiome profiling and targeted short-chain fatty acid (SCFA) metabolomics analyses indicated that POP supplementation contributed to the preservation of intestinal barrier integrity and intestinal microbiota stability, concurrent with the attenuation of AFB₁-induced intestinal and hepatic injury and elevated SCFA production by intestinal microbes. Overall, POP exerts prominent preventive protective effects against AFB₁-induced liver injury, which may be closely associated with alterations in intestinal microbiota composition and microbial short-chain fatty acid metabolism, as well as the activation of the PI3K/AKT signaling pathway. These findings provide novel insights into the mechanisms underlying AFB₁-induced hepatic injury. Full article

Background/Objectives: Multiple myeloma (MM) is an incurable, hematological malignancy caused by the abnormal proliferation of terminally differentiated plasma cells in the bone marrow. Current research indicates that N-azacytidine, as an epigenetic drug and nucleoside metabolic inhibitor, can be efficient in MM treatment. However, data on bone marrow mesenchymal stromal cells (BMSCs), as a critical cell population in the hematopoiesis and bone remodeling processes, are limited. Methods: The effect of N-azacytidine on the myeloma cell line AMO-1, bone marrow mesenchymal stromal cells from MM patients (MM-MSCs) and patients undergoing hip arthroplasty (BMSCs) as a healthy control in hypoxia (3% O₂) were examined. Cellular functions such as viability, proliferation, phenotype, and differentiation were determined by in vitro tests and flow-cytometry. Results: N-azacytidine (100 nM to 1000 nM) significantly inhibited metabolic activity, cell cycle, CFSE dilution and CD138+/CD38+ expression levels by myeloma cells after 72 h. No viability changes were detected in MM-MSCs and BMSCs treated with N-azacytidine. As for both BMSCs and MM-MSCs differentiation potential, N-azacytidine did not affect alkaline phosphatase (ALP) activity and adipogenesis but inhibited matrix mineralization (500 nM and 1000 nM). However, when BMSCs were pretreated with N-azacytidine for 72 h, changes in ALP activity and mineralization level were not detected. Conclusions: N-azacytidine, along with the suppressive effect on myeloma cells, did not change the differentiation potential of MSCs, but rather preserved their capacity. These findings are of particular importance considering MM progression and bone tissue destruction, suggesting that N-azacytidine may represent a promising therapeutic agent for myeloma disease. Full article

Background and Clinical Significance: Tenofovir disoproxil fumarate (TDF) is a widely prescribed nucleotide reverse transcriptase inhibitor (NtRTI) for HIV-1 infection. Though generally well-tolerated, proximal renal tubulopathy resulting in full-blown Fanconi syndrome remains a rare but severe complication (<0.1%). Case Presentation: We present the case of a 52-year-old female living with HIV-1 (diagnosed in 1999, CDC stage A3) who had been treated with a TDF-based antiretroviral regimen for 12 years. Upon admission, she complained of progressive bone pain and polyuria over the preceding six months. Laboratory investigations revealed profound hypokalemia, severe hypophosphatemia, hypouricemia, elevated alkaline phosphatase (ALP) and a decline in renal function (creatinine 1.3 mg/dL from a baseline of 0.7 mg/dL). Arterial blood gas (ABG) analysis showed a normal anion gap hyperchloremic metabolic acidosis alongside respiratory acidosis. Urinalysis demonstrated profound glycosuria in the setting of normal blood glucose levels, coupled with increased 24 h urinary excretion of potassium and phosphorus. A bone scintigraphy demonstrated a “super scan” pattern of metabolic etiology, establishing secondary osteomalacia driven by renal phosphate wasting. Secondary hyperparathyroidism and severe vitamin D3 deficiency were also recorded. The diagnosis of TDF-induced Fanconi syndrome was established. TDF was discontinued, and her antiretroviral regimen was modified to tenofovir alafenamide fumarate (TAF), emtricitabine (FTC), darunavir, and ritonavir, combined with vitamin D supplementation. Over a 6-month follow-up period, renal function normalized, electrolyte wasting resolved, and metabolic acidosis completely reversed. Conclusions: This case highlights that TDF-induced proximal tubulopathy can manifest even after a decade of uneventful therapy, particularly when co-administered with a boosted protease inhibitor. Full article

Guided bone regeneration (GBR) heavily relies on barrier membranes, with collagen being the clinical standard material. Human amniotic epithelial cells (hAECs) represent a promising, non-controversial stem cell source with substantial osteogenic and immunomodulatory potential. This study aimed to comparatively evaluate the structural characteristics of three commercial collagen membranes (Biocollagen^®, Derma^®, and VantyColl^®) and their influence on the biological behavior, viability, and osteogenic differentiation of hAECs and hFOB 1.19 human fetal osteoblasts. The microarchitecture was assessed via scanning electron microscopy (SEM). Biological response was evaluated over 14 days, using MTT assays, calcium and phosphorus quantification, alkaline phosphatase (ALP) activity, and quantitative real-time PCR (qRT-PCR) for osteogenic markers (Runx2, Osterix, ALP, and OPN). SEM revealed a dense lamellar structure for Biocollagen^®, a fibrillar and oriented architecture for Derma^®, and a highly porous network for VantyColl^®. Both cell types adhered to and proliferated on all membranes. Derma^® provided the best long-term proliferative support for both lineages. Conversely, VantyColl^® induced robust early osteoblastic differentiation, marked by exceptional upregulation of Osterix (24.93-fold) and Runx2 (2.64-fold), though it exhibited diminished long-term hAEC viability. Ultimately, collagen membrane microarchitecture dictates cell fate; dense fibrillar networks (Derma^®) favor sustained growth and late matrix maturation (OPN), whereas high-porosity scaffolds (VantyColl^®) amplify early osteoinductive cascades. Full article

Background: Although gemcitabine-based palliative chemotherapy remains widely used for advanced biliary tract cancer (BTC), practical pretreatment prognostic factors are needed. This study identified baseline prognostic factors associated with overall survival (OS) and explored a simple risk stratification approach for 12-month survival in advanced BTC patients treated with gemcitabine-based chemotherapy. Methods: This retrospective cohort study included advanced BTC patients treated with gemcitabine-based palliative chemotherapy between 2011 and 2025. Baseline clinical and laboratory variables were collected at treatment initiation. The Kaplan–Meier method estimated OS. Univariable and multivariable Cox proportional hazards regression analyses identified prognostic factors. A post hoc exploratory risk score was developed using routinely available factors independently associated with OS. Results: A total of 154 patients were included, gemcitabine plus cisplatin was administered to 95 patients, whereas 59 received gemcitabine plus carboplatin. Median OS was 9.43 months. Multivariable analysis showed that ECOG performance status ≥ 2 (adjusted HR, 5.68; 95% CI, 2.52–12.81), alkaline phosphatase (ALP) ≥ 2 × ULN (adjusted HR, 1.53; 95% CI, 1.01–2.33), and neutrophil-to-lymphocyte ratio (NLR) ≥ 3 (adjusted HR, 1.51; 95% CI, 1.03–2.20) were associated with worse OS. An exploratory score assigning one point to each factor stratified patients into low-, intermediate-, and high-risk groups. The estimated 12-month OS rates were 59.6%, 40.4%, and 10.8%, respectively. Conclusions: Poor performance status, elevated ALP, and elevated NLR were associated with worse OS in advanced BTC patients receiving gemcitabine-based palliative chemotherapy. However, the associations for ALP and NLR were modest and should be interpreted cautiously. A simple exploratory score based on routinely available factors demonstrated distinct 12-month survival across risk groups and may help inform prognostic discussions in routine practice. This approach should be considered hypothesis-generating, and external validation is warranted. Full article

This study aimed to investigate the effects of salinity changes on serum biochemistry, hormonal profiles, splenic immune function, hepatic lipid metabolism and intestinal microbiota of the F₂ generation of Chinese sturgeon (Acipenser sinensis) under freshwater and seawater acclimation (15–23.2 psu) conditions. A 30-day indoor culture experiment showed that seawater acclimation only induced a declining trend in juvenile growth without statistical significance compared to the freshwater group (p > 0.05). The levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alkaline phosphatase (ALP) and albumin II (ALBII) in the freshwater group were markedly lower than those in the seawater group (p < 0.05), while alanine aminotransferase (ALT), aspartate aminotransferase (AST), high-density lipoprotein cholesterol (HDL-C) and total protein (TPII) showed no significant differences (p > 0.05). The serum triiodothyronine (T3) concentration was significantly higher, and chloride ion (Cl⁻) was lower in freshwater individuals (p < 0.05). Cortisol, testosterone, K⁺, Na⁺, Ca²⁺, thyroid-stimulating hormone and T4 remained unchanged between the two salinity environments (p > 0.05). In gill tissues, lipase (LPS) and fatty acid synthase (FAS) activities were lower, whereas lipoprotein lipase (LPL) activity was higher in the freshwater group (p < 0.05), and no obvious difference was observed in hepatic metabolic enzymes. The splenic complement C4 content was significantly decreased in freshwater sturgeon (p < 0.05), while splenic C3, IgM and serum immune indices showed no statistical differences. All alpha-diversity indices of intestinal microbiota were significantly higher in the seawater group (p < 0.05). At the phylum level, the intestinal flora in the seawater group was dominated by Proteobacteria (69.6%) and Fusobacteriota (14.9%), whereas Fusobacteriota accounted for 81.5% in the freshwater group. At the genus level, seawater samples exhibited richer microbial composition including Sphingomonas, Cupriavidus and Cetobacterium, while the freshwater microbiota was overwhelmingly dominated by Cetobacterium (81.5%). In conclusion, salinity significantly regulates serum biochemistry, hormone secretion, lipid metabolism, splenic immunity and intestinal microbiota of the F₂ generation of Chinese sturgeon. The freshwater environment benefits lipid metabolism, thyroid hormone levels, and growth performance, with a simplified intestinal microbial structure. Seawater acclimation maintains higher gut microbial diversity and immune homeostasis, but induces osmotic stress, restricts thyroid hormone secretion and redistributes energy supply, thereby inhibiting fish growth. This study provides a theoretical basis for salinity domestication and scientific culture management of Chinese sturgeon. Full article

Soybean (Glycine max (L.) Merr.) is a key legume with high agronomic and nutritional value, widely cultivated for its high-protein seeds and its capability to improve soil fertility through biological nitrogen fixation. Recently, co-inoculation strategies combining Rhizobia bacteria with growth-enhancing fungi from the genus Trichoderma have gained increasing attention as a way to enhance soybean productivity and resilience under variable environmental conditions. The present study, conducted in 2023–2024, examined how seed inoculation treatments (Bradyrhizobium japonicum and Trichoderma viride) affect soybean productivity, seed quality, and soil biochemical changes expressed as the activity levels of selected soil enzymes—dehydrogenases (DHA), catalase (CAT), acid phosphatase (ACP), and alkaline phosphatase (ALP)—as well as the biological fertility index (BIF). The findings indicated that co-inoculation positively influenced plant productivity and produced the highest seed yields among all treatments tested, exceeding the control by 25.6%. Furthermore, inoculated seeds were characterized by improved seed quality, expressed by higher germination capacity (80%) and greater average seedling length (4.74 cm). The bacterial strains used to inoculate soybean seeds increased soil biochemical activity and improved fertility, particularly under unfavorable rainfall distribution during the growing season. Co-inoculation can be recommended as an effective and environmentally friendly element of soybean cultivation technology, supporting yield stability in variable weather conditions. Further research is recommended in longer multi-year series and under various habitat conditions. Full article

Partial substitution of chemical fertilizer with organic fertilizer is an important strategy for optimizing fertilization and mitigating soil degradation caused by excessive chemical fertilizer application. However, systematic studies comparing the effects of different substitution ratios on soil properties, enzyme activities, and microbial communities remain scarce. A two-year field experiment was conducted with five treatments: no fertilization (Control), chemical fertilizer alone (CF), 20% organic fertilizer substitution (M20), 40% substitution (M40), and 60% substitution (M60). High-throughput sequencing was used to analyze soil bacterial and fungal communities. The M40 treatment significantly increased soil organic matter (17.96% and 30.18%, respectively), available nitrogen (6.85% and 20.30%, respectively), and available phosphorus (30.74% and 52.65%, respectively) compared with CF in both years, with more pronounced improvements observed in 2025. Furthermore, the M40 treatment also enhanced urease and sucrase activities in both years but reduced alkaline phosphatase (ALP) activity in 2025. Microbial community analysis revealed that the M40 treatment enriched beneficial microorganisms, including Proteobacteria, Acidobacteriota, Basidiomycota, Vicinamibacteraceae, Botryotrichum, and Tausonia, while inhibiting the pathogenic fungus Fusarium. Compared with CF, the M40 treatment increased maize yield by 7.04% and 8.10% in 2024 and 2025, respectively, which was the highest among all treatments. Mantel tests indicated that yield was positively correlated with available phosphorus, available potassium, total nitrogen, total phosphorus, and urease activity, but negatively correlated with ALP activity in 2025. Our findings demonstrate that 40% organic fertilizer substitution synergistically improves soil fertility, optimizes microbial community structure, and promotes crop yield, providing empirical evidence for optimizing fertilization regimes in maize production. Full article

Background: Membrane potential represents one of the fundamental physiological characteristics of cells, playing a critical role in cellular function. Studies have shown that membrane hyperpolarization positively regulates the osteogenic differentiation of mesenchymal stem cells. Optogenetic technology based on the Natronomonas pharaonis halorhodopsin (NpHR) light-activated channel can induce membrane hyperpolarization through optical methods. Given the working principle of optogenetic technology, this study aimed to investigate whether optogenetic activation of NpHR channels could induce membrane hyperpolarization in human dental follicle stem cells (hDFCs)—mesenchymal stem cells derived from dental follicle tissue—to regulate their osteogenic differentiation. Methods: hDFCs were isolated and cultured. Engineered hDFCs expressing the NpHR channels were constructed through lentiviral transduction. Patch clamps were performed to observe the effects of optogenetic activation of NpHR channels on membrane potentials of hDFCs. Single-cell Ca²⁺ imaging were performed to observe the effects of membrane hyperpolarization via modulation of extracellular K⁺ concentration ([K⁺]_e) on the intracellular Ca²⁺ levels of hDFCs. Cell viability assay, transwell chamber assay, wound healing assay, osteogenic differentiation induction, alizarin red staining, alkaline phosphatase (ALP) staining, real-time reverse transcriptase polymerase chain reaction (RT-qPCR) and Western blot (WB) were performed to observe the effects of optogenetic activation of NpHR channels on proliferation, migration, and osteogenic differentiation of NpHR-hDFCs. Results: Reversing membrane hyperpolarization via modulation of extracellular K⁺ concentration ([K⁺]_e) was shown to suppress osteogenic differentiation of hDFCs, whereas promoting membrane hyperpolarization via opening ATP-sensitive K⁺ channels was shown to enhance osteogenic differentiation of hDFCs. Hyperpolarizing cells by decreasing [K⁺]_e increased intracellular Ca²⁺ levels of hDFCs. Optogenetic activation of NpHR channels by an optogenetic system induced membrane hyperpolarization and significantly enhanced the proliferation, migration, and osteogenic differentiation abilities of NpHR-hDFCs. Conclusions: Hyperpolarization by optogenetic activation of NpHR channels can promote hDFCs’ proliferation, migration, and osteogenic differentiation abilities. Full article

As a traditional element of Chinese medicine, Hippocampus erectus is well known for promoting adolescent growth, yet its active fractions and underlying molecular mechanisms remain unclear. In this study, the aqueous extract of H. erectus was subjected to in vitro simulated gastrointestinal digestion and ultrafiltration to separate three molecular weight fractions (<10 kDa, 10–30 kDa, >30 kDa). Their chemical profiles were characterized, and osteogenic activities were systematically evaluated using cell assays, a juvenile rat model, and integrated transcriptomics and data-independent acquisition (DIA) proteomics. Results revealed that chemical profiling showed the >30 kDa fraction was mainly composed of hemocyanin subunits, and the 10–30 kDa fraction was enriched in growth-related amino acids and steroid derivatives; functionally, the 10–30 kDa fraction promoted preosteoblast proliferation and early differentiation via enhanced alkaline phosphatase (ALP) activity, while the >30 kDa fraction dominated late osteoblast maturation and mineralization. Both fractions significantly increased rat body and bone length by expanding growth plate proliferative zones and elevating serum insulin-like growth factor-1 (IGF-1)/bone morphogenetic protein-2 (BMP-2) levels. Transcriptomic and proteomic analyses identified vascular endothelial growth factor (VEGF), Wingless-related integration site (Wnt), phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), and extracellular matrix (ECM)–receptor interaction as potential core regulatory pathways. Integrated multi-omics analysis further confirmed Frizzled-related protein B (Frzb) and AKT1 substrate 1 (Akt1s1) as candidate key regulatory targets enriched in the Wnt and adenosine monophosphate-activated protein kinase (AMPK) signaling pathways. These findings elucidate the multi-fraction, multi-pathway mechanism of H. erectus in promoting skeletal development, providing scientific evidence for its traditional use and a theoretical basis for growth-promoting functional food development. Full article

Salicylic acid (SA) is an important signaling molecule that regulates plant primary and secondary metabolites accumulation. Although SA has been shown to promote folate accumulation, the underlying mechanism remains unclear. In this study, the effect of SA on folate biosynthesis in spinach (Spinacia oleracea L.) and its regulatory mechanisms were investigated. Physiological and metabolomic analyses showed that foliar SA application increased the contents of folate, soluble protein, and soluble sugar and the abundance of 5-methyltetrahydrofolate, p-aminobenzoate (pABA), and Trp, while the abundance of Ser decreased. The expression of aminodeoxychorismate synthase (ADCS) and alkaline phosphatase (ALP) genes in the folate biosynthesis pathway was upregulated, while the expression of five genes in the folate interconversion pathway and two genes in the Phe/Tyr synthesis pathway was downregulated. Fifty-one transcription factors (TFs) showed expression patterns correlated with those of ADCS and ALP and were predicted to bind to their promoter regions. SA upregulated many hormone genes, and 12 of these correlated strongly with both ADCS and ALP. Moreover, transgenic Arabidopsis lines overexpressing SoADCS constitutively displayed higher folate content in leaves. Taken together, our results suggested that SA may promote folate accumulation by enhancing folate precursor supply, and several candidate TFs and hormone-related genes that may be involved in the regulation of this pathway warrant further study. Full article

The European mink is a critically endangered mustelid. Species-specific hematological and biochemical reference intervals are lacking, complicating accurate health assessments in conservation programs. This study aimed to determine these reference intervals for European mink, following international guidelines, with 110 blood samples collected under isoflurane anesthesia, outside the breeding season, from 75 captive individuals (37 females, 38 males). Results were broadly comparable to the American mink and domestic ferret. Several parameters varied significantly according to sex, age, and body condition. Males showed higher hemoglobin (p = 0.031), whereas females, higher platelet (p = 0.014) and leukocyte counts, cholesterol, urea, alkaline phosphatase (ALP) (p ≤ 0.002), and globulin concentrations (p = 0.005). Males also had higher creatinine and alanine aminotransferase (ALT) (p < 0.001). Juveniles had higher leukocyte counts (p = 0.047) and ALP and calcium concentrations (p ≤ 0.016), while adults showed higher globulin and creatinine values (p ≤ 0.014). Overweight individuals exhibited increased hemoglobin and hematocrit (p ≤ 0.018) and mild electrolyte differences (p ≤ 0.045). Separate intervals for sex and age were not warranted for most analytes. These results provided specific reference intervals useful for essential health monitoring and clinical decision-making in conservation breeding, translocation, and reintroduction programs of European mink. Full article

Background/Objectives: Managing bone diseases demands novel, natural compounds to bypass the heavy side effects of current therapies. Honey is well-known for its therapeutic traits, yet we know very little about how specific floral varieties impact bone tissue. This study confronts this gap by comparing how acacia, chestnut, and coriander honeys drive human osteoblast behavior in vitro. Methods: After mapping the phenolic/flavonoid profiles and antioxidant capacities of these honeys, we tested them on hFOB 1.19 human osteoblasts. We tracked cell migration via scratch assays and validated osteogenic maturation through Alkaline Phosphatase (ALP) activity and Alizarin Red (AR) mineralization over 7 days. Confocal time-lapse imaging with pharmacological inhibitors monitored intracellular calcium dynamics, while gene shifts were analyzed via qRT-PCR. Results: Coriander honey (CH) packed the highest polyphenol levels and antioxidant power. Biologically, while all honeys accelerated scratch closure, CH drove cell motility most potently. Remarkably, a 7-day treatment with these honeys sparked a significant and robust increase in ALP activity and mineralization, surpassing the osteogenic induction observed with standard osteoinductive media. Mechanistically, CH triggered a sharp [Ca²⁺] spike, relying on external calcium entry and IP3-dependent internal release via PLC activation. qRT-PCR confirmed this anabolic shift via OPG and OPN upregulation. Conclusions: Honey exerts pronounced multi-level osteopromotive effects at both the functional and transcriptional levels, tightly linked to its botanical source. Among the variants, coriander honey stands out for its exceptional ability to fast-track osteoblast migration, differentiation, and early mineral deposition. Therefore coriander honey represents a promising in vitro candidate that warrants further preclinical evaluation for bone repair applications. Full article

Background and Objectives: Routine laboratory markers may support diagnostic risk stratification for osteoporosis, but their incremental value beyond the Osteoporosis Self-Assessment Tool for Asians (OSTA) remains uncertain in referral-based practice. We evaluated whether serum uric acid, albumin, alkaline phosphatase (ALP), and systemic inflammatory indices improve prediction of DXA-defined osteoporosis beyond OSTA in postmenopausal women. Materials and Methods: This retrospective cross-sectional study included 3504 postmenopausal women referred for DXA between January 2021 and May 2025. Osteoporosis was defined as the lowest T-score ≤ −2.5 at the lumbar spine, total hip, or femoral neck. Sequential exclusions removed patients with chronic hepatobiliary disease, chronic systemic inflammatory disease, bone-active medication exposure, systemic glucocorticoid use, abnormal liver biochemistry, or missing required variables. Multivariable logistic regression assessed associations, and OSTA-based prediction models were internally validated using stratified 10-fold cross-validation. Results: Osteoporosis was present in 1660 women (47.4%). Higher BMI, uric acid, and albumin were independently associated with lower odds of osteoporosis, whereas ALP and calcium were associated with higher odds. OSTA alone achieved an AUC of 0.679. Adding uric acid, albumin, and ALP increased AUC to 0.695 and slightly improved the Brier score, with good calibration. Adding the systemic immune-inflammation index did not materially improve performance. Conclusions: Routine laboratory variables provided only modest incremental value beyond OSTA. The model should be interpreted as an exploratory referral-pathway prioritization approach, not as a standalone population-screening tool. It should not be used as a diagnostic surrogate for DXA or as a fracture-risk model. Full article