Elevated Alkaline Phosphatase Levels Research Articles

Optimization of Peri-Implant Bone Repair in Estrogen-Deficient Rats on a Cafeteria Diet: The Combined Effects of Systemic Risedronate and Genistein-Functionalized Implants

Estrogen deficiency, coupled with a cafeteria diet (CD), can impair peri-implant bone repair, posing a significant challenge to implant success in affected individuals. Thus, it is crucial to explore strategies for implant functionalization and systemic treatments that could alleviate these bone alterations. This study aimed to assess peri-implant bone repair in ovariectomized (OVX) rats subjected to a CD, with a focus on implants functionalized with genistein (GEN), compared to conventional implants (CONV), and the effects of systemic treatment with risedronate sodium (RIS). In total, thirty-six female rats were assigned to three groups: rats with estrogen (SHAM), rats with estrogen deficiency and CD (OVX-CD), rats with estrogen deficiency, CD, and systemic RIS treatment (OVX-CD-RIS). All rats underwent bilateral extraction of the first upper molars followed by implant installation. Each group was further subdivided based on implant type: conventional implants (CONV) or GEN-functionalized implants, resulting in six subgroups (n = 6). The study employed several analyses, including reverse torque testing, microcomputed tomography (Micro-CT), epifluorescence microscopy, and molecular assays. The main result demonstrated that the OVX-CD-RIS/GEN subgroup exhibited significantly higher reverse torque values, indicating stronger implant stability. Micro-CT scans revealed a greater bone volume in the OVX-CD-RIS/GEN subgroup compared to other subgroups. Epifluorescence microscopy also demonstrated an increased mineral apposition rate in both the OVX-CD/GEN and OVX-CD-RIS/GEN subgroups. Molecular analysis indicated elevated expression levels of osteocalcin, alkaline phosphatase, and vascular endothelial growth factor in the OVX-CD-RIS/GEN subgroup. In conclusion, the combined treatment of systemic RIS and GEN-functionalized implants significantly enhanced peri-implant bone repair, offering a promising strategy to improve implant outcomes in postmenopausal women with metabolic syndrome.

Clinical relevance of tumor fraction assessment from circulating tumor DNA in metastatic colorectal cancer.

237 Background: Both tissue (TBx) and liquid (LBx) biopsies are indicated for detecting actionable alterations in metastatic colorectal cancer (mCRC). LBx is easier to obtain and often has faster turnaround time, but its informative results depend on the ctDNA tumor fraction (TF) content. We aimed to (1) evaluate the concordance between LBx and TBx in CRC; and (2) determine baseline lab and clinical factors associated with TF. Methods: CRC patients (pts) with both tissue and liquid Foundation Medicine comprehensive genomic profiling within an interval of up to 90 days between samples collection were analyzed. Positive percent agreement (PPA) and negative predictive value (NPV) for RAS (KRAS/NRAS) and BRAFV600E detection were calculated with tissue as reference. Clinical data was obtained by the US-wide de-identified Flatiron Health-Foundation Medicine real-world clinicogenomic CRC database, from ~280 cancer clinics (~800 sites of care) between 1/2011-12/2023. mCRC pts with LBx collected up to 60 days prior to therapy (Tx) start were analyzed for association between TF and baseline factors using logistic regression with TF≥1% as the binary outcome. Baseline factors include age, ECOG, race/ethnicity, line of therapy, practice type, metachronous vs. synchronous disease, tumor side, albumin, alkaline phosphatase (AP), serum creatinine, hemoglobin, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio, opioid and steroid pre-Tx. Foundation Medicine’s ctDNA TF is a composite algorithm prioritizing aneuploidy at higher levels to avoid germline signal and prioritizing variant allele frequency of canonical alterations at lower levels to maximize dynamic range. Results: A total of 402 pts had TBx and LBx (268 [67%] TF≥1% and 134 [33%] TF<1%). Without accounting for TF, the overall PPA for RAS and BRAFV600E was 77% and 83%, and the NPV was 65% and 99%. In LBx with TF≥1%, the PPA for RAS and BRAFV600E was 99% and 100%, and NPV was 98% and 100%. In contrast, for TF<1% samples, the PPA for RAS and BRAFV600E was 37% and 50%, and NPV was 57% and 97%. Of the 633 pts with LBx collected prior to Tx, 474 (75%) had TF≥1%. TF≥1% was independently associated with ECOG 1+ (odds ratio [OR]: 1.58, p=0.038), community oncology care site (OR: 2.58, p=0.002), elevated levels of AP (OR: 3.00, p<0.001) and LDH (OR: 3.97,p=0.002). TF≥1% was less likely to occur in right-side tumors (OR: 0.53, p=0.012) and metachronous disease (OR: 0.48, p<0.001). Conclusions: Approximately 70% of LBx samples from CRC pts have TF≥1%, with near-perfect concordance for RAS/BRAFV600E. For LBx with TF<1%, interpretation of negative results can be challenging due to low tumor shedding, especially for RAS mutations, where 43% may be false negatives and a subsequent TBx will provide more confidence in the negative results. Clinical factors such as right-sided tumors and metachronous disease may help anticipate low TF and guide decisions to pursue TBx.

Efficacy of Second-line Nivolumab Versus Tyrosine Kinase Inhibitors for Renal Cell Carcinoma With Bone Metastases.

Combination therapy with immune checkpoint inhibitors has become the standard first-line treatment for metastatic renal cell carcinoma (mRCC), leading to changes in second-line treatment options, such as nivolumab or tyrosine kinase inhibitors (TKIs). However, very few studies have compared the efficacy of these drugs in patients with mRCC, particularly those with bone metastases (BM), which are associated with a poor prognosis. This study compared the efficacy of nivolumab and TKIs as second-line treatments for mRCC patients with BM and examined the microenvironments of primary tumors and BM lesions. This multi-institutional retrospective study included 87 mRCC patients with BM who received either nivolumab or TKIs as second-line treatments. We analyzed tumor-infiltrating immune cells expressing CD8 and CD20, along with PD-L1, HIF2α, c-MET, VEGFR2, and AXL, in primary tumors and BM sites using immunohistochemistry. This analysis indicated that poor-risk classification, as per the International Metastatic RCC Database Consortium criteria (p<0.01), and elevated serum alkaline phosphatase levels (p=0.031) were significantly associated with poor prognosis. No significant difference in overall survival was observed between patients receiving nivolumab and those receiving TKIs. However, the objective response rate of patients with BM lesions was significantly higher when receiving TKIs than when receiving nivolumab (p=0.014). Immunohistochemistry revealed significantly higher VEGFR2 expression in BM lesions than primary tumors. TKIs could be a promising second-line treatment option for mRCC patients with bone-limited metastases.

P-20 EARLY ZOLEDRONIC ACID TREATMENT IN A PEDIATRIC CASE OF OSTEOGENESIS IMPERFECTA TYPE V: CLINICAL OUTCOMES AND THE ROLE OF IFITM5 (BRIL) MUTATION

Abstract Introduction Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by bone fragility, low bone mass, and frequent fractures. OI is typically associated with mutations in the COL1A1 and COL1A2 genes, but a subset of cases, such as OI type V, is linked to mutations in the IFITM5 gene, also known as BRIL (bone-restricted IFITM-like). Clinical Case This report presents a case of a 2-year-old boy diagnosed with OI type V, a rare form of the disease caused by a mutation in BRIL. The patient exhibited multiple recurrent bone fractures beginning in infancy, though there was no family history of bone disease or consanguineous marriage. Physical examination revealed that the patient was of normal weight and height for his age, with neurodevelopmental milestones met. Laboratory tests showed elevated alkaline phosphatase (ALP) levels, indicative of increased bone turnover, while other values were within normal ranges. Radiological evaluations confirmed an active fracture in the left tibia but showed no additional pathological involvement. Genetic testing identified a de novo C&amp;gt;T variant in the IFITM5 gene, confirming the diagnosis of OI type V. The patient was treated with intravenous zoledronic acid (ZA), a bisphosphonate therapy, which is currently being tested in infants and toddlers for OI treatment. The treatment led to a significant reduction in fracture recurrence and a decrease in ALP levels, demonstrating its efficacy in managing the disease. Despite these positive outcomes, certain hallmark features of OI type V, such as hyperplastic callus formation and new periosteal bone growth, were not observed during follow-up, possibly due to the early initiation of ZA therapy. OI type V is distinguished from other forms of OI by hyperplastic callus formation and increased osteoblast activity, often accompanied by elevated ALP levels. Radiographic and histological findings specific to this type include periosteal bone growth and a reticular lamellation pattern in the bone matrix. Although ZA has shown promise in reducing fracture risk and improving clinical outcomes, its long-term efficacy in preventing other disease manifestations, such as intramembranous ossification, remains uncertain. The underlying pathological mechanisms of OI type V, particularly the role of BRIL, are not yet fully understood. Further research into the activation of BRIL in osteoblasts could lead to the development of targeted therapies that address the root cause of the disease. While ZA therapy has been effective in managing the immediate symptoms of OI type V, a deeper understanding of the disease's genetic and molecular basis is crucial for improving long-term treatment outcomes. In conclusion, the IFITM5 (BRIL) mutation is recognized as the genetic cause of OI type V. Early intervention with ZA has shown positive effects in managing the disease, but further research is needed to fully understand the pathological mechanisms and to develop treatments that can address all aspects of the disease.Table 1:Lab workout (age 2)ALP = alkaline phosphatase; AST = aspartate transaminase; BUN = blood urea nitrogen; GGT = gamma-glutamyl transferase; CBC: complete blood count

A Case Report on Diagnosis and Management of Paget’s Disease

Background: Paget’s disease (osteitis deformans) of bone is a localized skeletal disorder characterized by either mono or polyostotic manifestations. Paget's disease might be asymptomatic as with normal biomarkers or it can be symptomatic such as bony enlargement or deformity. Case Presentation: A 47-year-old female patient was presented to our facility with an elevated alkaline phosphatase (ALP) level for 1 year. Upon reviewing the patient's test results were suggestive of increased ALP, it was determined that the elevated ALP level was likely of osseous origin. However, no bone deformities were observed in the patient. A bone scan was conducted, which indicated the presence of Paget's disease, characterized by increased blood flow, pooling and intense osteoblastic activity observed in the patient's left sided pelvic bones. The diagnosis of Paget's disease was confirmed through a technetium-99m methylene diphosphonate (Tc-99m MDP) bone scan. Inj. Zoledronic acid and oral calcium supplements were advised. Subsequently, after two months follow-up, her results showed normal alkaline phosphatase (ALP) level. Conclusion: Paget's disease, despite being classified as a skeletal disorder, may manifest without any noticeable symptoms or deformities. Its diagnosis is typically confirmed through laboratory analyses, specific findings observed in radiology or radionuclide scans and occasionally, through the confirmation of bone biopsy.

Evaluation of the Therapeutic Potential of the Methanolic Extract and Fractions of Datura stramonium in Paracetamol-intoxicated Rabbits.

Datura stramonium (DS) possesses strong medicinal and therapeutic potential but has been rarely evaluated in this context. The present study was intended to evaluate the antioxidant, hepatoprotective, and nephroprotective potential of the crude methanolic leaf extract and ethyl acetate, chloroform, n-hexane, and aqueous fractions of DS in paracetamol-intoxicated rabbits. Paracetamol (2 g/Kg BW) was applied to induce liver and kidney injury in rabbits while the methanolic extract and fractions of DS were applied in the dose range of 150 mg/Kg to 300 mg/Kg body weight for 21 days. Histopathology of the liver, and kidney and analysis of ALT (Alanine Transaminase), ALP (Alkaline Phosphatase), total bilirubin, serum urea, serum creatinine, and serum uric acid were carried out. In-vitro antioxidant potential of the extract and fractions of DS was carried out through DPPH (1,1-diphenyl 2-picrylhydrazyl) free radical scavenging assays. The hepatoprotective and nephroprotective potential of the extract and fractions of DS at the dose level of 300 mg/Kg BW was highly significant (P ˂ 0.01). ALT was found elevated in the paracetamol-treated group (117.3 ± 1.61 U/L) compared to the group treated with methanolic extract of DS, (57.3 ± 0.87 U/L) and normal control group (60.6 ± 1.58 U/L) at 300 mg/kg BW. Elevated levels of ALP (120 ± 1.58 U/L) and Bilirubin (1.6 ± 0.32 mg/dl) were found in the paracetamol-treated group compared with the group treated with methanolic extract of DS (67.5 ± 1.35 U/L; 0.2 ± 1.0 mg/dl) and normal control group (70.1 ± 1.53 U/L; 0.4 ± 0.16 mg/dl) respectively at 300 mg/kg BW. The methanolic extract of DS produced a marked scavenging activity of the DPPH free radicals (88.2 ± 0.006 %) followed by the fractions of DS compared to ascorbic acid (95.5 + 0.003 %) at a concentration of 1000 μg/ml. The effects were comparable to those produced by ascorbic acid. Liver and kidney histology of the rabbits treated with extract, fractions, and ascorbic acid of DS caused reductions in the pathological features compared to the paracetamol-treated animals. The histological observations and chemical pathological alterations demonstrated the significant hepatoprotective and nephroprotective benefits of the DS extract and its fractions. It has been concluded that the methanolic extract and fractions of DS possess antioxidant, hepatoprotective, and nephroprotective properties in paracetamol-intoxicated rabbits.

Clinical Characteristics of Primary and Overlap Sjögren's Syndrome-Associated Pulmonary Arterial Hypertension: A Multicenter Retrospective Study.

To explore the clinical characteristics and risk factors for adverse outcomes in patients with Sjögren's Syndrome-associated pulmonary arterial hypertension (SS-PAH). A retrospective analysis was conducted on SS-PAH patients diagnosed by right heart catheterization (RHC) between March 2013 and March 2024 across four Chinese medical centers. Patients were categorized into primary SS-PAH (pSS-PAH) and overlap SS-PAH, based on the presence of additional autoimmune diseases. We compared clinical and demographic data, echocardiographic and hemodynamic parameters, treatment strategies, and event-free survival between the groups. Statistical analyses included t-tests, Wilcoxon rank-sum tests, χ2 tests, Fisher's exact tests, and Kaplan-Meier survival analysis. Overlap SS-PAH was most commonly associated with systemic lupus erythematosus (SLE). Compared with pSS-PAH, overlap SS-PAH patients had a lower proportion of WHO functional class III-IV, lower pulmonary vascular resistance (PVR), and higher cardiac index (CI). They also showed higher treatment success rates and better event-free survival. However, overlap SS-PAH patients with primary biliary cholangitis (PBC) or autoimmune hepatitis (AIH) had significantly lower 1-year event-free survival rates, older age, and elevated alkaline phosphatase (ALP) levels. Overlap SS-PAH generally has a better prognosis than pSS-PAH, with improved exercise capacity and milder hemodynamic abnormalities. However, overlap with PBC/AIH is associated with a poorer prognosis. These findings highlight the heterogeneity of SS-PAH and the need for tailored treatment based on underlying autoimmune conditions. NCT05980728, https://clinicaltrials.gov.

Association between alkaline phosphatase levels and mortality in Chinese patients with colorectal cancer with liver metastases: a retrospective cohort study.

Alkaline phosphatase (ALP) is a potential cancer biomarker. However, its prognostic value in patients with colorectal liver metastasis remains unclear. This study aimed to investigate the association between ALP levels and mortality risk in patients with colorectal liver metastases (CRLM), providing insights for enhancing prognostic assessments. Retrospective cohort study. This study included 195 patients with CRLM from a single centre in China. ALP level was the primary exposure variable, with demographic, clinical and pathological factors serving as covariates. Multivariate Cox regression analyses were used to evaluate the impact of ALP on mortality over a 4-year follow-up period. Covariates included the number of liver metastases, T stage, N stage, chemotherapy, tumour location, primary surgery, topical treatment, apolipoprotein A1, targeted therapy, tumour type, CA-199 levels, metastatic surgery, sex, Karnofsky Performance Status and age. Of 195 enrolled patients, 134 (68.72%) were male, and 61 (31.28%) were female, with ages ranging from January 2008 to December 2019. A total of 147 patients (76.96%) were diagnosed with left hemicolon cancer and 44 (23.04%) with right hemicolon cancer. After adjusting for the covariates, elevated ALP levels were significantly associated with an increased risk of mortality (hazard ratio = 1.24, 95% confidence interval: 1.08-1.43, p = 0.0029). Sensitivity analyses confirmed the robustness of these findings, reinforcing the association across different analytical approaches. ALP level is a valuable prognostic indicator in patients with CRLM. Integrating ALP measurement into clinical practice may enhance risk stratification and patient management. Future research should explore the role of ALP in broader populations and explore its implications for treatment strategies.

Elevated liver enzymes and diabetes in the PERSIAN Guilan cohort study.

Diabetes mellitus (DM) is highly consequential to global health among chronic diseases. Due to a limited researches that have examined relationships between liver enzymes and DM, this study aimed to investigate the link between elevated liver enzymes and diabetes among Prospective Epidemiological Research Studies in Iran (PERSIAN) Guilan cohort study (PGCS) population. This cross-sectional study was conducted on 10519 individuals. The demographic and clinical information of the participants was recorded. The changes in alanine aminotransferases (ALT) and aspartate aminotransferases (AST), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) were evaluated. IBM SPSS Version 21 was used to analyze the data, with a significance level < 0.05. The frequency of diabetes was 24.1% and was more prevalent in women than men (27.4% vs. 20.2%, p< 0.001). After removing all confederates, patients with elevated ALT, AST, GGT, and ALP levels were 1.27, 1.27, 1.52, and 1.46 times more likely to have diabetes, respectively. The likelihood of developing diabetes rose in correlation with the number of elevated liver enzymes, up to almost 1.77-fold among subjects with three or four increased liver enzymes. Patients diagnosed with diabetes exhibited significantly increased levels of liver enzymes compared to those without diabetes. Also, impairment of three or four liver enzymes demonstrated a positive correlation with an elevated likelihood of DM. This indicates the importance of considering the liver status in the management of the DM population.

Evaluating alloxan-induced diabetic rats

The increasing incidence of diabetes and the adverse effects of chemical medications underscore the importance of exploring alternative non-pharmacological treatments. Vernonia amygdalina, a widely utilized medicinal herb, shows promising therapeutic potential. This study investigated the impact of aqueous leaf extracts of Vernonia amygdalina on various biochemical parameters in alloxan-induced diabetic rats. Diabetes was induced in male Wistar rats through intraperitoneal injection of alloxan (150 mg/kg). The rats were then randomly divided into four groups: Group 1 (normal control), Group 2 (diabetic control), Group 3 (diabetic rats treated with Vernonia amygdalina at 80 mg/kg), and Group 4 (diabetic rats treated with glibenclamide at 5 mg/kg). The treatments were administered orally for 28 days. Results showed that Vernonia amygdalina significantly reduced blood glucose and glycated hemoglobin levels in diabetic rats compared to untreated diabetic controls (P &lt; 0.001). After 28 days of treatment, the extracts also notably improved altered biochemical parameters in diabetic rats versus the untreated controls (P &lt; 0.05). Specifically, Vernonia amygdalina reduced elevated levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) (P &lt; 0.05). Additionally, the extract demonstrated hepatoprotective and nephroprotective properties, indicated by reductions in liver enzyme levels and improvements in kidney function markers. In summary, the aqueous leaf extract of Vernonia amygdalina showed beneficial effects on selected biochemical markers in alloxan-induced diabetic rats, suggesting its potential role in diabetes management.

Antiplasmodial Potentials, Phytocompounds, and the Possible Toxic Effects of Administration of Ethylacetate Extract of Spondias mombin Linn.

Malaria, caused by Plasmodium parasites, is a global health concern. Natural products, such as plant extracts, are investigated for new antimalarial agents. Spondias mombin, traditionally used for medicinal purposes, was examined for its effects on parasitemia, hematological parameters, antioxidant activities, liver function biomarkers, and serum electrolytes in Plasmodium berghei-infected mice. Mice received varying doses of the ethylacetate extract. Various dosages of the extract and the prescribed medication dramatically slowed the parasite's growth. The extract significantly improved red blood cell (RBC) and platelet counts, particularly at higher doses. Hemoglobin levels were decreased dose-dependently. Antioxidant analysis showed increased superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced catalase (CAT) activities and malondialdehyde (MDA) levels, indicating robust antioxidant properties. Liver function tests showed mixed effects, with elevated aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB) levels at some doses, yet decreased alanine aminotransferase (ALT) at the highest dose, suggesting possible hepatoprotective effects. Serum electrolyte levels remained stable. Seventy-eight (78) bioactive components were identified in the extract by gas chromatography-mass spectrometry (GC-MS) analysis. The extract demonstrated substantial antimalarial and antioxidant capacities, with minimal liver stress and stable electrolyte levels, suggesting safety as an adjunct therapy for malaria. Further research is needed to ascertain the specific antimalarial bioactive constituents and their mechanisms of action.

Comparative Analysis of Alkaline Phosphatase Levels in Gingival Crevicular Fluid: A Three-Time Point Study Comparing Clear Aligners and Fixed Orthodontic Appliances

ABSTRACT Aim: To evaluate the alkaline phosphatase level in gingival crevicular fluid (GCF) at three time points using clear aligners and fixed orthodontic appliances. Materials and Methods: A prospective randomized controlled trial was conducted in a tertiary care hospital to treat patients with 4–6 mm crowding in their upper front teeth. The study involved 20 patients, with 10 assigned to each group. Eligible patients had fully erupted permanent teeth, moderate crowding, and excellent dental health. The study lasted for 14 days and involved thermoplastic trays, Gemini metal brackets, and micropipettes. Results: This clinical study analyzed 20 participants, comprising 11 females and 9 males, with an average age of 25.23 ± 3.56 years. The data showed no significant differences in alkaline phosphatase (ALP) levels between the fixed orthodontic appliance and clear aligner groups. However, there was a notable increase in ALP levels in the crevicular fluid across both groups. The clear aligner group had significantly higher ALP levels at time points T1 and T2. Conclusion: Clear aligners may facilitate faster tooth movement due to elevated crevicular ALP levels, although robust scientific evidence is limited. The light force exerted by clear aligners may not significantly impact the overall rate of tooth movement.

Alkaline phosphatase is associated with vascular depression in patients with severe white matter hyperintensities.

Cerebrovascular disease (CVD) poses a substantial risk for depression. Elevated levels of alkaline phosphatase (ALP) serve not only as an independent predictive factor for acute cerebrovascular events and unfavorable prognoses but also as a significant predictor of depression in premenopausal women. Nevertheless, the association between elevated ALP levels and vascular depression (VDe) in patients presenting with white matter hyperintensities (WMHs) remains unclear. In a cross-sectional survey, 265 individuals diagnosed with CVD were incorporated. Baseline demographic information, fasting blood parameters, and MRI data were systematically gathered for analysis. All patients were divided into a severe WMHs (sWMHs) group and a mild WMHs (mWMHs) group based on their Fazekas score. Univariate analysis of potential variables among different subgroups of patients with scores of Hamilton Rating Scale for Depression (HAMD) was performed. Subsequently, the diagnostic effectiveness of multivariables for positive VDe within two WMHs groups was assessed using binary logistic regression. The diagnostic capability of the multivariate approach for VDe was further scrutinized through ordinal logistic regression. (1) Hypersensitivity C-reactive protein (hs-CRP, p = 0.031), high-density lipoprotein cholesterol (HDL-C, p = 0.038), apolipoprotein A1 (APOA1, p = 0.009), and ALP (p = 0.011) exhibited distinct expression in patients with mWMHs across varying HAMD scores. In contrast, erythrocyte counts (p = 0.024), hemoglobin (Hb, p = 0.011), hs-CRP (p = 0.002), and ALP (p = 0.021) displayed differential expression in patients with sWMHs across different HAMD scores. (2) ALP and hs-CRP combined with APOA1 or Hb can improve the diagnostic efficiency of positive VDe in sWMHs [AUC = 0.849, 95% CI (0.753, 0.946), p < 0.001] or mWMHs [AUC = 0.718, 95% CI (0.603, 0.834), p = 0.002] patients, respectively. (3) Alkaline phosphatase (ALP) [OR = 1.016, 95% CI (1.003, 1.028), p = 0.016] is correlated with VDe in patients with sWMHs, a relationship that persisted even following adjustments for age and sex. The amalgamation of multiple markers enhances the diagnostic efficacy of VDe through WMHs classification. Serum ALP is associated with VDe in sWMHs patients.

Prevalence and heterogeneity of antinuclear antibody patterns in adult Italian patients with autoimmune liver diseases: Our experience

Background and aimThis study aims to explore the clinical significance of antinuclear antibodies (ANA) patterns in liver diseases. Materials and methodsWe included 396 patients with a request for ANA testing for suspected autoimmune liver disease (AILD). For each patient, we collected demographical, clinical, and laboratory data. ResultsAmong the patients, 33% had AILD, predominantly aiutoimmune hepatitis (AIH). The AC1 pattern was significantly more prevalent in AIH patients, while the AC21 pattern was strongly associated with primary biliary cholangitis (PBC). AC4-AC5 patterns were less frequent in AIH and PBC patients but more common in non-alcoholic hepatitis. Elevated alkaline phosphatase and gamma-glutamyl transferase levels were observed in AILD patients with AC11, AC12, and AC21 patterns. ConclusionsThese findings highlight the different distribution of ANA patterns in liver diseases, with specific patterns showing strong associations with distinct liver conditions.

Toxicological assessment of the aqueous extract of Juniperus oxycedrus L. on acute and subacute toxicities in rats

Juniperus oxycedrus L. (J. oxycedrus) has a rich historical background in herbal remedies to treating digestive system abnormalities. However, no comprehensive evaluation of its potential toxic effects has been conducted. The current investigation aimed to evaluate the acute and subacute toxicity of an aqueous extract of J. oxycedrus (AEJO). AEJO was prepared by the conventional Moroccan methods by decoction the arial part of the plant. The acute and subacute toxicity tests were conducted in mice and rats, respectively. Acute toxicity tests showed that the extract was not toxic even at high doses of 5000 mg/kg. In the subacute study, no detectable indications of toxicity or mortality were observed and there were no notable deviations in food intake or water consumption among all rats. However, changes in body weight of animals treated with 1000 and 2000 mg/kg underwent a significant decrease. AEJO administration decreased platelet number, elevated levels of alanine aminotransferase and alkaline phosphatase, and reduced albumin levels. Histological examination revealed normal renal parenchyma despite increased creatinine. It also showed binucleation, and hepatocyte vacuolation. The results indicate that AEJO has considerable tolerance for consumption, but repeated use can affect hepatocytes and kidneys. Therefore, additional analyses, such as subchronic, chronic, and neurotoxic studies, are required before using this plant in clinical research.

6976 Early-Onset Paget's Disease- A Unique Presentation In A Young Female With Elevated Alkaline Phosphatase And Low Back Pain

Abstract Disclosure: F. El Sayed: None. Background Paget disease of bone is an age-related disorder characterized by abnormal growth in certain bones, leading to changes in size and shape. Commonly affecting the skull, spine, pelvis, and long bones, it is more prevalent in men, those over 55, with a family history, and of European ancestry. The prevalence of Paget's disease of bone is approximately 2-3% in individuals over 55 in the United States and Europe, with higher rates in those of European descent. Symptoms, such as pain and deformities, may arise from the condition itself or complications like arthritis. While Paget disease can cause visible abnormalities and fractures in affected bones, most individuals remain asymptomatic. Diagnosis often involves blood tests measuring alkaline phosphatase levels, bone scans, and x-rays. Case Presentation We present the case of a 34-year-old woman who sought evaluation due to persistently elevated alkaline phosphatase (ALP) levels in the thousands. The abnormality was discovered during routine blood work conducted during her pregnancy in 2020, and subsequent investigation revealed a chronic elevation for over three years. The patient reported chronic lower back pain but denied other neurological symptoms. Quantification of ALP Bone showed elevated levels at 629, with normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as well as within-range calcium and gamma-glutamyl transferase (GGT). A whole-body bone scan revealed marked radio tracer uptake in the calvarium, raising concerns for Paget's disease. The patient received a one-time infusion of Zoledronic acid (5 mg), leading to a significant decrease in ALP levels to 182 after three months. Subsequent examination by an Ear, Nose, and Throat (ENT) specialist unveiled bilateral extra bone deposition and mild hearing loss in the right ear, adding a unique dimension to the patient's presentation. This case highlights the importance of a comprehensive approach to diagnose and manage Paget's disease, even in younger individuals with atypical symptoms. Discussion and conclusion Paget's disease presenting in young adults with back pain can be a diagnostic challenge due to its atypical occurrence in this age group. Although back pain is a common symptom, the underlying cause might not immediately be linked to Paget's disease, which typically affects older individuals. However, when encountering persistent back pain in young adults, especially when accompanied by elevated alkaline phosphatase levels, clinicians should consider Paget's disease as a potential differential diagnosis. Further investigation, including imaging studies and bone scans, becomes crucial to confirm the presence of Paget's disease and initiate appropriate management strategies to mitigate its impact on the patient's health and quality of life. Presentation: 6/2/2024

7063 Serum Alkaline Phosphatase Level as a Marker for Progressive Central Precocious Puberty

Abstract Disclosure: V.M. Figueredo: None. T. Seeherunvong: None. Background: Precocious puberty is typically associated with a speed up in growth, risk of premature growth plate closure and reduced adult height. Serum alkaline phosphatase (ALP) is a biochemical indicator of bone turnover and studies have shown greater serum ALP levels in pubertal individuals compared to prepubertal controls. We examined serum ALP levels among children with various form of early puberty. We investigated whether serum ALP levels were significantly different between children with premature thelarche or premature adrenarche compared to those with central precocious puberty (CPP). Methods: We conducted a retrospective chart review of patients with early pubertal development attending a pediatric endocrinology clinic between 2017 and 2023. Information on height, weight, serum ALP levels and bone age was obtained. Patients were considered to have CPP based on the results on a GnRH test. Patients with diagnosis of premature adrenarche or premature thelarche were included as controls. This study was approved by Institutional Review Board (IRB). Analysis of data was performed using IBM SPSS Statistics version 29.0.1.0 (171). Results: Among 72 patients included in the study, 22 patients had progressive CPP whereas 50 patients had premature adrenarche or premature thelarche. The prevalence of abnormally elevated serum ALP levels was greater among patients with CPP (22.7%) than among patients with premature adrenarche or premature thelarche (6%). Using logistic binomial regression analysis, serum ALP levels were significantly elevated (p=0.042) in subjects with progressive CPP compared to patients with premature adrenarche or premature thelarche. Both groups had similar BMI values. BMI z-scores and advanced bone age were positively correlated. BMI (p=0.08) and advanced bone age were not significantly different (p=0.12) in the group with CPP compared with the group comprising patients with either premature adrenarche or premature thelarche. Conclusion: These findings suggest that serum ALP levels are helpful as a tool to help distinguish CPP from premature adrenarche or premature thelarche in the evaluation of patients with initial early pubertal development. Presentation: 6/1/2024

9336 Bone Pain Caused By Computer Cleaners Huffing

Abstract Disclosure: M. Sokrab: None. V.S. Rao: None. P. Shah: None. J.L. Shaker: None. A 47 year-old woman was evaluated 2/2024 for bone pain especially in the forearms and lower legs. The symptoms were worse since about 4/2023. Initial evaluation 11/2023 revealed elevated alkaline phosphatase levels and markers of bone remodeling (P1NP 396 ug/dl, normal; 20-101 and C-telopeptide 4389, normal; 177-1015. The plasma fluoride level was 17.1 mcmol/L (normal; &amp;lt; 4.1). There was no history of excess exposure to fluoride from dental products. She did not drink powdered iced tea or use green tea capsules. There was no industrial fluoride exposure and she consumed city water. She used inhaled fluticasone twice weekly but was not taking other fluoride containing medications, particularly voriconazole. She reported huffing computer cleaner containing difluoroethane between mid 2023 and early 2024. On examination, she had diffuse skeletal tenderness especially over her forearms and lower legs. Lab data revealed calcium 9.2 mg/dl (normal, 8.6-10.2), albumin 4 g/dl, phosphorus 3.6 mg/dl (normal, 2.5-4.5), creatinine 1.08 mg/dl (normal, 0.5-1.1), ionized calcium 1.33 mmol/l (normal, 1.18-1.33), pH normalized ionized calcium 1.25 mmol/l (normal, 1.18-1.33), PTH 126 pg/ml (normal, 15-72), 25(OH)vitamin D 29.5 ng/ml (normal, 20-50), and alkaline phosphatase 287 u/l (normal, 40-120) with a predominant elevation of the bone isoenzyme. The bone specific alkaline phosphatase was 93.4 mcg/l (normal, 7.0-22.4). The SPEP revealed a biclonal IgG Kappa monoclonal protein too small to quantify. The repeat fluoride level was 1.2 mg/l (normal, &amp;lt;0.05). Imaging included diffuse uptake on bone scan as well as periostitis/periosteal thickening involving legs, arms, and hands. There was axial osteosclerosis. Our patient appears to have skeletal fluorosis. Although the time-line of reported huffing and symptoms is not completely consistent, we could find no other exposure to fluoride and speculate she may have been huffing before she recalls. Skeletal fluorosis (SF) is endemic in some countries generally related to drinking water or tea that is high in fluoride, In the US, SF is caused by abnormal use of fluoride-containing dental products, excessive consumption of powdered iced tea containing fluoride, chronic use of the antifungal agent voriconazole and now more often huffing abuse of computer cleaners containing difluoroethane. The number of reported cases of huffing-related SF appears to be increasing and greater awareness of this problem is needed. Presentation: 6/1/2024

An observational study of the causes of an isolated elevated alkaline phosphatase level of unclear etiology

BackgroundSerum alkaline phosphatase (ALP) is a commonly obtained laboratory test, but its diagnostic specificity is limited because it is found in multiple tissues. We investigated patients with isolated, elevated, ALP levels without an obvious etiology at presentation to determine the frequency of different causes of an isolated elevated ALP. MethodsThis was a retrospective, cohort study of adults (age >18 years old) from January 1st, 2013, to June 30th, 2020 in both the in- and outpatient setting at the Medical University of South Carolina. 260 patients with an isolated, elevated ALP of unknown etiology (patients with known biliary obstruction, underlying parenchymal liver disease, or pregnancy were excluded) were included. A secondary outcome was mean survival time from the ALP result. ResultsThe most common cause of ALP elevation was due to underlying malignancy (147, 57%), with 61 patients having infiltrative intrahepatic malignancy, 52 patients having bony metastasis, and 34 patients having both hepatic and bone metastasis. Bone disease (75, 29%), unsuspected parenchymal liver disease (18, 7%), non-malignant infiltrative liver disease (7, 2%), and other disorders (13, 5%) accounted for the remainder of the cohort. Notably, 123 of 260 (47%) patients died within an average of 58 months after identification of isolated, elevated ALP. ConclusionsAn isolated, elevated ALP of unclear etiology is associated with several very specific and important disorders, in particular metastatic intrahepatic malignancy - and is uncommonly associated with primary parenchymal liver disease. Providers should be aware of the potential clinical significance of an elevated ALP.

MORPHOLOGICAL CHANGES IN OSTEOPOROTIC BONES: A COMPARATIVE ANALYSIS USING BIOCHEMICAL AND IMAGING METHODS

Osteoporosis leads to significant bone mass loss and structural deterioration, increasing fracture risk. Objective: This study explores the morphological changes in osteoporotic bones through a comparative analysis using biochemical markers and imaging techniques. Methods: A cohort of 55 osteoporotic patients underwent evaluation. Biochemical markers were measured, including serum calcium, phosphorus, alkaline phosphatase, and vitamin D. Imaging assessments involved dual-energy X-ray absorptiometry (DEXA) for bone mineral density (BMD) and high-resolution computed tomography (HRCT) for bone microarchitecture analysis. Correlations between biochemical data and imaging results were examined. Results: Biochemical analysis showed elevated alkaline phosphatase levels (mean: 210 IU/L) and widespread vitamin D deficiency (mean: 16 ng/mL). DEXA revealed significant reductions in BMD (mean T-score: -3.2), while HRCT detected substantial trabecular thinning (mean trabecular thickness: 0.12 mm) and increased cortical porosity. A strong inverse correlation (r = -0.75, p &lt; 0.01) between BMD and alkaline phosphatase was observed, indicating a link between high bone turnover and reduced density. Vitamin D deficiency correlated with greater cortical porosity (r = 0.60, p &lt; 0.05). Conclusion: The study highlights that integrating biochemical markers and imaging methods provides a comprehensive understanding of osteoporotic bone morphology. These findings emphasize the need for multi-modal diagnostic approaches to enhance osteoporosis management and fracture risk assessment.