Increased Serum Alkaline Phosphatase Levels Research Articles

The Clinical Utility of the Saliva Proteome in Rare Diseases: A Pilot Study for Biomarker Discovery in Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory liver disease characterized by biliary strictures and cholestasis. Due to the lack of effective serological indicators for diagnosis and prognosis, in the present study, we examined the potentiality of the saliva proteome to comprehensively screen for novel biomarkers. Saliva samples of PSC patients and healthy controls were processed and subsequently analyzed using a liquid chromatography-tandem mass spectrometry technique. A bioinformatic approach was applied to detect the differentially expressed proteins, their related biological functions and pathways, and the correlation with the clinical evidence in order to identify a possible marker for the PSC group. We identified 25 differentially expressed proteins in PSC patients when compared to the healthy control group. Among them, eight proteins exhibited area under the curve values up to 0.800, suggesting these saliva proteins as good discriminators between the two groups. Multiple positive correlations were also identified between the dysregulated salivary proteins and increased serum alkaline phosphatase levels and the presence of ulcerative colitis. Pathway analysis revealed significant enrichments in the immune system, neutrophil degranulation, and in the interleukine-17 signaling pathway. We demonstrated the potentiality of saliva as a useful biofluid to obtain a fingerprint of the pathology, suggesting disulfide-isomerase A3 and peroxiredoxin-5 as the better discriminating proteins in PSC patients. Hence, analysis of saliva proteins could become, in future, a useful tool in the screening of patients with suspected PSC.

A rare case of adult hypophosphatasia masked with primary hyperparathyroidism

Abstract Introduction Hypophosphatasia (HPP) is a rare inherited disorder of bone and mineral metabolism due to mutations in the Alkaline Phosphatase-Liver (ALPL) gene encoding the tissue nonspecific alkaline phosphatase (TNSALP). Clinical features of HPP in adults include early loss of teeth, muscle weakness, musculoskeletal pain, osteoporosis and fragility fractures with delayed healing. The most typical biochemical manifestation of the disease is persistently low level of alkaline phosphatase (ALP). Primary hyperparathyroidism (PHPT) is a relatively common endocrine disorder leading to increase in bone turnover markers including ALP. Coexistence of HPP and PHPT is a very rare condition. Herein we present an adult HPP patient who presented with primary hyperparathyroidism and normal serum ALP levels, which decreased significantly after parathyroidectomy. Clinical Case A 33-year-old female with a past medical history of Hashimoto's thyroiditis and acne rosacea admitted to our outpatient clinic because of gradually increasing bone pain, fatigue and weakness. She had early teeth loss and dental problems, but she denied history of fractures and kidney stones. Her family history was remarkable for nephrolithiasis in both parents. On physical examination the patient had facial rash and telangiectasia. She also had teeth loss and many dental cavities. Her vital signs were within normal limits. In biochemical investigations creatinine was 0.45 mg/dL (0.7–1.4), ALP 81 U/L (35–105), PTH 531 pg/mL (15–65), calcium 10.84 mg/dL (8.5–10.5), albumin 4.9 g/dL (3.2–5.5), phosphorus 2.25 mg/dL (2.7–4.5), Vitamin D 5 ng/mL and urine calcium excretion 613 mg/day. Laboratory results were compatible with normocalcemic hyperparathyroidism and severe vitamin D deficiency. Bone mineral density of the lumbar spine and the femoral neck revealed osteopenia and 1/3 distal radius revealed osteoporosis. There was no evidence of nephrolithiasis and nephrocalcinosis on abdominal ultrasound. Neck ultrasound and CT scan and Tc-99m MIBI scanning of the patient revealed a parathyroid adenoma in the posteroinferior of thyroid gland's left lobe. A successful parathyroidectomy was performed. During follow-up the patient's serum ALP levels decreased significantly to 29 U/L with a repeat being 26 U/L. Bone-specific ALP was 4.2 μg/L (3–14 μg/L). Urine phosphoethanolamine was elevated to 68.6 μmol/g.Cr (0–48), which supported the diagnosis of HPP. Genetic analysis was performed and heterozygous p.N190del (c.568_570delAAC/c.566_568delACA) mutation was detected. This mutation was previously reported as pathogenic and has been associated with adult hypophosphatasia. Conclusion Although persistently low level of ALP is characteristic of HPP, disorders that increase bone turnover may result in an increase in serum ALP levels, which may mask underlying HPP. Acknowledgements We are thankful to Alexion Pharmaceuticals, Inc for providing fund for ALP substrates and genetic analysis of the patient.

Persistently elevated alkaline phosphatase could be related to Paget's disease of bone in a patient receiving tenofovir disoproxil fumarate.

The prevalence of Paget's disease of bone (PDB) reaches 1-2% of all adults aged ≥55years old. However, reports describing PDB among HIV positive patients are extremely rare. We report here the case of a HIV positive person receiving tenofovir disoproxil fumarate (DF)-based antiretroviral therapy and who had persistently elevated alkaline phosphatase (AP) revealing PDB. It is well established that tenofovir-DF use is associated with reversible increases in serum AP levels. Clinicians should bear in mind that persistently elevated AP in a person receiving tenofovir DF-based cART could be related to PDB, in particular in person older than 50 years with no other notable biological abnormalities related to kidney tubular dysfunction.

Serum alkaline phosphatase and infection-related mortality in hemodialysis patients: ten-year outcomes of the Q-cohort study.

High serum alkaline phosphatase (ALP) levels are associated with excess all-cause and cardiovascular mortality in patients undergoing hemodialysis (HD). However, the long-term relationship between serum ALP levels and infection-related mortality remains unclear. A total of 3502 maintenance HD patients were registered in the Q-Cohort Study, an observational cohort study in Japan. The primary outcome was infection-related mortality during a 10-year follow-up period. The covariate of interest was serum ALP levels at baseline. The association between serum ALP levels and infection-related mortality was calculated using a Cox proportional hazards model and a Fine-Gray subdistribution hazards model with non-infection-related death as a competing risk. During the follow-up period, 446 patients died of infection. According to their baseline serum ALP levels, the patients were categorized into sex-specific quartiles (Q1-Q4). Compared with patients in the lowest serum ALP quartile (Q1), those in the highest quartile (Q4) had a significantly higher multivariable-adjusted hazard ratio (HR) of 1.70 [95% confidence interval (CI) 1.24-2.32] for infection-related mortality. Furthermore, the HR for every 50U/L increase in serum ALP levels was 1.24 (95% CI 1.12-1.36) for infection-related mortality. These associations remained consistent in the competing risk model: subdistribution HR, 1.47; 95% CI 1.07-2.03 for Q4 compared with Q1. Higher serum ALP levels were significantly associated with a higher risk of infection-related mortality in patients undergoing HD.

Prognostic Value of Pre- and Post-Serum Alkaline Phosphatase Among Renal Transplant Recipients

Recent studies have shown that high levels of serum alkaline phosphatase (ALP) are associated with all-cause and cardiovascular death among patients undergoing hemodialysis. However, there is limited knowledge on the effect of ALP level in kidney transplant recipients (KTRs). The aim of this study was to evaluate if serum ALP levels before and after transplant and the changes in ALP levels are associated with graft failure and mortality. Between January 1997 and December 2012, 3029 KTRs were enrolled in a multicenter cohort. We examined the association of pre- and posttransplant serum ALP levels and long-term outcomes in KTRs. Pretransplant serum ALP level >80 IU/L was associated with a hazard ratio (HR) for graft failure of 1.571 in a fully adjusted model. The graft failure rate gradually increased with ALP level increments of 20 IU/L in KTRs with ALP levels >60 IU/L. An increase in serum ALP level by 40 IU/L during the first 3 months after kidney transplant was associated with higher rates of graft failure (HR, 2.353) and higher rates of mortality (HR, 2.733). Elevated pre-and posttransplant serum ALP levels and increases in the serum ALP levels after kidney transplant increase the risk of graft failure and mortality among KTRs.

Abstract 12: Prediction of rise in alkaline phosphatase at different vitamin D levels

Background: Vitamin D deficiency with rickets and tetany are common in young infants in India. The data on vitamin D status of healthy term breastfed Indian infants and mothers are scant. In fact the correlation of Vitamin D deficiency and alkaline phosphatase (ALP) are inaccurate in many studies.Aim and Objective: To determine whether serum vitamin D levels are correlated with serum levels of alkaline phosphatase or not and to study the point at which ALP surge occurs in Vitamin D deficiency.Results: At 9 months out of 96 samples, 16 had mild Insufficient (≥15 – 20 ng/mL) (20.8%), 42 had moderate Deficient (<15 ng/mL) (54.5%) and 0 had severe Severe deficient (<5 ng/mL) vitamin D deficiencies. All of the patients in the three groups had alkaline phosphatase within normal limits and The ROC curve demonstrated that low vitamin D level is predicted by a high ALP cut off of ALP is 190.90 IU/L with reasonable sensitivity and specificity The correlation coefficient of alkaline phosphatase and serum vitamin D3 levels was r =0.501 (p =0.001).Conclusion: Serum vitamin D3 levels correlated well with increased serum alkaline phosphatase levels but the level at which the ALP surge occur was on lower side.

Haemato- biochemical studies in spinal cord injured dogs treated with a combination of methylprednisolone sodium succinate and 4-aminopyridine or polyethylene glycol

The current study was conducted to compare the effect of 4-aminopyridine (4-AP)and polyethylene glycol (PEG) on haemto-biochemical parameters in methylprednisolone sodium succinate (MPSS) treated dogs for management of spinal cord injuries(SCI). The study was conducted on 14 dogs of different age, breed, sex and body weight, presented with clinical signs of SCI. Animals were randomly divided into two groups and subjected to two treatment protocols. One group was treated with MPSS and PEG intravenously on first day with oral follow up with prednisolone acetate, while the other group was treated with MPSS and 4-AP intravenously with oral follow up with 4-AP. All the selected dogs were subjected to detailed clinical, neurological, radiographic investigations at regular intervals to assess the effect of treatment upto eight weeks. Haematological and serum biochemical parameters were evaluated on the first day of treatment and then at fortnight intervals. The mean values of all the haematological parameters and serum biochemical parameters were found to be within the normal physiological range and were not significant. However a statistically significant increased serum alkaline phosphatase level was observed in the first group and a non-significant increase in second group throughout the period of study.

Estimation and Correlation of Serum Albumin and Serum Alkaline Phosphatase Levels Between Smokers and Non-smokers With Generalized Chronic Periodontitis.

BackgroundPeriodontal disease is a chronic low-grade inflammatory disease triggered by periodontal microbial interaction present in the dysbiotic biofilm and the host's immune response further leads to the destruction of the supporting periodontal apparatus, which may, in turn, lead to tooth loss. Smoking is an environmental risk factor for periodontitis, and it enhances the secretion of various enzymes from host cells, which results in the initiation and progression of periodontal disease. The albumin concentration is related to nutrition and inflammation. Alkaline phosphatase (ALP), an enzyme found in various cells of the periodontium, is considered to cause the destruction of the periodontium. The study aimed to compare the serum albumin and serum ALP levels in smokers and non-smokers with generalized chronic periodontitis.Materials and methodsThe cross-sectional study included a total of 60 subjects. Subjects were divided into two groups, which included non-smokers with generalized chronic periodontitis (NS+P) and smokers with generalized chronic periodontitis (S+P). Clinical parameters analyzed were plaque index, gingival index, probing pocket depth, and clinical attachment level. The serum ALP and albumin levels were analyzed using a fully automated analyzer.ResultsThe serum ALP levels were higher in the S+P group compared to the NS+P group. Conversely, the serum albumin levels were lower in the S+P group compared to the NS+P group.ConclusionThere was a significant correlation of increased serum ALP levels and decreased serum albumin levels in the S+P group compared to the NS+P group.

Evaluation of Serum Alkaline Phosphatase Changes and TGF- β Expression in the Liver of Cholestatic Rats Treated with Ethanolic Extract of Plantago Ovata

BACKGROUND: Induction of cholestasis is one of the methods of liver fibrosis which causes the development of oxidative stress, increased expression of fibrogenic markers, excessive deposition of extracellular matrix, and finally the incidence of fibrosis. Plantago ovata is known as a rich source of various secondary metabolites such as phenolic compounds, flavonoids, alkaloids, trypanoids, and ascorbic acid. OBJECTIVES: the present study, the expression of TGF- β as a fibrotic marker and serum alkaline phosphatase (ALP) changes in cholestatic rats treated with P. ovata extract were evaluated. METHODS: In this study, 48 adult Wistar rats were used. The rats were randomly divided into eight groups of six animals each as follows: (1) healthy control group without bile duct ligation (BDL) surgery and treatment; (2–4) three healthy experimental plus P. ovata groups: rats without BDL, treated with P. ovata at dose levels of 100, 200, and 400 mg/kg body weight, respectively; (5) the BDL group: rats with BDL and treated with distilled water; and (6–8) the BDL plus P. ovata groups: rats with BDL and treated with P. ovata at dose levels of 100, 200, and 400 mg/kg body weight, respectively. The rats were treated with P. ovata extract for 45 consecutive days (once per day). After euthanasia and serum isolation, ALP enzyme level was measured. Moreover, the rat liver was fixed in 10% formalin buffer solution. The immunohistochemical study was performed by TGF-β antibody. Data analysis was performed using the One-way ANOVA and Kruskal-Wallis test and the Prism statistical program (p <0.0001). RESULTS: The results showed a significant increase in the serum levels of ALP enzyme and TGF-β expression in BDL group. Treatment with P. ovata extract was able to significantly improve these changes in a dose-dependent manner. CONCLUSIONS: The results of this study showed that P. ovata extract probably due to its phenolic compounds and its antioxidant effect has a protective effect on the liver and subsequently improves the increased serum ALP level and also reduced TGF-β expression

Increased Serum Alkaline Phosphatase and Functional Outcome in Patients with Acute Ischemic Stroke Presenting a Low Ankle-Brachial Index.

Aims: Elevated serum alkaline phosphatase (ALP) levels are associated with an increased risk of cerebrocardiovascular diseases. However, the associations of ALP with peripheral arterial disease (PAD) and outcomes in patients with acute ischemic stroke (AIS) are not well-known. Methods: We examined the association between ALP levels and the ankle–brachial index (ABI) in 2111 consecutive patients with AIS. A poor functional outcome was defined as a modified Rankin Scale (mRS) score of 3–6 at 3 months after stroke. A low ABI was defined as a value of ≤ 0.9. Results: Of the total cohort, 482 patients (22.8%) had a low ABI. ALP levels were higher in patients with a low ABI than in those without (p＜0.001). The multivariable logistic analysis revealed that quartiles of ALP levels were significantly associated with a low ABI (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.08–1.33). Of the 1322 patients with a premorbid mRS score of 0–2, 434 patients (32.8%) had a poor outcome. The multivariable analysis revealed that elevated serum ALP levels and a low ABI were independently associated with poor stroke outcomes after adjustment for baseline characteristics (OR: 1.21, 95% CI: 1.07–1.38, and OR: 2.00, 95% CI: 1.40–2.84, respectively). Conclusions: Increased serum ALP levels are significantly associated with a low ABI. These indicators are independent prognostic factors for poor stroke outcomes at 3 months.

Genetic polymorphisms in CLDN14 (rs219780) and ALP (rs1256328) genes are associated with risk of nephrolithiasis in Egyptian children.

Nephrolithiasis results from metabolic and anatomic abnormalities together with genetic factors. Claudin 14 (CLDN14) is a protein that regulates the passage of small solutes through the kidneys. Alkaline phosphatase (ALPL) hydrolyzes the pyrophosphate to free phosphate, proposing its enabling role in nephrolithiasis development. Solute carrier family 13 member 2 (SLC13A2) encodes Na+-Pi cotransporter 2a, which is responsible for the renal absorption of phosphate. We aimed to detect the association between CLDN14, ALPL, and SLC13A2 genetic variants and susceptibility to nephrolithiasis in the Egyptian pediatric population. We enrolled 204 consecutive pediatric patients with nephrolithiasis, and 126 normal individuals served as controls. Real-time polymerase chain reaction analysis of CLDN14 rs219780, ALPL rs1256328, and SLC34A1 rs11746443 single-nucleotide polymorphisms (SNPs) was performed. We found that individuals carrying the T allele of CLDN14 rs219780 and ALPL rs1256328 SNPs had a significantly higher risk of nephrolithiasis than the controls (p=0.001 and 0.001, respectively). Genetic association analyses identified that CLDN14 rs219780 and ALPL rs1256328SNPs were significantly associated with the nephrolithiasis status (odds ratio [OR] =4.51; 95% confidence interval [CI]=2.758-7.374; p=0.001 and OR=6.088; 95% CI=3.651-10.152; p=0.001, respectively). The sequence variant ALPL rs1256328 T allele had a significant correlation with the increased serum alkaline phosphatase levels in children with nephrolithiasis (p=0.02). No significant association was found between SLC34A1 rs11746443 SNP and the risk of nephrolithiasis (p=0.5). CLDN14 rs219780 and ALPL rs1256328 SNPs might raise the risk of nephrolithiasis in Egyptian children, and might be used as genetic markers in these patients.

Toxicity assessment of saline extract and lectin-rich fraction from Microgramma vacciniifolia rhizome

Microgramma vacciniifolia is broadly used in folk medicine but safety information is unavailable. Therefore, we evaluated the toxicity of a saline extract and a lectin-rich fraction of M. vacciniifolia rhizome. The extract showed hemolytic activity on mice erythrocytes at 1000 μg/mL, whereas the fraction promoted hemolysis (8.57–26.15%) at all tested concentrations (10–1000 μg/mL). Acute toxicity test in mice indicated an LD50 of >5000 mg/kg. Hematological alterations and increased serum alkaline phosphatase level were observed in the treated animals. Transaminases and urea levels increased in the groups treated with the extract or fraction at 5000 mg/kg. Leukocyte infiltration was observed in the liver of extract-treated animals and in the liver and lungs of mice treated with the fraction. The kidneys of animals treated with the fraction at 5000 mg/kg presented hydropic degeneration. The extract and fraction did not induce oxidative stress in the liver and did not show genotoxicity, as examined by micronucleus and comet assays. In conclusion, the preparations were not lethal to mice but caused some signs of toxicity, mainly the fraction. The results indicated the need to evaluate the toxicity of M. vacciniifolia rhizome in other models and in chronic assays.

Bone mark changes after an eight-month intervention in an osteogenic sport and in physical education in low-income children

Summary Aim Regular physical activity and/or sports practice play an important role in peak bone mass. However, the role of different physical-sportive approaches on bone health is not fully understood, especially in low-income children. The aim of this study was to analyze the changes in bone markers (bone mineral density–BMD and bone metabolism) promoted by two different exercise programs (osteogenic sport and Physical Education–PE) in low-income children. Methods An 8-month intervention program in children (8.07 ± 1.38 years at baseline) was conducted in two groups, Martial Arts (G1, n = 14) and PE (G2, n = 12). BMD was obtained by dual energy X-ray absorptiometry. To determine bone metabolism, serum osteocalcin and alkaline phosphatase (ALP) were collected as indicators of bone formation. General Linear Model (GLM) - ANOVA was used to analyze longitudinal effects in repeated measures with adjustments for maturational stages, calcium consumption and serum vitamin D. Results The within the groups analysis highlighted significant differences for BMD at the arms and spine, and for serum ALP for both groups. After the interventions, G1 presented significant changes in BMD of the total body, femoral neck, proximal total femur and spine (P ≤ 0.05), while G2 presented statistically significant changes in serum ALP levels. The group × time analysis showed significant differences in BMD at the arms (Δ% G1 = 8.1 vs. Δ% G2 = 3.7), and at the spine (Δ% G1 = 5.7 vs. Δ% G2 = 5.0). and in serum ALP (Δ% G1 = 61.1 vs. Δ% G2 = 171.0). Conclusion Both exercise programs increased BMD in the arms and the spine and increased serum alkaline phosphatase levels of low-income children, even after adjustments for potential confounders.

The effects of focal brain damage on fracture healing: An experimental rat study.

This study aims to investigate whether the motor cortex (MC) or the somatosensory cortex (SC) is more active during the course of bone healing after traumatic brain injury (TBI). Thirty-three male Wistar albino rats (age, 8 to 10 months; weighing, 250 to 300 g) were randomized into three groups as the control group, MC damage group and SC damage group. Two rats from each brain damage group were sacrificed to verify the locations of the cortical injuries. Callus formation, callus/diaphysis ratios, and serum alkaline phosphatase (ALP) levels were measured at one, three and six weeks. The increases in callus masses in the control, MC, and SC groups were statistically significantly different between one and three weeks (p<0.05). Although this increase in the MC and SC groups was significant compared to the control group at the end of one week, no statistically significant difference was found between the MC and SC groups (p>0.05). There was a statistically significant difference in callus/diaphysis ratio between control, MC and SC groups in favor of MC group only at one week (p<0.05). The increase in serum ALP levels at three weeks was statistically significantly different in the MC and SC groups compared to the control group and significantly higher in the MC group compared to the SC group (p<0.05). There is a possible relationship between enhanced fracture healing after TBI and damage in the MC. Motor cortex plays a more active role on fracture healing in TBI.

Biochemical Risk Factors for Kidney Stones in Diabetic Patients

Objective: The aim of this study is to investigate the biochemical risk factors of kidney stones in diabetes. This includes the estimation of serum and urinary creatinine (Cr), albumin (Alb), sodium (Na+), potassium (K+), magnesium (Mg++), phosphorous (Po4++), calcium (Ca++), uric Acid (U.A), alkaline phosphatase (ALP), serum parathyroid hormone (PTH), reduced glutathione levels(GSH), urinary Oxalate, as well as citrate and nitric oxide (NO) levels were measured. Subjects and Methods: The clinical study was performed on 100 patients that attended Suez Health Insurance Organization and Ain Elhyah Hospital. Patients were divided into four groups; 25 diabetic patients (D) (mean age 52); 25 renal stone patients (R, S) (mean age 49); 25 diabetic renal stone patients (D R S)(mean age 51) and 25 control subjects (C)((mean age 47) age-matched, randomly selected. Blood and urine 24 hr samples were collected. Results: Serum (Cr) and (Alb) levels showed a non-significant changes in all patients. However, the data showed a significant decrease in (Mg++) level of all patients groups, with a significant level in (D R S) than (D) and (R, S) patients. Moreover, a significant increase in (U.A) levels of all patients groups but higher in (DRS) than (D) and (R, S) patients groups, the data revealed a significant decrease in urinary magnesium level in(DRS) patients group compared to (C), (R, S) and (D) patients groups. Moreover, a significant increase in urinary (U.A) level of all patients was noticed, it was significantly higher level in (DRS) than (R, S) patients groups. Oxalate level in all patients was increased, significantly. Meanwhile, the oxalate level was increased in (DRS) compared to (R, S) and (D) patients groups. The citrate level was decreased significantly in the urine of all patients groups with a significantly lower level of (DRS) than (R, S) and (D) patients groups. On other hand, a significant decrease in blood GSH level of all patients groups was observed where; its level in (DRS) was significantly lower than the (R, S) patients groups. However, data revealed a significant increase in serum (PTH) level of the (R, S) and (D R S) patients groups compared to (C) one. PTH level in (R, S) patients group was significantly higher than (D) and (DRS) patients groups. The data revealed a significant increase in serum ALP level of (D) and (D R S) groups compared to (C) group with a higher significant level in (DRS) than (R,S) patients groups. Moreover, the urinary 24h (NO) level was increased significantly in all patients groups compared to (C) group.

Identification of risk factors and development of detection algorithm for denosumab-induced hypocalcaemia.

This study used electronic medical records to identify risk factors and establish a detection algorithm for denosumab-induced hypocalcaemia. We identified 201 patients with cancer who were initially prescribed denosumab. Hypocalcaemia was defined as an adjusted serum calcium level of ≤2.13mmol/L. A diagnosis of denosumab-induced hypocalcaemia was confirmed by two physicians after reviewing patient medical records. We evaluated patient characteristics as potential screening factors. Moreover, a retrospective cohort study was conducted to identify risk factors for denosumab-induced hypocalcaemia. Odds ratios (ORs) were estimated using logistic regression analysis. We analysed 164 patients with a low risk of hypocalcaemia. Among these, 29 (17.7%) patients were suspected to have denosumab-induced hypocalcaemia. The times to onset of definitive hypocalcaemia were shorter among these patients than among patients with non-denosumab-induced hypocalcaemia. Based on receiver operating characteristic curve analysis, we used time to onset of hypocalcaemia of ≤90days as a second screening factor. The positive predictive value of this factor was 87.5%. In the retrospective cohort study, a significant difference was observed among patients with serum alkaline phosphatase (ALP) levels of >5.95μkat/L before initial prescription (P<0.01). Patients with higher serum ALP levels had a 6.63 times higher risk of developing hypocalcaemia than those without increased serum ALP levels (OR: 6.63, 95% confidence interval [CI]: 1.79-29.31). The same results were observed in a sensitivity analysis using another database. We developed a detection algorithm for denosumab-induced hypocalcaemia based on calcium levels and time to onset of hypocalcaemia. We also identified elevated ALP levels as a risk factor for hypocalcaemia. Clinicians should carefully monitor initial serum calcium levels and screen for signs of hypocalcaemia in patients receiving denosumab who demonstrate elevated serum ALP levels.

Therapeutic effect of Guijiajiao (Colla Carapacis et Plastri) on bone regeneration in rats and zebrafish

OBJECTIVETo investigate the effect of Guijiajiao (Colla Carapacis et Plastri, CCP), the glue of tortoise shell, on bone regeneration in zebrafish and male Wistar rats. METHODSIn this study, we applied in vitro and in vivo models, tissue section analysis, and quantitative polymerase chain reaction to assess the effects of CCP on bone repair. MG-63 cells were used in alkaline phosphatase (ALP) activity and mineralization assays. Zebrafish and male Wistar rats were used to evaluate the effects of CCP on bone repair in vivo. RESULTSA simple preparation of CCP promoted osteogenesis in vivo and in vitro, and promoted MG-63 cell proliferation as well as ALP activity and mineralization. In addition, CCP activated Akt and extracellular signaling-regulated kinase pathways and significantly increased the expression of ossification-related genes and proteins such as runt-related transcription factor-2, osteocalcin, and osteopontin. The in vivo results revealed promotion of osteogenesis by immersing zebrafish in CCP for 72 h. An oral dose of 1.25 g/kg CCP significantly improved skull defects in rats, which was accompanied by an increase in serum ALP levels. CONCLUSIONOne of the ingredients of Guilu Erxianjiao (tortoise shell and deer horn formula) provides a practical alternative therapy for bone regeneration.

Effects of Simvastatin and Combination of Simvastatin and Nylestriol on Bone Metabolism in Ovariectomized Rats.

We aim to compare the effects of simvastatin and combination of simvastatin and nylestriol on bone metabolism in ovariectomized (OVX) rats. Fifty healthy Wistar female rats were randomly allocated into 5 groups: sham + saline group (group A), OVX + saline group (group B), OVX + simvastatin (5 mg·kg·d) (group C), OVX + nylestriol (0.01 mg·kg·d) (group D), and OVX + simvastatin (3 mg·kg·d) + nylestriol (0.005 mg·kg·d) (group E). All mice were orally administrated with saline or medicine dissolved in saline for 10 weeks. Body weight of rats before and after the experiment was measured. Twenty-four hours after the experiment, calcium (Ca), creatinine (Cr), and hydroxyproline in urine were detected. Serum levels of osteocalcin (bone Gla-protein, BGP) and alkaline phosphatase (ALP) were measured. Bone mineral density was detected and trabecular bone was observed after the isolation of femur and tibia. Remarkably decreased serum BGP and increased serum ALP levels were detected in group B compared with those in group A. However, notably increased serum BGP and decreased serum ALP levels were found in groups C, D, and E compared with those in group B; femoral and tibial bone mineral density decreased in group B compared with that in group A, but increased in groups C, D, and E compared with that in group B. Simvastatin and combination of simvastatin and nylestriol promote formation of new bone, increase bone density, and improve bone microstructure damage in OVX rats.

Tumour-induced osteomalacia: An emergent paraneoplastic syndrome

Endocrine paraneoplastic syndromes are distant manifestations of some tumours. An uncommon but increasingly reported form is tumour-induced osteomalacia, a hypophosphatemic disorder associated to fibroblast growth factor 23 (FGF-23) secretion by tumours. The main biochemical manifestations of this disorder include hypophosphatemia, inappropriately low or normal tubular reabsorption of phosphate, low serum calcitriol levels, increased serum alkaline phosphatase levels, and elevated or normal serum FGF-23 levels. These tumours, usually small, benign, slow growing and difficult to discover, are mainly localized in soft tissues of the limbs. Histologically, phosphaturic mesenchymal tumours of the mixed connective tissue type are most common. Various imaging techniques have been suggested with variable results. Treatment of choice is total surgical resection of the tumour. Medical treatment includes oral phosphorus and calcitriol supplements, octreotide, cinacalcet, and monoclonal antibodies.

Osteomalacia tumoral: un síndrome paraneoplásico emergente

Endocrine paraneoplastic syndromes are distant manifestations of some tumours. An uncommon but increasingly reported form is tumour-induced osteomalacia, a hypophosphatemic disorder associated to fibroblast growth factor23 (FGF-23) secretion by tumours. The main biochemical manifestations of this disorder include hypophosphatemia, inappropriately low or normal tubular reabsorption of phosphate, low serum calcitriol levels, increased serum alkaline phosphatase levels, and elevated or normal serum FGF-23 levels. These tumours, usually small, benign, slow growing and difficult to discover, are mainly localized in soft tissues of the limbs. Histologically, phosphaturic mesenchymal tumours of the mixed connective tissue type are most common. Various imaging techniques have been suggested with variable results. Treatment of choice is total surgical resection of the tumour. Medical treatment includes oral phosphorus and calcitriol supplements, octreotide, cinacalcet, and monoclonal antibodies.