Serum Bone-specific Alkaline Phosphatase Levels Research Articles

Bone-specific alkaline phosphatase – a potential biomarker for skeletal growth assessment

The present study was aimed to assess levels of serum Bone-specific alkaline phosphatase (BALP) and serum Insulin-like growth factor-1 (IGF-1) and comparing with cervical vertebral maturation index (CVMI) stages. Cross-sectional study. Maulana Azad Institute of Dental Sciences, New Delhi, India. 150 subjects (75 males and 75 females) in the age group of 8-20 years. Subjects were divided into six CVMI stages. Enzyme-linked immunosorbant assay was performed for the estimation of serum BALP and serum IGF-1 levels. Mann-Whitney U test was performed to compare mean ranks of serum BALP and serum IGF-1 with different CVMI stages. Spearman correlation between serum BALP and serum IGF-1 was done across 6 CVMI stages. Peak serum IGF-1 levels were found at CVMI stages 4 and 3 for males and females respectively. Peak levels for serum BALP were found at stage 3 for both genders with significant differences from other stages. A statistically significant correlation was seen between serum IGF-1 and serum BALP from CVMI stages 1 to 3 and 4 to 6 (p < .01). BALP showed promising results and can be employed as a potential biomarker for the estimation of growth status.

Lower Bone Mass and Higher Bone Resorption in Pheochromocytoma: Importance of Sympathetic Activity on Human Bone.

Despite the apparent biological importance of sympathetic activity on bone metabolism in rodents, its role in humans remains questionable. To clarify the link between the sympathetic nervous system and the skeleton in humans. Among 620 consecutive subjects with newly diagnosed adrenal incidentaloma, 31 patients with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 280 patients with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively. After adjustment for confounders, subjects with pheochromocytoma had 7.2% lower bone mass at the lumbar spine and 33.5% higher serum C-terminal telopeptide of type 1 collagen (CTX) than those without pheochromocytoma (P = 0.016 and 0.001, respectively), whereas there were no statistical differences between groups in bone mineral density (BMD) at the femur neck and total hip and in serum bone-specific alkaline phosphatase (BSALP) level. The odds ratio (OR) for lower BMD at the lumbar spine in the presence of pheochromocytoma was 3.31 (95% confidence interval, 1.23 to 8.56). However, the ORs for lower BMD at the femur neck and total hip did not differ according to the presence of pheochromocytoma. Serum CTX level decreased by 35.2% after adrenalectomy in patients with pheochromocytoma, whereas serum BSALP level did not change significantly. This study provides clinical evidence showing that sympathetic overstimulation in pheochromocytoma can contribute to adverse effects on human bone through the increase of bone loss (especially in trabecular bone), as well as bone resorption.

Effects of Yishengukang decoction on expression of bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, and carboxyterminal cross-linked telepeptide of type I collagen in malignant tumor patients with bone metastasis

OBJECTIVETo investigate the effect of Yishengukang decoction on the expression of the metabolic bone markers, bone-specific alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), and carboxyterminal cross-linked telepeptide of type I collagen (ICTP), in cancer patients with bone metastasis. METHODSPatients (n = 180) were divided into three groups: (a) bone metastasis patients treated with Yishengukang and pamidronate disodium injection (treatment group, n = 60); (b) bone metastasis patients treated with pamidronate disodium injection alone (control group, n = 60); (c) cancer patients without metastatic bone lesion (non-bone metastasis group, n = 60). Serum levels of the metabolic markers BAP, PICP, and ICTP were detected by enzyme-linked immunosorbent assay pre- and post-therapy. RESULTSA significant decrease in serum BAP level was observed in the treatment group compared with the control group. However there were no significant differences in serum levels of PICP and ICTP before or after treatment compared with the control group. CONCLUSIONYishengukang decoction combined with pamidronate disodium injection reduced serum BAP level to a greater extent that pamidronate disodium injection alone. Furthermore, the combined therapy was more beneficial in regulating imbalanced bone metabolism after bone metastasis, and may represent the molecular mechanism underpinning the effects of Yishengukang decoction.

Investigating the Effects of Systemically Administered Strontium Ranelate on Alveolar Bone Loss Histomorphometrically and Histopathologically on Experimental Periodontitis in Rats.

The aim of this study is to investigate effects of strontium ranelate (SR) on alveolar bone loss (ABL) in rats with experimental periodontitis. Forty Wistar rats were randomly divided into five groups: 1) control (n = 8); 2) ligated (n = 8); 3) 300 mg/kg SR (SR300, n = 8); 4) 625 mg/kg SR (SR625, n = 8); and 5) 900 mg/kg SR (SR900, n = 8). To create experimental periodontitis, 4/0 silk ligatures were inserted submarginally around first molars at the right mandible. After 11 days, rats were sacrificed. ABL was calculated by measuring cemento-enamel junction and alveolar crest distance. Interleukin (IL)-1β, osteoprotegerin (OPG), and bone-specific alkaline phosphatase (BALP) serum levels were determined by enzyme-linked immunosorbent assay. Histopathologic analysis was used to evaluate inflammatory cell infiltration, numbers of osteoblasts and osteoclasts, and receptor activator of nuclear factor-kappa B ligand (RANKL) activity. ABL was significantly lower in SR900 group than in the ligated group (P <0.05). Osteoclast numbers in ligated group were significantly higher than in the control, SR300, and SR900 groups (P <0.05). In ligated, SR625, and SR900 groups, significantly higher osteoblast numbers were detected than in control group (P <0.05). Osteoblast numbers in SR625 group were significantly higher than in the SR300 group (P <0.05). RANKL activities in SR900 and control groups were close to each other (P >0.05). Serum IL-1β, OPG, and BALP levels revealed no significant difference (P >0.05). It can be concluded that SR can reduce RANKL activity and osteoclast numbers, as well as ABL.

Effects of glucocorticoid-induced osteoporosis on bone tissue of rats with experimental periodontitis

ObjectiveTo evaluate the effects of osteoporosis induced by glucocorticoid (GIOP) on bone tissue of rats with experimental periodontitis (EP). Design48 male Wistar rats divided into groups: Naïve, EP, GIOP and GIOP+EP. Rats of GIOP and GIOP+EP groups received 7mg/kg of dexamethasone intramuscularly once a week for 5 weeks. Following, EP and GIOP+EP groups were subjected to ligature-induced periodontitis. Naïve group experienced no manipulation. After 11 days, the animals were euthanized and left maxillae collected for macroscopic, radiographic, micro-tomographic and microscopic analysis of alveolar bone loss (ABL). Blood samples were collected for determination of bone-specific alkaline phosphatase (BALP) levels and the right femurs were removed for radiographic and biomechanical analysis. ResultsEP caused ABL and reduced BALP levels (p<0,05), but it did not change the architecture or biomechanics of femur, compared to Naïve. GIOP did not cause ABL, but it significantly decreased alveolar bone mineral density (ABMD), bone percentage and trabecular thickness (Tb.Th) and increased alveolar bone porosity (p<0.05) and significantly reduced BALP serum levels, as well as radiographic density and Young’s module of femur, compared to Naïve. There was a greater ABL in group GIOP+EP when compared to EP (p<0.05). GIOP+EP caused a greater decrease on ABMD, Tb.Th, bone percentage and increased bone porosity (p<0.05) and also presented a significant reduction in BALP levels (p<0.05), in radiographic density and in Young’s module of femur compared to EP (p<0.05). ConclusionsGIOP can potentiate the destructive effects of EP on alveolar bone and alter the systemic bone loss, by promoting bone resorption and reducing osteoblast activity.

Effects of Denosumab on Bone Metabolic Markers and Bone Mineral Density in Patients Treated with Glucocorticoids.

Objective We performed a prospective study to determine the efficacy and safety of denosumab on bone metabolic indices and bone mineral density (BMD) in 29 patients receiving long-term glucocorticoids (GCs) who had clinical risk factors for fracture. Methods Among these patients, 16 had systemic lupus erythematosus (SLE), 6 RA, 4 other autoimmune diseases, and 3 renal diseases. All patients received donosumab 60 mg at baseline and 6 months. Serum N-terminal cross-linked telopeptide of type I collagen (NTX) and bone-specific alkaline phosphatase (BAP) levels were measured as bone metabolic indices. BMD at the lumbar spine (LSBMD) and femoral neck (FNBMD) were measured using dual energy X-ray absorptiometry and expressed as a percentage of the young adult mean (%YAM). Results Denosumab therapy significantly reduced serum NTX and BAP levels from baseline after 12 months (from 19.2 to 13.9 nmol BCE/L; from 11.9 to 9.2 U/L, respectively). In 18 patients treated with bisphosphonates before the start of denosumab therapy, the improvements in the LSBMD and FNBMD values were 1.5%YAM/year and 1.1%YAM/year, respectively. The LSBMD and FNBMD values were both significantly higher 12 months after denosumab therapy (3.5%YAM/year and 3.0%YAM/year, respectively). The LSBMD gain was significantly higher after denosumab therapy than during bisphosphonate therapy. No fractures were observed in any patients during denosumab therapy. Conlusion Denosumab is effective and safe in preventing bone resorption and BMD loss in patients treated with long-term GCs for inflammatory diseases. This is the first study showing a significant increase in not only LSBMD but also FNBMD in GC-induced osteoporosis after denosumab therapy.

Anti-inflammatory and Anti-resorptive Effects of Atorvastatin on Alveolar Bone Loss in Wistar Rats.

The aim of this study was to evaluate the anti-inflammatory and anti-resorptive effect of atorvastatin (ATV) in an experimental alveolar bone loss (ABL) model. Wistar rats were subjected to ligature placement around the maxillary second molar for 11 days. The animals received 0.9% saline (2 mL/kg) or ATV (0.3, 3 or 27 mg/kg) daily by gavage. ABL was evaluated by resorption area and histopathological analysis. Serum bone-specific alkaline phosphatase (BALP) activity was also evaluated. Leukogram was performed at 0 h, 6th h, 2nd, 7th and 11th days. Kidney and liver conditions and the body mass variation were analyzed. ATV (3 and 27 mg/kg) inhibited ABL by 39% and 56%, respectively. Histopathological analysis showed that ATV 27 mg/kg prevented ABL and cemental resorption, and inflammatory cell infiltration induced by ligature. ATV (27 mg/kg) prevented serum BALP levels reduction. ATV (27 mg/kg) prevented leukocytosis and did not affect either kidney or liver function nor body mass weight. ATV showed a protecting effect in the ligature-induced periodontitis, without affecting system parameters, by inhibition of inflammatory process and by its anabolic activity on the alveolar bone.

Puerarin affects bone biomarkers in the serum of rats with intrauterine growth restriction

ObjectiveTo investigate serum bone biomarkers in rats with intrauterine growth restriction (IUGR) in order to determine the effects of puerarin on bone metabolism. MethodsA rat model of IUGR was induced using a low protein diet during pregnancy. The offspring were given puerarin or an identical volume of saline via subcutaneous abdominal injection. All rats were studied at 1,3, and 8 weeks of age. Serum biomarkers of bone formation, including insulin-like growth factor-1 (IGF-1), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), osteoprotegerin (OPG), receptor-activator of nuclear factor-KB ligand (RANKL), as well as blood levels of calcium and phosphorus were measured. ResultsSerum BALP, OPG, IGF-1, and OC levels, as well as the OPG/RANKL ratio, were lower in the IUGR group compared with the control group at 1 week of age (P = 0.024, 0.011, 0.014, 0.004, and 0.002, respectively). At 3 weeks of age, the serum BALP and OC levels were higher in the protein-restricted group compared with the control group (P = 0.003 and 0.001, respectively). A comparison between the IUGR plus puerarin intervention group and the IUGR group revealed differences in the levels of BALP and IGF-1 at 3 weeks of age (P = 0.008 and 0.003, respectively). In addition, serum OPG and OC levels and the OPG/RANKL ratio were higher at 8 weeks of age (P = 0.044, 0.007, and 0.016, respectively). No differences in serum calcium and phosphorus levels were observed among the three groups. ConclusionOur study demonstrates that the bone microenvironment of the fetus can be altered by a low protein maternal diet and that puerarin can reverse these effects. These results indicate that the nutritional environment plays an important role in early skeletal development and that the bone turnover of IUGR rats can be altered by puerarin treatment.

Abstract P3-07-45: Bone turnover marker levels and clinical outcomes in patients with breast cancer and bone metastases treated with bone antiresorptive therapies

Abstract INTRODUCTION AND OBJECTIVES: Patients with advanced breast cancer (BC) and metastatic bone disease typically have elevated serum levels of bone turnover markers (BTMs). Potent antiresorptive agents, such as denosumab and zoledronic acid, can significantly reduce BTM levels (Stopeck et al. J Clin Oncol 2010). Prior studies have provided evidence that higher BTM baseline levels may be associated with worse clinical outcomes (Ali et al. Ann Oncol 2004). In this analysis, we assessed the association between BTM levels after treatment with antiresorptive agents and overall survival (OS), disease progression (DP) and disease progression in the bone (DPB) in patients with advanced BC and bone metastases. METHODS: This post-hoc analysis included data from patients with BC and bone metastases enrolled in an international, blinded phase 3 trial who were randomized to receive either denosumab (120 mg SC) or zoledronic acid (4 mg IV, adjusted for creatinine clearance). The BTMs urinary N-telopeptide (uNTx) and bone-specific alkaline phosphatase (BSAP) were measured at study entry and at study month 3. The clinical outcomes of OS, DP, and DPB were compared in patients with BTMs above or below median levels at month 3 of antiresorptive therapy. These covariate analyses were based on Cox models stratified by treatment, prior SRE before month 3, prior bisphosphonate use, chemotherapy at randomization, and region (Japan or other countries). RESULTS: A total of 1705 patients were measured for uNTx serum levels, with 895 patients ≥ and 810 &amp;lt; the median of 10.40 nmol/mmol at month 3. Similarly, BSAP levels were measured in a total of 1708 patients, with 855 patients ≥ and 853 &amp;lt; the median BSAP level of 10.89 ng/mL at month 3. Patients with uNTx levels ≥ the median at month 3 had a significantly reduced OS (by 54%) and a greater risk of both DP (by 21%) and DPB (by 23%) than patients with uNTx levels &amp;lt; median (see Table). Similarly, patients with BSAP levels ≥ the median level at month 3 had an increased risk for reduced OS (by 197%), DP (by 67%) and DPB (by 56%) compared with patients whose BSAP levels &amp;lt; median. After adjusting for risk factors suggestive of more advanced disease such as visceral metastases or &amp;gt; 2 bone metastases, the correlation between elevated BTMs and reduced OS and greater risk of DP and DPB was maintained. CONCLUSIONS: Patients with BTM levels ≥ median at month 3 of antiresorptive therapy had generally worse clinical outcomes than patients whose BTM levels were &amp;lt; median. Assessment of uNTx and BSAP serum levels after treatment with antiresorptive therapy can add to our understanding of which patients with breast cancer and bone metastases are most at risk for decreased OS, or increased DP or DPB. Month 3*Covariate Analysis Results: Risk of Decreased OS or Increased DP or DPBClinical OutcomeHazard Ratio (95% Confidence Interval)P-valueDecrease in OSuNTXa1.539 (1.270, 1.866)&amp;lt;0.0001BSAPb2.966 (2.422, 3.633)&amp;lt;0.0001Increase in DPuNTXa1.214 (1.071, 1.377)=0.0024BSAPb1.666 (1.470, 1.888)&amp;lt;0.0001Increase of DPBuNTXa1.231 (1.054, 1.437)=0.0087BSAPb1.563 (1.342, 1.821)&amp;lt;0.0001*Comparing ≥ median to &amp;lt; median. aMedian uNTx levels=10.40 nmol/mmol. bMedian BSAP level=10.89 ng/mL. Citation Format: Lipton A, Stopeck A, Body J-J, Von Moos R, De Boer R, Paiva Gadelha Guimaraes A, Tonkin K, Fujiwara Y, Zhu L, Warner D. Bone turnover marker levels and clinical outcomes in patients with breast cancer and bone metastases treated with bone antiresorptive therapies. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-45.

Correlation between bone mineral density and serum trace elements in response to supervised aerobic training in older adults.

BackgroundLife style and physical activity play a pivotal role in prevention and treatment of osteoporosis. The mechanism for better bone metabolism and improvement of physical disorders is not clear yet. Trace minerals such as Ca, Mn, Cu, and Zn are essential precursors for most vital biological process, especially those of bone health.ObjectiveThe main target of this study was evaluating the effective role of supervised aerobic exercise for 1 hour/day, 3 days/week for 12 weeks in the functions of trace elements in bone health through measuring bone mineral density (BMD), osteoporosis (T-score), bone markers, and trace element concentrations in healthy subjects aged 30–60 years with age average of 41.2±4.9.MethodsA total of 100 healthy subjects (47 males, 53 females; age range 30–60 years) were recruited for this study. Based on dual-energy x-ray absorptiometry (DEXA) scan analysis, the participants were classified into three groups: normal (n=30), osteopenic (n=40), and osteoporotic (n=30). Following, 12 weeks of moderate aerobic exercise, bone-specific alkaline phosphatase (BAP), BMD, T-score, and trace elements such as Ca, Mn, Cu, and Zn were assessed at baseline and post-intervention.ResultsSignificant improvement in serum BAP level, T-score, and BMD were observed in all participants following 12 weeks of moderate exercise. Participants with osteopenia and osteoporosis showed significant increase in serum Ca and Mn, along with decrease in serum Cu and Zn levels following 12 weeks of aerobic training. In control group, the improvements in serum trace elements and body mass index were significantly linked with the enhancement in the levels of BAP, BMD hip, and BMD spine. These results supported the preventive effects of moderate exercise in healthy subjects against osteoporosis. In both sexes, the changes in serum trace elements significantly correlated (P<0.05) with the improvement in BAP, BMD hip, BMD spine, and body mass index in all groups.ConclusionThe observed changes in the levels of Ca, Mn, Cu, and Zn were shown to be positively correlated with improved bone mass density among control and osteoporosis subjects of both sexes. These results demonstrate that aerobic exercise of moderate intensity might protect bone and cartilage by regulation of body trace elements which are involved in the biosynthesis of bone matrix structures and inhibition of bone resorption process via a proposed anti-free radical mechanism.

Effects of Fok-I polymorphism in vitamin D receptor gene on serum 25-hydroxyvitamin D, bone-specific alkaline phosphatase and calcaneal quantitative ultrasound parameters in young adults.

Several genes have been implicated as genetic determinants of osteoporosis. Vitamin D receptor (VDR) is an intracellular hormone receptor that specifically binds to the biologically active form of vitamin D, 1-alpha, 25- dihydroxyvitamin D3 [1, 25(OH)2D], and mediates its effects. One of the most frequently studied single nucleotide polymorphisms is the restriction fragment length polymorphism (RFLP) Fok-I (rs2228570). The presence of a Fok-I site, designated f, allows protein translation to initiate from the first ATG. An allele lacking the site (ATG>ACG: designated F), initiates from a second ATG site. In the present study, we explored the effect of the VDR Fok-I genotype on associations among serum bone-specific alkaline phosphatase (ALP), 25- hydroxyvitamin D3 [25(OH)D], 1, 25(OH)2D, and the dietary nutrient intake in healthy young Japanese subjects (n=193). Dietary nutrient intakes were calculated based on 3-day food records before the day of blood examinations. Quantitative ultrasound (QUS) parameters at the right calcaneus (heel bone) were measured. The allele frequencies were 0.622 for the F allele and 0.378 for the f allele in all subjects. Grouped by the VDR genotype, a significant positive correlation between the levels of serum bone-specific ALP and 25(OH)D was observed in the FF-type (p=0.005), but not in the ff-type. In addition, there was a significant positive correlation between the level of serum 25(OH)D and osteo-sono assessment index (OSI) in the FF-type (p=0.008), but not in the ff-type. These results suggest that the level of circulating 25(OH)D is an important factor when assessing the VDR Fok-I polymorphism to prevent osteoporosis.

Prospective Evaluation of Zoledronic Acid in the Treatment of Bone Metastases from Differentiated Thyroid Carcinoma.

The objectives of this study were to prospectively delineate the efficacy and safety of zoledronic acid for treating bone metastases (BM) from differentiated thyroid carcinoma (DTC), and to evaluate the relationships between levels of bone metabolic markers and occurrence of skeletal-related events (SREs). This was a prospective, single-arm, single-center study. Nineteen patients with BM from DTC were assigned to receive zoledronic acid therapy every 4-5 weeks. Imaging studies for sites of BM were conducted every 6 months, and levels of bone metabolic markers, including serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide of type I collagen (NTx), were assessed every 3 months. To evaluate the efficacy of zoledronic acid use, data of SREs were compared with those of 16 historical controls. SREs developed in eight patients (42 %), but metastatic spinal cord compression (MSCC) appeared in only one patient. Pain scores were ameliorated in five patients, but aggravated in six patients. Ten patients had stable disease, six showed progressive disease, and none showed partial or complete response during the observation period. Decreases in levels of bone metabolic markers were observed in ten patients for BAP and 15 for NTx. However, no significant correlations were identified between changes in bone metabolic marker levels and development of SREs. Zoledronic acid may offer a mainstay of multidisciplinary treatment for patients with BM for the purpose of reducing SREs. Levels of serum BAP and urinary NTx do not appear reliable as indicators of amelioration of BM symptoms.

Pulsed electromagnetic fields inhibit bone loss in streptozotocin-induced diabetic rats.

Evidences have shown that pulsed electromagnetic fields (PEMFs) can partially prevent bone loss in streptozotocin (STZ)-induced diabetic rats. However, the precise mechanisms accounting for these favorable effects are unclear. This study aimed to investigate the effects of PEMFs on bone mass and receptor activator of nuclear factor κB ligand (RANKL)/osteoprotegerin (OPG) and Wnt/β-catenin signaling pathway in STZ rats. Thirty 3-month-old Sprague Dawley rats were randomly divided into the following three groups (n = 10): control group (injection of saline vehicle), DM group (injection of STZ), and PEMFs group (injection of STZ + PEMFs exposure). One week following injection of STZ, rats in the PEMFs group were subject to PEMFs stimulus for 40 min/day, 5 days/week, and lasted for 12 weeks. After 12 week intervention, the results showed that PEMFs increased serum bone-specific alkaline phosphatase level and bone mineral density, and inhibited deterioration of bone microarchitecture and strength in STZ rats. Furthermore, PEMFs up-regulated the mRNA expressions of low-density lipoprotein receptor-related protein 5, β-catenin and runt-related gene 2 (Runx2), and down-regulated dickkopf1 in STZ rats. However, mRNA expressions of RANKL and OPG were not affected by PEMFs. PEMFs can prevent the diabetes-induced bone loss and reverse the deterioration of bone microarchitecture and strength by restoring Runx2 expression through regulation of Wnt/β-catenin signaling, regardless of its no glucose lowering effect.

Impact of the serum bone-specific alkaline phosphatase level at the initiation of hemodialysis therapy for end-stage renal disease on cardiovascular events

BackgroundPatients with end-stage renal disease (ESRD) have high rates of hospitalization for cardiovascular (CV) events and short-term mortality after the initiation of hemodialysis (HD) therapy. To improve outcomes, it is important to identify predictive laboratory markers. We investigated whether the serum bone-specific alkaline phosphatase (BAP) level at the initiation of HD therapy for ESRD was associated with adverse events. MethodsThis was a retrospective cohort study of 47 ESRD outpatients who were referred to our clinic for HD. The serum BAP level was measured within 1month after the initiation of HD. Patients were divided into high-BAP and low-BAP groups according to the median serum BAP level (24.6U/L). The impact of the serum BAP level on CV events (coronary artery disease, peripheral arterial disease, cerebrovascular disease, other CV events including aortic dissection, and mortality) was investigated. ResultsDuring a median follow-up period of 72months, CV events occurred in 14 patients (29.8%). Kaplan–Meier analysis showed that the disease-free and overall survival rates were lower in the high-BAP group than in the low-BAP group (p=0.003 and p=0.037, respectively, log-rank test). After adjustment for age, sex, and other confounding factors, Cox proportional hazards analysis found that the high-BAP group had a 5.9-fold higher rate of CV events than the low-BAP group (hazard ratio: 5.89; 95% confidence interval: 1.184–29.309; p=0.030). ConclusionsThe serum BAP level at the initiation of HD therapy for ESRD is a useful non-invasive biomarker for predicting CV events.

Antiosteoporotic effects of Polycan in combination with calcium lactate-gluconate in ovariectomized rats.

The aim of the present study was to investigate the optimum composition of Polycan (β-glucan complex) and calcium lactate-gluconate (CaLG) that exhibited the most beneficial effects in ovariectomy (OVX)-induced osteoporotic rats. Polycan and CaLG single formulas (100 mg/kg each), and three doses (50, 100 and 200 mg/kg) of three mixed formulas [polycan:CaLG (PCLG)=1:99, 5:95 and 10:90] were orally administered once a day for 84 days. The effects of the test materials were compared with those of a risedronate sodium-treated group. OVX resulted in an increase in body weight, decreased bone formation, elevated serum osteocalcin levels and urine deoxypyridinoline/creatinine ratio, as well as decreased serum bone-specific alkaline phosphatase levels, femur indices, bone mineral content, bone mineral density and failure load. However, these OVX-induced osteoporotic changes markedly decreased following the administration of the test materials. Continuous oral treatment of Polycan or CaLG single formulas and the PCLG mixed formulas preserved bone mass and strength. The PCLG 10:90 mixed formula exhibited the most favorable synergistic antiosteoporotic effects in the OVX-induced osteoporotic rats as compared with equal doses of the Polycan or CaLG single formulas.

Effects of alendronate or alfacalcidol on bone metabolic indices and bone mineral density in patients with ophthalmologic disease treated with glucocorticoid

Objectives. Glucocorticoid (GC) is usually used for the treatment of systemic inflammatory diseases. We performed the prospective study to clarify the effects of alendronate or alfacalcidol on bone metabolic indices and bone mineral density (BMD) in 90 patients treated with GC for ophthalmologic diseases without systemic disorders for 12 months.Methods. BMD was measured with dual-energy X-ray absorptiometry. Serum bone-specific alkaline phosphatase (BAP) and urinary Type I collagen cross-linked N-telopeptide (NTx) were measured as bone metabolic indices.Results. BMD values in the alendronate group were significantly higher than those in the alfacalcidol group during 12 months. Alendronate significantly reduced urinary NTX levels from the baseline during 12 months, although alfacalcidol did not affect them. Serum BAP levels in the alendronate group were significantly lower than those in the alfacalcidol group during 9 months. The effects of alendronate on BMD and NTx in male patients seemed to be somewhat potent compared with those in female patients.Conclusions. Alendronate is effective to prevent BMD loss and bone resorption induced by GC treatment in patients with ophthalmic diseases without systemic disorders. There might be sex differences in the potency of alendronate effects.

Bone-specific alkaline phosphatase is elevated in insulin resistance: implications for vascular calcification in diabetes

Purpose: Previous studies showed that alkaline phosphatase (ALP) is a predictor of mortality and cardiovascular event. Insulin resistance (IR) is associated with vascular calcification, but the relationship between IR and ALP is unclear. We therefore studied the relationship between ALP (total and bone-specific) and IR-related traits. Methods: Data on 3,986 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2004 aged ≥20 years and free of diabetes were analyzed. Plasma glucose and serum insulin were measured from fasting blood samples using hexokinase enzymatic method and RIA, respectively. The homeostasis model assessment calculator was used to calculate the HOMA2 beta cell function (%B), insulin sensitivity (%S), and IR. Multivariable linear regression was used to assess the association of IR-related traits with ALP levels. Results: In linear regression, HOMA2-IR, HOMA2-B, and insulin were positively associated with bone-specific ALP, whereas HOMA2-S was negatively associated with bone-specific ALP, after adjustment for smoking, drinking, race/ethnicity, education, physical activity, age, and body mass index. After further adjustment for C-reactive protein, total cholesterol, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, triglycerides, HDL-cholesterol, and mean arterial pressure, the associations were attenuated but remained statistically significant (P<0.001). No significant association with total ALP was found. Conclusions: IR-related traits are strongly and independently associated with serum bone-specific ALP levels, but not total ALP levels. Whereas IR is expected to be associated with liver inflammation, the association with bone-specific ALP is novel and provides a mechanistic link between IR and vascular calcification. This raises the possibility that ALP inhibitors may prevent vascular calcification in people with diabetes.

The Relationship Between Glucose Metabolism, Metabolic Syndrome, and Bone-Specific Alkaline Phosphatase: A Structural Equation Modeling Approach

Serum alkaline phosphatase plays a role in vascular calcification. It is found in various tissues, whereas bone-specific alkaline phosphatase (BAP) more specifically reflects mineral metabolism. The relationship of serum alkaline phosphatase (total and bone-specific) with diabetes and metabolic syndrome (MetS), 2 major risk factors of vascular calcification, is largely unknown. We aimed to investigate the relationships between glucose metabolism, components of the MetS, and alkaline phosphatase. This was a cross-sectional study of a nationally representative sample of the U.S. population in 1999 through 2004. Participants were 3773 nondiabetic participants of the National Health and Nutrition Examination Survey 1999-2004. We measured serum BAP and total alkaline phosphatase. In multivariable linear regression, updated homeostasis model assessment (HOMA2) for insulin resistance (β = 0.068), HOMA2 for β-cell function (β = 0.081), insulin (β = 0.065), mean arterial pressure (β = 0.15), and high-density lipoprotein (HDL)-cholesterol (β = 0.209) were positively associated with BAP, whereas HOMA2 for insulin sensitivity (β = -0.065) was negatively associated with BAP. On the other hand, only mean arterial pressure and HDL-cholesterol were significantly associated with total alkaline phosphatase. Moreover, a structural equation model revealed that hypertension, low HDL, and insulin resistance had significant direct effects on serum BAP levels, whereas obesity and inflammation might have indirect effects on serum BAP levels. The overall model showed very good fit to the data (comparative fit index = 0.995, root mean square error of approximation = 0.037, and standardized root mean square residual = 0.006). Glucose metabolism and MetS are significantly related to serum BAP levels. How BAP mediates vascular calcification in diabetes and MetS warrants further studies.

Associations between serum bone-specific alkaline phosphatase activity, biochemical parameters, and functional polymorphisms of the tissue-nonspecific alkaline phosphatase gene in a Japanese population.

We had demonstrated that single nucleotide polymorphism (787T>C) in the tissue-nonspecific ALP (TNSALP) gene was associated with the bone mineral density (BMD). BMD was the lowest among TNSALP 787T homozygotes (TT-type) and highest among TNSALP 787T>C homozygotes (CC-type) in postmenopausal women. In the present study, we investigated the effects of the TNSALP genotype on associations among serum bonespecific alkaline phosphatase (BAP), serum calcium, and phosphorus in healthy young Japanese subjects. Young healthy adult subjects (n=193) were genotyped for the polymorphism, and we measured the levels of serum BAP, serum calcium, and phosphorus. Dietary nutrient intakes were calculated based on 3-day food records before the day of blood examinations. Grouped by the TNSALP genotype, a significant negative correlation between serum BAP and phosphorus was observed in 787T>C homozygotes (CC-type), but not in heterozygotes (TCtype), nor in 787T homozygotes (TT-type). In the present study, we revealed that the single nucleotide polymorphism 787T>C in the TNSALP gene had effects on the correlation between serum BAP and phosphorus in young adult subjects. These results suggest that variation in TNSALP may be an important determinant of phosphate metabolism. Our data may be useful for planning strategies to prevent osteoporosis.

Relationship Between vitamin D Deficiency and Bone Fragility in Sickle Cell Disease: A Cohort Study of 56 adults.

AbstractAbstract 2103▪▪This icon denotes a clinically relevant abstract Background:Recent studies suggest that patients with sickle cell disease (SCD) have profound vitamin D (VD) deficiency. Limited data exist on the effect of VD deficiency on bone fragility in these patients. Objectives:To assess the prevalence of VD deficiency in adults with SCD and its consequences on bone metabolism and fragility. Methods:This prospective study included 56 SCD adult patients (mean age 29.8 ± 9.5 years), in a clinically steady state. Clinical and laboratory data were recorded. Bone mineral density (BMD) was measured using dual X-ray absorptiometry. Fracture history, BMD, avascular osteonecrosis, H-shaped vertebra and markers of mineral metabolism were compared between two groups of patients presenting very low (≤6 ng/ml, n=26) (group 1) and low (>6 ng/ml, n=26) (group 2) 25(OH)D concentration, respectively. Results:Median 25(OH)D concentration was 6 ng/mL. VD deficiency (25(OH)D <10 ng/mL) was found in 42 out of 56 patients (75%) and secondary hyperparathyroidism in 40 (71.4%). History of fracture was documented in 17 patients (30.3%), osteopenia and/or ospeoporosis in 39.6% of patients. Overall, patients of group 1 were more likely to have sustained a fracture (42.8%) compared to patients of group 2 (17.8%) (p=0.04). These patients had also lower body mass index and significantly higher parathyroid hormone, C-terminal telopeptides of type I-collagen and bone-specific alkaline phosphatase serum levels. There was no difference between group for BMD, avascular osteonecrosis history, H-shaped vertebra, and disease severity markers. Conclusion:This study suggests that VD deficiency is a key feature in SCD-bone disease. It is highly prevalent and associated with hyperparathyroidism, bone resorption markers, and history of fracture. The optimal supplementation regimen remains to be determined. Disclosures:No relevant conflicts of interest to declare.