Serum Bone-specific Alkaline Phosphatase Research Articles

Changes in Bone Metabolism in Morbidly Obese Patients After Bariatric Surgery: A Meta-Analysis.

The aim is to evaluate via meta-analysis bone metabolism and bone mineral density (BMD) in morbidly obese patients before and after bariatric surgery. We searched Medline, EMBASE, and the Cochrane Library for relevant studies published before January 2014. The following outcomes were evaluated: serum calcium, serum parathyroid hormone (PTH), serum 25-hydroxyvitamin D [25(OH)D], serum or urinary N-telopeptide (NTX), bone-specific alkaline phosphatase (BSAP), and bone mineral density (BMD). Ten studies, including 344 patients, met our inclusion criteria. Results showed a significant decrease in serum calcium (MD = -0.10, 95 %CI -0.14 to -0.07, P < 0.00001) and increase in serum PTH (MD = 12.41, 95 %CI 6.51 to 18.31, P < 0.00001) but no significant difference in serum 25(OH)D (MD = 1.35, 95 %CI -1.12 to 3.83, P = 0.28) following bariatric surgery. There were significant increases in serum or urinary NTX (MD = 18.49, 95 %CI 3.33 to 33.66, P = 0.02) and BSAP (MD = 7.47, 95 %CI 0.21 to 14.72, P = 0.04) but a significant decrease in BMD (MD = -0.08, 95 %CI -0.13 to -0.04, P < 0.00001) after bariatric surgery. BMD was significantly decreased, while bone turnover was elevated, and bone remodeling was accelerated following bariatric surgery. Basal bone metabolism should be evaluated preoperatively. To prevent secondary hyperparathyroidism and bone loss, calcium and vitamin D should be monitored closely and supplemented accordingly after the surgery.

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.

Total 25(OH) vitamin D, free 25(OH) vitamin D and markers of bone turnover in cirrhotics with and without synthetic dysfunction

Current clinical assays for total 25-hydroxy (OH) vitamin D measure vitamin D bound to vitamin D-binding protein (DBP) and albumin plus unbound ('free') D. We investigated the relationship between total and free 25(OH)D with bone metabolism markers in normal (>3.5 g/dl) vs. low (≤3.5 g/dl) albumin cirrhotics. Eighty-two cirrhotics underwent measurement of free and total 25(OH)D by immunoassay, DBP and markers of bone metabolism [intact parathyroid hormone (iPTH), C-telopeptide (CTX), bone-specific alkaline phosphatase (BSAP), osteocalcin, amino-terminal pro-peptide of type 1-collagen (P1NP)]. Pearson's coefficients assessed relevant associations. Cirrhotics with low (n = 54) vs. normal (n = 28) albumin had lower total 25(OH)D (12.1 vs. 21.7 ng/ml), free 25(OH)D (6.2vs.8.6 pg/ml) and DBP(91.4 vs. 140.3 μg/ml) [P < 0.01 for each]. iPTH was similar in low and normal albumin groups (33 vs. 28 pg/ml; P = 0.38), although serum CTX(0.46vs.0.28 ng/ml) and BSAP(31.7 vs. 24.8 μg/L) were increased (P < 0.01). An inverse relationship was observed between total 25(OH)D and iPTH in normal (r = -0.47, P = 0.01) but not low albumin cirrhotics (r = 0.07, P = 0.62). Similar associations were seen between free 25(OH)D and iPTH(Normal: r = -0.46, P = 0.01; Low: r = -0.03, P = 0.84). BSAP, osteocalcin and P1NP were elevated above the normal range in all cirrhotics but not consistently associated with total or free 25(OH)D. Cirrhotics with low vs. normal albumin have lower levels of DBP, total and free 25(OH)D. The expected relationship between total or free 25(OH)D with iPTH was observed in normal but not in low albumin cirrhotics, demonstrating that total 25(OH)D is not an accurate marker of bioactive vitamin D status in cirrhotics with synthetic dysfunction. Additional investigation into the role of vitamin D supplementation and its impact on bone mineral homoeostasis in this population is needed.

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.

Bone metabolism biomarkers in men with advanced prostate cancer (PC) and bone metastases treated with denosumab versus zoledronic acid (ZA).

267 Background: Denosumab, compared with ZA, has recently demonstrated significant benefits in preventing skeletal-related events (SREs) in a double-blind phase 3 study of men with castration-resistant PC and bone metastases (N=1901). This post hoc analysis was performed to determine if key bone metabolism biomarker levels correlated with time-to-first SRE. Methods: Time-to-Grade ≥2 increase in total serum alkaline phosphatase (ALP) was assessed for correlation with time-to-first SRE. Levels of urinary N-telopeptide (uNTX) and serum bone-specific alkaline phosphatase (BSAP) markers were measured at baseline and study week 13, and correlations with time-to-first SRE were assessed. Covariate analyses were performed using a Cox proportional hazards model, stratified by treatment group or (for baseline analyses) with treatment group as the independent variable. Results: Analysis of the relationship between time-to-Grade ≥2 increase in total ALP and time-to-first SRE demonstrated that Grade ≥2 increases in ALP of PC patients were associated with a higher risk of first SRE (hazard ratio [HR] 1.838, 95% confidence interval [CI] 1.559, 2.167; P&lt;0.0001). In dichotomized analyses (&lt; vs ≥ median), a higher level of uNTX and BSAP (at baseline or week 13) was correlated with an increased risk of first SRE (Table). In baseline covariate analyses, treatment benefit for denosumab was maintained after adjusting for either baseline uNTX (HR 0.818, 95% CI 0.703, 0.951; P=0.0091) or BSAP (HR 0.813, 95% CI 0.700, 0.943; P=0.0061). Conclusions: Higher levels of uNTX or BSAP at baseline or week 13 were associated with worse SRE outcomes in men with advanced PC and bone metastases. Denosumab was more efficacious for preventing or delaying SREs compared with ZA, regardless of bone-related biomarker levels. Relationship of covariate to time-to-first SRE Clinical trial information: NCT00321620. [Table: see text]

Dickkopf-1 and sclerostin serum levels in patients with systemic mastocytosis.

Bone involvement, mainly osteoporosis but also osteosclerosis, is frequent in patients with indolent systemic mastocytosis (ISM). The recent characterization of the canonical Wnt/β-catenin pathway in the regulation of bone remodeling provided important insights for our understanding of the pathophysiology of a number of conditions. The regulation of Wnt pathway in bone is predominantly driven by the production of receptor inhibitors such as Dickkopf-1 (DKK1) and sclerostin (SOST). This study aimed to explore if the various bone involvements in patients with ISM might be explained by variations in serum levels of DKK1 and SOST. This is a cross-sectional study in an adult ISM cohort (13 men and 13 women with diagnosed ISM) and fifty-two healthy sex and age-matched controls. Early morning, fasting and venous sampling was obtained in all subjects. The main outcome measures were serum bone-specific alkaline phosphatase (bALP), C-terminal telopeptides of type I collagene (CTX), DKK1, SOST, parathyroid hormone (PTH), bone mineral density, and prevalent vertebral fractures. Mean DKK1 serum levels were about two-folds higher in patients, than in controls (65,0 ± 43.3 vs. 33.1 ± 19.4 pmol/L, respectively; p < 0.001), irrespective of the presence of osteoporotic or diffuse osteosclerotic bone involvement. DKK1 serum levels were positively correlated with PTH and both CTX and bALP. Mean SOST serum levels were not significantly different in patients versus controls, and we did not observe any significant correlation between SOST and any available clinical or laboratory parameters, with the only exception of a positive correlation with age. In conclusion, in our study, we observed that DKK1, but not SOST, serum levels significantly increased in ISM patients with various bone involvements, and correlated with PTH and bone turnover markers. Our results suggest that the Wnt/β-catenin pathway is not primarily involved in the pathophysiology of the array of bone involvement in ISM.

Eldecalcitol, in Combination with Bisphosphonate, Is Effective for Treatment of Japanese Osteoporotic Patients.

Alfacalcidol (ALF) and eldecalcitol (ELD) are vitamin D analogues that can be combined with anti-resorption drugs, such as bisphosphonate (BP) for the treatment of osteoporosis (OP). There has been no report comparing the effects of those vitamin D analogs in combination with BPs. Twenty female patients with OP were enrolled, and all of them were treated with ALF and BPs. After switching from ALF to ELD, we examined the effectiveness of ALF and ELD. The averaged age was 69.4 years and the period of BP usage was between 1 to 13.4 years (mean period was 3.7 years). Serum corrected calcium, serum inorganic phosphorus, serum bone specific alkaline phosphatase (BAP), and serum tartrate-resistant acid phosphatase (TRACP)-5b were measured prior to ELD and at 6 months afterwards. Bone mineral density (BMD) of the lumbar spine (L-BMD), femoral neck, and total hip BMD were assessed one year before, prior to, and one year after ELD therapy commencement. Six months after switching from ALF to ELD, BAP and TRACP-5b values significantly decreased. After one year of ALF therapy, L-BMD, total hip BMD and femoral neck H-BMD values slightly increased. In contrast, a year following the change from ALF to ELD, L-BMD significantly increased and femoral neck BMD slightly increased, but total hip BMD did not. These results suggest that the treatment with ELD after ALF significantly suppressed bone turnover and increased L-BMD. Thus, the combined therapy with ELD is more effective for OP treatment than that with ALF.

Comparison between recombinant human parathyroid hormone (1-34) and elcatonin in treatment of primary osteoporosis.

To evaluate the efficacy and safety of rhPTH (1-34) vs. elcatonin. Sixty patients with primary OP were randomly divided into two groups according to the ratio of 3:1. rhPTH (1-34) group (PTH group) was treated with subcutaneous injection of rhPTH (1-34) 20 μ g daily for 18 months, and the elcatonin group (CT group) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months. Bone mineral density (BMD) of the lumbar spine 2-4 (L2-4) and femoral neck, serum calcium and phosphorus, urinary calcium, serum bone specific alkaline phosphatase (BSAP), and urinary c-terminal telopeptides of type I collagen/creatinine (uCTX-I/Cr) were tested at baseline, and 6, 12, and 18 months after treatment. In PTH group, BMD of L2-4 at 6, 12, and 18 months, BDM of femoral neck at 18 month, BSAP at 6 and 12 months and uCTX- I/Cr at 6, 12 and 18 months were all significantly raised. In CT group, BMD of L2-4 at 12 month and that of femoral neck at 12 and 18 months were significantly elevated, while BSAP was significantly decreased at 12 and 18 months, and no significant difference on CTX- I/Cr was observed. When BMD growth and growth rate between two groups were compared, PTH group had better improvement in L2-4 BMD and growth rate than CT group at 6, 12, and 18 months. BMD growth and growth rate of femoral neck at 12 month and its growth at 18 month in CT group were higher than in PTH group, but there was no significant difference between two groups regarding the growth rates at 18 month. Besides, there were no significant differences regarding the rates of adverse reactions between two groups. rhPTH (1-34), is safe and effective in the treatment of primary OP. It is superior to elcatonin in improving vertebral BMD at onset time, growth rate and growth range, but inferior to elcatonin at BMD of femoral neck.

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.

Paricalcitol for secondary hyperparathyroidism in renal transplantation.

Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 μg/d for 3 months and then uptitrated to 2 µg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8-152.0) to 63.3 (52.0-79.7) pg/ml (P<0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P<0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P<0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P<0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P<0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Long-term studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.

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.

Fracture prediction after discontinuation of 4 to 5 years of alendronate therapy: the FLEX study.

Discontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered, but methods to monitor fracture risk after discontinuation have not been established. To test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years. The prospective Fracture Intervention Trial Long-term Extension (FLEX) study randomized postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003; the present analysis includes only the placebo group. Hip and spine dual-energy x-ray absorptiometry (DXA) were measured when placebo was begun (FLEX baseline) and after 1 to 3 years of follow-up. Two biochemical markers of bone turnover, urinary type 1 collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP), were measured at FLEX baseline and after 1 and 3 years. Symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover. During 5 years of placebo, 94 of 437 women (22%) experienced 1 or more symptomatic fractures; 82 had fractures after 1 year. One-year changes in hip DXA, NTX, and BAP were not related to subsequent fracture risk, but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk (lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio, 2.17 [95% CI, 1.38-3.41]; total hip DXA relative hazard ratio, 1.87 [95% CI, 1.20-2.92]). Among postmenopausal women who discontinue alendronate therapy after 4 to 5 years, age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years. Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and cannot be recommended. clinicaltrials.gov Identifier: NCT00398931.

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.

AB0838 Bone Metabolism Biomarkers in Tunisian Hemodialysis Patients

BackgroundAlthough bone biopsy is a golden standard in the diagnosis of chronic kidney disease mineral and bone disorders (CKD-MBD), this method is invasive and repetitive evaluation of bone status cannot...

Effect of Moderate Aerobic Training on Bone Metabolism Indices among Adult Humans.

This study assessed the osteogenic effect (T-Score) and changes in bone markers in healthy subjects by 12-weeks of aerobic training. Total 65 healthy subjects (36 males, 29 females), their age ranged between 30 and 60 years with normal body mass index, were recruited to participate in this study and they were selected among healthy subjects who do not have any metabolic disorders and were not receiving any medication that could affect the bone turnover. Standardized physical examination and collection of serum samples were performed at base line and after 12 weeks of moderate aerobic training to measure bone formation markers (osteocalcin (OC) and bone specific alkaline Phosphatase (BAP) and bone resorption marker Deoxypyridinoline (DPD), and serum calcium. Each subject participated in exercise training program for 12 weeks, three times per week. The results showed that the 12 weeks of moderate aerobic training produced a significant improvement in all bone metabolism indices including Serum bone-specific alkaline phosphatase, serum osteocalcin, serum free Calcium and bone mineral density among all subjects. Conclusion : Moderate intensity of aerobic training exerts significant positive effects on bone formation marker and bone density associated with a significant decrease in the rate of bone resorption that could assist in preventing or decelerating osteoporosis.

Bone turnover in long‐term survivors of childhood acute lymphoblastic leukemia

We investigated the effects of demographic, lifestyle (self-reported smoking status and physical activity levels), cancer-related treatment factors (radiation and chemotherapy), and diet (calcium and vitamin D intake) on bone turnover and the relationship of bone turnover to lumbar spine bone mineral density (BMD) Z-scores (LS-BMD Z-scores) determined by quantitative computed tomography (QCT) in 418 ≥5-year survivors of childhood acute lymphoblastic leukemia (ALL). Bone turnover was assessed by biomarkers including serum bone-specific alkaline phosphatase (BALP), osteocalcin (OC), and urinary N-telopeptide of type I collagen indexed to creatinine (NTX/Cr). The 215 males ranged in age from 9 to 36 years (median age 17 years). Age and tanner score were inversely associated with all biomarkers (BALP, OC, NTX/Cr) (P < 0.001). Males had higher BALP and OC than females (P < 0.001). Body mass index (BMI) was inversely associated with OC and NTX/Cr (P < 0.001). There was no significant association of biomarkers with lifestyle related factors, ALL treatment-related factors, dietary calcium, vitamin D, or LS-BMD Z-score. In this population of long-term survivors of ALL, bone turnover was significantly associated with age, gender, tanner stage, and BMI. ALL-related treatments did not influence bone turnover and bone turnover was not predictive of volumetric LS-BMD Z-score.

A phase II, multicentre trial evaluating the efficacy of de-escalated bisphosphonate therapy in metastatic breast cancer patients at low-risk of skeletal-related events

The optimal frequency of intravenous (IV) bisphosphonate administration is unclear. We thus performed a study evaluating the effects of switching from 3–4 to 12 weekly therapy in patients with biochemically defined low-risk bone metastases. Patients with serum C-telopeptide (CTx) levels ≤600 ng/L after ≥3 months of 3–4 weekly IV pamidronate were switched to 12 weekly therapy for 48 weeks. Primary endpoint was the proportion of patients maintaining CTx levels in the lower-risk range. All endpoints (serum CTx and bone-specific alkaline phosphatase (BSAP), skeletal-related events (SREs) and self-reported pain) were measured at baseline, 6, 12, 24, 36 and 48 weeks. Treatment failure was defined as biochemical failure (CTx > 600 ng/L) or a SRE. Exploratory biomarkers including; serum TGF-β, activin-A, bone sialoprotein (BSP), procollagen type 1 N-terminal propeptide and urinary N-telopeptide (NTx) were assessed at baseline as predictors for failure to complete treatment. Seventy-one patients accrued and 43 (61 %) completed 48 weeks of de-escalated therapy. Reasons for failure to complete treatment included; biochemical failure (CTx > 600 ng/L) (n = 10, 14.1 %), on-study SRE (n = 9, 12.7 %), disease progression (n = 7, 9.9 % including death from disease [n = 1, 1.4 %]) or patient choice (n = 2, 2.8 %). Elevated baseline levels of CTx, BSAP, NTx and BSP were associated with treatment failure. The majority of patients in this biochemically defined low-risk population could switch from 3–4 weekly to 12 weekly bisphosphonate therapy with no effect on CTx levels or SREs during the 48 week study. Larger trials are required to assess the roles of biomarkers as predictors of adequacy of de-escalated therapy.

Adipose tissue cytokines: Relation to glycemic control, insulin resistance and biochemical bone markers in type 2 diabetic Saudi male patients

To assess the plasma levels and relations of adipocytokines and biochemical bone markers in type 2 diabetes mellitus (T2DM) Saudi males with insulin resistance. This case-control study included 80 overweight/obese males with T2DM on oral anti-diabetic medications recruited from the diabetic center and 40 healthy lean males of matched age. Measurements included fasting plasma glucose (FBG), fasting plasma insulin, serum calcium (Ca 2 + ), HbA1c, plasma adiponectin and resistin, serum bone-specific alkaline phosphatase (B-ALP), plasma osteocalcin (OC), and plasma osteoprotegerin (OPG). Waist and hip circumferences were measured. Body mass index, waist/hip ratio (WHR), and insulin resistance (HOMA-IR) were calculated. Compared to the control group, diabetic patients showed significantly both lower adiponectin ( p = 0.000) and Ca 2 + ( p = 0.000) but significantly higher resistin ( p = 0.000), OC ( p = 0.000), B-ALP level ( p = 0.000) and OPG ( p = 0.000). After multivariate adjustment in diabetic patients, resistin predicted OC, (beta = −0.30, p = 0.005), WC and resistin predicted Ca 2+ (beta = −0.34, p = 0.035 and beta = −0.25, p = 0.033), adiponectin and resistin predicted B-ALP, (beta = −0.35, p = 0.010 and beta = 0.35, p = 0.004), and FBG, HOMA-IR and age predicted OPG, (beta = −0.66, p = 0.010, beta = 0.58, p = 0.024 and beta = 0.27, p = 0.031 respectively). Also, FBG, WHR and HOMA-IR predicted adiponectin (beta = −0.79, p = 0.001, beta = −0.60, p = 0.001 and beta = 0.80, p = 0.001 respectively), while OC and OPG predicted HbA1c (beta = −0.32, p = 0.007 and beta = 0.28, p = 0.016 respectively). Uncontrolled T2DM Saudi males with insulin resistance have abnormal bone markers with unfavorable levels of adipocytokines. Strong associations between bone markers, adipocytokines, insulin resistance and metabolic control may suggest interaction in multiple direction feedback loops exacerbating hyperglycemia.

Age-related bone turnover markers and osteoporotic risk in native Chinese women

BackgroundThe rate of bone turnover is closely related to osteoporosis risk. We investigated the correlation between bone turnover markers and BMD at various skeletal sites in healthy native Chinese women, and to study the effect of changes in the levels of bone turnover markers on the risk of osteoporosis.MethodsA cross-section study of 891 healthy Chinese women aged 20–80 years was conducted. The levels of serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP), serum cross-linked N-terminal telopeptides of type I collagen (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were determined. BMD at the posteroanterior spine and the hip was measured using DXA.ResultsPearson’s correlation coefficient found significant negative correlation between bone turnover marker and BMD T-score at different skeletal sites (r = −0.08 to −0.52, all P = 0.038–0.000). After adjustments for age and body mass index, the partial correlation coefficients between the OC, BAP, sNTX, sCTX and uCTX, and the T-scores at various skeletal sites were still significant. After adjustment of height and weight, the correlation coefficients between most BTMs and PA lumbar spine BMD were also significant. Multiple linear regression analysis showed that bone turnover markers were negative determinants of T-scores. BAP and OC accounted for 33.1% and 7.8% of the variations in the T-scores of the PA spine, respectively. Serum OC, BAP, uDPD, and sNTX accounted for 0.4–21.9% of the variations in the femoral neck and total hip T-scores. The bone turnover marker levels were grouped as per quartile intervals, and the T-scores, osteoporosis prevalence and risk were found to markedly and increase with increase in bone turnover marker levels.ConclusionsThis study clarified the relationship between bone turnover markers and osteoporosis risk in native Chinese women. Bone turnover marker levels were found to be important determinants of BMD T-scores. Furthermore, osteoporotic risk significantly increased with increase in the levels of bone turnover markers.

Serum bone-specific alkaline phosphatase as a biomarker for osseous metastases in patients with malignant carcinomas: a systematic review and meta-analysis.

Bone metastasis was common in patients with malignant tumors. The purpose of this study was to investigate the serum bone-specific alkaline phosphatase (B-ALP) as a biomarker in the diagnosis of osseous metastases in patients with cancers. We searched the databases of Pubmed, Cochrane Library, Medline, CNKI and Wanfang to screen the relevant articles about the serum B-ALP detection in the diagnosis of osseous metastases in patients with malignant carcinomas. The pooled sensitivity, specificity, summary receiver operating characteristic (SROC) curve were calculated by STATA12.0 software. Nineteen trials with 3 268 subjects were finally included in this study. The mean level of serum B-ALP was 41.50 ± 26.61 μg/L (216.90 ± 139.00U/L) in patients with osseous metastases and 14.49 ± 5.52 μg/L (103.30 ± 39.44 U/L) in patients without osseous metastases. The serum level of B-ALP was significant higher in the osseous metastases group than that in the control group (P < 0.05); The pooled sensitivity and specificity for diagnosis of osseous metastases were 0.74 with its 95% confidence interval (95% CI) of 0.62-0.83 and 0.80 (95% CI: 0.67-0.89), respectively. The area under the SRCO was 0.86 (95% CI: 0.83-0.89). Serum B-ALP can be a promising biomarker for detection of osseous metastases in patients with cancers.