Diagnostic value of alkaline phosphatase and bone-specific alkaline phosphatase for metastases in breast cancer: a systematic review and meta-analysis.

PURPOSE: Numerous studies had reported the diagnostic value of alkaline phosphatase (ALP) and its bone-specific isoforms (BAP) in the metastases of breast cancer (BC). The purpose of this meta-analysis was to summarize the diagnostic value of serum ALP and BAP in metastatic BC, especially focused on bone metastases. METHODS: We searched comprehensively in the PubMed, Cochrane Library, and EMBASE for studies to explore the diagnostic accuracy of serum ALP/BAP level for metastatic BC. Qualities of including studies were assessed and pooled sensitivity, specificity, and summary receiver operating characteristic curve were calculated. Publication bias was assessed and meta-regression was conducted. RESULTS: We finally included 25 studies with a total of 12,155 BC patients (1681 metastatic cases and 10,474 controls). According to the QUADAS-2 tool to assessment the methodological quality, most of the included studies were judged as high risk of patient selection bias. High serum levels of ALP/BAP in bone metastatic BC patients could be found compared with non-metastatic BC patients. The pooled sensitivity and specificity of ALP for BC bone metastases were 0.62 and 0.86, and the area under the curve (AUC) was 0.80. The pooled sensitivity and specificity of ALP for all site metastases (mainly bone and liver) were 0.56 and 0.91, and the AUC was 0.90. The pooled sensitivity and specificity of BAP for BC bone metastases were 0.66 and 0.92, and the AUC was 0.89. CONCLUSION: Although not promising, serum ALP and BAP could bring useful information for the early detection of BC metastases especially for the bone metastases.

Low bone mineral density and reduced bone-specific alkaline phosphatase in 5q spinal muscular atrophy type 2 and type 3: A 2-year prospective study of bone health.

AIM: Individuals with spinal muscular atrophy (SMA) are at risk of developing skeletal problems. This study investigated bone mineral density (BMD), bone turnover markers and motor function in children and adolescents with SMA type 2 and type 3 over a two-year period. The effect of nusinersen was studied in a subgroup. METHODS: Single-centre study, including 20 patients, 2-18 years, of whom ten patients received nusinersen treatment. BMD was measured by dual-energy X-ray absorptiometry. RESULTS: All patients had low BMD levels at baseline; mean Z-score -2.3 for total body less head (TBLH) and -2.9 for total hip left (THL). Significant correlations were found both at baseline and for the follow-up change for motor function and Z-scores (TBLH and THL). For the whole study group, reduced bone formation and unchanged bone resorption, assessed by bone-specific alkaline phosphatase (BALP) (p = 0.0006, ES = -0.83) and C-terminal cross-linking telopeptide of type I collagen (CTX), respectively, were found over the study period. However, BALP decreased less in the nusinersen treatment group, which suggests a positive development on bone mass in these patients. CONCLUSION: Bone health evaluation is important in follow-up programmes for SMA patients. Further investigations are warranted for individuals on survival motor neuron-targeted treatments.

The correlation of two bone turnover markers with bone mineral density: a population-based cross-sectional study.

OBJECTIVE: Exploring the correlation between bone turnover marks (BTMs) with lumbar BMD in middle-aged populations. METHODS: The cross-sectional analysis fetched data came from NHANES. The level of serum bone alkaline phosphatase (sBAP) and urinary N-telopeptide (uNTx) were regarded as representative of bone turnover. Lumbar BMD was the outcome of the study. Multivariable linear regression models were utilized to detect the correlation of sBAP and uNTx with Lumbar BMD. RESULTS: The level of sBAP and uNTx was negatively correlated with lumbar BMD in every multivariable linear regression. For sBAP, this inverse correlation was stable in both men and women (P < 0.01). uNTx indicated a negative association after all relevant covariables were adjusted (P < 0.01). The men group remained the negative correlation in gender subgroup analysis (P < 0.01). CONCLUSION: This study indicated that the increased level of sBAP and uNTx associated with lumbar BMD decreased among middle-aged adults. This correlation could prompt researchers to explore further the relationship between bone turnover rate and BMD, which may provide information for the early detection of BMD loss and provide a new strategy for clinical practice.

Incidence of bone fractures among patients on maintenance hemodialysis.

BACKGROUND: Patients with chronic kidney disease, especially those undergoing hemodialysis (HD), have a higher risk of fragility fractures. However, the magnitude of the problem and risk factors associated with fracture incidence have not been well studied in the Kingdom of Saudi Arabia. METHODS: This multicenter retrospective study involved HD centers in Jeddah from 2015 to 2021. This study included all adult HD patients. Patient demographics, medication usage, and clinical and biochemical parameters were collected from the registry records. RESULTS: The study included 328 patients on HD, with a mean age of 53 years. The median duration of HD was 47 months. Osteoporosis was found in 9% of the patients, and 8% had a previous parathyroidectomy. Over the observation period, fractures occurred in 32 patients, with an incidence rate of 20 case/1000 end stage kidney disease patients-year. Patients with fractures had a higher rate of osteoporosis, underwent more parathyroidectomy, had longer HD vintage, and higher bone-specific alkaline phosphatase (BSAP) levels. BSAP was the most significant predictor of fracture incidence in the regression analysis. Using a BSAP cutoff value of 96.6 µg/L, the sensitivity and specificity to predict fractures were 81.8% and 49%, respectively. CONCLUSION: The main risk factors for incident fractures were osteoporosis, previous parathyroidectomy, longer HD vintage, and higher BSAP level. A higher BSAP score was the most significant predictor of incident fractures. This may highlight the importance of monitoring bone turnover markers and the negative impact of high bone turnover on patient health.

Factors associated with osteoporosis and fractures in patients with systemic lupus erythematosus: Kyoto Lupus Cohort.

OBJECTIVES: Osteoporosis and compression fractures of the lumbar spine are some of the major adverse effects of glucocorticoid therapy in patients with systemic lupus erythematosus (SLE). This study examined the association between bone mineral density, bone turnover markers, presence of vertebral fractures, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in SLE patients. METHODS: This was a cross-sectional study of 246 outpatients with SLE at the Kyoto University Hospital. Lumbar and femoral bone mineral density was measured with dual-energy X-ray absorptiometry, and the presence of vertebral fractures was determined using X-ray, computed tomography, or magnetic resonance imaging. RESULTS: On multiple regression analysis, both high lumbar and femoral T-scores were associated with the concomitant use of hydroxychloroquine (P = .018 and P = .037, respectively), no use of bisphosphonate or denosumab (P = .004 and P = .038, respectively), high body mass index (P < .001), and low bone-specific alkaline phosphatase level (P = .014 and P = .002, respectively). Vertebral fractures showed a significant association with Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score (P < .001) and femoral T-score (P < .001). CONCLUSION: Vertebral fracture was associated with SLE-associated organ damage, and serum bone-specific alkaline phosphatase level is a potentially useful marker for osteoporosis monitoring in SLE patients.

Changes in blood bone markers after the first and second bouts of whole-body eccentric exercises.

The present study compared the first (EC1) and second (EC2) bouts of whole-body eccentric exercises to examine the effects of the magnitude of muscle damage on changes in blood bone markers. Fifteen sedentary young men performed nine eccentric exercises of arm, leg, and trunk muscles, and repeated them 2 weeks later. Blood samples were taken before and 2 h and 1-5 days following each bout to analyze plasma creatine kinase (CK) activity and myoglobin concentration, serum tartrate-resistant acid phosphatase (TRAP), type 1 C-terminal telopeptide (CTX-1), procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BAP), undercarboxylated-osteocalcin (ucOCN), carboxylated-osteocalcin (cOCN), and leptin concentrations. All except ucOCN changed significantly (p < 0.05) after both bouts. When comparing bouts for peak changes, P1NP (bone formation marker) and CTX-1 (bone resorption marker) increased less after EC2 (peak: 137±96% and 7±6%, respectively) than after EC1 (146 ± 80% and 30 ± 21%, respectively), whereas BAP (bone formation marker) increased more after EC2 (18 ± 16%) than after EC1 (4 ± 15%) (p < 0.05). Leptin (49 ± 58%) and cOCN (14 ± 10%) increased more (p < 0.05) after EC2 than after EC1 (-30 ± 15%, 9 ± 26%). Significant (p < 0.05) correlations were evident between peak CK activity and peak CTX-1 (r = 0.847), P1NP (r = 0.815), BAP (r = -0.707), ucOCN (r = 0.627), cCON (r = -0.759), and leptin (r = -0.740) changes after EC1, but many of these correlations disappeared after EC2. This was also found for the relationships between other muscle damage markers (myoglobin, muscle soreness, and muscle strength) and the bone markers. It was concluded that bone turnover was affected by eccentric exercise, but muscle damage was unfavorable for bone formation.

Acute effects of the resistance exercise associated with different blood flow restriction pressures on bone remodeling biomarkers.

Background: The present study analyzed the acute responses of parathyroid hormone (PTH) and bone-specific alkaline phosphatase (BSAP) to the low-intensity resistance exercise with blood flow restriction using different occlusion pressures. Methods: Twelve women completed the three protocols of this crossover study: resistance exercise without blood flow restriction (RE), resistance exercise with blood flow restriction and occlusion pressure corresponding to 70% of systolic blood pressure (RE + BFR70), and resistance exercise with blood flow restriction and occlusion pressure corresponding 130% of systolic blood pressure (RE + BFR130). All exercises were performed in a guided squat apparatus with load corresponded to 30% of one-repetition maximum test. Results: Relative to resting levels, PTH concentrations decreased significantly (p = .000) post-exercise in all groups and increased significantly (p = .000) 15 min post-exercise in RE + BFR70 and RE + BFR130 groups; PTH concentrations returned to resting levels after the 30-min recovery period in all groups. There was no significant difference (p >.05) between BSAP values at rest and 30 min post-exercise. Conclusion: In conclusion, our results showed that protocols with blood flow restriction using occlusion pressures equivalent to 70% and 130% of systolic blood pressure were more effective than RE alone to induce PTH peaks, and to promote a metabolic condition favorable to bone anabolism.

New Markers of Bone Fragility in Hemodialysis Patients: A Monocentric Study.

INTRODUCTION: Mechanisms underlying bone fragility in patients under dialysis are various. The assessment of bone disorder is not yet codified in these patients. Our study aimed to determine the relationship between the serum fibroblast growth factor 23 (FGF23) level and bone fragility. We also aimed to assess the bone alkaline phosphatase (bAP) to the C-terminal telopeptide of type I (CTX) ratio and the FGF23*bAP product to CTX ratio in patients under hemodialysis. METHODOLOGY: We conducted a cross-sectional study, including 76 patients under hemodialysis. To assess bone fragility, we measured bAP, CTX, and FGF 23. We calculated the bAP to the CTX ratio (bAP/CTX) and the FGF23*bAP product to the CTX ratio (FGF23*bAP/CTX). We defined bone fragility as the existence of osteoporosis or fragility fractures. Receiver operating characteristic (ROC) curves were evaluated for each biological using the existence of osteoporosis or fragility fracture as the gold standard for bone fragility. RESULTS: There were 51 men. The mean age was 53.36 ± 14.27 years. Bone fragility was noted in 25 cases. Patients with osteoporosis had higher FGF*bAP/CTX and bAP/CTX ratios. The ability of the ratio (bAP/CTX) to distinguish patients with osteoporosis from those without osteoporosis was good, with a ROC AUC of 0.707. The optimal ratio cut-off value with the highest accuracy was 9.72. The ability of the ratio (FGF23*bAP/CTX) to distinguish patients with bone fragility was good, with a ROC AUC of 0.701. The optimal ratio cut-off value with the highest accuracy was 1621.89 (sensitivity 60%, specificity 78.4%). CONCLUSION: Our study showed FGF23, FGF23*bAP product to CTX ratio, and the bAP to CTX ratio can be used as markers of bone fragility in hemodialysis patients. Therefore, these noninvasive and relatively inexpensive methods may serve to diagnose bone fragility in patients under hemodialysis.

Icariin regulates miR-23a-3p-mediated osteogenic differentiation of BMSCs via BMP-2/Smad5/Runx2 and WNT/ß-catenin pathways in osteonecrosis of the femoral head.

Icariin is commonly used for the clinical treatment of osteonecrosis of the femoral head (ONFH). miR-23a-3p plays a vital role in regulating the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). The present study aimed to investigate the roles of icariin and miR-23a-3p in the osteogenic differentiation of BMSCs and an ONFH model. BMSCs were isolated and cultured in vitro using icariin-containing serum at various concentrations, and BMSCs were also transfected with a miR-23a inhibitor. The alkaline phosphatase (ALP) activity and cell viability as well as BMP-2/Smad5/Runx2 and WNT/ß-catenin pathway-related mRNA and protein expression were measured in BMSCs. Additionally, a dual-luciferase reporter assay and pathway inhibitors were used to verify the relationship of icariin treatment/miR-23a and the above pathways. An ONFH rat model was established in vivo, and a 28-day gavage treatment and lentivirus transfection of miR-23a-3p inhibitor were performed. Then, bone biochemical markers (ELISA kits) in serum, femoral head (HE staining and Digital Radiography, DR) and the above pathway-related proteins were detected. Our results revealed that icariin treatment/miR-23a knockdown promoted BMSC viability and osteogenic differentiation as well as increased the mRNA and protein expression of BMP-2, BMP-4, Runx2, p-Smad5, Wnt1 and ß-catenin in BMSCs and ONFH model rats. In addition, icariin treatment/miR-23a knockdown increased bone biochemical markers (ACP-5, BAP, NTXI, CTXI and OC) and improved ONFH in ONFH model rats. In addition, a dual-luciferase reporter assay verified that Runx2 was a direct target of miR-23a-3p. These data indicated that icariin promotes BMSC viability and osteogenic differentiation as well as improves ONFH by decreasing miR-23a-3p levels and regulating the BMP-2/Smad5/Runx2 and WNT/ß-catenin pathways.

Comparison of the clinical effect of DHS and PFNA on senile osteoporotic fracture and their significance of changes in BALP expression level.

OBJECTIVE: To investigate the clinical effects of dynamic hip screw (DHS) and proximal femoral nail anti-rotation (PFNA) on senile osteoporosis patients and their effects on the expression level of bone-specific alkaline phosphatase (BALP). METHODS: 116 elderly patients with osteoporotic fracture were divided into DHS group (n=67) and PFNA group (n=49). BALP values were measured by ELISA before operation and 30 days after operation. RESULTS: The operation time, the bleeding volume, and the weight-bearing time of PFNA group was shorter than DHS group (p<0.05); the dominant blood loss and occult blood loss in PFNA group were less than those in DHS group (p<0.05); the healing time and detumescence time, the complications of PFNA group was fewer than the DHS group (p<0.05). The ten-meter walking speed and the five sitting tests in PFNA group were shorter than that in DHS group (p<0.05); the excellent and good rate and Harris score in PFNA group were higher than those in DHS group (p<0.05). The expression of BALP in PFNA group was lower than that in DHS group (p<0.05). CONCLUSION: PFNA surgery has less trauma, fewer complications, more optimistic postoperative healing and recovery degree, and is more conducive to the reduction of BALP expression level.

Expressiveness of Bone Markers in Breast Cancer with Bone Metastases.

INTRODUCTION: On a global scale, the malignant growth of mammary gland is the most common type of cancer in women. In the progress of mammary carcinoma, osseous metastatic invasion has a pivotal significance because it is a frequent complication occurring at an early stage of the disease. BACKGROUND: Bone metastases in breast cancer patients lead to increased mortality and decreased health-related quality of life. Therefore, early diagnostic assessment and treatment is requested. Meanwhile the progress of the disease should be monitored closely. Regarding health-related quality of life and lifetime prolongation, osseous metastases should be early diagnosed, therapied, and monitored. Up to date the gold standard is the whole-body scintigraphy. This kind of bone imaging features has high sensitivity but shows loss of specificity. AIM: This study aims to investigate the diagnostic versatility of bone markers in its resorption and formation function to detect bone metastases in patients with breast cancer. PATIENTS, MATERIALS, AND METHODS: For this purpose, the concentration of competing bone processing tumor markers in serums of 78 patients was detected and analyzed. Two groups of women with mammary carcinoma with and without osseous metastases were built to examine the presence (or absence) of statistically significant disparity of tumor marker concentration. The tumor markers employed in this study were the carboxyterminal collagen type I telopeptid (CTX), known as beta-crosslaps (ß-CTx), the alkaline phosphatase (AP), and its isoenzymes (especially the bone-specific AP [B-AP]). Additionally, the tumor markers for breast cancer (CA 15-3 and CEA) were analyzed in both groups. RESULTS: Our results provide evidence that in both groups, tumor markers such as ß-CTx and B-AP were a promising tool for the detection and exclusion of bone metastases in breast cancer. This comprehensive investigation shows both ß-CTx and B-AP are able to fulfill the conditions of a competent appliance to detect osseous metastases of patients with mammary carcinoma. CONCLUSION: Concerning the urgency of early and frequent detection, staging, and disease monitoring of mammary carcinoma with osseous metastases, this study renewed and underlined the importance of biochemical tumor markers - especially ß-CTx and B-AP - and laid a clinical-based cornerstone to build up on a prospective research.

Depletion and repletion of fruit and vegetable intake alters serum bone turnover markers: a 28-week single-arm experimental feeding intervention.

This study was designed to evaluate the effects of elevated fruit and vegetable intake on bone turnover markers. In all, twenty-nine subjects (nine male and twenty female, with a mean age of 32·1 (sem 2·5) years) participated in a 28-week single-arm experimental feeding intervention trial and consumed a prescribed low-fruit and vegetable diet for 6 weeks (depletion-1), a provided high-fruit and vegetable diet for 8 weeks (fruit: 360-560 g; vegetables: 450-705 g), another prescribed low-fruit and vegetable diet for 6 weeks (depletion-2) and then their usual diets for 8 weeks (repletion). Serum bone-related biomarkers were analysed with commercial ELISA kits. Plasma carotenoid levels decreased as a result of the depletion phase and increased with the high-fruit and vegetable diet. Compared with the baseline, depletion-1 resulted in higher serum bone resorption marker C-terminal telopeptide of type 1 collagen (CTX) and lower bone formation marker alkaline phosphatase (BAP) (CTX, 0·68 (sem 0·05) v. 0·97 (sem 0·08) ng/ml and BAP, 10·7 (sem 0·7) v. 9·5 (sem 0·8) µg/l for the baseline and the depletion-1, respectively, P<0·05). High intake of fruit and vegetables decreased serum CTX (P<0·05) to 0·60 (sem 0·04) ng/ml and increased serum BAP to 11·3 (sem 0·7) µg/l (P<0·05), compared with the depletion-1 phase. Serum concentrations of CTX were inversely correlated and those of BAP were positively correlated with blood lycopene. These data show that increased fruit and vegetable consumption at or above federal dietary guidance may be beneficial to bone health.

Associations Between Intravenous Iron, Inflammation and FGF23 in Non-Dialysis Patients with Chronic Kidney Disease Stages 3-5.

BACKGROUND/AIMS: Both iron deficiency and chronic inflammation are highly prevalent in patients with chronic kidney disease (CKD). The effect of intravenous iron infusion on mineral metabolism in CKD may be modified by inflammation. Intravenous iron theraphy may reduce peripheral degradation, secretion, clearence of iFGF23 and lead to hypophosphatemia. The aim of the study was to evaluate the effect of intravenous iron on mineral metabolism in CKD patients. METHODS: 35 non-dialysis patients with CKD stages 3-5. received 100 mg/24h of ferric oxide saccharated solution for 5 days. Serum calcium (Ca), phosphorus (P), parathormone (PTH), intact-FGF23 (iFGF23), C-terminal-FGF23 (cFGF23), bone alkaline phosphatase (BAP) and high-sensitive CRP were assessed on day 1 and 3 at baseline and 2 hours after each dose administration and once on day 6. Plasma iFGF23 and cFGF23, as well as serum BAP were measured with ELISA and other parameters with standard automated laboratory methods. RESULTS: Serum iFGF23 increased after iv iron on day 1 and 6 (from 268.9±446.5 to 326.3±529.9 on day 1; p=0.05 and to 451.4±601 pg/mL on day 6; p=0.03). cFGF23 was reduced only on day 1 (from 654.3±441.3 to 473.6±414 RU/mL; p=0.016). P concentration decreased significantly two hours after the first iron infusion (from 1.69±0.5 to 1.54±0.35 mmol/l; p=0.003). In following days the changes of cFGF23, P and of other calcium-phosphate metabolism were not significant. Serum CRP correlated neither with iFGF-23 nor cFGF-23. CONCLUSION: Intravenous iron supplementation may only transiently affect the production and degradation of FGF23 resulting in hypophosphatemia at the commencement of iron therapy. Chronic low-grade inflammation does not seem to play a role in that mechanism.

Imbalanced bone turnover markers and low bone mineral density in patients with osteonecrosis of the femoral head.

PURPOSE: There have been few studies investigating the cumulative effect of individual factors related to bone metabolism on the systemic balance between bone formation and resorption in patients with osteonecrosis of the femoral head (ONFH). We investigated bone mineral density (BMD) of lumbar spine and bone turnover markers that reflect systemic bone metabolism. METHODS: Two-hundred twenty patients with ONFH were matched to 220 healthy subjects according to age, gender, and body mass index. ONFH patients were divided into steroid-induced (18%), alcoholic (21%), and idiopathic ONFH (61%) and subgroup analysis was performed to exclude the effect of steroid and malnutrition on bone metabolism. We compared lumbar spine bone mineral density (BMD) between groups and measured serum bone-specific alkaline phosphatase (BALP) and urinary deoxypyridinoline/creatinine (Dpd/Cr) ratio. RESULTS: Logistic regression analysis revealed low spine BMD was significantly associated with each subgroup of ONFH when compared with that of the control group (odds ratio of 2.27, 4.24, and 1.86 in alcoholic, steroid, and idiopathic ONFH, respectively). The mean value of serum BALP (27.02 U/L) was within the normal reference range while average urine Dpd/Cr ratio (6.24 nM/mM) increased in ONFH group when compared with respective reference range. CONCLUSION: Spine BMD decreased and urinary Dpd/Cr ratio increased in patients with non-traumatic ONFH. Further studies will be necessary to identify whether non-traumatic ONFH is merely a regional disease confined to the femoral head or may affect systemic bone metabolism.

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

OBJECTIVE: 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. DESIGN: Cross-sectional study. SETTING: Maulana Azad Institute of Dental Sciences, New Delhi, India. PARTICIPANTS: 150 subjects (75 males and 75 females) in the age group of 8-20 years. METHODS: 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. RESULTS: 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). CONCLUSIONS: BALP showed promising results and can be employed as a potential biomarker for the estimation of growth status.

The use of bone turnover markers in chronic kidney disease-mineral and bone disorders.

Bone turnover markers assist in fracture risk prediction, management and monitoring of osteoporosis in patients without chronic kidney disease (CKD). The use in CKD-mineral bone disorder (MBD) has been limited as many of these markers and breakdown products are renally excreted, including the most commonly used and well standardized procollagen type I N propeptide and C-terminal cross-linking telopeptide of type I collagen. Of the markers unaffected by renal function, bone specific alkaline phosphatase is associated with mortality and fracture rate in CKD subjects and is now available on several automated analysers. When used in combination with PTH, bone specific alkaline phosphatase as a bone formation marker correlated well with bone biopsy histomorphometry in predicting adynamic bone disease. Tartrate-resistant acid phosphatase 5b is a resorption marker that is under development for automation. Both high and low bone turnover in CKD-MBD patients are associated with increased fracture and mortality risk. Bone biopsy as the gold standard to differentiate between adynamic bone disease and osteitis fibrosa is limited by availability and cost. Appropriate use of bone turnover markers is vital in the decision to commence anti-resorptive agents, and to monitor efficacy in order to avoid over suppression of bone turnover, which may lead to stress fractures. Further efforts are required to develop markers unaffected by renal function with standardized cut-off values and fracture as well as vascular calcification end-points.

Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis.

BACKGROUND: The management of chronic kidney disease-mineral and bone disorder requires the assessment of bone turnover, which most often is based on parathyroid hormone (PTH) concentration, the utility of which remains controversial. STUDY DESIGN: Cross-sectional retrospective diagnostic test study. SETTING & PARTICIPANTS: 492 dialysis patients from Brazil, Portugal, Turkey, and Venezuela with prior bone biopsy and stored (-20 °C) serum. INDEX TESTS: Samples were analyzed for PTH (intact [iPTH] and whole PTH), bone-specific alkaline phosphatase (bALP), and amino-terminal propeptide of type 1 procollagen (P1NP). REFERENCE TEST: Bone histomorphometric assessment of turnover (bone formation rate/bone surface [BFR/BS]) and receiver operating characteristic curves for discriminating diagnostic ability. RESULTS: The biomarkers iPTH and bALP or combinations thereof allowed discrimination of low from nonlow and high from nonhigh BFR/BS, with an area under the receiver operating characteristic curve > 0.70 but < 0.80. Using iPTH level, the best cutoff to discriminate low from nonlow BFR/BS was <103.8 pg/mL, and to discriminate high from nonhigh BFR/BS was >323.0 pg/mL. The best cutoff for bALP to discriminate low from nonlow BFR/BS was <33.1 U/L, and for high from nonhigh BFR/BS, 42.1U/L. Using the KDIGO practice guideline PTH values of greater than 2 but less than 9 times the upper limit of normal, sensitivity and specificity of iPTH level to discriminate low from nonlow turnover bone disease were 65.7% and 65.3%, and to discriminate high from nonhigh were 37.0% and 85.8%, respectively. LIMITATIONS: Cross-sectional design without consideration of therapy. Potential limited generalizability with samples from 4 countries. CONCLUSIONS: The serum biomarkers iPTH, whole PTH, and bALP were able to discriminate low from nonlow BFR/BS, whereas iPTH and bALP were able to discriminate high from nonhigh BFR/BS. Prospective studies are required to determine whether evaluating trends in biomarker concentrations could guide therapeutic decisions.

The importance of assessing the rate of bone turnover and the balance between bone formation and bone resorption during daily teriparatide administration for osteoporosis: a pilot study.

This study aimed to examine the importance of simultaneously measuring bone formation and resorption markers during daily teriparatide administration. In 135 women with osteoporosis, bone mineral density (BMD) was measured at 0, 24, and 48 weeks after teriparatide administration. Bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b were measured at 0, 4, 12, 24, 36, and 48 weeks. Subanalyses were performed in groups divided according to the BMD change at 48 weeks (increased and decreased groups), history of fragility fracture (acute and chronic groups), and treatment prior to teriparatide administration (alendronate, raloxifene, and naïve groups). The scatter diagram of multiple of median formation (MoMf) and multiple of median resorption (MoMr) showed that the distribution gradually spread to a high turnover by week 24. A significant correlation was observed between the rate of change in BMD at week 48 and the turnover rate [√(MoMf(2) + MoMr(2))] at week 0. Significant differences were observed in the turnover rate between the acute and chronic groups at weeks 0 and 4 and between the groups divided according to prior treatment from week 0 to 24. Because the assessment of either bone formation markers or bone resorption markers may result in erroneous data, it is necessary to assess them together during teriparatide treatment. The turnover rate at treatment initiation is a useful indicator to predict changes in BMD. When evaluating the turnover rate and balance (MoMf/MoMr), one should consider patient characteristics, including history of fragility fracture and prior treatment.

A biochemical approach for assessing cutoffs at the age thresholds of 14 and 18 years: a pilot study on the applicability of bone specific alkaline phosphatase on an Italian sample.

BACKGROUND: The majority of age estimation methods analyze morphological changes of specific skeletal (or dental) structures reflecting global bone development (biological parameter) in order to estimate a chronological value. This morphological and structural development is the consequence of a very active tissue metabolism and intensive modeling process which involve both bone formation and bone resorption. Several biochemical markers of bone formation and bone resorption are available, and specific biochemical tests can be performed on blood or urine samples, but such markers of bone turnover have never been employed for age estimation in living individuals for forensic purposes. The aim of this study was to ascertain the applicability of serum bone alkaline phosphatase (BALP) concentration in the age estimation for forensic purposes. We focused on the legal age thresholds of 14 and 18 years (LAT) because, in Italy, the former is considered the minimum age for criminal responsibility and the latter defines adult age and the possibility of applying general criminal laws. MATERIALS AND METHODS: This study analyzed, from a forensic point of view, BALP and Tanner stages of 202 healthy white individuals (116 females and 86 males) between the ages of 10 and 30 years. We derived a linear logistic model to estimate the probability that an individual was older or younger than LAT using two variables: BALP concentration and Tanner stages. The predictive accuracy of the test was assessed by the determination of the receiver-operating characteristic curve (ROC curve). The test was performed to identify a threshold (cutoff) that could be used to assign an individual to the population of those younger or older than LAT. RESULTS: ROC curve showed that the use of both serum BALP concentration and Tanner stages has a very good level of reliability in age assessment (the area under the ROC curve, AUC, ranged from 0.918 to 0.962). Best results were obtained in the assessment of male over 18 years of age (sensibility and specificity respectively of 0.90 and 0.93 with an accuracy of 0.92). Worst results were obtained in the assessment of female over 18 years of age (sensibility and specificity respectively of 0.87 and 0.82 with an accuracy of 0.84). We also calculated the probability of the correctness in the age estimation. CONCLUSION: The results showed that the use of serum BALP concentration in the age assessment could be a promising and integrative method to established ones, but more research has to be done to validate the value of the proposed method in the forensic practice.

Decreased serum bone specific alkaline phosphatase and increased urinary N-terminal telopeptide of type I collagen as prognostic markers for bone mineral density loss in HIV patients on cART.

OBJECTIVES: Bone mineral density (BMD) loss is a major chronic complication in HIV patients. We performed a prospective study to determine the time course of BMD changes and to find prognostic factors of BMD loss in HIV patients on combination antiretroviral therapy (cART). PATIENTS AND METHODS: Subjects were 54 male Japanese HIV patients who had been on cART ≥1 year with no therapeutic agents for osteoporosis. Patients were observed for ≥1 year (median 3.1 years) and underwent annual BMD analyses using dual energy X-ray absorptiometry. Changes in BMD at lumbar spine and femoral neck were calculated for each person-year of all the patients. Clinical factors were also collected simultaneously with BMD examinations to determine prognostic factors for BMD loss. RESULTS: In total, 173 person-years in 54 patients were observed. One third (19, 35.2%) and slightly over half (30, 55.6%) patients showed BMD decreases at lumbar spine and femoral neck, respectively. However, the median BMD changes at lumbar spine and femoral neck were 0.0% and -0.52% per year, respectively. Monovariant and mixed model analyses determined that decreased serum bone specific alkaline phosphatase (BAP, p = 0.0047) and increased urinary N-terminal telopeptide (uNTx, p = 0.0011) were prognostic factors for BMD loss at lumbar spine and femoral neck, respectively. CONCLUSIONS: BMD at both lumbar spine and femoral neck changed little on average in HIV patients on cART. Decreased serum BAP or increased uNTx may be helpful to predict progressive BMD loss in the following year and to select patients for BMD follow-up or initiation of anti-osteoporosis treatment.