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Preoperative radiotherapy (RT) for non-metastatic rectal cancer reduces local recurrence rates but can cause pelvic insufficiency fractures. Despite the high morbidity from RT-induced skeletal injuries, predictive and preventive measures are lacking. How these injuries are reflected by bone biomarkers are largely unknown. The aim was to assess longitudinal changes in bone biomarkers and their relation to RT-related bone injuries in women with rectal cancer. This longitudinal cohort study includes 47 women with non-metastatic rectal cancer treated with surgery ± preoperative RT with or without chemotherapy. Sclerostin, bioactive sclerostin, C-terminal telopeptide cross-links of collagen type I (CTX), bone-specific alkaline phosphatase (BALP), and type I procollagen intact N-terminal propeptide (PINP) were measured at baseline, after RT, and 1 yr postoperatively. Pelvic magnetic resonance imaging was used for detection of skeletal injury. Sixteen of 36 (44%) irradiated women had radiation-induced bone injuries and were compared to 11 women (RT–) and 20 women (RT+) without bone injuries. Serum CTX, BALP, and PINP increased during the first year after RT in women with radiation-induced bone injuries. The difference in mean change of CTX (p=.037) and BALP (p=.042) was conferred by longitudinal regression analyses adjusted for serum estradiol. Serum sclerostin and bioactive sclerostin remained stable over time. Taken together, bone markers may be of interest for future research on fracture prediction or preventive measures in women susceptible to radiation-induced bone injury. Due to few measure points, the full pattern cannot be captured regarding the relation over time between bone biomarkers and skeletal injury from irradiation. Lay Summary: Radiation therapy (RT) for rectal cancer before surgery reduces the risk of cancer recurrence, but can cause injuries to the pelvic bone. Despite the high morbidity from RT-caused skeletal injuries, predictive and preventive measures are lacking. How these bone injuries are reflected by bone biomarkers measured in serum is largely unknown. The aim of this study was to measure serum bone biomarkers and their relation to RT-related bone injuries in women with rectal cancer. The study group included 47 women with rectal cancer treated with surgery ± preoperative RT. Pelvic magnetic resonance imaging was used for detection of skeletal injury. The bone biomarkers sclerostin, bioactive sclerostin, C-terminal telopeptide cross-links of collagen type I (CTX), bone-specific alkaline phosphatase (BALP), and type I procollagen intact N-terminal propeptide (PINP) were measured at baseline, after RT, and 1 yr after surgery. Sixteen of 36 (44%) irradiated women had radiation-caused bone injuries and were compared to 31 women without bone injuries. Serum CTX, BALP, and PINP increased during the first year after RT in women with radiation-caused bone injuries. In summary, bone markers may be of interest for future research on fracture prediction or preventive measures in women prone to radiation-caused bone injury. [ABSTRACT FROM AUTHOR]

Purpose: Statin therapy is widely used for the management of dyslipidemia and the prevention of cardiovascular diseases (CVDs). However, there is a growing concern about its potential effects on bone metabolism markers and mineral density. The aim of this systematic review and meta-analysis was to investigate the effect of statin therapy on these parameters. Methods: PubMed/MEDLINE, Scopus, and Clarivate Analytics Web of Science databases were searched from inception to August 2023, using MESH terms and keywords. Results: After screening 2450 articles, 16 studies that met the inclusion criteria were included, of which 12 randomized controlled trials (RCTs) were used for meta-analysis. The findings showed that statin therapy significantly reduced bone-specific alkaline phosphatase (B-ALP) levels (WMD=-1.1 U/L; 95% CI -2.2 to -0.07; P =0.03; I2=0%,), and bone mineral density (BMD) at different sites (WMD=-0.06 g/cm2; 95% CI -0.08 to -0.04; P <0.001;>2=97.7%, P <0.001).> Conclusion: This systematic review and meta-analysis provide evidence that statin therapy is associated with a significant reduction in B-ALP levels and BMD at different sites of the skeleton. Further studies are needed to investigate the long-term effects of statin therapy on bone health and to identify the potential underlying mechanisms. [ABSTRACT FROM AUTHOR]

This article discusses a study that examined potential biomarkers for assessing bone health in apparently healthy adults. The study focused on Vitamin D, Vitamin D binding protein (VDBP), and bone-specific alkaline phosphatase (BALP) as markers for overall bone turnover. The study found that the participants had low levels of serum vitamin D and VDBP, and increased BALP levels. The researchers suggest that these biomarkers could be used to assess bone health and emphasize the importance of public health education on the role of vitamin D in maintaining bone health. [Extracted from the article]

Osteoprotegerin (OPG) is a trap receptor for the receptor activator of the nuclear factor kappa B ligand (RANKL). We aimed to determine the OPG and free soluble RANKL (sRANKL) concentrations in girls during puberty and their relationships with pubertal stage, growth rate and serum concentrations of estradiol, as well as classical bone formation (N-terminal propeptide of type I collagen (PINP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC)) and bone resorption (C-terminal telopeptide of type I collagen (CTX)) markers. The semi-longitudinal study involved 88 healthy girls, aged 11.8-13.2 years. Their weight and height were measured twice at one-year intervals. Pubertal stages were assessed using the Tanner (T) scale. Blood samples were taken at the first examination. Serum concentrations of OPG, sRANKL, CTX and BALP were determined by enzyme-linked immunosorbent assay, estradiol and PINP by radioimmunoassay and osteocalcin by immunoradiometric assay. The one-year increase in height and weight of girls in the T2 and T3 pubertal stages was greater than that of girls in the T4 stage (p=0.000, p<0.03). OPG concentrations (T2: 4.04±0.62; T3: 4.31±0.79; T4: 4.46±0.84 pmol/L) sRANKL concentrations (T2: 0.22 (IQR 0.09-0.54); T3: 0.42 (IQR 0.22-0.79); T4: 0.35 (IQR 0.16-1.04) pmol/L) and sRANKL/OPG ratios (T2: 0.05 (IQR 0.03-0.13); T3: 0.11 (IQR 0.05-0.19); T4: 0.09 (IQR 0.05-0.19) did not differ significantly between pubertal stages. Concentrations of PINP, CTX, BALP and OC were higher in girls at T3 stage than at the T4 stage (p=0.000, p=0.001, p=0.046, p=0.038; respectively). Concentrations of sRANKL and OPG did not correlate with body weight, height, growth rate, or concentrations of estradiol, PINP, CTX, BALP and OC. There were correlations between the increase in height over one year and the concentrations of PINP (r=0.499, p=0.000), CTX (r=0.311, p=0.003) and BALP (r=0.224, p=0.036), as well as of estradiol (r=-0.473, p=0.000). Unlike PINP, OC, BALP, CTX or estradiol concentrations, sRANKL and OPG concentrations do not change in girls during puberty. Neither OPG nor sRANKL concentrations correlate with somatic characteristics and classical bone turnover markers concentrations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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

AbstractBackground 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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: Primary – a study of the correlation between serum osteoprotegerin (OPG), and biomarkers of bone metabolism in patients with treatment-naive Graves' disease (GD). Secondary – serum level of OPG, TNF-alfa, and biomarkers of bone metabolism in patients three months after treatment of GD with methimazole (MMI). Materials and Methods: A total of thirty-five treatment-naive newly diagnosed GDs were recruited for the study, most of them female. All patients started with MMI for treatment and various blood parameters were measured at baseline and three months after treatment. Measurements: Serum calcium (Ca), phosphorus (P), bone-specific alkaline phosphatase (B-ALP), OPG, TNF-alfa, and urine deoxypyridinoline (U-DPD) along with serum-free T3 and T4, thyroid-stimulating hormone (TSH) and thyroid receptor antibody (TR-ab) were analysed at baseline and three months after MMI treatment. All the patients had euthyroid at three months of MMI treatment. Results: Mean serum OPG (0.94 ± 1.39 vs. 0.63 ± 0.27 ng/ml; P = 0.262) level at baseline and after treatment with MMI did not show any significant change. Mean TSH level (0.207 ± 0.59 vs. 1.00 ± 1.95, P = 0.025) was significantly low at baseline than after treatment; FT4 (5.9 ± 5.22 v 1.77 ± 1.89 ng/dl; P < 0.001), FT3 (12.19 ± 6.91 vs. 4.99 ± 3.55 pg/ml; P < 0.001), and TNF-alfa values decreased significantly after treatment, however, PTH (58.09 ± 28.75 vs. 75.57 ± 41.50; P < 0.026) increased significantly after treatment. Discussion: There is no correlation of OPG with thyroid hormone profile, TSH, thyroid receptor antibody (TR-ab), and bone metabolic parameters such as serum Ca, P, B-ALP, TNF-alfa, and U-DPD in our study. Mean TNF-alfa decreased significantly (393.43 ± 270.473 vs. 139.34 ± 101.264 pg/ml; P = 0.001) level after treatment with MMI. TNF-alfa was positively correlated with TR-ab (r = 0.374; P = 0.027) and B-ALP (r = 0.388; P = 0.021). Conclusion: The bone turnover marker in GD seems to be mediated other than OPG. We observed an increase in circulating TNF-alfa in GD with a significant decrease after treatment. TNF-alfa could be a marker of GD activity as evidenced by a close positive correlation with TR-ab, a sensitive marker of GD autoimmunity. TNF-alfa could be a factor associated with bone turnover markers in GD despite its euthyroid state.

Background and Aims: Alkaline phosphatase (ALP) enzyme has been linked to vascular calcification. Unexplained elevations in serum ALP levels have been reported in patients with type 2 diabetes mellitus (T2DM). We assessed bone-specific alkaline phosphatase (BAP) levels in patients with T2DM who had unexplained ALP elevations and studied the association between BAP and other markers of vascular calcification. Methods: Patients with T2DM who had high serum ALP in the absence of known causes of ALP elevation were studied. The control group was T2DM patients with normal ALP. We measured the serum levels of BAP along with the leptin, fetuin-A, and vitamin K2 levels. Ankle–brachial index (ABI) was also measured in both groups. Results: Serum BAP levels were significantly higher in the group with high ALP when compared with the normal ALP group. A significant positive correlation was present between BAP and serum fetuin-A as well as between BAP and Vit K2 levels. There was no correlation between BAP and serum leptin. ABI was comparable between the two groups. Conclusions: Patients with T2DM may have unexplained elevation in ALP due to an increase in BAP. Elevation in BAP may be associated with other markers of vascular calcification suggesting an increased risk of vascular calcification.

Objective: to learn more about the therapeutic impact of treating children with idiopathic short stature with calcium lysine phosphate hydrogen calcium granules and recombinant human growth hormone. Methods: From May 2021 to May 2022, 114 children with idiopathic low stature received treatment at Marjan Teaching Hospital. They were split into a control group and a treatment group, each of which had 57 instances, depending on the pharmaceutical differences. The treatment group received oral lysine phosphate hydrogen calcium granules, 5 g/time, twice daily, while the children in the control group received subcutaneous injections of recombinant human growth hormone solution, 0.033-0.050 mg/kg, once daily. The two study groups have been received care for a full year. Results: Following treatment, the overall success ratio in the treatment group was meaningfully greater than that in the control group (95.21% vs 82.31%), (P value lower than 0.05). The two groups experienced much faster development rates in terms of height and weight, bone age, and growth. The serological parameters and bone metabolism indices in both groups significantly increased following therapy (P value lower than 0.05). Conclusion: In the treatment of children with idiopathic short stature, calcium lysine phosphate hydrogen granules and recombinant human growth hormone are successful in promoting the growth of height in these children. To encourage the improvement of bone metabolism indicators, it has some clinical application benefit. [ABSTRACT FROM AUTHOR]

Objectives: Primary – a study of the correlation between serum osteoprotegerin (OPG), and biomarkers of bone metabolism in patients with treatment-naive Graves' disease (GD). Secondary – serum level of OPG, TNF-alfa, and biomarkers of bone metabolism in patients three months after treatment of GD with methimazole (MMI). Materials and Methods: A total of thirty-five treatment-naive newly diagnosed GDs were recruited for the study, most of them female. All patients started with MMI for treatment and various blood parameters were measured at baseline and three months after treatment. Measurements: Serum calcium (Ca), phosphorus (P), bone-specific alkaline phosphatase (B-ALP), OPG, TNF-alfa, and urine deoxypyridinoline (U-DPD) along with serum-free T3 and T4, thyroid-stimulating hormone (TSH) and thyroid receptor antibody (TR-ab) were analysed at baseline and three months after MMI treatment. All the patients had euthyroid at three months of MMI treatment. Results: Mean serum OPG (0.94 ± 1.39 vs. 0.63 ± 0.27 ng/ml; P = 0.262) level at baseline and after treatment with MMI did not show any significant change. Mean TSH level (0.207 ± 0.59 vs. 1.00 ± 1.95, P = 0.025) was significantly low at baseline than after treatment; FT4 (5.9 ± 5.22 v 1.77 ± 1.89 ng/dl; P < 0.001), FT3 (12.19 ± 6.91 vs. 4.99 ± 3.55 pg/ml; P < 0.001), and TNF-alfa values decreased significantly after treatment, however, PTH (58.09 ± 28.75 vs. 75.57 ± 41.50; P < 0.026) increased significantly after treatment. Discussion: There is no correlation of OPG with thyroid hormone profile, TSH, thyroid receptor antibody (TR-ab), and bone metabolic parameters such as serum Ca, P, B-ALP, TNF-alfa, and U-DPD in our study. Mean TNF-alfa decreased significantly (393.43 ± 270.473 vs. 139.34 ± 101.264 pg/ml; P = 0.001) level after treatment with MMI. TNF-alfa was positively correlated with TR-ab (r = 0.374; P = 0.027) and B-ALP (r = 0.388; P = 0.021). Conclusion: The bone turnover marker in GD seems to be mediated other than OPG. We observed an increase in circulating TNF-alfa in GD with a significant decrease after treatment. TNF-alfa could be a marker of GD activity as evidenced by a close positive correlation with TR-ab, a sensitive marker of GD autoimmunity. TNF-alfa could be a factor associated with bone turnover markers in GD despite its euthyroid state. [ABSTRACT FROM AUTHOR]

Background/Objectives: 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.

Conflicting results have been reported concerning a relationship between smoking and serum PTH. Our study objective was to examine whether smoking was associated with serum PTH independent of correlates of PTH among young adults, and explore potential mechanisms. This was a cross-sectional study of healthy individuals, 24-36 years old, examined during 1992 through 1993 in California, USA (a subset of Coronary Artery Risk Development in Young Adults study). Linear regression was used to obtain adjusted means of PTH according to smoking habit (current, former, never). Biomarkers for calcium metabolism and bone turnover (including serum concentrations of osteocalcin, bone-specific alkaline phosphatase, and 24-hour urinary excretion of calcium) and bone mineral density were similarly compared by smoking. 376 participants were analyzed (171 women, 181 black). Over half reported never smoking. We observed lower PTH in current smokers compared to non-smokers and found no evidence of an interaction by race and sex. PTH was lowest in current smokers, intermediate in former smokers, and highest in never smokers (geometric mean PTH: 23.6, 26.7, 27.4 pg/mL, respectively: P for trend, 0.006) after adjusting for potential confounders including calcium intake. Among the biomarkers, serum osteocalcin concentration and 24-hour urinary excretion of calcium were lowest in current smokers. We observed no smoking-related difference in bone mineral density. In this community-based sample of young adult men and women, smoking was associated with significantly lower PTH concentration. The mechanism and clinical implication of the finding, however, remains uncertain.

Abstract Background Chronic kidney disease increases the risk of fractures and altered bone and mineral metabolism. Exercise training could be a non-pharmacological therapeutic intervention. The aim of this work is to evaluate the effect of intradialytic exercise training on bone markers in hemodialysis (HD) patients. Results Forty adult patients on regular HD participated in the study. Twenty of which completed 3 months supervised intradialytic cycling exercise program and 20 served as controls. At baseline, there was no difference between both groups regarding age, sex, physical performance, and laboratory studies performed. After 3 months, the exercise group showed significant improvement in short performance battery test (SPBT) total score (P

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Aim: Anti-epileptic drugs are long-term medications; thus, side-effects are frequently seen. An important but insufficiently known side-effect is the emergence of metabolic bone diseases. The mechanism of this entity is not clearly known, but it is usually seen with the use of cytochrome P450 enzyme-inducing anti-epileptics. However, recent studies demonstrated that non-enzyme-inducing molecules also cause bone mineral impairment. The aim of this study was to shed light on the pathogenesis of anti-epileptic metabolic bone disease using bone turnover markers. Methods: This comparative, prospective case-control study included 37 patients followed-up in our outpatient clinic and 39 healthy control subjects. All the patients were female, aged over 18 years and in the premenopausal period, and had received the same anti-epileptic treatment for at least 3 months. Male patients, females who were <18 years old, pregnant, in the postmenopausal period, those with osteoporosis, gastrointestinal malabsorption, physical impairment that may prevent normal ambulation, endocrine and metabolic disease, musculoskeletal and joint disease or a history of medication use were excluded from the study. A healthy control group was formed of age-matched premenopausal women, with no disorders causing gastrointestinal malabsorption, no physical impairment preventing normal ambulation, no endocrine or metabolic disorder, or history of medication use that may affect bone turnover. The levels of serum calcium, alkaline phosphatase, 25-hydroxyvitamin D, osteoprotegerin and bone-specific alkaline phosphatase were assessed, and the results were recorded. Results: Evaluation was made of 37 female epilepsy patients with a mean age of 30.8 (8.1) years and a healthy control group of 39 age- and body mass index-matched females (P=0.69, P=0.85, respectively). The mean duration of AED use was 6.1 (5.5) years. The calcium (P=0.09), phosphate (P=0.906) and alkaline phosphatase (P=0.22) levels were similar in both groups. The levels of 25-hydroxyvitamin D (P=0.049), osteoprotegerin (P=0.025), and bone- specific alkaline phosphatase (P=0.037) were significantly lower in the epilepsy group. Conclusion: Our study showed that serum levels of osteoprotegerin and bone-specific alkaline phosphatase, which are markers of increased bone formation, were lower in epilepsy patients. Probably many factors cause the bone mineral disorder seen in epilepsy patients. Antiepileptic use is one of them. These results suggest that antiepileptics may not only affect enzyme induction but also bone turnover. Neurologists should be aware of this issue and monitor patients regularly with respect to bone mineralization to enable early treatment when necessary. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency and a high-fat diet are considered health problems worldwide. The aims of this study were to examine the prevalence of vitamin D deficiency/insufficiency in young adults, factors related to the vitamin D status, and the influence of vitamin D deficiency and/or a high-fat diet on bone parameters. Here, we investigated the hypothesis that a high-fat diet in the presence of a vitamin D-deficient status would have a more negative influence on bone parameters than a normal-fat diet with such a status. In the present study, we targeted young Japanese adults aged 21-23 (n = 175). We conducted a diet survey based on 3-day food records, biochemical examination of serum, and quantitative ultrasound measurements at the calcaneus. As a result, the rates of vitamin D deficiency {serum 25-hydroxyvitamin D 3 [25(OH)D] concentration less than 20 ng/mL} and insufficiency [serum 25(OH)D concentration less than 30 ng/mL but not less than 20 ng/mL] were 60.6 and 30.9%, respectively. A positive correlation was observed between the serum 25(OH)D level and serum bone-specific alkaline phosphatase level, which is a serum marker of bone formation (r = 0.253, P <.01) or the speed of sound (SOS) as an index of bone density (r = 0.259, P <.01). A negative correlation was observed between the ratio of fat intake to total energy intake (%E) and serum 25(OH)D levels (r = −0.206, P <.01). Furthermore, we revealed that a high-fat diet in the presence of a vitamin D deficient status reduced the SOS parameter compared with a normal-fat diet with a vitamin D-deficient status (P <.05). [ABSTRACT FROM AUTHOR]

Objective To analyze lhe correlation between bone mineral density (BMD) and bone metabolism biochemical indicators in patients wilh chronic kidney disease (CKD). To explore the value of BMD and biochemical indexes of bone metabolism in CKD-MBD. Methods From January 1, 2018 to September 30, 2019, 128 patients wilh stage CKD3 to SD who were treated in the Department of Nephrology of The Second Hospital of Anhui Medical University were selected. The CKD group was divided into the CKD3 stage group and CKD4 stage group, stage 5 non-dialysis group (CKD5ND stage group), and stage 5 hem odialysis group (CKD5HD stage group). Another 15 healthy persons were selected as the control group. Detect blood calcium (Ca), blood phosphorus (P), bone specific alkaline phosphatase (BALP), parathyroid hormone (PTH), and serum creatinine (SCr) Laboratory indicators, perfect lumbar spine and left total hip bone mineral density (BMD) examination. Compared each index differences between the groups, and analyzed the correlation between the lumbar and total hip BMD and each index, and analyzed the risk factors affecting BMD by multiple linear regression. Results (The total hip BMD of the CKD3, CKD4, CKD5ND, and CKD5HD stage groups was lower than that of the control group, and it continued to decrease as the CKD stage progressed (all P< 0. 05). BALP, Ca, P and LogPTH levels: The BALP concentrations in the CKD3, CKD4, CKD5ND, and CKD5HD groups were higher than that in the control group. (all PO. 05). Multiple linear regression analysis showed that age, BMI, SCr, and PTH were the risk factors affecting BMD of the total hip. Conclusion Compared with the BMD of lumbar spine, BMD of total hip is a sensitive indicator of early bone metabolism abnormality, and gradually decreases with the progress of CKD. BMD of total hip is negatively correlated with P, PTH and BALP. PTH is a risk factor for BMD of total hip. Early combined detection of BMD and bone metabolism biochemical indicators of the total hip has important value for the early detection and management of CKD-MBD. [ABSTRACT FROM AUTHOR]

To determine the laboratory reproducibility of urine N-telopeptide and serum bone-specific alkaline phosphatase measurements, we sent identical specimens to six US commercial labs over an 8-month period. Longitudinal and within-run laboratory reproducibility varied substantially. Efforts to improve the reproducibility of these tests are needed.We assessed the laboratory reproducibility of urine N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP).Serum and urine were collected from five postmenopausal women, pooled, divided into identical aliquots, and frozen. To evaluate longitudinal reproducibility, identical specimens were sent to six US commercial labs on five dates over an 8-month period. To evaluate within-run reproducibility, on the fifth date, each lab was sent five identical specimens. Labs were unaware of the investigation.Longitudinal coefficients of variation (CVs) ranged from 5.4% to 37.6% for NTX and from 3.1% to 23.6% for BAP. Within-run CVs ranged from 1.5% to 17.2% for NTX. Compared to the Osteomark NTX assay, the Vitros ECi NTX assay had significantly higher longitudinal reproducibility (mean CV 7.2% vs. 30.3%, p

SummaryTo determine the laboratory reproducibility of urine N-telopeptide and serum bone-specific alkaline phosphatase measurements, we sent identical specimens to six US commercial labs over an 8-month period. Longitudinal and within-run laboratory reproducibility varied substantially. Efforts to improve the reproducibility of these tests are needed.IntroductionWe assessed the laboratory reproducibility of urine N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP).MethodsSerum and urine were collected from five postmenopausal women, pooled, divided into identical aliquots, and frozen. To evaluate longitudinal reproducibility, identical specimens were sent to six US commercial labs on five dates over an 8-month period. To evaluate within-run reproducibility, on the fifth date, each lab was sent five identical specimens. Labs were unaware of the investigation.ResultsLongitudinal coefficients of variation (CVs) ranged from 5.4% to 37.6% for NTX and from 3.1% to 23.6% for BAP. Within-run CVs ranged from 1.5% to 17.2% for NTX. Compared to the Osteomark NTX assay, the Vitros ECi NTX assay had significantly higher longitudinal reproducibility (mean CV 7.2% vs. 30.3%, p < 0.0005) and within-run reproducibility (mean CV 3.5% vs. 12.7%, p < 0.0005).ConclusionsReproducibility of urine NTX and serum BAP varies substantially across US labs.

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.

Context: Bone-specific alkaline phosphatase (B-ALP), a product of osteoblasts, is a bone formation marker whose serum levels fluctuate with puberty and adolescence. Aims: This study aims to assess B-ALP levels in saliva and correlate it with different skeletal maturity stages of hand-wrist radiographs using Hagg and Taranger method. Settings and Design: Observational study and cross-sectional design. Subjects and Methods: Total sample comprised of 90 individuals, right hand-wrist radiographs, and 2 ml unstimulated whole saliva samples taken from each patient on the same day. The hand-wrist radiographs were traced and staged into 5 subgroups (18 individuals each) according to Hagg and Taranger method. Statistical Analysis Used: One-way analysis of variance (ANOVA) and Tukey's multiple post hoc test. Results: The comparison of salivary B-ALP values between the different skeletal subgroups using one-way ANOVA depicted statistically significant results (P = 0.0003). Pairwise comparison using Tukey's multiple post hoc procedures showed that salivary B-ALP levels were comparatively higher in subgroup 3 and that the difference between subgroups 1 and 3 (P = 0.0109) and subgroups 3 and 5 (P = 0.0014) was statistically significant. Conclusion: B-ALP could be successfully identified and quantitatively estimated in saliva and showed significant correlation with different skeletal age subgroups as determined by Hagg and Taranger method.

Abstract Background Tartrate-resistant acid phosphatase-5b (TRACP-5b) and bone-specific alkaline phosphatase (BALP) levels have not been evaluated following ibandronate treatment in hemodialysis (HD) patients. Methods To evaluate the efficacy and tolerability of ibandronate, including TRACP-5b and BALP levels, in patients on HD, we conducted a 6-month retrospective study of 13 HD patients who were administered ibandronate at Kaetsu Hospital in Japan. All enrolled patients were placed on a regimen of intravenous ibandronate at a dose of 1 mg once every 4 weeks, from August 2015 to October 2016. Baseline and end-of-study levels of TRACP-5b and BALP were determined 1 month before and 6 months after the start of ibandronate treatment. Results TRACP-5b levels were significantly decreased from 785.3 ± 385.8 mU/dL at baseline to 638.2 ± 423.4 mU/dL at end of study (P = 0.03). Additionally, the changing levels of TRACP-5b were positively associated with baseline hip bone mineral density (BMD) (P = 0.02, r = 0.65). In contrast, BALP levels were not significantly changed. Moreover, hip BMD tended to decrease from 0.51 ± 0.10 g/cm2 at baseline to 0.47 ± 0.11 g/cm2 at end of study (P = 0.07). The tolerability index showed no statistical difference between baseline and end of study. Conclusion Our results indicate that ibandronate treatment in HD patients—especially those with low BMD—might sufficiently reduce TRACP-5b levels with no long-term changes in other clinical laboratory parameters. Therefore, ibandronate might be a feasible treatment option for HD patients who develop low BMD.

In the early twenty-first century, societies around the world are facing the paradoxal epidemic development of PCa as a non-communicable disease. PCa is the most frequently diagnosed cancer for men in several countries such as the USA. Permanently improving diagnostics and treatments in the PCa management causes an impressive divergence between, on one hand, permanently increasing numbers of diagnosed PCa cases and, on the other hand, stable or even slightly decreasing mortality rates. Still, aspects listed below are waiting for innovate solutions in the context of predictive approaches, targeted prevention and personalisation of medical care (PPPM / 3PM). PCa belongs to the cancer types with the highest incidence worldwide. Corresponding economic burden is enormous. Moreover, the costs of treating PCa are currently increasing more quickly than those of any other cancer. Implementing individualised patient profiles and adapted treatment algorithms would make currently too heterogeneous landscape of PCa treatment costs more transparent providing clear "road map" for the cost saving. PCa is a systemic multi-factorial disease. Consequently, predictive diagnostics by liquid biopsy analysis is instrumental for the disease prediction, targeted prevention and curative treatments at early stages. The incidence of metastasising PCa is rapidly increasing particularly in younger populations. Exemplified by trends observed in the USA, prognosis is that the annual burden will increase by over 40% in 2025. To this end, one of the evident deficits is the reactive character of medical services currently provided to populations. Innovative screening programmes might be useful to identify persons in suboptimal health conditions before the clinical onset of metastasising PCa. Strong predisposition to systemic hypoxic conditions and ischemic lesions (e.g. characteristic for individuals with Flammer syndrome phenotype) and low-grade inflammation might be indicative for specific phenotyping and genotyping in metastasising PCa screening and disease management. Predictive liquid biopsy tests for CTC enumeration and their molecular characterisation are considered to be useful for secondary prevention of metastatic disease in PCa patients. Particular rapidly increasing PCa incidence rates are characteristic for adolescents and young adults aged 15–40 years. Patients with early onset prostate cancer pose unique challenges; multi-factorial risks for these trends are proposed. Consequently, multi-level diagnostics including phenotyping and multi-omics are considered to be the most appropriate tool for the risk assessment, prediction and prognosis. Accumulating evidence suggests that early onset prostate cancer is a distinct phenotype from both aetiological and clinical perspectives deserving particular attention from view point of 3P medical approaches. [ABSTRACT FROM AUTHOR]

Summary: Bone formation markers bone-specific alkaline phosphatase and osteocalcin are used in many clinical situations. Therefore, we calculated reference intervals for the two markers and investigated how they are influenced by several factors including sex and age. Furthermore, we established clinically relevant reference intervals for the two markers. Objective: The bone turnover markers (BTMs), bone-specific alkaline phosphatase (bone ALP), and osteocalcin (OC), are frequently measured formation markers. The purpose of this study was to establish reference intervals (RIs) for the two BTMs in a general adult Danish population. Methods: Bone ALP and OC were measured on the iSYS (IDS Plc) automatic analyzer in samples from the Danish Health2006 5-year follow-up study on serum from 2308 participants (54% women, age range 24–76). Participants with self-reported diagnosis of osteoporosis or receiving hormonal replacement were excluded from analyses while participants on hormonal contraceptives were included. Results: The geometric mean and 95%RI for bone ALP were 13.9 μg/L (7.6–25.6) for men and 13.8 μg/L (7.0–27.4) for women, while for OC 16.0 μg/L (7.5–34.4) for men and 18.6 μg/L (8.1–42.9) for women. Levels of bone ALP increased with increasing age (β 1.004, p < 0.001), while female sex had no effect. OC levels decreased with increasing age (β 0.998, p = 0.009) and increased with female sex (β 1.104, p < 0.001). Based on our findings, we propose for bone ALP and OC three clinical RIs for men based on age and three clinical RI for women based on age and menopausal status. Conclusion: The RI for bone ALP and OC varies with age and sex and the BTMs are influenced differently by the two factors. Consequently, the need for establishing valid RIs is of great importance before the full potential of BTM can be used in clinical practice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Imbalance between subchondral bone resorption and bone fonnation occurs in osteoarthritis. Our preliminary study has found that the subchondral bone changes precede the articular cartilage changes in knee osteoarthritis rats. OBJECTIVE: To observe the changes of subchondral bone in knee osteoarthritis rats, and to explore the effect of elcatonin on the expression of p38 MAPK and absorption of subchondral bone. METHODS: Female Sprague-Dawley rats, 3 months of age, were randomly divided into three groups: sham operation group (n=6, the adipose tissue of the same size as the ovary was removed without ovariectomy, the bilateral knee joints were opened, but without cruciate ligament injury); model group (n=6, bilateral ovariectomy plus bilateral cruciate ligament injury, no treatment); elcatonin group (n=6, ovariectomy plus cruciate ligament injury, intramuscular injection of 5lU/kg elcatonin, twice weekly). The bone mineral density and p38 protein expression levels in subchondral bone were detected at 12 weeks. The serum levels of C-terminal crosslinking telopeptides of type I collagen, C-terminal crosslinking telopeptides of type II collagen, interleukin-1, interleukin-6 and bone-specific alkaline phosphatase, tartrate resistant acid phosphatase 5b were detected. RESULTS AND CONCLUSION: (1) The bone volume fraction and trabecular bone number in the elcatonin group were significantly higher than those in the model group (P < 0.05), and the trabecular separation in the elcatonin group was lower than that in the model group (P < 0.05). (2) The bone volume fraction, trabecular bone number and trabecular thickness in the model group were lower than those in the sham operation group (P < 0.01 or P < 0.05), and the trabecular separation was higher than that in the sham operation group (P < 0.01). (3) The serum levels of C-tenninal crosslinking telopeptides of type I collagen, C-tenninal crosslinking telopeptides of type II collagen, interleukin-1, interleukin-6 and tartrate resistant acid phosphatase 5b in the elcatonin group was significanUy lower than those the model group (P < 0.05). and the above levels in the model group were significantly higher than those in the sham operation group (P < 0.05). (4) The p38 expression level in subchondral bone in the elcatonin group was significantly lower than that in the model group (P < 0.01 ), and the level in the model group was significantly higher than that in the sham operation group (P < 0.01). (5) These results indicate that elcatonin may inhibit the secretion of osteoarthritis pro-inflammatory factors and subchondral bone resorption by down-regulating the expression level of p38 MAPK. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of teriparatide and hyaluronic-calcitonin combination treatment in Chinese osteoporotic patients with risk of bone fracture. Methods: Osteoporotic patients aged 30 to 80 years, with at least one vertebral fracture and immediate risk of new vertebral fractures, were recruited from Hangzhou First People's Hospital. They were randomly assigned to two groups (50/group) treated with either teriparatide (20 μg/day) or hyaluronic acid + calcitonin (1:1 ratio, 200 IU daily) for 12 months. The patients were followed up every 3 months. Bone mineral density (BMD) was evaluated using x-ray absorptiometry. The proportion of patients with new fractures was recorded. Changes in serum osteocalcin and serum bone alkaline phosphatase (BSAP) from baseline to endpoint were also measured. Results: Treatment with teriparatide at a dose of 20 μg/day resulted in a significant reduction in the proportion of patients with new fractures (p < 0.05), when compared to patients treated with a combination of hyaluronic acid + calcitonin (200 IU daily). Teriparatide treatment for 12 months resulted in significant increase in lumbar BMD. Significant increases in spine BMD were evident after 3 months of treatment. There were significantly greater increases in serum osteocalcin and BSAP levels in teriparatide-treated patients than in those given hyaluronic acid + calcitonin. The most common treatment adverse event reported by both sexes was dizziness. Conclusion: These results demonstrate that teriparatide is efficacious and well tolerated in Chinese men and post-menopausal women with osteoporosis, when compared to the combination of hyaluronic acid and calcitonin. The efficacy of teriparatide is not associated with gender differences. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the correlation between bone mineral density (BMD) and the turnover rate [√(MoMf2 + MoMr2), multiple of median formation (MoMf) was calculated as bone-specific alkaline phosphatase (BAP) value/18.6 and multiple of median resorption (MoMr) as tartrate-resistant acid phosphatase 5b (TRACP-5b) value/463] and the balance (MoMf/MoMr) and to compare differences in therapeutic effects evoked by differences in previous treatments. Methods: In 51 osteoporotic women treated with bisphosphonates (BPs) or selective estrogen receptor modulators (SERMs), BMD was measured at 0, 24, and 48 weeks after denosumab administration. The values of BAP and TRACP-5b were measured at 0, 4, 12, 24, 36, and 48 weeks. Results: The turnover rate decreased at week 4 and decreased further at week 12. The balance indicated a relative predominantly formative state at week 4. This balance became higher in the SERM group than in the BP group at week 4. A correlation was observed between the rate of BMD change and turnover rate at weeks 0 and 4. Conclusions: It is necessary to evaluate the turnover rate and balance to determine the therapeutic effect of denosumab, which induces dissociation between the trends in the bone turnover markers. Turnover rate and balance during the early stages of denosumab treatment may be predictive factors of BMD. When switching from bone resorption inhibitors to denosumab, it was necessary to consider the beginning values that were affected by the previous treatment. The state of relative anabolism is greater at 4 weeks when the previous treatment involved SERMs rather than BPs.

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., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

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 (β-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 β-CTx and B-AP were a promising tool for the detection and exclusion of bone metastases in breast cancer. This comprehensive investigation shows both β-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 β-CTx and B-AP – and laid a clinical-based cornerstone to build up on a prospective research. [ABSTRACT FROM AUTHOR]

Background: Alkaline phosphatase isoenzyme analysis is an expensive and time-consuming laboratory test. We evaluated the effect of a locally derived screening algorithm for alkaline phosphatase isoenzyme requests on the number of alkaline phosphatase isoenzyme analyses performed, laboratory cost and patient care.Method: A total of 110 alkaline phosphatase isoenzyme analysis requests from the year 2015 were reviewed and subsequent alkaline phosphatase concentrations were monitored over a two-year period, to determine if the decision of performing/not performing alkaline phosphatase isoenzyme analysis, based on the algorithm, had an impact on patient care and laboratory cost. All alkaline phosphatase isoenzyme analysis requests with two consecutive elevated alkaline phosphatase concentrations (>upper limit of reference interval) were screened and, subject to the gamma glutamyl transferase being within the reference interval, either Bone alkaline phosphatase or 25 hydroxyvitamin D was measured depending on the age of the patient.Results: Compliance with this algorithm led to the normalization of subsequent serum alkaline phosphatase in 97% of patients without requiring alkaline phosphatase isoenzyme analysis. The cost of performing Bone alkaline phosphatase and 25 hydroxyvitamin D in-house was £778.50, while the cost of performing alkaline phosphatase isoenzyme analysis would have been £3040. This resulted in a laboratory saving of £2261.50.Conclusions: Implementation of this algorithm led to a significant reduction in alkaline phosphatase isoenzyme analysis, without compromising patient care. Total savings could be increased if 25 hydroxyvitamin D was used as a first-line test, for all patients with an elevated alkaline phosphatase and a normal gamma glutamyl transferase regardless of age. This algorithm is cost-effective and can be implemented in laboratories with 25 hydroxyvitamin D assay. [ABSTRACT FROM AUTHOR]

Background/Aims: Sclerostin, osteoprotegerin, and bone-specific alkaline phosphatase (B-ALP), which are primarily related to bone metabolism, have been linked with insulin resistance in adults. We aimed to evaluate the association of these markers with growth, obesity, and parameters of insulin resistance in lean and obese children and adolescents. Methods: We measured sclerostin, osteoprotegerin, and B-ALP in fasting and oral glucose tolerance test (oGTT) serum samples from 1,325 children and adolescents, and during 24-h profiles and after exercise and glucose exposure in young adults. Results: In addition to the positive relationship with height standard deviation scores (SDS), sclerostin (r = 0.035, p < 0.001) and B-ALP (r = 0.06, p = 0.028) increased, whereas osteoprotegerin (r = –0.098, p < 0.001) decreased with BMI SDS. Furthermore, B-ALP correlated with fasting- and oGTT-derived markers of glucose and insulin metabolism suggestive of insulin resistance. To evaluate potential confounding diurnal variation of bone markers, we performed 24-h profiles. B-ALP and osteoprotegerin had lower night-time levels. Exercise acutely and transiently increased B-ALP and osteoprotegerin levels, but glucose ingestion had no effect. Conclusions: Besides their association with growth, sclerostin and osteoprotegerin levels are altered in childhood obesity. Particularly B-ALP was related to insulin resistance indices. Our findings accent the link between bone, growth, and insulin resistance. [ABSTRACT FROM AUTHOR]

Bone metastasis is one of the most frequent and dangerous complications of malignant tumors. The last years, achievements in the study of bone remodeling mechanisms promoted the search of sensitive and specific criteria reflecting the intensity of osteolysis and osteosynthesis in bone metastatic lesions. The most informative and clinically valid biochemical markers of bone formation and resorption are characterized in this review. The data on their possible implications in diagnostics, monitoring and prognosis of skeletal lesions by various malignant tumors are presented. The attention to biochemical markers of bone remodeling as noninvasive methods for oncologic patients examination is gradually increasing with adoption of modern laboratory technologies to clinical practice. The last years, publications suggest the possibility of their use both for monitoring, prognosis and early diagnostics of bone metastasis. We present the results of our own investigation of serum C-telopeptide of type I collagen (СТX) as bone resorption marker and bone-specific alkaline phosphatase (BAP) as formation marker in 238 breast cancer patients using ELISA methods. The elevation of studied biochemical parameters in breast cancer patients was significantly associated with the extent of skeletal metastases (р < 0.02–0.00001), pathological fractures (р < 0.005–0.0001) and the severity of pain (р < 0.01–0.00002). Elevated rate of bone turnover was associated with reduced overall survival of breast cancer patients. The significant difference of overall survival estimated on a base of cut-off values of CTX (0.74 ng/ml) and BAP (43.7 IU/L) was found both in the groups of breast cancer patients with and without bone metastases. Serum СТХ and BAP are of value in monitoring and predicting the status of breast cancer bone metastases.

OBJECTIVE: This study aimed to investigate the impact of the different therapy regimens used in multiple myeloma (MM) on bone-specific alkaline phosphatase (BALP) levels. METHODS: One hundred and thirteen patients with MM were included in the study. Patients were grouped according to the regimens they received, as follows: group 1, melphalan and prednisolone (MP); group 2, vincristine, adriablastin, and dexamethasone (VAD); group 3, thalidomide plus dexamethasone; and group 4, bortezomib plus dexamethasone. BALP levels were measured before treatment and at the third and sixth months of treatment. A fifth group consisted of patients in the post-treatment remission period at study entry (no-treatment group). RESULTS: The BALP levels at the third and sixth months of the treatment were significantly higher than the pre-treatment levels in the bortezomib and the no-treatment groups, whereas no significant difference was observed in the MP, VAD, and thalidomide groups. CONCLUSION: Considering that BALP is a surrogate marker of bone formation, our study suggests that bortezomib more efficiently leads to the improvement of bone disease in myeloma than other treatment options.

Context: Bone-specific alkaline phosphatase (B-ALP), a product of osteoblasts, is a bone formation marker whose serum levels fluctuate with puberty and adolescence.Aims: This study aims to assess B-ALP levels in saliva and correlate it with different skeletal maturity stages of hand-wrist radiographs using Hagg and Taranger method.Settings and Design: Observational study and cross-sectional design.Subjects and Methods: Total sample comprised of 90 individuals, right hand-wrist radiographs, and 2 ml unstimulated whole saliva samples taken from each patient on the same day. The hand-wrist radiographs were traced and staged into 5 subgroups (18 individuals each) according to Hagg and Taranger method.Statistical Analysis Used: One-way analysis of variance (ANOVA) and Tukey's multiple post hoc test.Results: The comparison of salivary B-ALP values between the different skeletal subgroups using one-way ANOVA depicted statistically significant results (P = 0.0003). Pairwise comparison using Tukey's multiple post hoc procedures showed that salivary B-ALP levels were comparatively higher in subgroup 3 and that the difference between subgroups 1 and 3 (P = 0.0109) and subgroups 3 and 5 (P = 0.0014) was statistically significant.Conclusion: B-ALP could be successfully identified and quantitatively estimated in saliva and showed significant correlation with different skeletal age subgroups as determined by Hagg and Taranger method. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Bed rest studies document that a lower dietary acid load is associated with lower bone resorption. Objective: We tested the effect of dietary acid load on bone metabolism during spaceflight. Design: Controlled 4-d diets with a high or low animal protein-to-potassium (APro:K) ratio (High and Low diets, respectively) were given to 17 astronauts before and during spaceflight. Each astronaut had 1 High and 1 Low diet session before flight and 2 High and 2 Low sessions during flight, in addition to a 4-d session around flight day 30 (FD30), when crew members were to consume their typical in-flight intake. At the end of each session, blood and urine samples were collected. Calcium, total protein, energy, and sodium were maintained in each crew member's preflight and in-flight controlled diets. Results: Relative to preflight values, N-telopeptide (NTX) and urinary calcium were higher during flight, and bone-specific alkaline phosphatase (BSAP) was higher toward the end of flight. The High and Low diets did not affect NTX, BSAP, or urinary calcium. Dietary sulfur and age were significantly associated with changes in NTX. Dietary sodium and flight day were significantly associated with urinary calcium during flight. The net endogenous acid production (NEAP) estimated from the typical dietary intake at FD30 was associated with loss of bone mineral content in the lumbar spine after the mission. The results were compared with data from a 70-d bed rest study, in which control (but not exercising) subjects' APro:K was associated with higher NTX during bed rest. Conclusions: Long-term lowering of NEAP by increasing vegetable and fruit intake may protect against changes in loss of bone mineral content during spaceflight when adequate calcium is consumed, particularly if resistive exercise is not being performed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background/Aims: Bone-specific alkaline phosphatase (BAP) hydrolyzes pyrophosphate, which inhibits vascular calcification. We examined association between serum BAP and vascular calcification of male hemodialysis patients. Methods: Hand roentgenography of 167 male maintenance hemodialysis patients was conducted, and visible vascular calcification of the hand arteries was evaluated. Serum levels of 3 bone formation markers (BAP, osteocalcin, and N-terminal propeptide of type I collagen) and 2 bone resorption markers (C-terminal telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured, along with serum intact parathyroid hormone (PTH). Results: Of 167 patients, visible vascular calcification was seen in 37 patients. Among the bone formation and resorption markers, serum BAP was significantly higher in patients with vascular calcification than in those without (pConclusions: Higher serum BAP, but not other bone markers, is significantly associated with the presence of vascular calcification in male hemodialysis patients.

Despite the substantial preclinical evidence for a positive effect of the polyphenolic compound resveratrol, human data are very scarce, and currently no clinical data addressing the potential impact on bone metabolism have been published. In the present study we addressed this issue in order to identify potential bone metabolic effects of resveratrol in human subjects. In a randomised, placebo-controlled, double-blinded and parallel-group design, 24 obese [BMI (kg/m2): 34.2 ± 0.7] non-diabetic men were randomly assigned to 500 mg resveratrol or placebo treatment three times daily for four weeks. Biomarkers of bone metabolism, inflammatory parameters and circulating hormones were measured before and after the intervention period. Plasma levels of bone-specific alkaline phosphatase increased significantly in the resveratrol group as compared to placebo [delta changes (U/l); resveratrol: 4.9 ± 0.6 vs. placebo: −1.7 ± 0.7; P