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To explore how sex hormone fluctuations may affect bone metabolism, this study aimed to examine P1NP and β-CTX-1 concentrations across the menstrual and oral contraceptive (OC) cycle phases in response to running. 17β-oestradiol, progesterone, P1NP and β-CTX-1 were analysed pre- and post-exercise in eight eumenorrheic females in the early-follicular, late-follicular, and mid-luteal phases, while 8 OC users were evaluated during the withdrawal and active pill-taking phases. The running protocol consisted of 8 × 3min treadmill runs at 85% of maximal aerobic speed. 17β-oestradiol concentrations (pg·ml−1) were lower in early-follicular (47.22 ± 39.75) compared to late-follicular (304.95 ± 235.85;p = < 0.001) and mid-luteal phase (165.56 ± 80.6;p = 0.003) and higher in withdrawal (46.51 ± 44.09) compared to active pill-taking phase (10.88 ± 11.24;p < 0.001). Progesterone (ng·ml−1) was higher in mid-luteal (13.214 ± 4.926) compared to early-follicular (0.521 ± 0.365; p < 0.001) and late-follicular phase (1.677 ± 2.586;p < 0.001). In eumenorrheic females, P1NP concentrations (ng·ml−1) were higher in late-follicular (69.97 ± 17.84) compared to early-follicular (60.96 ± 16.64;p = 0.006;) and mid-luteal phase (59.122 ± 11.77;p = 0.002). β-CTX-1 concentrations (ng·ml−1) were lower in mid-luteal (0.376 ± 0.098) compared to late-follicular (0.496 ± 0.166; p = 0.001) and early-follicular phase (0.452 ± 0.148; p = 0.039). OC users showed higher post-exercise P1NP concentrations in withdrawal phase (61.75 ± 8.32) compared to post-exercise in active pill-taking phase (45.45 ± 6;p < 0.001). Comparing hormonal profiles, post-exercise P1NP concentrations were higher in early-follicular (66.91 ± 16.26;p < 0.001), late-follicular (80.66 ± 16.35;p < 0.001) and mid-luteal phases (64.57 ± 9.68;p = 0.002) to active pill-taking phase. These findings underscore the importance of studying exercising females with different ovarian hormone profiles, as changes in sex hormone concentrations affect bone metabolism in response to running, showing a higher post-exercise P1NP concentrations in all menstrual cycle phases compared with active pill-taking phase of the OC cycle. [ABSTRACT FROM AUTHOR]

Osteoporosis is a chronic disease that affects millions of patients worldwide and is characterized by low bone mineral density (BMD) and increased risk of fractures. Notably, natural molecules can increase BMD and exert pro-osteogenic effects. Noteworthily, the nutraceutical BlastiMin Complex® (Mivell, Italy, European Patent Application EP4205733A1) can induce differentiation of human bone marrow mesenchymal stem cells (BM-MSCs) in osteoblasts and can exert in vitro pro-osteogenic and anti-inflammatory effects. Thus, the purpose of this study was to verify the effects of BlastiMin Complex® on bone turnover markers (BTMs) and BMD in patients with senile and postmenopausal osteopenia or osteoporosis. The efficacy of BlastiMin Complex® on BTMs in serum was evaluated through biochemical assays. BMD values were analyzed by dual-energy X-ray absorptiometry (DXA) and Radiofrequency Echographic Multi Spectrometry (R.E.M.S.) techniques, and the SNPs with a role in osteoporosis development were evaluated by PCR. Clinical data obtained after 12 months of treatment showed an increase in bone turnover index, a decrease in C-reactive protein levels, and a remarkable increase in P1NP levels, indicating the induction of osteoblast proliferation and activity in the cohort of 100% female patients recruited for the study. These findings show that the nutraceutical BlastiMin Complex® could be used as an adjuvant in combination with synthetic drugs for the treatment of osteoporosis pathology. [ABSTRACT FROM AUTHOR]

Growth hormone therapy (GHT) can improve growth velocity and final height, but can also accelerate the process of bone growth, which is related to structural bone modeling in both formation and resorption. This study evaluated the capacity of bone turnover markers to predict early growth response to one year of GHT in short stature children born small for gestational age (SGA). This study included 25 prepubertal children born SGA. We estimated P1NP (N-terminal procollagen type 1), CTX (C-terminal telopeptide of collagen type 1), P3NP (N-terminal procollagen type 3), NT-pro-CNP (amino-terminal C-type natriuretic peptide) and Ca-P metabolism using standard ECLIA (electrochemiluminescence), RIA (radioimmunoassay), and ELISA (enzyme-linked immunosorbent assay) methods. A statistically significant increase in bone resorption markers (CTX) was found at both 6 and 12 months. P1NP bone markers were increased at 6 months and after 12 months of therapy. The P3NP marker for collagen synthesis also increased after 12 months of therapy. We obtained significant increases in phosphorus levels at 6 and 12 months, and similar ALP (alkaline phosphatase) increases. We found a significant correlation between height (cm) and CTX after 6–12 months, as well as a P1NP/height (SD) correlation after 12 months. Calcium levels significantly correlated with height (SD) after 12 months. We found strong reactions of bone resorption and bone formation markers during growth hormone therapy, which may determine their selection as predictors of GHT outcome in children born SGA. However, the issue requires further research. [ABSTRACT FROM AUTHOR]

Lijing Huo,1 Xuexin Liu,2 Changmei Wei,1 Fang Yu,1 Luping Ren,3 Yanqing Tie1 1Department of Medical Laboratory, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 2Health Check-up Centers, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Lijing Huo, Department of Medical Laboratory, Hebei General Hospital, 348 Heping West Road, Xinhua District, Shijiazhuang, Hebei Province, People’s Republic of China, Email huolijing1979@126.comAim: This study was intended to establish the reference intervals of bone turnover markers (BTMs) for healthy populations.Methods: According to the Clinical Laboratory Standards Institute (CLSI) EP28-A3c, we recruited 774 healthy Chinese and investigated their clinical characteristics and relationships among gender, age, season and BTMs. The reference intervals of BTMs for healthy populations in Hebei of China were established through defining the central 95% range of all observations.Results: We found that gender were associated with 25(OH)D, OC, β-CTX, and P1NP (P < 0.05), but not PTH1-84 (P=0.138). All serum BTMs showed differences among different age groups (P < 0.01). The level of 25 (OH) D in winter showed statistical differences with spring, summer, and autumn (P< 0.05). The OC level showed statistical difference between summer and winter (P=0.000). The P1NP levels showed statistical difference between spring and winter (P=0.019), summer and winter (P=0.000), and summer and autumn (P=0.012), respectively. The PTH1-84 levels in winter showed statistical differences with spring, and summer (all P=0.000), while there was no statistically significant difference in β- CTX levels between seasons.Conclusion: We have established the reference intervals of several BTMs for healthy individuals in Hebei of China, which have statistical significance across different age groups and genders, and there are also significant differences between different seasons. Therefore, the Chinese medical laboratories in different locations should group individuals according to gender and age groups in different seasons, and establish corresponding biological reference intervals.Keywords: 25-hydroxyvitamin D, 25(OH)D, osteocalcin, OC, β-carboxy-terminal cross-linking telopeptide of type I collagen, β-CTX, N-terminal procollagen of type I collagen, P1NP, parathyroid hormone 1-84, PTH1-84

Context Individuals with type 2 diabetes (T2D) have an increased risk of bone fractures despite normal or increased bone mineral density. The underlying causes are not well understood but may include disturbances in the gut-bone axis, in which both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are regulators of bone turnover. Thus, in healthy fasting participants, both exogenous GIP and GLP-2 acutely reduce bone resorption. Objective The objective of this study was to investigate the acute effects of subcutaneously administered GIP and GLP-2 on bone turnover in individuals with T2D. Methods We included 10 men with T2D. Participants met fasting in the morning on 3 separate test days and were injected subcutaneously with GIP, GLP-2, or placebo in a randomized crossover design. Blood samples were drawn at baseline and regularly after injections. Bone turnover was estimated by circulating levels of collagen type 1 C-terminal telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), sclerostin, and PTH. Results GIP and GLP-2 significantly reduced CTX to (mean ± SEM) 66 ± 7.8% and 74 ± 5.9% of baseline, respectively, compared with after placebo (P =.001). In addition, P1NP and sclerostin increased acutely after GIP whereas a decrease in P1NP was seen after GLP-2. PTH levels decreased to 67 ± 2.5% of baseline after GLP-2 and to only 86 ± 3.4% after GIP. Conclusion Subcutaneous GIP and GLP-2 affect CTX and P1NP in individuals with T2D to the same extent as previously demonstrated in healthy individuals. [ABSTRACT FROM AUTHOR]

Context Osteoporosis and/or bone fractures are indications of parathyroidectomy in primary hyperparathyroidism (PHPT), especially in women. However, the benefit of surgery in patients with osteopenia remains unclear. Objective To evaluate bone mineral density (BMD) and bone remodeling biomarkers changes 1 year after parathyroidectomy in women with PHPT. Design In the prospective, monocentric, observational prospective cohort with primary hyperparathyroidism patients (CoHPT) cohort, women operated for sporadic PHPT since 2016 with ≥1 year follow-up were included. BMD (dual-X ray absorptiometry) and bone remodeling biomarkers [cross-linked C-telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatases] were assessed before and 1 year after parathyroidectomy. Setting Referral center. Patients A total of 177 women with PHPT (62.5 ± 13.3 years, 83.1% menopausal, 43.9% osteopenic, and 45.1% osteoporotic) were included. Intervention Parathyroidectomy. Main Outcome Measure BMD change between before and 1 year after parathyroidectomy. Results Parathyroidectomy resulted in significant increase in BMD and decrease in serum bone remodeling biomarker concentrations. In the 72 patients with baseline osteopenia, mean BMD significantly increased at the lumbar spine [+0.05 g/cm2 (95% confidence interval [CI], 0.03–0.07)], the femoral neck [+0.02 g/cm2 (95% CI 0.00–0.04)], the total hip [+0.02 g/cm2 (95% CI 0.01–0.02)], and the forearm [+0.01 (95% CI 0.00–0.02)], comparable to osteoporotic patients. Among osteopenic patients, those with individual BMD gain (>0.03 g/cm2) at ≥1 site had higher preoperative serum CTX, P1NP, and urine calcium concentrations than those without improvement. Conclusion Parathyroidectomy significantly improved BMD and remodeling biomarkers in women with osteopenia, thereby supporting the benefit of parathyroidectomy in these patients. Preoperative serum CTX and P1NP concentrations could be useful to predict expected BMD gain. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the correlation between the triglyceride-glucose (TyG) index and bone turnover markers (BTMs) in osteoporotic fractures (OPFs) patients hospitalized for surgical intervention.MethodsA retrospective cross-sectional study was conducted on 3558 OPFs patients hospitalized for surgical intervention between January 2017 and July 2022. The study obtained baseline values for various biomarkers and covariates, including fasting blood glucose, β-C-terminal telopeptide of type I collagen (β-CTX), procollagen type 1 N-terminal propeptide (P1NP), triglycerides, age, sex, body mass index, smoking, drinking, low-density lipoprotein, high-density lipoprotein, aspartate aminotransferase, uric acid, the score of American society of anesthesiologists, homocysteine, parathyroid hormone, apolipoprotein B, apolipoprotein A, magnesium, phosphorus and calcium. Multiple linear regression, curve fitting, threshold effects, and subgroup analyses were also applied.ResultsAfter adjusting for covariates in the regression analysis, the results revealed a negative correlation between β-CTX and P1NP levels and the baseline TyG index. Specifically, a one-unit increase in the TyG index was associated with a reduction in β-CTX levels of -0.06 (95% CI: -0.10, -0.01; P-value = 0.012) and a reduction in P1NP levels of -4.70 (95% CI: -9.30, -0.09; P-value = 0.046). Additionally, the inflection points for the nonlinear correlation between the TyG index and β-CTX and P1NP were found to be K = 6.31 and K = 6.63, respectively.ConclusionThe study demonstrated a negative, non-linear relationship among the TyG index, β-CTX and P1NP in OPFs patients hospitalized for surgical intervention. These findings suggest that elevated TyG index levels may adversely affect bone turnover, potentially contributing to the progression of OP.

Context: Anamorelin, a ghrelin receptor agonist known to stimulate the pulsatile release of GH from the pituitary, has the potential to improve musculoskeletal health in adults with osteosarcopenia. Objective: To determine the effect of anamorelin treatment for 1 year on muscle mass and strength and on biochemical markers of bone turnover in adults with osteosarcopenia (OS). Design: Randomized, placebo-controlled, 1-year anamorelin intervention trial Setting: The Bone Metabolism Laboratory at the USDA Nutrition Center at Tufts University. Participants: 26 men and women, age 50 years and older, with OS. Main outcome measures: Muscle mass by D3-creatine dilution and lean body mass (LBM) and bone mineral density (BMD) by dual-energy X-ray absorptiometry, muscle strength, serum IGF-1, and bone turnover markers, serum procollagen 1 intact N-terminal (P1NP), and C-terminal telopeptide (CTX). Results: Anamorelin did not have a significant effect on muscle mass or LBM; it significantly increased knee flexion torque at 240°/s by 20% (P = .013) and had a similar nonstatistically significant effect on change in knee extension; it increased bone formation (P1NP) by 75% (P = .006) and had no significant effect on bone resorption (CTX) or BMD. Serum IGF-1 increased by 50% in the anamorelin group and did not change in the placebo group (P = .0001 for group difference). Conclusion: In this pilot study, anamorelin did not significantly alter muscle mass; however, it may potentially improve lower extremity strength and bone formation in addition to increasing circulating IGF-1 levels in adults with OS. Further study of anamorelin in this population is warranted. [ABSTRACT FROM AUTHOR]

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan–Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance. [ABSTRACT FROM AUTHOR]

Growth hormone therapy (GHT) can improve growth velocity and final height, but can also accelerate the process of bone growth, which is related to structural bone modeling in both formation and resorption. This study evaluated the capacity of bone turnover markers to predict early growth response to one year of GHT in short stature children born small for gestational age (SGA). This study included 25 prepubertal children born SGA. We estimated P1NP (N-terminal procollagen type 1), CTX (C-terminal telopeptide of collagen type 1), P3NP (N-terminal procollagen type 3), NT-pro-CNP (amino-terminal C-type natriuretic peptide) and Ca-P metabolism using standard ECLIA (electrochemiluminescence), RIA (radioimmunoassay), and ELISA (enzyme-linked immunosorbent assay) methods. A statistically significant increase in bone resorption markers (CTX) was found at both 6 and 12 months. P1NP bone markers were increased at 6 months and after 12 months of therapy. The P3NP marker for collagen synthesis also increased after 12 months of therapy. We obtained significant increases in phosphorus levels at 6 and 12 months, and similar ALP (alkaline phosphatase) increases. We found a significant correlation between height (cm) and CTX after 6–12 months, as well as a P1NP/height (SD) correlation after 12 months. Calcium levels significantly correlated with height (SD) after 12 months. We found strong reactions of bone resorption and bone formation markers during growth hormone therapy, which may determine their selection as predictors of GHT outcome in children born SGA. However, the issue requires further research.

Osteoporosis is a chronic disease that affects millions of patients worldwide and is characterized by low bone mineral density (BMD) and increased risk of fractures. Notably, natural molecules can increase BMD and exert pro-osteogenic effects. Noteworthily, the nutraceutical BlastiMin Complex® (Mivell, Italy, European Patent Application EP4205733A1) can induce differentiation of human bone marrow mesenchymal stem cells (BM-MSCs) in osteoblasts and can exert in vitro pro-osteogenic and anti-inflammatory effects. Thus, the purpose of this study was to verify the effects of BlastiMin Complex® on bone turnover markers (BTMs) and BMD in patients with senile and postmenopausal osteopenia or osteoporosis. The efficacy of BlastiMin Complex® on BTMs in serum was evaluated through biochemical assays. BMD values were analyzed by dual-energy X-ray absorptiometry (DXA) and Radiofrequency Echographic Multi Spectrometry (R.E.M.S.) techniques, and the SNPs with a role in osteoporosis development were evaluated by PCR. Clinical data obtained after 12 months of treatment showed an increase in bone turnover index, a decrease in C-reactive protein levels, and a remarkable increase in P1NP levels, indicating the induction of osteoblast proliferation and activity in the cohort of 100% female patients recruited for the study. These findings show that the nutraceutical BlastiMin Complex® could be used as an adjuvant in combination with synthetic drugs for the treatment of osteoporosis pathology.

Background: Well defined reference intervals are central to the utility of serum C-terminal telopeptide of type 1 collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP), designated as reference markers in osteoporosis, and useful for monitoring therapeutic response in that condition. This study reports the reference intervals for plasma CTX and serum P1NP in a multi-ethnic Malaysian population. Methods: Ethnic Malay, Chinese or Indian subjects aged 45-90 years old were recruited from Selangor, Malaysia from June 2016 to August 2018. Subjects with known medical conditions (e.g., bone disorders, malnutrition, immobilisation, renal impairment, hormonal disorders) and medications (including regular calcium or vitamin D supplements) that may affect CTX and P1NP were excluded. Additionally, subjects with osteoporosis or fracture on imaging studies were excluded. The blood samples were collected between 8 a.m. and 9 a.m. in fasting state. The CTX and P1NP were measured on Roche e411 platform in batches. Results: The 2.5th-97.5th percentiles reference intervals (and bootstrapped 90%CI) for plasma CTX in men (n = 91) were 132 (94-175) - 775 (667-990) ng/L; in post-menopausal women (n = 132) 152 (134-177) - 1025 (834-1293) ng/L. The serum P1NP reference intervals in men were 23.7 (19.1-26.4) - 83.9 (74.0-105.0) µg/L, and in post-menopausal women, 25.9 (19.5-29.3) - 142.1 (104.7-229.7) µg/L. Conclusion: The reference intervals for plasma CTX and serum PINP for older Malaysian men and post-menopausal women are somewhat different to other published studies from the region, emphasising the importance of establishing specific reference intervals for each population. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Osteoporosis is a leading public health problem that contributes to increasingly high rates of osteoporotic vertebral compression fractures among older adults. This study was developed with the goal of assessing serum C1q/TNF-related protein-3 (CTRP3) levels in postmenopausal osteoporosis (PMOP) patients and exploring the correlations between these levels and PMOP severity. PATIENTS AND METHODS: A population-based cross-sectional study of old women with osteoporosis was conducted. All women underwent both clinical and dual-energy X-ray absorptiometry examinations. Serum CTRP3, procollagen type I N propeptide (P1NP), and C-terminal telopeptide of type I collagen (CTX-1) concentrations in these patients were measured via ELISA. Bone tumor markers were additionally assessed. Receiver operating characteristic (ROC) analyses were utilized to assess the diagnostic performance of CTRP3 when identifying PMOP. RESULTS: This study included 54 PMOP patients, 62 patients with osteopenia, and 60 agematched patients without PMOP. Serum CTRP3 concentrations in PMOP patients were significantly lower than in the other two groups. Bone mineral density (BMD) was positively correlated with serum CTRP3 levels in all study participants, whereas it was negatively correlated with levels of P1NP and CTX-1. ROC analyses also suggested that reductions in serum CTRP3 levels may offer value as a diagnostic indicator of PMOP. CONCLUSIONS: Present data highlight a close relationship between CTRP3 and PMOP, with lower serum CTRP3 levels being closely associated with BMD, such that they may represent a protective marker for PMOP. [ABSTRACT FROM AUTHOR]

Context: Hyponatremia is associated with increased risk for osteoporosis. Preclinical studies in untreated hyponatremia suggest osteoclast upregulation, whereas a clinical study showed improved osteoblast function after hyponatremia normalization in hospitalized patients with syndrome of inappropriate antidiuresis (SIAD). Objective: This work aimed to investigate the effect of an increase in sodium on bone turnover, that is, the ratio of the osteoblast marker procollagen type 1 N-terminal propeptide (P1NP) to the osteoclast marker cross-linked C-terminal telopeptide of type 1 collagen (CTX), in outpatients with chronic SIAD. Methods: A predefined secondary analysis was conducted of the 2-month double-blind, crossover, placebo-controlled SANDx Trial (NCT03202667) performed from December 2017 to August 2021. Participants included 11 outpatients with chronic SIAD: 6 women, median age 73 years, who received a 4-week treatment with 25-mg empagliflozin or placebo. Main outcome measures included the relationship between the change in bone formation index (BFI), defined as P1NP/CTX, and the change in plasma sodium levels. Results: Changes in sodium were positively correlated with changes in BFI and P1NP (BFI: ρ=.55; P < .001; P1NP: ρ=.45; P = .004) but not with CTX (P = .184) and osteocalcin (P = .149). A sodium increase of 1 mmol/l was associated with an increase of 5.21 in BFI (95% CI, 1.41-9.00; P = .013) and with an increase of 1.48 µg/l in P1NP (95% CI, .26-2.62; P = .03). The effect of sodium change on bone markers was independent of the study medication empagliflozin. Conclusion: An increase in plasma sodium levels in outpatients with chronic hyponatremia due to SIAD, even when mild, was associated with an increase in bone formation index (P1NP/CTX) triggered by an increase in P1NP, a surrogate marker of osteoblast function. [ABSTRACT FROM AUTHOR]

Levels of bone turnover markers (BTM) can be measured using saliva. The aim of the present study was to determine the Biological Variability of BTM in young subjects, on serial biological salivary samples. Saliva samples of 20 apparently healthy young subjects (9 females and 11 males) have been analyzed. Samples collected using salivette with cotton swabs were obtained three times every 15 days. PTHrP; TRAcP-5b and P1NP have been assayed. The ANOVA test was used to calculate intra and interindividual variance (CVI and CVG). The individuality index (II) and reference change value (RCV) were evaluated for the clinically significant variation between two results in the same individual. CVI was highest for PTHrP and lowest for P1NP while CVG was highest for TRAcP-5b. RCV was maximum for PTHrP and minimum for P1NP. The critical difference (RCV) is of particular interest in evaluating variations in the concentrations of BMT on the salivary matrix during oral pathologies and/or dental treatments The salivary dosage of BMT during dental treatments could be fundamental to establishing establish the timing of the treatment and, in the case of orthodontic treatments, to evaluate the effectiveness of the applied forces. [ABSTRACT FROM AUTHOR]

Night shift work is related to sleep disorders, disruption of circadian rhythm and low serum levels of vitamin D. It is known that all these conditions can adversely affect bone mass. The rate of bone turnover can be assessed through the measurement of molecules called bone turnover markers, including C-terminal telopeptide fragment of type I collagen (CTX) and procollagen type I N-terminal propeptide (P1NP). In this study, we evaluated the serum levels of CTX, P1NP and 25-Hydroxy Vitamin D in 82 male subjects (42 daytime workers and 40 night shift workers) to assess the possible risk of osteoporosis in male shift workers. Serum levels of CTX and P1NP were found to be higher in night shift workers than in daytime workers. No significant difference was found in vitamin D levels between night shift and daytime workers. The increased CTX and P1NP levels reveal a higher rate of bone turnover in night shift workers and thus a possible increased risk of osteoporosis in this category of workers compared with daytime workers. In view of this, our results highlight the importance of further studies investigating the bone health in male night shift workers. [ABSTRACT FROM AUTHOR]

Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAb) are an effective treatment of migraine however may have possible off-target effects. Pre-clinical studies implicate CGRP in several aspects of bone turnover and homeostasis. The clinical effect of CGRP mAb on bone turnover is not known, however. Methods: Between June 2021 and July 2022, a multi-centre prospective cohort study was undertaken with eligible patients undergoing paired testing of the validated bone turnover markers procollagen type I N-terminal propeptide (P1NP) and serum C-terminal telopeptide of type I collagen (CTX) prior to and at least three months following administration of a CGRP mAb. Results: A total of 45 patients with a mean age of 41.8 (SD 11.9) were included in the final analysis, all of whom received a ligand-targeting CGRP mAb. Administration of a CGRP mAb was associated with a statistically significant increase in P1NP from 44.5 microg/L to 51.5 microg/L (p = 0.004), but no significant change in CTX. Conclusion: In otherwise homeostatic conditions, short-term administration of a CGRP mAb is associated with increased P1NP, a bone formation marker but not with increased CTX, a bone resorption marker. Further study is required to validate these findings over longer time periods, in a larger cohort, and in pre-existing states of increased calcium stress and bone-turnover. [ABSTRACT FROM AUTHOR]

Background: With adequate blood transfusion and iron chelation, thalassemia patients have a longer life expectancy and experience long-term metabolic complications, including osteoporosis, fractures, and bone pain. Alendronate, an oral bisphosphonate, is currently used to treat various types of osteoporosis. However, the efficacy for the treatment of thalassemia-associated osteoporosis remains unclear. Methods: We conducted a randomized controlled trial to evaluate the efficacy of alendronate for the treatment of osteoporosis in thalassemia patients. Patients were included if they were males (18-50 years) or premenopausal females with low bone mineral density (BMD) (Z-score < -2.0 SD) or positive vertebral deformities from vertebral fracture analysis (VFA). Stratified randomization was performed according to sex and transfusion status. Patients were 1:1 allocated to receive once weekly alendronate 70 mg orally or placebo for a total duration of 12 months. BMD and VFA were re-evaluated at 12 months. Markers of bone resorption (C-terminal crosslinking telopeptide of type I collagen; CTX) and bone formation (Procollagen type I N-terminal propeptide; P1NP), and pain scores were measured at baseline, 6 months, and 12 months. The primary outcome was the change of BMD. The secondary endpoints were changes in bone turnover markers (BTM) and pain scores. Results: A total of 51 patients received the study drug, 28 patients were assigned to receive alendronate and 23 patients to receive placebo. At 12 months, patients in the alendronate group had significant improvement of BMD at L1-L4 compared to their baseline (0.72 ± 0.11 vs 0.69 ± 0.11 g/cm², p = 0.004), while there was no change in the placebo group (0.69 ± 0.09 vs 0.70 ± 0.06 g/cm², p = 0.814). There was no significant change of BMD at femoral neck in both groups. Serum BTMs were significantly decreased among patients receiving alendronate at 6 and 12 months. The mean back pain score was significantly reduced compared to the baseline in both groups (p = 0.003). Side effects were rarely found and led to a discontinuation of the study drug in 1 patient (grade 3 fatigue). Conclusion: Alendronate 70 mg orally once weekly for 12 months effectively improves BMD at L-spine, reduces serum BTMs, and alleviates back pain in thalassemia patients with osteoporosis. The treatment was well tolerated and had a good safety profile. [ABSTRACT FROM AUTHOR]

Purpose: This study is aimed at investigating the role of preoperative procollagen type 1 N-terminal peptide (P1NP) and collagen type 1 C-telopeptide (CTx) levels in predicting the development of postoperative hypocalcemia in primary hyperparathyroidism (PHPT). Methods: In this prospective observational study, preoperative complaints of patients with primary hyperparathyroidism and their urea, creatinine, glomerular filtration rate (GFR), calcium, albumin, urinary calcium, parathyroid hormone, and bone mineral density (BMD) were recorded. P1NP and CTx levels were analyzed in blood samples taken the day before surgery, and their relationship with calcium levels obtained on the first postoperative day was examined. Results: The median age was 53 years for patients who developed hypocalcemia and 62 years for those who did not develop hypocalcemia (p = 0.01). The urea, creatinine, and GFR values were determined as 22 mcg/dl, 0.61 mcg/dl, and 105 ml/min, respectively, for the hypocalcemia group (Group 1) and 30.5 mcg/dl, 0.74 mcg/dl, and 90 ml/min, respectively, for the non-hypocalcemia group (Group 2) (p = 0.02, 0.001, and 0.01, respectively). The BMD femur Z-score was − 0.1 in Group 1 and 0.8 in the Group 2 (p = 0.02). The mean CTx values were 4.14 pg/dl and 1.98 pg/dl (p = 0.036), and the mean P1NP values were 252.84 mcg/dl and 269.04 mcg/dl (p = 0.427) for Groups 1 and 2, respectively. According to multivariate analysis, only CTx was a significant independent predictor of hypocalcemia (odds ratio 1.739). Conclusion: CTx level is a significant factor in predicting the risk of developing early postoperative hypocalcemia in patients scheduled for surgery due to primary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

BackgroundWith adequate blood transfusion and iron chelation, thalassemia patients have a longer life expectancy and experience long-term metabolic complications, including osteoporosis, fractures, and bone pain. Alendronate, an oral bisphosphonate, is currently used to treat various types of osteoporosis. However, the efficacy for the treatment of thalassemia-associated osteoporosis remains unclear.MethodsWe conducted a randomized controlled trial to evaluate the efficacy of alendronate for the treatment of osteoporosis in thalassemia patients. Patients were included if they were males (18–50 years) or premenopausal females with low bone mineral density (BMD) (Z-score < -2.0 SD) or positive vertebral deformities from vertebral fracture analysis (VFA). Stratified randomization was performed according to sex and transfusion status. Patients were 1:1 allocated to receive once weekly alendronate 70 mg orally or placebo for a total duration of 12 months. BMD and VFA were re-evaluated at 12 months. Markers of bone resorption (C-terminal crosslinking telopeptide of type I collagen; CTX) and bone formation (Procollagen type I N-terminal propeptide; P1NP), and pain scores were measured at baseline, 6 months, and 12 months. The primary outcome was the change of BMD. The secondary endpoints were changes in bone turnover markers (BTM) and pain scores.ResultsA total of 51 patients received the study drug, 28 patients were assigned to receive alendronate and 23 patients to receive placebo. At 12 months, patients in the alendronate group had significant improvement of BMD at L1-L4 compared to their baseline (0.72 ± 0.11 vs 0.69 ± 0.11 g/cm2, p = 0.004), while there was no change in the placebo group (0.69 ± 0.09 vs 0.70 ± 0.06 g/cm2, p = 0.814). There was no significant change of BMD at femoral neck in both groups. Serum BTMs were significantly decreased among patients receiving alendronate at 6 and 12 months. The mean back pain score was significantly reduced compared to the baseline in both groups (p = 0.003). Side effects were rarely found and led to a discontinuation of the study drug in 1 patient (grade 3 fatigue).ConclusionAlendronate 70 mg orally once weekly for 12 months effectively improves BMD at L-spine, reduces serum BTMs, and alleviates back pain in thalassemia patients with osteoporosis. The treatment was well tolerated and had a good safety profile.

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan–Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance.

Background: In patients with type 1 diabetes mellitus (T1DM), accelerated bones turnover and bone loss are caused by increased inflammation. The serum levels of the bones turnover markers (BTM), serum procollagen type 1 N-terminal propeptide (P1NP) and serum C-terminal telopeptide of type I collagen (CTX), can help identify increasing bones fragility in T1DM earlier on. Objective: The aim of the study is to measure the levels of BTM in children with T1DM, specifically serum P1NP and serum CTX, and to look into the relationships between BTM and indicators of glycemic control and diabetics micro-vascular problems. Patients and Methods: A total of 40 pediatric and adolescent T1DM children were compared with a control group of healthy control, age- and sex-matched participants. HbA1c, fasting lipids profiles, microalbumin in urine, fasting serum P1NP, and serum CTX concentrations were measured in the laboratory. Results: P1NP and CTX concentrations in the sick group were statistically significantly higher than those in the control group (p<0.001), according to the findings of our research. LDL-C and TDD of insulin, which rose in the uncontrolled sample, were determined to differ significantly between participants with HbA1c =7% and participants with HbA1c =7% (p<0.001 and p=0.008, respectively), although there was no differences in the levels of serum P1NP and CTX between the two samples. Conclusion: In younger T1DM children, serum concentrations of P1NP and CTX may offer predictive information on bones health. To demonstrate that oxidative stress causes major changes in the activities of bone production and resorption, more research should be conducted. [ABSTRACT FROM AUTHOR]

Physical activity can affect the bone remodeling process and has an impact on bone health. The bone remodeling through a coupling process consisting of formation and reabsorption. The process stimulates molecules to release collagen into the circulation, i.e., P1NP (osteoblast marker) and CTx (osteoclast marker). However, the acute effect of continous and interval physical activity at moderate intensity on P1NP and CTx has not been recognized yet. This study aims to analyze the disparity of acute effects caused by intervals and continous physical activity with moderate intensity during the growth period of the bone. This study uses a pre-test and post-test design experimental study. The total sample is 16 which were divided into two groups (interval physical activity group and continous physical activity group). There was no acute effect on the moderate intensity of continous physical activity on P1NP (p=0.759), but it has shown a decline. Likewise, moderate intensity of acute interval physical activity has shown no effect on P1NP (p=0.013). This phenomenon happened in the moderate intensity of continous physical activity on CTx (p=0.173), as well as the moderate intensity of interval physical activity on CTx (p=0.693). The study revealed no difference in the acute effect of continous and interval physical activity with moderate intensity on P1NP (p=0.209) and CTx (p=0.164). The acute effect of interval physical activity on moderate-intensity can decrease P1NP levels. Hence, continous physical activity was better than interval physical activity. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to bone loss due to an imbalance of the bone turnover process that could be evaluated using bone turnover markers. Inflammation in RA is mainly mediated by Tumor necrosis factor- α (TNF- α) that will increase osteoclastogenesis. In recent studies, Dickkopf-1 (DKK-1) is a key regulatory pathway for bone formation that affects osteoblastogenesis. Objective: This study aims to examine the imbalance of the bone turnover process in RA patients. Methods: This was a cross-sectional study with 38 subjects of premenopausal women with RA. Serum levels of TNF- α , DKK-1, and bone turnover markers (CTx and P1NP) were investigated. Result: The median duration of RA in this study was 5 years with 60.5% of subjects in remission or with low disease activity. The median value of TNF- α was 10.6 pg/mL, the mean value of DKK-1 was 4027 pg/mL, the mean value of CTx was 2.74 ng/mL, and the mean value of P1NP was 34 pg/mL. This study revealed a weak positive correlation between TNF- α and P1NP (r = 0. 3 6 ; p = 0. 0 3). Conclusion: This study found a low level of TNF- α , a high level of DKK-1, a high level of CTx and a low level of P1NP that indicates an imbalance of bone turnover process in RA patients that is in favor of bone resorption. [ABSTRACT FROM AUTHOR]

Reactivation of bone lining cells (BLCs) is a crucial mechanism governing the anabolic action of anti-sclerostin antibody (Scl-Ab) via modeling-based bone formation; however, it remains unclear whether this reactivation can be attenuated after persistent administration of Scl-Ab. Here, we aimed to investigate the reproducibility of persistent Scl-Ab administration for the reactivation of BLCs, and to elucidate the relationship between the activity of BLCs and serum levels of N-terminal procollagen type I (P1NP) during chronic Scl-Ab administration. We conducted an osteoblast lineage tracing study. Briefly, Dmp1-CreERt2(+):Rosa26R mice were injected with 1 mg of 4-hydroxy-tamoxifen weekly from postnatal weeks four to eight. Mice were treated twice with either vehicle or Scl-Ab (25 mg/kg) at weeks 12, 16, and 20, and were euthanized at weeks 8, 12, 13, 16, 17, 20, and 21 (4-6 mice in each group). After euthanization, the number and thickness of X-gal (+) cells on the periosteum of the femoral bones and the serum levels of P1NP were quantified at each time point. Scl-Ab induced a significant increase in the thickness of X-gal (+) cells on periosteal bone surfaces at postnatal weeks 13 (after 1st dose), 17 (after 2nd dose), and 21 (after 3rd dose) compared to that in vehicle-treated mice (all P < 0.001). In the Scl-Ab group, significant increases in the thickness of labeled cells were observed between weeks 16 and 17 and weeks 20 and 21 (both P < 0.001). The percentage increase in X-gal (+) cell thickness was 108.9% from week 12 to week 13, 54.6% from week 16 to week 17, and 49.2% from week 20 to week 21 in the Scl-Ab group. Although Scl-Ab treatment increased the serum levels of P1NP at postnatal weeks 13 and 17 compared with those at week 12 (P = 0.017 and P = 0.038, respectively), the same was not observed at week 21 (P = 0.296). A significant increase in P1NP levels was observed between weeks 16 and 17 and weeks 20 and 21 in the Scl-Ab group (P = 0.005 and P = 0.007, respectively). The percentage increase in P1NP levels was 141.7% from weeks 12 to 13, 114.8% from weeks 16 to 17, and 99.4% from weeks 20 to 21. Serum P1NP levels were positively correlated with X-gal (+) cell thickness (R2 = 0.732, P < 0.001). Reactivation of BLCs is modestly attenuated, but reproducible, during persistent Scl-Ab administration. Serum P1NP levels appear to be an indicator of the impact of Scl-Ab on the conversion of BLCs into mature osteoblasts on periosteal bone surfaces, thus contributing to modeling-based bone formation. [ABSTRACT FROM AUTHOR]

Aims: Bone turnover markers (BTMs) follow distinct trends after fractures and limited evidence suggests differential levels in BTMs in patients with delayed healing. The effect of vitamin D, and other factors that influence BTMs and fracture healing, is important to elucidate the use of BTMs as surrogates of fracture healing. We sought to determine whether BTMs can be used as early markers of delayed fracture healing, and the effect of vitamin D on BTM response after fracture. Methods: A total of 102 participants aged 18 to 50 years (median 28 years (interquartile range 23 to 35)), receiving an intramedullary nail for a tibial or femoral shaft fracture, were enrolled in a randomized controlled trial comparing vitamin D3 supplementation to placebo. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and N-terminal propeptide of type I procollagen (P1NP; bone formation marker) were measured at baseline, six weeks, and 12 weeks post-injury. Clinical and radiological fracture healing was assessed at three months. Results: CTX and P1NP concentrations peaked at six weeks in all groups. Elevated six-week CTX and P1NP were associated with radiological healing at 12 weeks post-injury (odds ratio (OR) 10.5; 95% confidence interval 2.71 to 53.5, p = 0.002). We found no association between CTX or P1NP and functional healing. Baseline serum 25(OH)D showed a weak inverse relationship with P1NP (p = 0.036) and CTX (p = 0.221) at 12 weeks, but we observed no association between vitamin D supplementation and either BTM. Conclusion: Given the association between six-week BTM concentrations and three-month radiological fracture healing, CTX and P1NP appear to be potential surrogate markers of fracture healing. Cite this article: Bone Joint Res 2022;11(4):239–250.

Romosozumab is an anti-sclerostin antibody that increases bone formation and decreases bone resorption. It became available for patients at high risk of osteoporotic fractures in Japan in 2019. The aim of this study was to clarify the clinical effects, safety, and predictors of the effectiveness of 12 months of romosozumab therapy. The study had an observational pre-post design and included 460 patients. Romosozumab was administered at a dose of 210 mg subcutaneously every 4 weeks for 12 months. The incidence of new fractures, safety, and changes in bone mineral density (BMD) and bone turnover markers were recorded. New fractures occurred in 11 cases (3.0 %). Nine patients (2.0 %) experienced cardiovascular events, which were fatal in 3 (0.65 %). Percent changes in BMD at the spine and total hip at 12 months from baseline were +7.7 % and +1.8 %, respectively. Romosozumab had better effects in patients with good renal function, low spine BMD, and high TRACP-5b at baseline and low TRACP-5b or high P1NP after 1 month of treatment. The percent change in spine BMD at 12 months was significantly lower in patients transitioning from denosumab than in those not previously treated with other anti-osteoporosis agents. Romosozumab is considered to be relatively safe in patients with primary osteoporosis compared to those with secondary osteoporosis. Romosozumab resulted in larger increases in spine BMD in patients with primary osteoporosis who were not previously treated with other anti-osteoporosis therapies and those with low spine BMD at the start of treatment. • Romosozumab markedly increased BMD in patients who were treatment naïve. • Romosozumab following denosumab attenuated the effect of increasing BMD. • Romosozumab was especially effective in patients with high eGFR and low spine BMD. • Romosozumab was also especially effective in patients with high TRACP-5b. • All cardiovascular events occurred in patients with secondary osteoporosis. [ABSTRACT FROM AUTHOR]

Levels of bone turnover markers (BTM) can be measured using saliva. The aim of the present study was to determine the Biological Variability of BTM in young subjects, on serial biological salivary samples. Saliva samples of 20 apparently healthy young subjects (9 females and 11 males) have been analyzed. Samples collected using salivette with cotton swabs were obtained three times every 15 days. PTHrP; TRAcP-5b and P1NP have been assayed. The ANOVA test was used to calculate intra and interindividual variance (CVI and CVG). The individuality index (II) and reference change value (RCV) were evaluated for the clinically significant variation between two results in the same individual. CVI was highest for PTHrP and lowest for P1NP while CVG was highest for TRAcP-5b. RCV was maximum for PTHrP and minimum for P1NP. The critical difference (RCV) is of particular interest in evaluating variations in the concentrations of BMT on the salivary matrix during oral pathologies and/or dental treatments The salivary dosage of BMT during dental treatments could be fundamental to establishing establish the timing of the treatment and, in the case of orthodontic treatments, to evaluate the effectiveness of the applied forces.

We aimed to investigate intra-individual changes in total procollagen-type 1 N-terminal pro-peptide (P1NP), a biochemical marker of bone turnover, to understand patient populations and test utilization in a Korean adult population while considering different definitions of least significant changes by sex, age, and medical institution type. Overall, 31,501 P1NP tests were performed on 24,644 Korean adults (3389 men and 21,255 women) with a median age of 68.9 years (interquartile range, IQR, 61.2–77.2) for osteoporosis evaluation. Among these, 1331 (5.4%) patients (127 men and 1204 women) underwent ≥3 follow-up P1NP measurements. The median follow-up period was 12.5 months (IQR, 11.7–15.9). Among 1331 patients, 64.4% experienced a decrease in P1NP and 35.6% experienced an increase in P1NP during follow-up. Among these, the proportion of patients who experienced serum P1NP changes ≥14.4% from baseline was 92.3%, and the proportion of patients who achieved ≤40 ng/mL (a median level of premenopausal Korean women) during follow-up was 31.8%. The overall proportion of patients that experienced a serum P1NP change exceeding the least significant change during follow-up was not significantly different by the type of medical institution. [ABSTRACT FROM AUTHOR]

Summary: We investigated whether the drug denosumab modulates the inflammatory response after total hip arthroplasty in a randomized controlled trial. Significantly increased expression of RANKL was found in patients treated with denosumab. This could provide an explanation for the rebound effect with rapid loss of BMD seen after discontinuation of denosumab treatment. Purpose: To evaluate whether denosumab, a human monoclonal antibody directed against receptor activator of nuclear factor kappa-B ligand (RANKL), modulates the inflammatory response after cementless total hip arthroplasty (THA) in patients with osteoarthritis of the hip. Methods: Sixty-four patients operated with cementless THA were randomized to two doses of 60-mg denosumab or placebo 1–3 days and 6 months postoperatively. Serum samples were analyzed by a multiplex extension assay detecting 92 inflammation-related proteins. Bone turnover markers were assessed. Proteins were analyzed using linear mixed effect models. Validation of conspicuous findings was performed with ELISA. Results: Two proteins were significantly affected by denosumab treatment: RANKL and tumor necrosis factor receptor super family member 9 (TNFRSF9). Serum levels of RANKL were more than twice as high in the denosumab than in the placebo group 3 months after surgery (ratio 2.10, p<0.001). Six and 12 months after surgery, the expression of RANKL was still elevated in the denosumab-treated group (ratios 1.50, p < 0.001; 1.47, p =0.002). The expression of TNFRSF9 was lower in the denosumab group at 3 months (ratio 0.68, p<0.001). In the denosumab group, concentrations of bone turnover markers were substantially reduced after 3 months, remained suppressed after 6 and 12 months, but increased above baseline at 24 months after surgery. Conclusion: Two subcutaneous denosumab injections 6 months apart increase RANKL and depress TNFRSF9 after THA. This provides a possible explanation for the rebound effect on bone turnover markers as well as bone mineral density (BMD) upon withdrawal of denosumab. None of the other measured markers of inflammation was influenced by denosumab treatment. [ABSTRACT FROM AUTHOR]

Aims: The osteo‐metabolic changes in type 2 diabetes (T2D) patients are intricate and have not been fully revealed. It is not clear whether glucagon is entirely harmful in the pathogenesis of diabetes or a possible endocrine counter‐regulation mechanism to reverse some abnormal bone metabolism. This study aimed to investigate the association between glucagon and bone turnover markers (BTMs) in T2D patients. Methods: A total of 3984 T2D participants were involved in a cross‐sectional study in Shanghai, China. Serum glucagon was measured to elucidate its associations with intact N‐terminal propeptide of type I collagen (P1NP), osteocalcin (OC), and β‐C‐terminal telopeptide (β‐CTX). Glucagon was detected with a radioimmunoassay. Propeptide of type I collagen, OC, and β‐CTX were detected using chemiluminescence. The diagnosis of T2D was based on American Diabetes Association criteria. Results: The concentration of glucagon was positively correlated with two BTMs [OC–β: 0.034, 95% CI: 0.004, 0.051, p = 0.024; CTX–β: 0.035, 95% CI: 0.004, 0.062, p = 0.024]. The result of P1NP was [P1NP–regression coefficient (β): 0.027, 95% CI: −0.003, 0.049, p = 0.083]. In the glucagon tertiles, P for trend of the BTMs is [P1NP: 0.031; OC: 0.038; CTX: 0.020], respectively. Conclusions: Glucagon had a positive effect on bone metabolism. The concentrations of the three BTMs increased as glucagon concentrations rose. This implied that glucagon might speed up skeletal remodelling, accelerate osteogenesis, and promote the formation of mature bone tissue. At the same time, the osteoclastic process was also accelerated, providing raw materials for osteogenesis to preserve the dynamic balance. In view of the successful use of single‐molecule as well as dual/triple agonists, it would be feasible to develop a preparation that would reduce osteoporosis in diabetic patients. [ABSTRACT FROM AUTHOR]

This study examined potential fluctuations in bone metabolic markers across the menstrual cycle both at rest and after a 30-min bout of continuous running at 80% of V̇O2max. Resting and post-exercise (0, 30, 90 min) sclerostin, parathyroid hormone (PTH), carboxy-terminal cross-linking telopeptide of type I collagen (β-CTXI), and procollagen type 1 N propeptide (PINP) were assessed in 10 eumenorrheic women (age: 21 ± 3 y, BMI: 23.2 ± 3.0 kg.m2) during the mid- to late-follicular (FP: day 8.0 ± 1.4) and mid-luteal (LP: day 22.0 ± 2.5) phases of the menstrual cycle. Ovulation was determined using ovulation kits and daily measurement of oral body temperature upon awakening. Menstrual cycle phase was subsequently confirmed by measurement of plasma estradiol and progesterone. On average, resting estradiol concentrations increased from 46.3 ± 8.9 pg·mL−1 in the FP to 67.3 ± 23.4 pg·mL−1 in the LP (p = 0.015), and resting progesterone increased from 4.12 ± 2.36 ng·mL−1 in the FP to 11.86 ± 4.49 ng·mL−1 in the LP (p < 0.001). At rest, there were no differences between menstrual cycle phases in sclerostin (FP: 260.1 ± 135.0 pg·mL−1; LP: 303.5 ± 99.9 pg·mL−1; p = 0.765), PTH (FP: 0.96 ± 0.64 pmol·L−1; LP: 0.79 ± 0.44 pmol·L−1; p = 0.568), β-CTXI (FP: 243.1 ± 158.0 ng·L−1; LP: 202.4 ± 92.3 ng·L−1; p = 0.198), and PINP (FP: 53.6 ± 8.9 μg·L−1; LP: 66.2 ± 20.2 μg·L−1; p = 0.093). Main effects for time (p < 0.05) were shown in sclerostin, PTH, β-CTXI and PINP, without phase or interaction effects. Sclerostin increased from pre- to immediately post-exercise (45%; p = 0.007), and so did PTH (43%; p = 0.011), both returning to resting concentrations 30 min post-exercise. β-CTXI decreased from pre- to post-exercise (20%; p = 0.027) and was still below its pre-exercise concentrations at 90 min post-exercise (17%; p = 0.013). PINP increased immediately post-exercise (29%; p < 0.001), returning to resting concentrations at 30 min post-exercise. These results demonstrate no effect of menstrual cycle phase on resting bone marker concentrations or on the bone metabolic marker response to intense exercise. [ABSTRACT FROM AUTHOR]

Context: Exercise is recognized as an important strategy to prevent bone loss, but its acute effects on bone turnover markers (BTMs) and related markers remain uncertain. Objective: To assess the acute effects of two different exercise modes on BTMs and related markers in young adults of both sexes and elderly men. Design, Setting, Participants: This was a three-group crossover within-subjects design study with a total of 53 participants—19 young women (aged 22–30), 20 young men (aged 21–30 years), and 14 elderly men (aged 63–74 years)—performing two different exercise sessions [strength training (ST) and high-intensity interval training (HIIT)] separated by 2 weeks, in a supervised laboratory setting. Main Outcome Measures: Plasma volume-corrected serum measurements of the BTMs C-terminal telopeptide of type 1 collagen (CTX-I) and procollagen of type 1 N-terminal propeptide (P1NP), total osteocalcin (OC), sclerostin, and lipocalin-2 (LCN2) at baseline, immediately after, and 3 and 24 h after each of the two exercise modes were performed. Results and Conclusion: Analyses revealed sex- and age-dependent differences in BTMs and related bone markers at baseline and time-, sex-, and age-dependent differences in response to exercise. No differences between exercise modes were observed for BTM response except for sclerostin in young men and LCN2 in elderly men. An acute, transient, and uniform increase in P1NP/CTX-1 ratio was found in young participants, demonstrating that beneficial skeletal effects on bone metabolism can be attained through both aerobic endurance and resistance exercise, although this effect seems to be attenuated with age. The acute effects of exercise on bone-related biomarkers were generally blunted after 24 h, suggesting that persistent alterations following prolonged exercise interventions should be assessed at later time points. [ABSTRACT FROM AUTHOR]

Patients with spinal cord injury (SCI) experience a high osteoporosis incidence, which increases fracture risk. Recently, a sclerostin antibody was introduced as a target biomarker to treat osteoporosis. We aimed to determine the serum concentration of sclerostin and factors affecting its concentration over time. This was a prospective cross-sectional study. The inclusion criteria were (1) SCI patients with a grade 3 modified functional ambulatory category score (FAC—patients requiring firm continuous support) and (2) patients whose injury occurred >1 month ago. The exclusion criterion was a history of osteoporosis medication administration within 6 months. The collected data included bone biomarkers (carboxy-terminal collagen crosslinks (CTX), procollagen type 1 intact N-terminal propeptide, and sclerostin), clinical data (FAC, lower extremity motor score), body mass index, SCI duration, and hip bone mineral density (BMD). This study recruited 62 patients with SCI. Sclerostin levels significantly correlated with age, CTX level, and hip BMD. SCI duration was negatively correlated with sclerostin levels. Lower extremity motor scores were not significantly correlated with sclerostin levels. The acute SCI state showed a higher sclerostin level than the chronic SCI state. Sclerostin showed a significant relationship with CTX. In conclusion, age and BMD affect sclerostin concentration in patients with SCI. [ABSTRACT FROM AUTHOR]

Abstract Background Little is known about the clinical value of Insulin-like growth factor-binding protein-7 (IGFBP7), a cellular senescence marker, in an elderly general population with multiple co-morbidities and high prevalence of asymptomatic cardiovascular ventricular dysfunction. Inflammation and fibrosis are hallmarks of cardiac aging and remodelling. Therefore, we assessed the clinical performance of IGFBP7 and two other biomarkers reflecting these pathogenic pathways, the growth differentiation factor-15 (GFD-15) and amino-terminal propeptide of type I procollagen (P1NP), for their association with cardiac phenotypes and outcomes in the PREDICTOR study. Methods 2001 community-dwelling subjects aged 65–84 years who had undergone centrally-read echocardiography, were selected through administrative registries. Atrial fibrillation (AF) and 4 echocardiographic patterns were assessed: E/e’ (> 8), enlarged left atrial area, left ventricular hypertrophy (LVH) and reduced midwall circumference shortening (MFS). All-cause and cardiovascular mortality and hospitalization were recorded over a median follow-up of 10.6 years. Results IGFBP7 and GDF-15, but not P1NP, were independently associated with prevalent AF and echocardiographic variables after adjusting for age and sex. After adjustment for clinical risk factors and cardiac patterns or NT-proBNP and hsTnT, both IGFBP7 and GDF-15 independently predicted all-cause mortality, hazard ratios 2.13[1.08–4.22] and 2.03[1.62–2.56] per unit increase of Ln-transformed markers, respectively. Conclusions In a community-based elderly cohort, IGFBP7 and GDF-15 appear associated to cardiac alterations as well as to 10-year risk of all-cause mortality.

Summary: Zoledronic acid (ZOL) is a therapy inhibiting bone resorption. In this study, generic ZOL (Yigu®) showed its clinical efficacy consistency with original ZOL (Aclasta®) in Chinese postmenopausal women with osteoporosis. This study provides a practical basis for the application of Yigu® in Chinese population. Introduction: Yigu® has been approved its bioequivalence to Aclasta®. However, the clinical efficacy and safety of Yigu® have not been evaluated yet. Here, we compared the effectiveness and safety between Yigu® and Aclasta® in Chinese postmenopausal women with osteoporosis and assessed the efficacy of intravenous infusion of ZOL. Methods: This was a randomized open-label, active-controlled study in postmenopausal women with osteoporosis of 14 clinical centers in China. Postmenopausal women with osteoporosis were recruited and randomized to receive a single infusion of 5 mg Yigu® or Aclasta®. The primary endpoint was the percentage change in bone mineral density (BMD) at lumbar spine after 12 months of treatment and was assessed for equivalence. The secondary endpoint was the percentage change in BMD at proximal femur after 12 months. Additional secondary endpoints were percentage changes in BMD at the above sites after 6 months of treatment and changes in bone turnover biomarkers during ZOL treatment. Safety was also evaluated and compared between two groups. Results: A total of 458 postmenopausal women with osteoporosis were enrolled (n = 227, Yigu®; n = 231, Aclasta®). The mean percentage change in the BMD had no statistical difference at the lumbar spine (5.32% vs 5.18%), total hip (2.72% vs 2.83%), and femoral neck (2.37% vs 2.81%) between Yigu® and Aclasta® groups after 12 months of treatment. The mean difference of BMD change at the lumbar spine after 12 months between two groups was 0.15% (95% CI: − 0.71 to 1.00, equivalence margin: − 1.5%, 1.5%), demonstrating the treatments were equivalent. Meanwhile, the decreases in the P1NP and β-CTX showed no difference between two groups after 14 days and 6 and 12 months of treatment. As regards the whole sample, BMD significantly increased after 12 months of treatment. Also, serum C-terminal telopeptide of type 1 collagen (β-CTX) and procollagen 1 N-terminal peptide (P1NP) significantly decreased at each visit period. The overall adverse events were comparable and quite well between two groups. Conclusion: Intravenous infusion of zoledronic acid achieved the potent anti-resorptive effects which led to significant increase in BMD of Chinese postmenopausal women with osteoporosis. Yigu® was equivalent to Aclasta® with respect to efficacy and safety. [ABSTRACT FROM AUTHOR]

Background: Secondary osteoporosis is a significant problem, especially in patients with endocrine pathology, which is not accompanied constantly by distinct clinical symptoms. Markers of bone origin are needed, which could be used in osteoporosis diagnosis to clarify its genesis, especially in young people who have secondary osteoporosis more often than older patients. In Cushings disease (CD), such a marker, in addition to osteocalcin, could be another bone formation marker, procollagen type 1 N-terminal propeptide (P1NP). Aims: To study the diagnostic potential of P1NP as an additional marker of endogenous hypercortisolism (Cushings disease) compared to osteocalcin. Materials and methods: The study involved patients with Cushings disease and healthy volunteers, matched by gender, age, and body mass index. The levels of osteocalcin and P1NP were assessed in both groups, the electrochemiluminescence method for P1NP (Cobas e411 (Roche, Switzerland)) and for osteocalcin (Cobas 6000 Module e601 (Roche, Switzerland)) was used. ROC analysis was performed with the calculation of sensitivity and specificity of the method to determine the cut-off point for P1NP in CD diagnosis. Results: 29 patients with Cushings disease and 27 healthy individuals from the control group were included in the study. There were no differences in age, sex and body mass index (p = 0.488, 0.426 and 0.531, respectively). Both studied bone formation markers (osteocalcin and P1NP) were reduced in patients with CD: 8.53 ng/ml (Q25%;Q75% 5.40; 12.41) versus 22.45 ng/ml (Q25%;Q75% 17.36; 26.31) (p 0.001) and 28.50 ng/ml (Q25%;Q75% 18.00; 44.00) versus 56.50 ng/ml (Q25%;Q75% 39.50; 65.50) (p 0.001), respectively. The area under the receiver operating characteristic curve (AUC) was 0.808 (95% CI 0.6930.924) for P1NP and 0.925 (95% CI 0.8570.992) for osteocalcin, that indicates the greater diagnostic value of osteocalcin for CD verification in healthy controls. Optimal cut-off points were obtained: 53.4 ng/ml (values below are more typical for patients with CD; sensitivity of the method is 96.55%, specificity 57.69%) for P1NP and 15.285 ng/ml (below for patients with CD; sensitivity was 92.59%, specificity 77.78 %) for osteocalcin. Conclusions: The diagnostic potential of osteocalcin to detect Cushings disease in the population is higher compared to P1NP. However, applying of P1NP can be useful because, unlike osteocalcin, it is a direct indicator of the formation of bone matrix collagen structures, that is important for assessing the degree of inhibition of collagen type 1 synthesis in CD and deterioration of bone tissue due to glucocorticoid-induced osteoporosis.

Dairy products can act as a dietary source of lithium (Li), and a recent study in university-aged males demonstrated that Greek yogurt (GY) supplementation augmented gains in fat free mass, strength and bone formation after 12 weeks of resistance exercise training compared to carbohydrate (CHO) pudding supplementation. Here, we performed secondary analyses to explore whether GY would alter serum Li levels and whether changes in serum Li would associate with changes in body composition, strength, and bone turnover markers. Results show that the GY group maintained serum Li levels after exercise training, whereas the CHO group did not. Maintaining/elevating serum Li levels was also associated with greater gains in strength and reductions in bone resorption. However, controlling for other dietary factors in GY such as protein and calcium weakened these associations. Thus, future studies should assess the causative role, if any, of dietary Li alone on strength and bone resorption in humans.

Melatonin is the primary circadian output signal from the brain and is mainly synthesized in pinealocytes. The rhythm and secretion of melatonin are under the control of an endogenous oscillator located in the SCN or the master biological clock. Disruptions in circadian rhythms by shift work, aging, or light at night are associated with bone loss and increased fracture risk. Restoration of nocturnal melatonin peaks to normal levels or therapeutic levels through timed melatonin supplementation has been demonstrated to provide bone‐protective actions in various models. Melatonin is a unique molecule with diverse molecular actions targeting melatonin receptors located on the plasma membrane or mitochondria or acting independently of receptors through its actions as an antioxidant or free radical scavenger to stimulate osteoblastogenesis, inhibit osteoclastogenesis, and improve bone density. Its additional actions on entraining circadian rhythms and improving quality of life in an aging population coupled with its safety profile make it an ideal therapeutic candidate for protecting against bone loss in susceptible populations. The intent of this review is to provide a focused discussion on bone loss and disorders of the bone as it relates to melatonin and conditions that modify melatonin levels with the hope that future therapies include those that include melatonin and correct those factors that modify melatonin levels like circadian disruption. [ABSTRACT FROM AUTHOR]

We aimed to investigate intra-individual changes in total procollagen-type 1 N-terminal pro-peptide (P1NP), a biochemical marker of bone turnover, to understand patient populations and test utilization in a Korean adult population while considering different definitions of least significant changes by sex, age, and medical institution type. Overall, 31,501 P1NP tests were performed on 24,644 Korean adults (3389 men and 21,255 women) with a median age of 68.9 years (interquartile range, IQR, 61.2–77.2) for osteoporosis evaluation. Among these, 1331 (5.4%) patients (127 men and 1204 women) underwent ≥3 follow-up P1NP measurements. The median follow-up period was 12.5 months (IQR, 11.7–15.9). Among 1331 patients, 64.4% experienced a decrease in P1NP and 35.6% experienced an increase in P1NP during follow-up. Among these, the proportion of patients who experienced serum P1NP changes ≥14.4% from baseline was 92.3%, and the proportion of patients who achieved ≤40 ng/mL (a median level of premenopausal Korean women) during follow-up was 31.8%. The overall proportion of patients that experienced a serum P1NP change exceeding the least significant change during follow-up was not significantly different by the type of medical institution.

Background: Little is known about the clinical value of Insulin-like growth factor-binding protein-7 (IGFBP7), a cellular senescence marker, in an elderly general population with multiple co-morbidities and high prevalence of asymptomatic cardiovascular ventricular dysfunction. Inflammation and fibrosis are hallmarks of cardiac aging and remodelling. Therefore, we assessed the clinical performance of IGFBP7 and two other biomarkers reflecting these pathogenic pathways, the growth differentiation factor-15 (GFD-15) and amino-terminal propeptide of type I procollagen (P1NP), for their association with cardiac phenotypes and outcomes in the PREDICTOR study.Methods: 2001 community-dwelling subjects aged 65-84 years who had undergone centrally-read echocardiography, were selected through administrative registries. Atrial fibrillation (AF) and 4 echocardiographic patterns were assessed: E/e' (> 8), enlarged left atrial area, left ventricular hypertrophy (LVH) and reduced midwall circumference shortening (MFS). All-cause and cardiovascular mortality and hospitalization were recorded over a median follow-up of 10.6 years.Results: IGFBP7 and GDF-15, but not P1NP, were independently associated with prevalent AF and echocardiographic variables after adjusting for age and sex. After adjustment for clinical risk factors and cardiac patterns or NT-proBNP and hsTnT, both IGFBP7 and GDF-15 independently predicted all-cause mortality, hazard ratios 2.13[1.08-4.22] and 2.03[1.62-2.56] per unit increase of Ln-transformed markers, respectively.Conclusions: In a community-based elderly cohort, IGFBP7 and GDF-15 appear associated to cardiac alterations as well as to 10-year risk of all-cause mortality. [ABSTRACT FROM AUTHOR]

Objectives: SLE is a chronic autoimmune disease, which can affect the level of bone metabolism and increase the risk of osteoporosis and fracture. The purpose of this research is to study the effect of SLE on bone turnover markers without the influence of glucocorticoids. Methods: A total of 865 female subjects were recruited from Zhejiang Provincial People's Hospital and the First Hospital of Jiaxing, including 391 SLE patients without the influence of glucocorticoids and 474 non-SLE people. We detected Bone turnover markers including amino-terminal propeptide of type 1 procollagen (P1NP), C-terminal turnover of β - I collagen (β-CTX), N-terminal midfragment of osteocalcin (NMID) and 25(OH)D, and analyzed the difference in Bone turnover markers between the SLE group and the control group, as well as the influence of age and season on bone metabolism in female SLE patients. Results: In the SLE group, the average age was 43.93±13.95 years old. In the control group, the average age was 44.84±11.42 years old. There was no difference between the two groups (t = 1.03, P = 0.30). P1NP, NMID and 25(OH)D in the SLE group were significantly lower than those in the control group (Z = 8.44, p < 0.001; Z = 14.41, p < 0.001; Z = 2.19, p = 0.029), and β-CTX in the SLE group was significantly higher than that in the control group (Z = 2.61, p = 0.009). In addition, the levers of β-CTX, NMID, P1NP and 25(OH)D in older SLE female patients were statistically significantly higher than those in younger (ρ = 0.104, p = 0.041; ρ = 0.223, p < 0.001; ρ = 0.105, p = 0.038; ρ = 0.289, p < 0.001). Moreover, β-CTX reached a high value in summer and PINP reached a low value in winter. Conclusion: The bone formation markers of female SLE patients without glucocorticoid were lower than those of normal people and the bone resorption marker was higher than that of normal people. The 25 (OH) D of female SLE patients without glucocorticoid was lower than that of normal people. The risk of osteoporosis and fracture may be higher in elderly women with SLE. The bone resorption level of female SLE patients is high in summer and the bone formation level is low in winter. [ABSTRACT FROM AUTHOR]

Introduction. Significant prevalence of rheumatoid arthritis (RA), an unceasing increase in morbidity, affliction of working age population, late diagnosis, not always effective treatment and large economic damage due to this disease and its complications, are the actual problems in medical field and should be further explored. The aim of the studi. To make the review of the literature and the description of the clinical case devoted to finding out the features of pathogenesis, diagnosis and principles of differentiated treatment of calcium­phosphorus metabolism and bone state in patients with RA. Materials and methods. The content analysis, the method of system and comparative analysis, the bibliosemantic method of studying the actual scientific research of the features of calcium­phosphorus metabolism and the state of bones in patients with RA, pathogenesis, diagnostic methods and principles of differentiated treatment were used. The search for the sources was carried out in the scientific­medical databases: PubMed­NCBI, Medline, CochraneLibrary, EMBASE, ResearchGate by keywords: RA, osteoporosis, RANK / RANKL / OPG, densitometry, P1NP, calcium, phosphorus, vitamin D, parthyroid hormone. In total, 75 sources in English and Ukrainian have been analyzed. The selected sources highlight the pathogenesis, diagnostic methods with proven high sensitivity and specificity, treatment principles. In addition, the clinical case is described. Results. RA and its complications, which are mostly the result of calciumphosphorus exchange disorders, lead to early disability of people of working age, due to the occurrence of fractures. Clinical signs of osteoporosis in patients with RA are often nonspecific and diagnosed untimely. Therefore, the issue of early diagnosis and treatment principles is still relevant. Conclusions. The overview of modern literature and the description of the clinical case suggest that patients with rheumatoid arthritis exhibit the significant disturbances in calcium­phosphorous metabolism with bone defeat, but the information on pathogenetic mechanisms, optimal methods for diagnosis of osteoporosis and its treatment are insufficient, and sometimes contradictory. That is why there is a need to continue the research in this direction.

Patients with spinal cord injury (SCI) experience a high osteoporosis incidence, which increases fracture risk. Recently, a sclerostin antibody was introduced as a target biomarker to treat osteoporosis. We aimed to determine the serum concentration of sclerostin and factors affecting its concentration over time. This was a prospective cross-sectional study. The inclusion criteria were (1) SCI patients with a grade 3 modified functional ambulatory category score (FAC—patients requiring firm continuous support) and (2) patients whose injury occurred >1 month ago. The exclusion criterion was a history of osteoporosis medication administration within 6 months. The collected data included bone biomarkers (carboxy-terminal collagen crosslinks (CTX), procollagen type 1 intact N-terminal propeptide, and sclerostin), clinical data (FAC, lower extremity motor score), body mass index, SCI duration, and hip bone mineral density (BMD). This study recruited 62 patients with SCI. Sclerostin levels significantly correlated with age, CTX level, and hip BMD. SCI duration was negatively correlated with sclerostin levels. Lower extremity motor scores were not significantly correlated with sclerostin levels. The acute SCI state showed a higher sclerostin level than the chronic SCI state. Sclerostin showed a significant relationship with CTX. In conclusion, age and BMD affect sclerostin concentration in patients with SCI.

BackgroundThe interrelation between glucose and bone metabolism is complex and has not been fully revealed. This study aimed to investigate the association between insulin resistance, β-cell function and bone turnover biomarker levels among participants with abnormal glycometabolism.MethodsA total of 5277 subjects were involved through a cross-sectional study (METAL study, http://www.chictr.org.cn, ChiCTR1800017573) in Shanghai, China. Homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell dysfunction (HOMA-%β) were applied to elucidate the nexus between β-C-terminal telopeptide (β-CTX), intact N-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC). β-CTX, OC and P1NP were detected by chemiluminescence.ResultsHOMA-IR was negatively associated with β-CTX, P1NP and OC (regression coefficient (β) -0.044 (-0.053, -0.035), Q4vsQ1; β -7.340 (-9.130, -5.550), Q4vsQ1 and β -2.885 (-3.357, -2.412), Q4vsQ1, respectively, all P for trend

Background: The interrelation between glucose and bone metabolism is complex and has not been fully revealed. This study aimed to investigate the association between insulin resistance, β-cell function and bone turnover biomarker levels among participants with abnormal glycometabolism. Methods: A total of 5277 subjects were involved through a cross-sectional study (METAL study, http://www.chictr.org.cn , ChiCTR1800017573) in Shanghai, China. Homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell dysfunction (HOMA-%β) were applied to elucidate the nexus between β-C-terminal telopeptide (β-CTX), intact N-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC). β-CTX, OC and P1NP were detected by chemiluminescence. Results: HOMA-IR was negatively associated with β-CTX, P1NP and OC (regression coefficient (β) -0.044 (-0.053, -0.035), Q4vsQ1; β -7.340 (-9.130, -5.550), Q4vsQ1 and β -2.885 (-3.357, -2.412), Q4vsQ1, respectively, all P for trend <0.001). HOMA-%β was positively associated with β-CTX, P1NP and OC (β 0.022 (0.014, 0.031), Q4vsQ1; β 6.951 (5.300, 8.602), Q4vsQ1 and β 1.361 (0.921, 1.800), Q4vsQ1, respectively, all P for trend <0.001). Conclusions: Our results support that lower bone turnover biomarker (β-CTX, P1NP and OC) levels were associated with a combination of higher prevalence of insulin resistance and worse β-cell function among dysglycemia patients. It is feasible to detect bone turnover in diabetes or hyperglycemia patients to predict the risk of osteoporosis and fracture, relieve patients' pain and reduce the expenses of long-term cure. [ABSTRACT FROM AUTHOR]

Introduction: Accelerated bone loss and osteoporosis are multifactorial comorbidities related to HIV and its treatments; however, their mechanisms remain elusive. Identifying HIV treatments that are differentially linked to osteoporosis risk, and clinical factors associated with HIV-related osteoporosis may enable optimizing anti-retroviral treatment (ART) and anti-osteoporosis therapy in preventing or treating this debilitating complication. This study aims to evaluate the dynamics of bone turnover markers after initiation of two commonly used antiretroviral regimens. Methods: A prospective matched cohort study. Thirty treatment-naïve male patients (mean age 40 ± 10y) who initiated treatment with truvada (tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)) + raltegravir or TDF/FTC + efavirenz were included in the study. Control group included 15 treatment-naive HIV patients. Serum morning fasting level of P1NP and CTX were measured 0, 1, 6, and 12 months after treatment initiation in the two study groups, and at 0, 6 and 12 months in the control group. Results: In both treatment groups, but not in the control group, both markers increased significantly over time with no difference in BTM between patients treated with raltegravir or efavirenz. Levels of P1NP were statistically higher at 6 and 12 months after treatment initiation in both treatment groups compared to the controls, while CTX during treatment increased in both treatment groups but was significantly higher only in the raltegravir treatment group after 12 months. The ratio of area under the curve of P1NP/CTX correlated with CD4 increment. Conclusions: Treatment initiation with raltegravir or efavirenz combined with TDF/FTC is associated with increased bone turnover. Thus, therapy that optimize bone turnover is needed to reduce bone loss at this vulnerable period and improve long-term bone health.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively., Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT 3 and FT 4 before and after treatment (FT 3 -P/FT 3 -A, FT 4 -P/FT 4 -A) on whether BTMs recovered., Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT 3 -P/FT 3 -A and FT 4 -P/FT 4 -A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05)., Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT 3 decreased more than 51% and FT 4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Chai, Zheng, Jia, Tan, He, Zhang, Men, Liu, Shi, Ren, Dong, Liu and Meng.)

Introduction: Cannabidiol (CBD) has been shown to maintain bone integrity in pre-clinical models, but little is known about the effects of delta-9-tetrahydrocannabinol (THC) on bone turnover. In this study we explored the effects of two oral medical cannabis products on normal bone homeostasis through evaluation of markers of bone resorption (carboxyl-terminal collagen crosslinks, CTx) and bone formation (procollagen type 1 N-terminal propeptide, P1NP; alkaline phosphatase, ALP). Methods: This study is an analysis of secondary data from two Phase 1 double-blind, placebo-controlled trials of Spectrum Yellow (0.9 mg THC, 20 mg CBD/mL of oil) and Spectrum Red (2.5 mg THC, 0.3 mg CBD/softgel). Healthy participants ( n =38 men, 45 women) were randomized to receive 5-20 mg THC (CBD levels varied as a function of administered product) or placebo daily (BID) for 7 days. Bone markers were assessed at baseline, upon completion of product administration (day 8), and after a 5-day washout (day 13). Results: All bone markers were significantly higher in men at baseline ( p ≤0.008). For CTx, there was a significant day×group interaction ( F =3.23, p =0.04); CTx levels were significantly lower in participants treated with Spectrum Red ( b =-164.28; 95% confidence interval [CI], -328 to -0.29; p =0.04) and marginally lower in participants treated with Spectrum Yellow ( b =-157.31; 95% CI, -323 to 8.68; p =0.06) versus placebo on day 8. For P1NP and ALP, there were no significant differences between treatments across study days. Bone marker values outside the reference range (RR) were observed; CTx > RR ( n =71) was predominantly (85.9%) observed in male participants, whereas P1NP > RR ( n =100) was more evenly distributed between sexes (53.0% in men). These were not considered clinically significant and did not differ between treatment groups. Conclusions: These are the first interventional human data on the effect of cannabinoids on biomarkers of bone turnover. Short-term treatment with CBD- or THC-dominant medical cannabis products resulted in attenuation of a marker of bone resorption. Although the attenuation was not clinically significant, this finding may be indicative of protective properties of cannabinoids in bone. Further research over longer dosing durations in individuals exhibiting bone-specific conditions (e.g., osteoporosis) is warranted. ClinicalTrials.gov IDs: ACTRN12619001723178 and ACTRN12619001450101.