Procollagen Type 1 Amino-terminal Propeptide Research Articles

Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density, Fracture Risk, and Bone Metabolism in Adults With Osteoporosis/Fractures

ObjectiveTo evaluate the association of serum 25-hydroxyvitamin D (25(OH) D) levels with bone mineral density (BMD), fracture risk, and bone metabolism. MethodsThis multicenter cross-sectional study recruited menopausal females and males greater than or equal to 50 year old with osteoporosis/fractures between September 2016 and September 2021. Assessment included clinical data, 25(OH)D, intact parathyroid hormone (iPTH), procollagen type 1 amino-terminal propeptide (P1NP), carboxy-terminal collagen crosslinks (CTX), lateral thoracolumbar spine x-rays, and BMD. ResultsA total of 3003 individuals were stratified by 25(OH) D levels: 720 individuals (24%) <20 ng/mL, 1338 individuals (44.5%) 20 to 29 ng/mL, and 945 individuals (31.5%) ≥30 ng/mL. In unadjusted and multivariable models, BMD T-score, except spine, was significantly and positively associated with 25(OH)D levels. 25(OH) D levels were inversely associated with Fracture Risk Assessment Tool scores. Patients with 25(OH)D <20 ng/mL had significantly higher iPTH and bone turnover markers (P1NP and CTX) than patients with 25(OH)D ≧20 ng/mL in all models. When analyzing bone-related markers and BMD, total hip and femoral neck BMD T-scores were positively correlated with 25(OH)D concentrations and BMI but negatively correlated with iPTH, P1NP, CTX, and age. In multivariate models with all bone-related markers, only 25(OH)D levels were significantly associated with total hip and femoral neck BMD. ConclusionVitamin D deficiency is significantly associated with decreased total hip and femoral neck BMD and increased fracture risk as assessed by Fracture Risk Assessment Tool. In those with osteoporosis/fractures, vitamin D is implicated in the causal relationship between bone remodeling and BMD. Assessing vitamin D status is imperative for those at risk for osteoporosis/fractures.

Acromegaly versus hypogonadism: Bone fragility and evaluation

IntroductionOsteopathy in patients with acromegaly is characterized by increased prevalence of vertebral fragility fractures (VF). However, the diagnostic criteria for osteoporosis are seldomly met in terms of bone mineral density (BMD), as patients with acromegaly frequently present normal BMD for age and gender. MethodologyWe performed a cross-sectional study on 71 patients with acromegaly and 75 patients with hypogonadism. Turnover markers comprised alkaline phosphatase, osteocalcin, the C-terminal telopeptide of type I collagen and total procollagen type-1 amino-terminal propeptide; imaging comprised dual x-ray absorptiometry for BMD, T and Z scores of the lumbar spine, femoral neck and total hip, trabecular bone score (TBS), and x-ray scans of the thoracic and lumbar spine. ResultsVertebral fractures (VF) in subjects with acromegaly were significantly more frequent than in subjects with hypogonadism, with a prevalence of 29.6% compared to 9.3%. Patients with acromegaly had significantly higher BMD at all skeletal sites but lower TBS than hypogonadal subjects. This difference remained statistically significant after grouping patients with acromegaly according to gonadal status and comparing them with patients with hypogonadism. However, presence of hypogonadism in patients with acromegaly did not influence BMD, TBS or VF prevalence. Moreover, patients with active acromegaly did not have significantly different BMD, TBS and VF prevalence compared to patients with controlled disease. Patients with acromegaly with VF had significantly lower BMD at all skeletal sites than those without VF, but no difference in TBS. ConclusionsVertebral fractures are frequent in acromegaly, and are associated with lower BMD but not with TBS. Patients with acromegaly, regardless of gonadal status, have significantly higher BMD but lower TBS than hypogonadal patients. Moreover, disease activity and hypogonadism do not influence BMD, TBS or VF in acromegaly.

Bone health, body composition and physical fitness dose–response effects of 16 weeks of recreational team handball for inactive middle-to-older-aged males – A randomised controlled trial

ABSTRACT In this study we aimed at analysing the effects of different weekly exercise volumes (1, 2 or 3 times 60-min) on bone health, body composition and physical fitness of inactive middle-to-older-aged males, after 16 weeks of recreational team handball (RTH). Fifty-four men (68 ± 4 years, stature 169 ± 6 cm; body mass 78.4 ± 10.7 kg; fat mass 27.1 ± 5.3%; BMI 27.4 ± 2.9 kg/m2; VO2peak 27.3 ± 4.8 mL/min/kg) were randomised into three intervention groups (TH1, n = 13; TH2, n = 15; or TH3, n = 12, performing 1, 2 and 3 weekly 60-min training sessions, respectively), and a control group (CG, n = 14). The training sessions consisted mainly of RTH matches played as small-sided and formal game formats (4v4, 5v5, 6v6 or 7v7) with adapted rules. Matches’ mean and peak heart rate (HR) ranged from 78–80% and 86–89%HRmax, respectively, and distance covered from 4676 to 5202 m. A time x group interaction was observed for procollagen type-1 amino-terminal propeptide (P1NP), osteocalcin (OC), carboxy-terminal type-1 collagen crosslinks (CTX), sclerostin, upper and lower body dynamic strength, right arm fat mass, left and right arm, right leg and android total mass (TM; p ≤ 0.047) with the greatest effects being shown for TH2 and TH3 groups. Post-intervention group differences were observed in CTX, left arm and right leg TM (TH3 > TH1), P1NP (TH2 > CG), OC, right arm TM (TH3 > CG), upper (CG < TH1, TH2 and TH3) and lower body dynamic strength (CG < TH1 and TH3) (p ≤ 0.047). RTH was effective in enhancing bone health, body composition and physical fitness in middle-to-older-aged males, especially for the intervention groups that performed 2–3 weekly training sessions. ClinicalTrials.gov ID: NCT05295511. Trial registration: ClinicalTrials.gov identifier: NCT05295511. Highlights After 16 weeks of recreational team handball small-sided and formal matches, inactive middle-to-older-aged males improved bone health, body composition and physical fitness, by performing 1, 2 or 3 60-min weekly sessions, however, greater improvements were shown in the groups that performed 2 or 3 weekly training sessions. Training intensity was similar across the intervention groups that performed recreational team handball for 1, 2 or 3 60-min weekly sessions, which means that training volume is most likely to be the reason for the different health effects shown. The very high fun levels reported by all intervention groups shows that recreational team handball is a social and fun exercise modality for middle-to-older-aged males, with potential to intrinsically motivate the participants and assure long-term adherence to exercise.

Association between Vitamin D, P1NP, and BMD as major indicators of bone health in local population of Pakistan

It is commonly known that the Pakistani population has inadequate vitamin D levels, but its effects on bone health and the level of N-terminal peptide of procollagen (PINP) have not yet determined. The aim of the research work was to check the vitamin D grade of exercisers and non-exercisers and examine how it related to P1NP concentration, a biochemical marker of bone production, and bone mineral density. A random sampling technique was used to select males and females who were staying in neighborhood. They were between the ages of 18 and 35 years. 92 people of Pakistani ancestry made up the total population. With 46 people, Group A was a non-exercising control group. Group B has 46 individuals in it. Both of these groups were gathered for the data analysis. BMD, procollagen type-1 amino-terminal pro-peptide, calciferol, and other biological indicator of bone remodeling were measured in serum. (P1NP). Using broadband ultrasound attenuation, the quality of the bones was evaluated. Before training, the total 25(OH)D serum were considerably less in non-exercising group than they were during or after training. (Mean: 0.4992, Standard Deviation: -1.6075; P 0001).

Bone turnover markers reference database at University Medical Center, Ho Chi Minh city

Objectives: To establish reference ranges for serum bone turnover markers including Osteocalcin (OC), Procollagen type 1 amino-terminal propeptide (P1NP), and Beta-CrossLaps (beta-CTX) in premenopausal women at University Medical Center, Ho Chi Minh City. Methods: A cross-sectional study was conducted on 157 women aged 20 to 44 years at University Medical Center, Ho Chi Minh City from December 2022 to February 2023. Demographic information, biochemical markers, and serum levels of OC, P1NP, and beta-CTX were recorded. Results: The mean serum levels of OC, P1NP, and beta-CTX were 15.57 ± 4.75 ng/mL, 41.98 ± 16.62 μg/L, and 314.03 ± 150.42 pg/mL, respectively. The levels of bone turnover markers varied significantly among different age groups (p &lt; 0.01). Serum levels of OC, P1NP, and beta-CTX were negatively correlated with age, with r values of -0.44, -0.35 and -0.43 respectively (p &lt; 0.01). Conclusion: The reference ranges for serum markers of bone turnover including OC, P1NP, and beta-CTX were 15.57 ± 4.75 ng/mL, 41.98 ± 16.62 μg/L, and 314.03 ± 150.42 pg/mL, respectively, in premenopausal women aged 20 to 44 years. Serum levels of OC, P1NP, and beta-CTX were negatively correlated with age in a moderate degree Key words: osteocalcin, P1NP, beta-CTX, bone turnover markers, premenopausal women.

Effects of Calcium Lactate-Enriched Pumpkin on Calcium Status in Ovariectomized Rats.

This study aimed to evaluate the effects of enriched pumpkin on calcium status in ovariectomized rats. The study was conducted in sixty female Wistar rats, which were divided into six groups: a group fed a standard diet (C) and five ovariectomized groups fed a standard diet (OVX_C) or a diet with calcium lactate (CaL), with calcium lactate-enriched pumpkin (P_CaL), with calcium lactate and alendronate (CaL_B), or with calcium lactate-enriched pumpkin with alendronate (P_CaL_B). After 12 weeks of the intervention, the rats were sacrificed, and their blood and tissues were collected. The calcium concentrations in serum and in tissues were measured using flame atomic absorption spectrometry (AAS). Serum concentrations of procollagen type-1 amino-terminal propeptide (PINP), parathyroid hormone PTH, estrogen (ES), and osteocalcin (OC) were determined with enzyme-linked immunosorbent assay (ELISA). It was found that enriched pumpkin increased the calcium level in the kidneys (194.13 ± 41.01 mg) compared to the C (87.88 ± 12.42 mg) and OVX_C (79.29 ± 7.66 mg) groups. The addition of alendronate increased the calcium level in the femurs (267.63 ± 23.63 mg) and more than six times in the kidneys (541.33 ± 62.91 mg) compared to the OVX_C group (234.53 ± 21.67 mg and 87.88 ± 12.42 mg, respectively). We found that the CaL, P_CaL, and CaL_B groups had significantly lower PINP serum concentrations (4.45 ± 0.82 ng/mL, 4.14 ± 0.69 ng/mL, and 3.77 ± 0.33 ng/mL) and higher PTH serum levels (3.39 ± 0.54 ng/dL, 3.38 ± 0.57 ng/dL, and 3.47 ± 0.28 ng/dL) than the OVX_C group (4.69 ± 0.82 ng/mL and 2.59 ± 0.45 ng/dL, respectively). In conclusion, pumpkin enriched with calcium lactate affects calcium status and normalizes PINP and PTH serum levels in ovariectomized rats. Diet with enriched pumpkin and alendronate increase calcium concentration in the femur. Enriched pumpkin causes calcium to accumulate in the kidneys of ovariectomized rats; alendronate significantly exacerbates this effect.

The effect of Cissus quadrangularis L. on delaying bone loss in postmenopausal women with osteopenia: A randomized placebo-controlled trial

BackgroundOsteopenia refers to bone density that is not normal but also not as low as that noted in osteoporosis. Osteopenia leads to osteoporosis and increases the risk of fractures. Current research is focused on agents that will prevent or slow the progression of bone loss. On the basis of published evidence, Cissus quadrangularis (CQ) might potentially provide a novel natural treatment for osteopenia. PurposeTo determine the effect of 24 weeks of consecutive treatment with CQ on delaying bone loss and safety in postmenopausal women (PMW) with osteopenia. MethodsThis study is a randomized, placebo-controlled trial. Here, 134 enrolled PMW with osteopenia (> 40 years and having no period for 1–10 years) received CQ at 1.2 (CQ1.2) or 1.6 g/day (CQ1.6) or placebo. The %change in bone mineral density (BMD) at the lumbar spine (L1–L4), femoral neck, and total hip served as the primary outcome. The %change in bone turnover markers (BTMs), including C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), was the secondary outcome. These outcomes were compared between the CQ vs. placebo group at weeks 12 and 24. The least significant change (LSC) was used to monitor clinical changes. The adverse events (AE) were monitored. ResultsA total of 108 participants completed this study. The %BMD changes in the CQ-treated groups did not differ at any site after 24 weeks compared to the placebo. Statistically significant differences were detected in CQ1.6 at the lumbar spine (0.011 ± 0.025 g/cm2, p = 0.008) and CQ1.2 at the femoral neck (–0.015 ± 0.036 g/cm2, p = 0.024) compared to baseline, but these changes did not exceed the LSC. Reduced bone remodeling activity was detected in both CQ-treated groups. Compared to the placebo, the %P1NP change was significantly reduced in CQ1.6 (–2.46 ± 26.05%; p < 0.01) at week 12 and in CQ1.2 (–3.36 ± 29.47%; p < 0.01) and CQ1.6 (–9.95 ± 22.22%; p < 0.01) at week 24. These results correlated with the within-group comparison, which showed a continuously significant increase in both BTMs in the placebo group. However, a stable CTX and a significant reduction in P1NP (p < 0.05) were detected in both CQ-treated groups. This reduction exceeded the LSC of P1NP. The incidence of adverse events did not differ among the three groups. ConclusionThis is the first clinical report that showed a promising effect on delaying bone loss of orally administration of CQ for 24 weeks, as indicated by a slower bone remodeling process via a reduction in BTMs. However, no change in BMD was observed.

Stratification by Non-invasive Biomarkers of Non-alcoholic Fatty Liver Disease in Children.

BackgroundThe spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from isolated hepatic steatosis to non-alcoholic steatohepatitis to fibrosis. We aimed to introduce useful biomarkers released during liver inflammation and fibrogenesis that are easy to use in outpatient clinic and adjust to children to evaluate each NAFLD stage without biopsy.MethodsThis prospective study included 60 patients aged under 19 years whose alanine aminotransferase (ALT) levels were elevated from March 2021. All patients were proven to have NAFLD by ultrasonography and laboratory work-up to exclude other causes of hepatitis. Fibroscan and additional laboratory tests for biomarkers [procollagen type1 amino-terminal propeptide (P1NP), osteocalcin, interleukin-6 (IL-6), and Mac-2 binding protein glycosylated isomer (M2BPGi)] were performed. Fibroscan-AST (FAST) score was used for the comparison of steatohepatitis and liver stiffness measurement (kPa) was used for the comparison of advanced fibrosis.ResultsThe biomarker that showed a significant difference between the FAST-positive and negative groups was the P1NP/osteocalcin ratio with a p-value of 0.008. The area under receiver operating characteristic (AUROC) of P1NP/osteocalcin ratio*ALT values (values obtained through multivariate analysis) was 0.939 with the cut-off value of 305.38. The biomarkers that showed a significant difference between the LSM-positive and negative groups were IL-6 and M2BPGi with a p-values of 0.005 and <0.001. AUROC of IL-6 *AST values (values obtained through multivariate analysis) was 0.821 with the cut-off value of 228.15. M2BPGi showed a significant linear relationship with LSM in Pearson correlation analysis (Pearson correlation coefficient = 0.382; p = 0.003). The diagnostic capability of M2BPGi to evaluate advanced fibrosis showed an acceptable result (AUROC = 0.742; p = 0.022).ConclusionsNon-invasive biomarkers can be used to predict each stage of NAFLD in children. The measurements of P1NP, IL-6 or M2BPGi along with the basic chemistry tests would help determine the stage of NAFLD they correspond to at the time of initial diagnosis and predict responsiveness after the treatment.

RISK FACTORS FOR THE DEVELOPMENT OF OSTEOPOROSIS IN TYPE 2 DIABETES MELLITUS IN POST-MENOPAUSAL PERIOD

ABSTRACT Women with type 2 diabetes mellitus (T2DM) are at a significantly higher risk of fractures, even with normal or elevated bone mineral density (BMD). It was found that in the general population among women, the incidence of osteoporosis is more than 30% in the menopausal period and 43.3% among postmenopausal women, while among people with type 2 diabetes it reaches 75%. An aggravating risk factor in this case is the period of transition of patients with diabetes to postmenopausal age. DM, already predisposing to osteoporotic processes, is aggravated by postmenopausal osteoporosis. Comorbid exacerbation of these processes, which have different mechanisms of action on the bone structure, exacerbates changes in bone characteristics. At the same time, for DM, the most characteristic is a violation of the structure of the cortical bone, mainly the femoral neck and peripheral skeleton, and in postmenopausal osteoporosis, mainly trabecular tissue is damaged, with a predominant lesion of the vertebrae. However, the pathogenetic mechanisms of this influence remain poorly understood. Objective: to evaluate the features of changes in BMD in the lumbar spine and proximal femur in patients with type 2 DM aggravated by postmenopausal osteoporosis. Methods: A total of 96 postmenopausal women with T2DM and 32 control women without diabetes were assessed for bone mineral density (BMD, using dual energy X-ray absorptiometry), biochemical bone markers β-isomerized C-terminal telopeptides (β-CTx) and total procollagen type 1 amino-terminal propeptide (P1NP) and glucose metabolism. Results: In patients with type 2 diabetes When comparing the indicators of phosphorus-calcium metabolism and bone density, a fairly high degree of correlation was found only between the indicators of bone mineral density and ionized calcium (r = -0.321; p = 0.03), as well as between the BMD of the LI-LIV zone and beta-CTx marker (r = -0.436; p = 0.006), which indicates increased bone resorption. At the same time, starting from the state of diabetes subcompensation, bone tissue resorption significantly and significantly increased bone resorption (increased levels of beta-CTx) in 76% of patients and reduced bone mineral density. Conclusion: Our data support the ability of the beta-CTx marker to detect differences in the risk of osteoporotic fractures in postmenopausal women with T2DM compared with non-diabetic controls. The activity of total alkaline phosphatase does not reflect the essence of metabolic changes in bone tissue in diabetes mellitus. It should be noted that in patients suffering from type 2 diabetes, osteopenic syndrome depends not so much on age as on the duration of the disease, the degree of compensation of the glycemic profile. Also, the higher the HbA1c level in women with diabetes, the lower the bone density of the lumbar spine. Assessment of the state of bone mineral density and indicators of its metabolism in postmenopausal women with diabetes will allow timely detection of changes in bone remodeling and contribute to the prevention of fractures, including such a severe injury as a fracture of the femoral neck. Keywords: osteoporosis, diabetes mellitus type 2, post menopause.

SATB2-associated syndrome: characterization of skeletal features and of bone fragility in a prospective cohort of 19 patients

BackgroundIndividuals with pathogenic variants in SATB2 display intellectual disability, speech and behavioral disorders, dental abnormalities and often features of Pierre Robin sequence. SATB2 encodes a transcription factor thought to play a role in bone remodeling. The primary aim of our study was to systematically review the skeletal manifestations of SATB2-associated syndrome. For this purpose, we performed a non-interventional, multicenter cohort study, from 2017 to 2018. We included 19 patients, 9 females and 10 males ranging in age from 2 to 19 years-old. The following data were collected prospectively for each patient: clinical data, bone markers and calcium and phosphate metabolism parameters, skeletal X-rays and bone mineral density.ResultsDigitiform impressions were present in 8/14 patients (57%). Vertebral compression fractures affected 6/17 patients (35%). Skeletal demineralization (16/17, 94%) and cortical thinning of vertebrae (15/17) were the most frequent radiological features at the spine. Long bones were generally demineralized (18/19). The distal phalanges were short, thick and abnormally shaped. C-telopeptide (CTX) and Alkaline phosphatase levels were in the upper normal values and osteocalcin and serum procollagen type 1 amino-terminal propeptide (P1NP) were both increased. Vitamin D insufficiency was frequent (66.7%).ConclusionWe conclude that SATB2 pathogenic variants are responsible for skeletal demineralization and osteoporosis. We found increased levels of bone formation markers, supporting the key role of SATB2 in osteoblast differentiation. These results support the need for bone evaluation in children and adult patients with SATB2-associated syndrome (SAS).

Intravenous Zoledronate 4 mg for the treatment of post-menopausal osteoporosis: A prospective open-labeled study

BackgroundZoledronate 5 mg intravenous (IV) annually is approved for treatment of post-menopausal osteoporosis. Zoledronate 4 mg which is approved for the treatment of cancer related hypercalcemia can be an alternative for Asian women who have smaller stature. ObjectivesTo examine the efficacy and safety of Zoledronate 4 mg IV annually for the treatment of post-menopausal osteoporosis. MethodA prospective open-labeled study was performed on 33 post-menopausal osteoporosis patients. All patients received a dose of IV Zoledronate 4 mg. Bone mineral density (DXA) was examined at baseline and 12 months after treatment. Beta-C-terminal telopeptide (β-CTX) and procollagen type-1-amino-terminal propeptide (P1NP) were obtained at baseline, 6, and 12 months after treatment. Adverse events were recorded. ResultsThe mean age (SD) was 69 (11.1) years old. The lumbar spine BMD increased significantly from the mean (SD) lumbar spine BMD at baseline of 0.833 (0.132) g/cm2 to 0.862 (0.132) after treatment (p = 0.001). There was no significant differences in total hip and femoral neck BMDs between baseline and 12 months after treatment. The β-CTX and P1NP decreased significantly from the mean (SD) of 0.44 (0.24) and 55.57 (38.6) ng/ml at baseline to 0.21 (0.11) and 27.26 (10.95) ng/ml after treatment (p < 0.001), respectively. Infusion reaction was observed in five patients. There were two fractures observed. ConclusionZoledronate 4 mg improved lumbar BMD and decreased β-CTX and P1NP significantly after 12 months of treatment. Zoledronate 4 mg could be an alternative to Zoledronate 5 mg for the treatment of post-menopausal osteoporosis.

Metabolomics analysis in adults with high bone mass identifies a relationship between bone resorption and circulating citrate which replicates in the general population

Objective Bone turnover, which regulates bone mass, may exert metabolic consequences, particularly on markers of glucose metabolism and adiposity. To better understand these relationships, we examined cross-sectional associations between bone turnover markers (BTMs) and metabolic traits in a population with high bone mass (HBM, BMD Z-score >=+3.2). Design beta-C-terminal telopeptide of type-I collagen (beta-CTX), procollagen type-1 amino-terminal propeptide (P1NP) and osteocalcin were assessed by electrochemiluminescence immunoassays. Metabolic traits, including lipids and glycolysis-related metabolites, were measured using nuclear magnetic resonance spectroscopy. Associations of BTMs with metabolic traits were assessed using generalized estimating equation linear regression, accounting for within-family correlation, adjusting for potential confounders (age, sex, height, weight, menopause, bisphosphonate and oral glucocorticoid use). Results A total of 198 adults with HBM had complete data, mean [SD] age 61.6 [13.7] years; 77% were female. Of 23 summary metabolic traits, citrate was positively related to all BTMs: adjusted beta(beta-CTX) = 0.050 (95% CI 0.024, 0.076), P = 1.71 x 10(-4), beta(osteocalcin) = 6.54 x 10(-4) (1.87 x 10(-4), 0.001), P = .006 and beta(P1NP) = 2.40 x 10(-4) (6.49 x 10(-5), 4.14 x 10(-4)), P = .007 (beta = increase in citrate (mmol/L) per 1 mu g/L BTM increase). Inverse relationships of beta-CTX (beta = -0.276 [-0.434, -0.118], P = 6.03 x 10(-4)) and osteocalcin (-0.004 [-0.007, -0.001], P = .020) with triglycerides were also identified. We explored the generalizability of these associations in 3664 perimenopausal women (age 47.9 [4.4] years) from a UK family cohort. We confirmed a positive, albeit lower magnitude, association between beta-CTX and citrate (adjusted beta(women) = 0.020 [0.013, 0.026], P = 1.95 x 10(-9)) and an inverse association of similar magnitude between beta-CTX and triglycerides (beta = -0.354 [-0.471, -0.237], P = 3.03 x 10(-9)). Conclusions Bone resorption is positively related to circulating citrate and inversely related to triglycerides. Further studies are justified to determine whether plasma citrate or triglyceride concentrations are altered by factors known to modulate bone resorption, such as bisphosphonates.

The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy-A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy.

AimsTo determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients.Methods and resultsWe quantified fibrosis in 209 DCM patients at three levels: (i) non‐invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino‐terminal propeptide of procollagen type III (PIIINP) and carboxy‐terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life‐threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90–6.60; P < 0.001 and PICP 1.02, 95% CI 1.01–1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log‐rank P < 0.001). RNA‐sequencing and gene enrichment analysis of EMB showed an increased expression of pro‐fibrotic and pro‐inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE‐/PICP‐). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles.ConclusionThe combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro‐fibrotic and pro‐inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP.

Effect of Cholecalciferol Supplementation on Bone Turnover Markers in Children and Adolescents With Type 1 Diabetes Mellitus

Background: Cholecalciferol is known to play an important role in bone mineral metabolism. Its deficiency may affect growth and status of bone markers in children. Aim of the study: to evaluate the correlation between serum 25(OH)D and bone markers and impact of vitamin D supplementation on serum bone formation [procollagen type 1 amino-terminal propeptide (P1NP)] and bone resorption [β-cross laps (CTx)] markers among children and adolescents with type 1 diabetes mellitus (DM). Materials and Methods: Total 58 children and adolescents with type 1 DM, who were given 2000 UI of cholecalciferol supplementation, were included in the study. These 58 children with available anthropometry, serum biochemistry, 25-hydroxyvitamin D ([25(OH)D]), and parathormone (PTH) were evaluated for bone formation (procollagen type 1 amino-terminal propeptide [P1NP]) and resorption (β-cross laps [CTx]) markers. Results: The mean age and body mass index of these children were 11.6 ± 2.3 years (boys: 11.7 ± 2.4; girls: 12.2 ± 1.4 years; p = 0.04) and 18.2 ± 3.9 kg/m2 (boys: 18.1 ± 3.8; girls: 17.8 ± 3.4 kg/m2; p = 0.206), respectively. Baseline serum P1NP levels were positively correlated with serum phosphates (r = 0.281, p < 0.001), PTH (r = 0.291, p < 0.001), and CTx (r = 0.425, p < 0.001) but not with age (r = -0.016, p = 0.404), BMI (r = -0.080, p = 0.032), serum calcium (r = -0.038, p = 0.107), and baseline 25(OH)D (r = -0.069, p = 0.035). Postsupplementation serum P1NP and CTx levels maintained similar correlations. There was a significant decline in serum P1NP (from 681 ± 223 ng/ml to 630 ± 279 ng/ml, p < 0.01) and CTx (from 1.63 ± 0.51 ng/ml to 1.37 ± 0.53 ng/ml, p < 0.01) following supplementation. Though decline in serum P1NP and CTx levels was observed in both boys and girls, among all supplementation patients, the effect was more marked in serum CTx than P1NP levels. Conclusions: Vitamin D supplementation in children resulted in decrease in both bone formation (P1NP) and resorption (CTx). The impact, however, was more marked on bone resorption than bone formation.

Bone Metabolism in the Healing Process of Lumbar Interbody Fusion: Temporal Changes of Bone Turnover Markers.

Prospective longitudinal study. The aim of this study was to evaluate temporal changes of bone turnover markers (BTMs) after lumbar spinal fusion in patients without osteoporosis. Radiological studies are the standard method to monitor bony fusion, but they do not allow a timely assessment of bone healing. BTMs react rapidly to changes in bone metabolism during fusion process and could be an additional tool to monitor this process. A total of 78 nonosteoporosis patients who had undergone one- or two-level transforaminal lumbar interbody fusion were included. Fusion status was assessed using computed tomography sagittal and coronal images. Serum levels of bone-specific alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP), and osteocalcin (OC) were measured to assess bone formation, and tartrate-resistant acid phosphatase 5b (TRACP-5b) was measured to assess bone resorption. Serum samples were obtained before surgery and at 1, 2, 4, 8, 13, 26, 39, and 52 weeks after surgery. A solid fusion was achieved in 71 of 78 patients (91%), and seven patients resulted in pseudarthrosis. In the fusion group, the level of all BTMs once decreased at 1 postoperative week. Then, BAP and P1NP reached a peak at 4 weeks after surgery, and TRACP-5b and OC peaked at 8 weeks. Thereafter, the level of P1NP and TRACP-5b gradually got closer to the baseline over a year, and BAP kept high until 52 postoperative weeks. In the pseudarthrosis group, peak level of BTMs was significantly higher and the increased level of BAP and P1NP was kept until 52 weeks. The present study demonstrated dynamics of BTMs after lumbar spinal fusion in patients without osteoporosis. These normal population data contribute as a baseline to evaluate the effect of osteogenic agents on bone metabolism after spinal fusion.Level of Evidence: 2.

Association of environmental cadmium exposure and bone remodeling in women over 50 years of age

Chronic cadmium (Cd) toxicity is a significant health concern, and the mechanism of long-term low-dose Cd exposure on bone has not been fully elucidated yet. This study aimed to assess the association between long-term environmental Cd exposure and bone remodeling in women who aged over 50. A total of 278 non-smoking subjects from Cd-polluted group (n = 191) and non-Cd polluted group (n = 87) were investigated. Bone mineral density (BMD), the levels of three bone turnover markers (BTMs), including total procollagen type 1 amino-terminal propeptide (P1NP), collagen type 1 cross-linked C-telopeptide (β-CTX), bone-specific alkaline phosphatase (BALP), together with serum soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin (OPG) were determined. Early markers of renal dysfunction were measured as well. Urinary Cd concentrations ranged from 0.41 to 87.31 μg/g creatinine, with a median of 4.91 μg/g creatinine. Age, BMD, T-score, and prevalence of osteoporosis showed no statistical differences among the quartiles of urinary Cd concentrations, while serum levels of P1NP, β-CTX, and OPG were higher in the upper quartiles. Multivariate linear regression models indicated significantly positive associations of urinary Cd concentration with serum levels of P1NP, β-CTX, BALP, sRANKL, and OPG. A ridge regression analysis with T-score and the three BTMs, sRANKL, and OPG, adjusted for age and body mass index (BMI), indicated that except for age and Cd exposure, β-CTX was a predictor of T-score. These findings demonstrated that Cd may directly accelerate bone remodeling. Serum β-CTX might be an appropriate biochemical marker for evaluating and monitoring Cd-related bone loss.Capsule: Cadmium (Cd) may directly accelerate bone remodeling and serum β-CTX is a valuable biochemical marker for evaluating Cd-related bone loss.

Effects of recreational team handball on bone health, postural balance and body composition in inactive postmenopausal women - A randomised controlled trial.

This study reports the effects of a recreational team handball exercise programme (randomised controlled trial, RCT) on bone health, postural balance and body composition in inactive postmenopausal women without previous experience of the sport. Sixty-seven postmenopausal women (68.3±6.2years, stature 156.9±5.8cm, body mass 65.6±9.6kg, body fat 40.9±5.9%, VO2peak 25.2±3.6mL·min-1·kg-1) were randomised into team handball (THG, n=41) and control (CG, n=26) groups. During the 16-week intervention period, THG performed two to three 60-min training sessions per week, while CG continued with their habitual physical activity. Bone mineral density (BMD) and content (BMC), biochemical bone formation (osteocalcin (OC), procollagen type-1 amino-terminal propeptide (P1NP)) and resorption (carboxy-terminal type-1 collagen crosslinks (CTX)) markers, postural balance, body fat and lean mass were evaluated at baseline and post intervention. A time x group interaction (p≤0.02) was shown for lumbar spine BMD (+1.5%) and BMC (+2.3%), P1NP (+37.6±42.4%), OC (+41.9±27.0%) and postural balance (-7±37% falls), in favour of THG with no changes in CG. This RCT showed that short-term recreational team handball practice had an impact on bone turnover and was effective for improving bone health and postural balance in postmenopausal women without previous experience of the sport, hence potentially helping to reduce the risk of falls and fractures.

Bone turnover and metabolite responses to exercise in people with and without long-duration type 1 diabetes: a case–control study

IntroductionExercise acutely alters markers of bone resorption and formation. As risk of fracture is increased in patients with type 1 diabetes, understanding if exercise-induced bone turnover is affected within this...

Relationship between bone turnover markers and oxidative stress in children with type 1 diabetes mellitus.

Oxidative stress in children with type 1 DM (T1DM) may negatively affect the bone. This study included 40 children with T1DM as the patient group and 40 healthy childrenof matched age and sex as the control group. Plasma alkaline phosphatase, procollagen type-1 amino-terminal propeptide (P1NP), and urinary deoxypyridinoline (DPD) were measured to assess bone turnover. Glutathione, superoxide dismutase (SOD), and malondialdehyde (MDA) were measured to assess oxidative stress. Patients with T1DM had a significantly lower P1NP level but a significantly higher urinary DPD level compared to the control group. Moreover, there were significantly lower glutathione and SOD levels with significantly higher MDA levels in patients with T1DM. We found a significant positive correlation between P1NP level and both glutathione and SOD levels but a significant negative correlation between P1NP and MDA in patients with T1DM. There was a significant negative correlation between DPD levels and both glutathione and SOD levels and a significant positive correlation between DPD and MDA. Moreover, glutathione was a significant predictor for both P1NP and DPD levels, while MDA was a significant predictor for P1NP levels. There is an association between oxidative stress and bone turnover markers in children with T1DM. Oxidative stress can negatively affect bone but the exact relationship between oxidative stress and bone turnover in T1DM has not been previously studied in pediatrics. For the best of our knowledge, our study was the first to assess the relationship between oxidative stress and bone turnover in children with T1DM. We revealed that increased oxidative stress in children and adolescents with T1DM may be involved in the impairment of bone turnover process, so treatment strategies toward better glycemic control and decreasing oxidative stress may be beneficial in preventing and treating diabetic bone disease in these children.

Tuberculous osteomyelitis of OS Calcis

There is little data regarding Vitamin D deficiency in Greece. Also conflicting are the data regarding the bone turnover during the acute hip fracture interval and the situation is even more complex considering the recently developed bone turnover markers (BTMs). The aim of this study was to evaluate the parameters of bone mineral homeostasis of women with fragility hip fracture using the recently developed BTMs of carboxy-terminal collagen crosslinks (CTx) and the procollagen type 1 amino-terminal propeptide (PINP) and to determinate vitamin D (25-OHD) levels of elderly Greek women with acute hip fracture. 38 self-sufficient, community-living Greek women with acute hip fracture were included. A similar number of age- and sex-matched controls with no clinically evident fractures were included in the study meeting the same inclusion and exclusion criteria. To exclude the effect of trauma blood samples were drawn within 24 hours from the fracture. Hip fracture group had significantly lower serum 25-OHD levels and significantly higher intact parathormone (PTH) levels compared to the control group but no correlation between PTH and 25-OHD was found in both groups. CTx was significantly correlated with PINP in the total group and in both groups separately but there was no statistical difference of their levels between the two groups. There was high prevalence of severe Vitamin D deficiency within the postmenopausal Greek women with acute hip fracture and the fracture did not influence the above mentioned BTMs. The processes of bone resorption and bone production are in balance during the first 24 hours after the fracture.