Collagen Cross-linked N-telopeptide Research Articles

Bone turnover markers in the preoperative assessment of bone quality - A prospective investigation of bone microstructure and advanced glycation endproducts in lumbar fusion patients.

Effective tools to evaluate bone quality preoperatively are scarce and the standard method to determine bone quality requires an invasive biopsy. A non-invasive, and preoperatively available method for bone quality assessment would be of clinical value. The purpose of this study is to investigate the associations of bone formation marker, serum bone alkaline phosphatase (BAP), and bone resorption marker, urine collagen cross-linked N-telopeptide (uNTX) to volumetric bone mineral density (vBMD), fluorescent advanced glycation endproducts (fAGEs) and bone microstructure. A cross-secional analysis using prospective data of patients undergoing lumbar spinal fusion was performed. BAP and uNTX were preoperatively collected. Quantitative computed tomography (QCT) was performed at the lumbar spine (vBMD ≤ 120mg/cm3 osteopenic/osteoporotic). Bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton fluorescence microscopy for fAGEs and microcomputed tomography (µCT) for bone microarchitecture. Correlations between BAP/uNTX to vBMD, fAGEs and µCT parameters were assessed with Spearman's ρ. Receiver operating characteristic (ROC) analysis evaluated BAP and uNTX as predictors for osteopenia/osteoporosis. Multivariable linear regression models adjusting for age, sex, BMI, race and diabetes mellitus determined associations between BAP/uNTX and fAGEs. 127 prospectively enrolled patients (50.4% female, 62.5 years, BMI 28.7kg/m2) were analyzed. uNTX (ρ=-0.331,p < 0.005) and BAP (ρ=-0.245,p < 0.025) decreased with cortical fAGEs, and uNTX (ρ=-0.380,p < 0.001) decreased with trabecular fAGEs. BAP and uNTX revealed no significant correlation with vBMD. ROC analysis for BAP and uNTX discriminated osteopenia/osteoporosis with AUC of 0.477 and 0.561, respectively. In the multivariable analysis, uNTX decreased with increasing trabecular fAGEs after adjusting for covariates (β = 0.923;p = 0.031). This study demonstrated an inverse association of bone turnover markers and fAGEs. Both uNTX and BAP could not predict osteopenia/osteoporosis in the spine. uNTX reflects collagen characteristics and might have a complementary role to vBMD, as a non-invasive tool for bone quality assessment in spine surgery.

Changes in Testing and Treatment Methods in Osteoporosis Care.

Osteoporosis treatment plays a crucial role in preventing fractures, particularly in bedridden patients. We conducted a questionnaire survey presenting hypothetical clinical cases in 2015 and 2020 to investigate trends over a 5-year period. The target population included physicians working in clinics and hospitals within our neighbourhood. The cases were presented, and the questionnaire was administered in a confidential format. The orthopaedic surgeons were matched for age and practice, resulting in 74 cases being included in the analysis. Comparing the 2015 and 2020 results, we observed a notable increase in physicians who would perform "bone mineral density measurements of the lumbar spine and hip." Furthermore, there was a significant rise in the percentage of respondents willing to test for bone metabolic markers, such as serum type I collagen cross-linked N-telopeptide (NTX), procollagen I N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b (TRACP-5b). Regarding therapeutic agents, bisphosphonates decreased in usage, whereas parathyroid hormone and romosozumab witnessed an increase. In conclusion, the percentage of physicians requesting bone mineral density measurements of the lumbar spine and hip increased over the five-year period. In addition, more physicians chose to utilise bone metabolic markers due to their ease of measurement through blood tests and reduced diurnal variation. Finally, there was a marked trend towards the administration of drugs capable of rapidly and effectively increasing bone mineral density at an early stage of treatment.

Effect of vitamin D supplementation or fortification on bone turnover markers in women: a systematic review and meta-analysis.

Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0·038, n 22) and OC (MD: -0·610, n 24) with high heterogeneity and uNTX (MD: -8·188, n 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 μg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.

Daily supplement of sesame oil prevents postmenopausal osteoporosis via maintaining serum estrogen and aromatase levels in rats

Estrogen deficiency is one of the main causes of postmenopausal osteoporosis in elderly women. Hormone replacement therapy has been employed to manage postmenopausal osteoporosis; however, it has raised concerns related to heart attacks and breast cancer. Sesame oil has been reported to affect sex hormone status. The aim of the present study is to evaluate the effect of sesame oil supplement on postmenopausal osteoporosis in rats. We used female Sprague Dawley rats that underwent bilaterally ovariectomy (OVX) as an experimental postmenopausal osteoporosis animal model. These rats were orally administrated sesame oil (0.25 or 0.5 mL/kg/day) for four months as the therapeutic group. We assessed bone mineral density (BMD) and the levels of osteocalcin, procollagen-I C-terminal propeptide (PICP), collagen cross-linked N-telopeptide (NTx), estradiol, and aromatase in the sera. The daily supplementation of sesame oil significantly increased BMD, serum osteocalcin levels, and trabecular areas in the OVX-treated rats. Sesame oil also elevated serum PICP levels and decreased NTx levels in these rats. Furthermore, sesame oil effectively maintained serum estradiol and aromatase levels in the OVX-induced osteoporosis rats. In conclusion, daily supplementation of sesame oil prevents postmenopausal osteoporosis by maintaining serum estrogen and aromatase levels, while also modulating the imbalance between bone formation and resorption in osteoporosis rats.

Clinical Outcomes of Switching from Zoledronic Acid to Denosumab for the Management of Severe Bone Metastasis from Hepatocellular Carcinoma: A Single-Center, Open-Label, Prospective Intervention Trial.

Zoledronic acid reduces the risk of bone metastasis, but denosumab is a better option for treating bone metastases. However, few studies have evaluated the use of denosumab to treat bone metastasis originating from hepatocellular carcinoma. This study aimed to assess the clinical outcomes of switching from zoledronic acid to denosumab for treating bone metastasis in patients with hepatocellular carcinoma. This prospective study enrolled 10 patients with HCC and bone metastases. The levels of type 1 collagen cross-linked N-telopeptide (NTx) and tumor growth remained abnormal in these patients despite administration of zoledronic acid for over 3 months. We switched from zoledronic acid to 120 mg denosumab every 4 weeks and evaluated the clinical outcomes, including changes in the NTx level, pain level, and activities of daily living, as well as adverse events, after each administration. Urinary NTx clearance was normal in all patients. The average urinary NTx clearance increased from 13.2 to 21.2 nmol BCE/nmol · Cre (P = 0.54) after the switch to denosumab. Serum NTx levels were abnormal in all cases. The serum NTx level decreased from 142 nmol BCE/L to 126 nmol BCE/L (P = 0.56). The answers to questionnaires on pain and activities of daily living did not change significantly. Some patients showed elevated transaminase levels, but this was not due to the drug switch. Switching to denosumab did not show a significant change of the pain and activity of daily living for the patients with severe bone metastasis from hepatocellular carcinoma, in whom the efficacy of zoledronic acid was limited.

Associations between physical physique/fitness in children and bone development during puberty: a 4-year longitudinal study

Bone growth is most remarkable during puberty. This study aimed to clarify the effects of physique and physical strength on bone mineral density and bone metabolism markers during puberty to help improve bone growth during puberty and prevent future osteoporosis. There were 277 pubertal participants (125 boys and 152 girls) in this survey from 2009 to 2015, all aged 10/11 and 14/15 years. The measures included physical fitness/physique indices (such as muscle ratio etc.), grip strength, bone density (osteo sono-assessment index, OSI), and bone metabolism markers (bone-type alkaline phosphatase and type I collagen cross-linked N-telopeptide). At 10/11-years-old for girls, a positive correlation was found between body size/grip strength and OSI. At 14/15-year-old for boys, all body size factors/grip strength were positively correlated with OSI. The change in body muscle ratio was positively correlated with change in OSI for both sexes. The height, body muscle ratio and grip strength at 10/11-year-old were significantly associated with OSI (positively) and bone metabolism markers (negatively) at 14/15-year-old for both sexes. Adequate physique building after 10/11 years for boys and before 10/11 years for girls may be effective in increasing peak bone mass.

Efficacy and Safety of Monthly Minodronate Therapy in Postmenopausal Breast Cancer Patients Receiving Aromatase Inhibitors.

Post-menopausal breast cancer (BC) patients who receive adjuvant aromatase inhibitor (AI) therapy may be at increased risk of bone loss, osteoporosis, and bone fracture. We aimed to evaluate the efficacy and safety of oral bisphosphonate minodronate in preventing bone loss complications. Patients receiving AI and 80% of those with suboptimal bone mineral density (BMD) were prescribed monthly oral minodronate 50 mg every 4 weeks for 72 weeks. BMD, bone metabolism markers, incidence of bone fractures, medication compliance, and other adverse events (AE) were examined every 24 weeks following administration. Fifty postmenopausal BC patients with a median age of 64.0 years were enrolled. The mean value of lumbar spine BMD was higher than that of the value before the minodronate administration at each observation point. Before and after the treatment, the median serum values of Tartrate-resistant Acid Phosphatase 5b (TRACP-5b) (mU/dl) and serum type I collagen cross-linked N-telopeptide (NTX) (nmolBCE/l) were decreased from 535.7 and 18.5 to 230.1 and 11.9, respectively. No adverse grade 2 or higher event was observed throughout this study. The combined administration of minodronate and AIs was safe and effective in preventing bone loss complications in postmenopausal BC patients.

Twice-weekly teriparatide improves lumbar spine BMD independent of pre-treatment BMD and bone turnover marker levels.

There have been no reports of the effects of baseline lumbar spine bone mineral density (LS-BMD) and bone turnover marker levels on the therapeutic effect of a 28.2-μg teriparatide formulation for twice-weekly use (2/W-TPTD). An analysis was performed using data from a double-blind, randomized, non-inferiority trial (TWICE study) conducted with patients who received 2/W-TPTD or a 56.5-μg teriparatide formulation for once-weekly use (1/W-TPTD) for 48weeks. The patients were divided into tertile groups based on baseline LS-BMD, urinary type I collagen cross-linked N-telopeptide (u-NTX), and serum type I procollagen-N-propeptide (P1NP) levels, respectively. Time profiles of these measurements were analyzed. Furthermore, whether a change in P1NP is a predictor for percentage change in BMD was assessed. Across all tertile groups divided based on baseline LS-BMD and levels of bone turnover markers, the LS-BMD increased significantly. The u-NTX level decreased throughout the study period in the high- and middle-u-NTX-level groups. The P1NP level increased after 4weeks, but subsequently decreased after 12weeks and thereafter in the high-P1NP-level group; it increased after 4weeks and subsequently fluctuated near the baseline level in the middle-P1NP-level group. A cut-off value of 12.0µg/L for change in P1NP after 4weeks of 2/W-TPTD as a predictor for percentage change in LS-BMD of 3% or more after 48weeks gave a positive predictive value of 89.6%. 2/W-TPTD, just like 1/W-TPTD, improved LS-BMD significantly, regardless of baseline LS-BMD and bone turnover marker levels.

Effects of paprika carotenoid supplementation on bone turnover in postmenopausal women: a randomized, double-blind, placebo-controlled, parallel-group comparison study.

BackgroundPaprika (Capsicum annuum L.) is a good source of carotenoids, including capsanthin, β-carotene, β-cryptoxanthin, and zeaxanthin. Several epidemiological studies have shown a beneficial association of intake of these carotenoids or their blood concentration with bone mineral density (BMD) and fracture risk. However, little information is available regarding the effect of intake of these carotenoids on bone metabolism in postmenopausal women.ObjectiveThe objective of the present study was to investigate the effects of paprika carotenoid extract (PCE) on bone turnover in healthy, postmenopausal women.DesignWe conducted a randomized, double-blind, placebo-controlled, parallel-group comparison study. One hundred participants were randomly assigned to PCE or placebo groups. Each group was given a 20 mg PCE (equivalent to 1.4 mg of carotenoids) a day or a placebo for 24 weeks. We measured bone resorption markers (tartrate-resistant acid phosphatase 5b [TRACP-5b] and serum type I collagen cross-linked N-telopeptide [sNTX]) at 12 and 24 weeks and bone formation markers (bone alkaline phosphatase and osteocalcin) at 24 weeks.ResultsThe percentage decrease of TRACP-5b at 24 weeks was significantly higher for PCE than the placebo. There were no significant differences in sNTX or bone formation markers, although PCE decreased each marker compared with the placebo.ConclusionOur findings suggest that PCE supplementation suppresses bone resorption and contributes to maintaining bone quality in postmenopausal women.

Effects of boric acid supplementation on bone health in crossbred calves under tropical condition

IntroductionBoron (B) is thought to play key role in proper bone growth and development as well as have some role in regulation of minerals such as calcium (Ca), phosphorus (P) and magnesium (Mg) which act synergistically with vitamin D. ObjectivePresent study was planned in two phases to assess the effect of optimum and supranutritional levels of (B) in the form of boric acid (BA) supplementation on bone health of growing cross bred calves. MethodDuring Phase-1, twenty four male crossbred calves were blocked into four groups (n = 6) on the basis of their body weight (154.83 ± 8.5 kg), age (7–9 months) and were supplemented with 0 (C), 2.6 (T-1), 5.4 (T-2) and 10.7 (T-3) g BA for appropriate B (0.175 adjustment factor to calculate B form BA) consumption i.e. 0, 100, 200 and 400 ppm in each group respectively, for 90 days. During phase 2, twenty-one male crossbred calves were divided into 3 groups (n = 7) on the basis of their body weight (103.76 ± 4.34 kg) and age (5–8 months). All the groups were on similar dietary regimen with additional supplementation of boric acid as 0 g (control); 3.6 g (200 ppm B; T-1) and 10.8 g (600 ppm B; T-2), respectively for a period of 120 d. ResultsFrom the first experiment it is reported that plasma levels of bovine alkaline phosphatase (BALP), type I collagen cross-linked N-telopeptide (NTx) and Ca were significantly (P < 0.05) affected in T-2 and T-3 groups as compared to T-1 and control groups. Whereas, plasma osteocalcin (OCN) concentration was found to be higher in T-2 and T-3 groups as compared to control group. However, plasma concentrations (ng/mL) of tartrate resistant acid phosphatase (TRAP) remained unaltered due to dietary treatments. Based on the results, another experiment was conducted to validate the above findings and further to determine the effect of still higher i.e supranutritional levels of BA supplementation on bone health of calves. Results revealed that supplementation of BA in T-2 group had no beneficial effect on bone health as the plasma concentration of BALP, OCN, NTx, 25 (OH) vitamin D and Ca as compared to T-1 group in phase 2. Other possible attributes of bone health i.e. plasma concentration of Mg, P, parathyroid hormone (PTH), and calcitonin were not affected by BA supplementation at any levels. ConclusionOverall from present study it can be concluded that supplementation of boric acid 3.6 g/d (equivalent to 200 ppm B) in the diet of growing animals has positive effect on bone health related biomarkers (OCN, NTx and BALP) and supplementation of supranutritional level of BA i.e. 10.8 g (equivalent to 600 ppm B) level had neither additional beneficial nor harmful effect on bone health of calves.

Utility of urinary type I collagen cross-linked N-telopeptide as a prognostic indicator in breast cancer patients with bone metastases.

Breast cancer patients with bone metastases are usually managed with bone modifying agents, such as zoledronic acid and denosumab, and some bone turnover markers (BTMs) have been recognized as prognostic indicators in such patients. Although several studies have demonstrated the validity of BTMs as prognostic markers in patients treated with zoledronic acid, few studies have reported the utility of BTMs with denosumab treatment. In this study, we evaluated whether urinary N-telopeptide of type I collagen (u-NTX) can be a prognostic indicator in patients treated with denosumab. Thirty-six breast cancer patients newly diagnosed with bone metastases were evaluated retrospectively. Patients were treated with denosumab and anti-cancer drugs. u-NTX levels were measured 1month before and after administration of denosumab, and the ratio of u-NTX levels before and after denosumab (change ratio) was assessed for its association with prognosis. Levels of u-NTX decreased after denosumab administration in all patients except for one. The median value of the u-NTX change ratio was 0.766. Based on the change ratio, patients were divided into either a "high group" (n = 18) or a "low group" (n = 18). The low group showed significantly shorter overall survival (OS) compared with the high group (low group 15.0months; high group 54.0months; P = 0.012). Multivariate analysis indicated that the "low group" was an independent prognostic factor for OS (P = 0.028). We demonstrated that the u-NTX change ratio in denosumab-treated breast cancer patients with bone metastases can be a prognostic marker.

SUN-412 Graves’ Disease Displayed as a Risk Factor of Vertebral Fracture Even in Premenopausal Women

BackgroundHyperthyroidism is a known risk factor for osteoporosis and fractures especially in older men and postmenopausal women. However, it remains unclear whether younger patients with Graves’ diseases are at a higher risk of fracture compared to healthy individuals.ObjectiveThis study aimed to clarify whether premenopausal women with Graves’ disease represents a risk factor for vertebral fracture (VF).Patients and MethodsWe enrolled 30 premenopausal women (mean age, 32 ± 10 years) who were diagnosed with Graves’ disease at our institution between April 2007 and December 2017. We also enrolled 40 healthy control women who visited our hospital. The control subjects were confirmed to have no endocrine disease or any condition that might affect bone metabolism. None of the study subjects had taken drugs known to influence bone and calcium metabolism such as vitamin D, bisphosphonates, or glucocorticoids. Also, none has taken an oral contraceptive. Serum and urinary biological parameters, alkaline phosphatase (ALP), glycosylated hemoglobin (HbA1c), creatinine, serum calcium, total cholesterol, intact parathyroid hormone, free triiodothyronine (Free T3), free thyroxin (Free T4), thyroid-stimulating hormone (TSH) and urinary type I collagen cross-linked N-telopeptides (NTX; a bone resorption marker) were compared between the groups. Bone mineral density (BMD) of the lumbar spine and femoral neck was determined using dual-energy X-ray absorptiometry and vertebral fractures were diagnosed from lateral X-rays of the thoracic and lumbar spine. The chi-square and unpaired t-tests for two groups comparison were utilized to determine the statistical significance (P < 0.05). Multiple logistic regression analyses were proceeded after adjustments for variables.ResultsPatients with Graves’ disease displayed the higher ALP, eGFR, Ca, free T3, free T4 and urinary NTX levels, and lower body mass index (BMI), Alb, total cholesterol and intact PTH compared to controls.The prevalence of VFs was significantly higher in patients with Graves’ disease (20.0%) than in controls (2.5%, <0.05). Such association remained significant even after adjustment for age, BMI, ALP, eGFR and free T3, but except for BMD. Among premenopausal patients with Graves’ disease, the values of several parameters, such as BMI, ALP, HbA1c, serum Ca, intact PTH and BMD and the prevalence of thyroid related antibodies did not differ significantly between those with and without VF; subjects with VF were older and exhibited lower free T3, free T4 and urinary NTX levels compared to subjects without VF. The mean value of lumbar BMD T score in subjects with VF among premenopausal patients with graves’ disease was -1.0, indicating osteopenia.ConclusionsVF risk could be elevated even in the premenopausal women with Graves’ disease, although the BMD risk levels is not equivalent to that of osteoporosis.

Effect of continuous long-term treatment for 10years with bisphosphonate on Japanese osteoporosis patients.

In terms of the balance between benefits and risks of long-term treatment with bisphosphonate, uncertainties remain regarding the optimal treatment duration. We investigated effects of continuous long-term treatment for 10 years with bisphosphonate in postmenopausal osteoporosis patients. Fifty five patients in the outpatient clinic of our hospital have been continuously treated with alendronate or risedronate for 10 years. All data were retrospectively collected. The age, height, weight, total muscle volume, total fat volume, and BMD at the lumbar spine, total hip and distal 1/3 radius, alkaline phosphatase (ALP), urinary type I collagen cross-linked N-telopeptide (uNTX) and tartrate-resistant acid phosphatase-5b (TRAP5b), calcium (Ca) and phosphate (P) levels were measured pre- and after the start of 10-year continuous treatment. BMD at the lumbar spine increased continuously over the 10-year period, while BMD at the total hip slightly but significantly decreased, and that at the 1/3 radius did not show any significant change over the 10 years. Serum Ca value was significantly decreased after the start of treatment, and became stable within the reference range from the second year. Bone resorption markers such as uNTX and TRAP5b significantly decreased from the second year after the start of treatment and no significant changes were observed thereafter. There were no serious medical adverse events including atypical femoral fractures and osteonecrosis of the jaw. We believe that the continuous use of alendronate and risedronate for 10 years could be an option for the treatment of postmenopausal osteoporosis patients.

Bone metabolism markers and hungry bone syndrome after parathyroidectomy in dialysis patients with secondary hyperparathyroidism.

To explore the short-term variation in bone metabolic markers and the characteristics of hungry bone syndrome (HBS) after parathyroidectomy (PTX) with forearm autotransplantation in uremic patients with secondary hyperparathyroidism (SHPT) and to provide a basis for the pathogenesis, diagnosis and treatment of metabolic bone disease in SHPT. A total of 115 patients with SHPT receiving PTX from July 2015 to December 2017, hospitalized at the First Affiliated Hospital of Nanjing Medical University, were enrolled in our study. We retrospectively analyzed the baseline clinical data, the levels of bone metabolism markers before and on the third day after PTX, and the risk factors predicting HBS. Preoperative baseline data showed that the levels of bone metabolic markers such as bone metabolism-regulating hormones: iPTH, calcitonin (CT); bone formation markers: phosphatase (ALP), osteocalcin (OC); bone resorption markers: type I collagen cross-linked N-telopeptides (NTX), type I collagen cross-linked C-telopeptides (CTX), tartrate-resistant acid phosphatase 5b (TRAP-5b) were all increased compared to normal levels. The levels of postoperative serum iPTH, CT, CTX and TRAP-5b decreased significantly compared to preoperative levels, while the levels of OC and ALP increased significantly. Of the 115 patients, 101 (87.8%) developed HBS after PTX. High preoperative serum ALP and low preoperative serum calcium level independently predicted the occurrence of HBS. Younger preoperative age, high preoperative serum ALP and iPTH level independently predicted the severity of HBS. In severe SHPT, both bone formation and resorption were active, which suggested the presence of high-turnover bone diseases characterized by up-regulation of osteoclasts-osteoblasts functionally coupling activation in the patients. PTX could promote osteoblast activity and reduce osteoclast activity. HBS was common after PTX. Preoperative higher serum ALP and lower calcium were independent predictors of the occurrence of HBS. Younger patients with higher preoperative ALP and PTH may need to closely monitor serum calcium levels and intensive calcium supplementation after PTX.

Effect of Bacillus subtilis C-3102 on bone mineral density in healthy postmenopausal Japanese women: a randomized, placebo-controlled, double-blind clinical trial.

Gut microbiota influence the host immune system and are associated with various diseases. In recent years, postmenopausal bone loss has been suggested to be related to gut microbiota. In the present study, we investigated the treatment effect of the probiotic Bacillus subtilis C-3102 (C-3102) on bone mineral density (BMD) and its influence on gut microbiota in healthy postmenopausal Japanese women. Seventy-six healthy postmenopausal Japanese women were treated with a placebo or C-3102 spore-containing tablets for 24 weeks. When compared with the placebo, C-3102 significantly increased total hip BMD (placebo = 0.83 ± 0.63%, C-3102 = 2.53 ± 0.52%, p=0.043). There was a significant group-by-time interaction effect for urinary type I collagen cross-linked N-telopeptide (uNTx) (p=0.033), a marker of bone resorption. Specifically, the C-3102 group showed significantly lower uNTx when compared with the placebo group at 12 weeks of treatment (p=0.015). In addition, in the C-3102 group, there was a trend towards a decrease in the bone resorption marker tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) when compared with the placebo group at 12 weeks of treatment (p=0.052). The relative abundance of genus Bifidobacterium significantly increased at 12 weeks of treatment compared with the baseline in the C-3102 group. The relative abundance of genus Fusobacterium was significantly decreased in the C-3102 group at 12 and 24 weeks of treatment compared with the baseline. These data suggested that C-3102 improves BMD by inhibiting bone resorption and modulating gut microbiota in healthy postmenopausal women.

Comparison of bone metabolism based on the different ages and competition levels of junior and high school female rhythmic gymnasts.

[Purpose]This study was to clarify the effect of age and competition level by measuring bone metabolism markers and bone mineral density measurements of junior high school and high school female rhythmic gymnasts, who restrict their diets to maintain a low body weight, while routinely undertaking long hours of high-intensity exercise, comparing the gymnasts based on their elite/non-elite. [Methods]The study investigated 7 junior high school and 12 high school female rhythmic gymnasts. For comparison by competition level, the 7 junior high school gymnasts were separated into 3 gymnasts who competed at national level (junior high school elite), and 4 gymnasts who did not compete at that level (junior high school non-elite), and the 12 high school gymnasts were separated into 7 gymnasts who competed at national level (high school elite) and 5 gymnasts who did not compete at that level (high school non-elite). The measurement items were bone mineral density, bone metabolism markers (undercarboxylated osteocalcin (ucOC), osteocalcin (OC), bone-specific alkaline phosphatase (BAP), calcium (Ca), inorganic phosphorus (P), alkaline phosphatase (ALP), parathyroid hormone (PTH), type 1 collagen cross-linked N-telopeptide (NTx)). We also surveyed the gymnasts’ height, weight and nutrition. [Results]In this study we found: 1) The high school gymnasts who competed at high-level rhythmic gymnastics had good results for bone metabolism markers and bone mineral density. 2) Elite high school gymnasts had restricted diets. 3) Nutritionally, their energy intake and carbohydrate intake was low, but their intake of protein, calcium, iron, vitamin D and vitamin K was good. [Conclusion]The results found that the elite gymnastics showed a higher bone density than the non-elite group that suggests the possibility of inhibiting bone formation in the bone metabolism.

Fingolimod suppresses bone resorption in female patients with multiple sclerosis

Fingolimod is a sphingosine-1-phosphate receptor agonist used to inhibit the inflammatory activity of multiple sclerosis (MS), and has been shown to suppress osteoporosis in mouse models. In this study, levels of bone turnover markers were quantified in serum and urine samples from MS patients treated with fingolimod. Compared with untreated MS patients and healthy controls, fingolimod-treated MS patients had a significantly lower level of the bone resorption marker type I collagen cross-linked N-telopeptide in urine. This finding was prominent in female but was not seen in male subjects. Our results suggest that fingolimod may have a beneficial effect on bone mass loss in female MS patients.

Serum Fibroblast Growth Factor 23 (FGF23) in Patients with Rheumatoid Arthritis.

Objective Rheumatoid arthritis (RA) is a chronic inflammatory disease accompanied by periarticular and systemic osteoporosis. Fibroblast growth factor 23 (FGF23), which is mainly produced by osteocytes, circulates to the kidneys and regulates bone metabolism. We herein assessed serum FGF23 and its relationship to inflammation and osteoporosis in patients with RA. Methods Sixty-one patients with RA were included. Serum concentrations of FGF23 were determined using a sandwich enzyme-linked immunosorbent assay. Results The mean (± standard deviation) serum FGF23 concentration was 34.9±9.2 (range, 21.0-61.0) pg/mL. The serum FGF23 level was significantly and positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, disease activity score-28 based on the ESR (DAS-28 ESR) and DAS-28 CRP (r=0.261, p=0.044, r=0.280, p=0.029, r=0.409, p=0.001 and r=0.421, p=0.001, respectively). The serum matrix metalloproteinase-3 level was also significantly and positively correlated with the serum FGF23 level (r=0.331, p=0.015). Concentrations of type I collagen cross-linked N-telopeptide in the serum was significantly correlated with the serum FGF23 level (r=0.272, p=0.034). Neither the bone mineral density in the femoral neck nor lumbar was significantly correlated with the serum FGF23 level. Serum phosphate, calcium, 25-hydroxy vitamin D, and intact parathyroid hormone were not related to the serum FGF23 level. Conclusion In patients with RA, serum FGF23 is correlated with inflammation, the disease activity of RA, and bone absorption markers. Serum FGF23 may be associated with abnormal bone absorption related to RA inflammation. Further studies are necessary to clarify the mechanism underlying this association.

Changes in serum vitamin D and PTH values using denosumab with or without bisphosphonate pre-treatment in osteoporotic patients: a short-term study.

BackgroundDenosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor kappa-β ligand (RANKL). Previous reports have shown that denosumab treatment of osteoporotic patients decreases bone resorption and fracture risk, but there have been no clinical studies on changes in bone turnover markers, 1,25(OH)2D3, or parathyroid hormone (PTH) in denosumab therapy with or without bisphosphonate (BP) pre-treatment in Japan.MethodsHere, we report such findings in 22 patients (11 in the denosumab alone group and 11 in the BP pre-treated group) with osteoporosis following 4 months of treatment. Bone metabolism had been inhibited by prior BP administration in the BP pre-treated group.ResultsThe bone resorption markers serum tartrate-resistant acid phosphatase type 5b and urinary type I collagen cross-linked N-telopeptide were significantly decreased from baseline values for the entire study period in both groups. The bone formation marker bone alkaline phosphatase was significantly decreased at 4 months in the denosumab alone group only, and N-terminal propeptide of type 1 procollagen was significantly decreased at 2 and 4 months in the denosumab alone group versus no remarkable change in the BP pre-treated group. In the denosumab alone group, 1,25(OH)2D3 and PTH were significantly increased at 1 week and decreased gradually thereafter, but these did not change notably in the BP pre-treated group.ConclusionsOur results suggest that treatment with denosumab causes a strong inhibitory effect on bone resorption markers and mild inhibitory effect on bone formation markers. 1,25(OH)2D3 and PTH were significantly increased by denosumab but these did not change in the BP pre-treated group.Trial registrationCurrent Controlled Trials NCT02156960. Registered 31 May 2014.

Changes in the plasma levels of several bone markers in newborn calves during the first two days of life.

The fluctuations in the plasma levels of several bone markers were investigated in newborn calves. Experiment 1 monitored the postnatal changes in the plasma levels of tartrate-resistant acid phosphatase isoform 5b (TRAP5b), total alkaline phosphatase (t-ALP) and bone-specific alkaline phosphatase (BAP) in four calves. These markers increased significantly from 9−20 hr after the first colostrum-suckling compared with the values immediately after birth. Experiment 2 evaluated changes in the plasma TRAP5b, t-ALP, BAP and type I collagen cross-linked N-telopeptide (NTx) levels within 2 days post-birth in five calves with successful passive immunization via colostrum (non-deficient group) and five others with poor colostrum intake (deficient group). The non-deficient group had significantly higher plasma levels of the four parameters around 12 hr of life compared with the deficient group. The results suggest that the increase in plasma bone markers in calves in the first day of life is related to the colostrum intake.