N-terminal Telopeptide Of Type Research Articles

S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation.

Osteoarthritis (OA) is a chronic degenerative disease leading to articular cartilage destruction. Menopausal and postmenopausal women are susceptible to both OA and osteoporosis. S-equol, a soy isoflavone-derived molecule, is known to reduce osteoporosis in estrogen-deficient mice, but its role in OA remains unknown. This study aimed to explore the effect of S-equol on different degrees of menopausal OA in female Sprague-Dawley (SD) rats induced by estrogen deficiency caused by bilateral ovariectomy (OVX) combined with intra-articular injection of mono-iodoacetate (MIA). Knee joint histopathological change; serum biomarkers of bone turnover, including N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX-I) and N-terminal telopeptide of type I collagen (NTX-I); the cartilage degradation biomarkers hyaluronic acid (HA) and N-terminal propeptide of type II procollagen (PIINP); and the matrix-degrading enzymes matrix metalloproteinases (MMP)-1, MMP-3 and MMP-13, as well as the oxidative stress-inducing molecules nitric oxide (NO) and hydrogen peroxide (H2O2), were assessed for evaluation of OA progression after S-equol supplementation for 8 weeks. The results showed that OVX without or with MIA injection induced various severity levels of menopausal OA by increasing pathological damage, oxidative stress, and cartilage matrix degradation to various degrees. Moreover, S-equol supplementation could significantly reduce these increased biomarkers in different severity levels of OA. This indicates that S-equol can lessen menopausal OA progression by reducing oxidative stress and the matrix-degrading enzymes involved in cartilage degradation.

High-dose vitamin D to attenuate bone loss in patients with prostate cancer on androgen deprivation therapy: A phase 2 RCT.

Androgen deprivation therapy (ADT) inhibits prostate cancer growth. However, ADT causes loss of bone mineral density (BMD) and an increase in fracture risk; effective interventions for ADT-induced bone loss are limited. A phase 2 randomized controlled trial investigated the feasibility, safety, and preliminary efficacy of high-dose weekly vitamin D (HDVD, 50,000 IU/week) versus placebo for 24 weeks in patients with prostate cancer receiving ADT, with all subjects receiving 600 IU/day vitamin D and 1000 mg/day calcium. Participants were ≥60 years (mean years, 67.7), had a serum 25-hydroxyvitamin D level <32 ng/mL, and initiated ADT within the previous 6 months. At baseline and after intervention, dual-energy x-ray absorptiometry was used to assess BMD, and levels of bone cell, bone formation, and resorption were measured. The HDVD group (N=29) lost 1.5% BMD at the total hip vs. 4.1% for the low-dose group (N=30; p=.03) and 1.7% BMD at the femoral neck vs. 4.4% in the low-dose group (p=.06). Stratified analyses showed that, for those with baseline 25-hydroxyvitamin D level <27 ng/mL, the HDVD group lost 2.3% BMD at the total hip vs 7.1% for the low-dose group (p<.01). Those in the HDVD arm showed significant changes in parathyroid hormone (p<.01), osteoprotegerin (p<0.01), N-terminal telopeptide of type 1 collagen (p<0.01) and C-terminal telopeptide of type 1 collagen (p<0.01). No difference in adverse events or toxicity was noted between the groups. HDVD supplementation significantly reduced hip and femoral neck BMD loss, especially for patients with low baseline serum 25-hydroxyvitamin D levels, although demonstrating safety and feasibility in prostate cancer patients on ADT.

Actigraphic sleep patterns are associated with bone turnover and bone mineral density among university students.

Poorer sleep is associated with poorer bone health among older adults but the role of sleep in bone health during younger adulthood is understudied. In this observational study, the averages and variability in total sleep time (TST), sleep efficiency (SE), and sleep midpoint of university students were examined in relation to levels of bone turnover markers (BTMs) and bone mineral density (BMD) at the lumbar spine and femur. A sample of healthy, university students (N = 59, aged 18-25 years, 51.8% female, body mass index <30 kg/m2 ), wore a wrist actigraph for 7 days, completed a dual-energy X-ray absorptiometry scan, and underwent blood sampling to assess serum BTM concentrations of osteocalcin (OC) and N-terminal telopeptide of type 1 collagen. A sub-sample (n = 14) completed a one-year follow-up. Multiple regression models examined the associations between each sleep metric and bone health outcome at baseline and 1-year follow-up. At baseline, greater variability in sleep midpoint was cross-sectionally associated with greater OC (β = 0.21, p = 0.042). In the exploratory, follow-up sub-sample, lower average TST (β = -0.66, p = 0.013) and SE (β = -0.68, p = 0.01) at baseline were associated with greater increases in OC at follow-up. Greater delays in mean sleep midpoint over follow-up were significantly associated with decreases in lumbar spine BMD (β = -0.49, p = 0.03). In a sample of young adults, variable sleep schedules were associated with greater bone turnover suggesting the potential importance of regular sleep for optimising bone health into early adulthood.

The skeletal safety of milk-derived proteins: A meta-analysis of randomized controlled trials.

There has been a persistent claim that dairy products contain calcium-leaching proteins, although the soundness of such a claim has been challenged. A meta-analysis of randomized controlled trials (RCTs) on the effects of milk-derived protein supplementation on bone health indices in adults was performed to reconcile the controversy surrounding the potential skeletal safety concerns of proteins of dairy origin. The PubMed and Web of Science databases were searched for relevant RCTs. A random-effects model was used to generate pooled effect sizes and 95% confidence intervals. Milk-derived protein supplementation did not significantly affect whole-body BMD (n = 7 RCTs) and BMD at the lumbar spine (n = 10), hip (n = 8), femoral neck (n = 9), trochanter (n = 5), intertrochanter (n = 2), and ultradistal radius (n = 2). The concentrations of bone formation markers (bone-specific alkaline phosphatase [n = 11], osteocalcin [n = 6], procollagen type 1 amino-terminal propeptide [n = 5]), bone resorption markers (N-terminal telopeptide of type 1 collagen [n = 7], C-terminal telopeptide of type 1 collagen [n = 7], deoxypyridinoline [n = 4]), and parathyroid hormone (n = 7) were not significantly affected. However, increased insulin-like growth factor-1 (IGF-1) concentrations (n = 13) were observed. Reduced IGF-1 concentrations were observed when soy protein was used as a comparator, and increased IGF-1 concentrations were observed when carbohydrate was used. Our findings do not support the claim that proteins of dairy origin are detrimental to bone health.

A longitudinal observational study of skeletal development between ages 3 mo and 6 y in children fed human milk, milk formula, or soy formula

BackgroundEarly infant feeding can affect skeletal development. Most children are fed with breast milk, dairy-based infant formula, or soy-based infant formula during the first year of life. The National Health and Nutrition Examination Survey 2003–2010 reports that 12% of the US infants consume soy-based infant formula. Despite potential effects of soy-associated isoflavones on skeletal development, studies investigating bone metabolism and structural and functional bone indices in children are lacking. ObjectiveThe aim of this observational study was to investigate early effects of soy-based infant formula (SF group) intake on bone metabolism and structure during the first 6 y of life comparing with those of infants fed with breast milk (BF group) and dairy-based infant formula (MF group). MethodsA total of 433 healthy infants were followed up from 3 mo to 6 y of age. Children’s skeletal development was assessed using dual-energy X-ray absorptiometry (DXA; N = 433) and peripheral quantitative computed tomography (pQCT; n = 78). The urinary biomarkers of bone metabolism (N-terminal telopeptide of type I collagen [NTx] and osteocalcin) were evaluated using immunoassays at 6, 24, 60, and 72 mo. ResultsNo statistically significant group differences were observed in bone mineral density (BMD) between the BF, MF, and SF groups, assessed using DXA or pQCT. At 6 y of age, children in the SF group showed significantly greater whole-body bone mineral content measured using DXA than those in the MF group. Six-month-old boys in the SF group demonstrated significantly greater levels of NTx than those in the MF group and significantly greater osteocalcin levels than those in the BF group. ConclusionsTogether, these data suggest that although infants at age 6 mo in the SF group showed some enhanced bone metabolism compared with those in the BF and MF groups, as indicated by the urinary biomarkers, no differences in bone metabolism or BMD were noted between ages 2 and 6 y.This trial was registered at clinicaltrials.gov as NCT00616395.

Gujiansan Ameliorates Avascular Necrosis of the Femoral Head by Regulating Autophagy via the HIF-1α/BNIP3 Pathway.

Background Clinically, the traditional Chinese medicine compound Gujiansan has been widely used in the treatment of steroid-induced avascular necrosis of the femoral head (SANFH). The present study aimed to investigate the mechanisms underlying the therapeutic effect of Gujiansan. Methods A rat model of SANFH was established by the injection of dexamethasone (DEX) at a high dosage of 25 mg/kg/d. Then, Gujiansan was intragastrically administered for 2 weeks, 4 weeks, and 8 weeks, and histological examination of the femoral head was performed. The expression levels of related mRNAs and proteins were analyzed by qRT-PCR, Western blotting, and immunohistochemistry, and the levels of bone biochemical markers and cytokines were detected with ELISA kits. Results Gujiansan administration ameliorated SANFH and induced the expression of hypoxia-inducible factor-1α (HIF-1α), Bcl-2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), LC3, and Beclin-1 in the rat model in a dose- and time-dependent manner, and Gujiansan promoted osteocalcin secretion at the femoral head. In addition, Gujiansan increased the levels of bone formation- and bone resorption-specific markers (osteocalcin (OC), bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase-5b (TRACP-5b), N-terminal telopeptides of type I collagen (NTX-1), and C-terminal telopeptide of type I collagen (CTX-1)) and decreased the levels of proinflammatory cytokines (TNF-α, IL-6, and CRP) in a dose- and time-dependent manner. Conclusions Gujiansan accelerates the formation of a new bone, promotes the absorption of the damaged bone, inhibits the inflammatory response, induces autophagy of the femoral head via the HIF-1α/BNIP3 pathway, and ultimately ameliorates SANFH.

Assessment of Clinical Utility of Assaying FGF-23, Klotho Protein, Osteocalcin, NTX, and Sclerostin in Patients with Primary Hyperparathyroidism.

The purpose of this study was to assess the clinical usefulness of assaying the fibroblast growth factor (FGF-23), Klotho, osteocalcin, N-terminal telopeptide of type I collagen (NTX), and sclerostin levels in patients with primary hyperparathyroidism (PHPT) as markers of bone damage as well as for surgical treatment success. Seventeen patients with hypercalcemic PHPT and normal kidney function were studied. In all patients, PTH (parathormone), serum calcium, and creatinine were performed before and six months after parathyroidectomy (PTX). The studied group included patients whose PTH and calcium concentrations normalized post-operatively and with confirmed histopathological diagnosis. The control group consisted of nine age-matched healthy volunteers. The PHPT patients had elevated concentrations of FGF-23, osteocalcin, and NTX and reduced levels of sclerostin, as compared to the control group. After PTX, osteocalcin, NTX, and sclerostin levels normalized. The plasma values of FGF-23 decreased significantly, but remained higher than in healthy subjects. Serum Klotho protein levels did not differ significantly in the two groups. These results suggest that osteocalcin and NTX may potentially be considered as markers of PHPT progression. Additionally, serum normalization of osteocalcin, NTX, and sclerostin might be considered as indicators of PTX success. On the other hand, FGF-23 can represent a parameter reflecting the degree of calcium–phosphate imbalance in PHPT patients, but its usefulness in monitoring the effects of PTX requires further research. The clinical utility of assaying Klotho in PHPT remains to be confirmed.

Bone turnover and mineral metabolism in adult patients with hypophosphatasia treated with asfotase alfa

SummaryThere is limited understanding of how asfotase alfa affects mineral metabolism and bone turnover in adults with pediatric-onset hypophosphatasia. This study showed that adults with hypophosphatasia treated with asfotase alfa experienced significant changes in biochemical markers of bone and mineral metabolism, possibly reflecting enhanced bone remodeling of previously osteomalacic bone.IntroductionHypophosphatasia (HPP), due to a tissue nonspecific alkaline phosphatase (TNSALP) deficiency, can cause impaired bone mineralization and turnover. Although HPP may be treated with asfotase alfa, an enzyme replacement therapy, limited data are available on how treatment with asfotase alfa affects mineral metabolism and bone turnover in adults with HPP.MethodsALP substrates, bone turnover and mineral metabolism markers, and bone mineral density (BMD) data from EmPATHY, a single-center, observational study of adults (≥ 18 years) with pediatric-onset HPP treated with asfotase alfa (NCT03418389), were collected during routine clinical care and analyzed from baseline through 24 months of treatment.ResultsData from 21 patients showed significantly increased ALP activity and reduced urine phosphoethanolamine (PEA)/creatinine (Cr) ratios after baseline through 24 months of asfotase alfa treatment. There were significant transient increases in parathyroid hormone 1-84 (PTH), osteocalcin, and procollagen type 1 N-propeptide (P1NP) levels at 3 and 6 months and in tartrate-resistant acid phosphatase 5b (TRAP5b) levels at 3 months, with a significant decrease in N-terminal telopeptide of type 1 collagen (NTX) levels at 24 months. Lumbar spine BMD T scores continuously increased during treatment.ConclusionSignificant changes in bone turnover and mineral metabolism markers after asfotase alfa treatment suggest that treatment-mediated mineralization may enable remodeling and bone turnover on previously unmineralized surfaces. Urine PEA/Cr ratios may be a useful parameter in monitoring treatment during routine care.

Serum N-terminal telopeptide of type I collagen as a biomarker for predicting bone density loss in patients with Crohn disease.

The serum N-terminal telopeptide of type I collagen (NTx) is significantly higher in patients with Crohn disease (CD) than in healthy individuals and patients with ulcerative colitis. This study aimed to investigate whether an elevated serum NTx level is a risk predictor of osteoporosis in patients with CD. Based on whether the femoral Z-score decreased over a 2-year period, 41 CD patients were divided into the ΔZ-score <0 group (Z-score decreased) and the ΔZ-score ≥0 group (Z-score did not decrease). The risk predictors of a femoral Z-score decrease were examined. Furthermore, we investigated the correlations between the ΔZ-score (which represents the change in the Z-score over a 2-year period) and the mean levels of biomarkers, including the Crohn Disease Activity Index (CDAI), serum albumin, C-reactive protein, and bone metabolism markers (including NTx) measured initially (i.e., in our previous study) and 2 years later (present study). The relationships between anti-tumor necrosis factor α (anti-TNF-α) therapy and serum NTx levels were also examined. Although there was no correlation between the mean CDAI and the ΔZ-score, the mean serum NTx and albumin levels were significantly correlated with the ΔZ-score (P<0.01 and P = 0.02, respectively). Furthermore, the femoral Z-score tended to be lower in the anti-TNF-α administration group than in the non-administration group. These observations indicated that an elevated serum NTx could be a useful marker for predicting a decrease in the femoral bone mineral density in CD patients. Anti-TNF-α therapy maintained an elevated serum NTx level, suggesting that treatment with anti-TNF-α may help control increased bone resorption in CD patients.

Disrupted Sleep Architecture Is Associated With Incident Bone Loss in Indian Postmenopausal Women: A Prospective Study.

Inadequate sleep has been shown to be detrimental to several body systems, including the bone. We proposed to study the impact of insomnia on bone health in Indian postmenopausal women. In a 2-year prospective study, ambulant community-dwelling postmenopausal women aged >50 years were recruited through simple random sampling. Sleep duration was recorded based on self-reported sleep duration and sleep quality using the Women's Health Initiative Insomnia Rating Scale (WHIIRS). Anthropometry, bone biochemistry including bone turnover markers (C-terminal telopeptide of type 1 collagen [CTX], N-terminal telopeptide of type 1 pro-collagen [P1NP]), bone mineral density (BMD), and trabecular bone score (TBS) were assessed at baseline and at the end of 2 years. Among 190 postmenopausal women with mean (SD) age of 58.2 (6.9) years, 65/190 (34.2%) had insomnia (WHIIRS ≥ 9) and 20/190 (10.5%) developed osteoporosis at any site on follow-up. The percentage decline over 2 years in BMD in women with insomnia was significantly (p < 0.001) higher at femoral neck (2.9 [1.6] versus 1.2 [1.2]%) and lumbar spine (4.5 [2.0] versus 1.6 [1.1]%). The decrement in TBS was also significantly higher (p < 0.001) in women with suboptimal sleep (1.5 [2.1] versus 0.5 [1.0] %) when compared with those with adequate sleep. The increment in CTX (46.4 [32.2] versus 18.9 [26.4]) and decrement in P1NP (35.4 [9.1] versus 16.7 [18.9]), respectively, were also greater (p < 0.001) in women with insomnia compared with those without. On multivariate analysis, insomnia was the sole factor that was predictive (adjusted odds ratio [OR]= 9.3; 95% confidence interval [CI] 2.9-29.6; p < 0.001) of incident osteoporosis. In conclusion, poor sleep quality was associated with incident osteoporosis in Indian postmenopausal women. Optimal sleep may help to retard ongoing bone loss that results from sleep deprivation and requires further research. © 2022 American Society for Bone and Mineral Research (ASBMR).

Icariin Accelerates Fracture Healing via Activation of the WNT1/β-catenin Osteogenic Signaling Pathway.

Icariin has been shown to enhance bone formation. The present study aimed to investigate whether icariin also promotes bone fracture healing and its mechanisms. First, we isolated and cultured rat bone marrow stromal cells (rBMSCs) with icariincontaining serum at various concentrations (0%, 2.5%, 5% and 10%) and then measured alkaline phosphatase (ALP) activity and the expression of Core-binding factor, alpha 1 (Cbfα1), bone morphogenetic protein-2 (BMP-2) and bone morphogenetic protein-4 (BMP-4) in the rBMSCs. Second, we established a model of fracture healing in rats and performed gavage treatment for 20 days. Then, we detected bone biochemical markers (ELISA kits) in the serum, fracture healing (digital radiography, DR), and osteocalcin expression (immunohistochemistry). Icariin treatment increased ALP activity and induced the expression of Cbfα1, BMP-2 and BMP-4 in rBMSCs in a dose-dependent manner. In addition, Icariin increased the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), N-terminal telopeptides of type I collagen (NTX-1), C-terminal telopeptide of type I collagen (CTX-1) and tartrate-resistant acid phosphatase 5b (TRACP-5b); promoted osteocalcin secretion at the fracture site; and accelerated fracture healing. Icariin can promote the levels of bone-formation markers, accelerate fracture healing, and activate the WNT1/β-catenin osteogenic signaling pathway.

Relationship between GDF15 level and bone metabolism in postmenopausal Chinese women

Background: Growth differentiation factor 15 (GDF15), is a newly identified member of the transforming growth factor-beta (TGF-β) family. It circulates as a 24.5-kDa homodimer. However, the function of GDF15 in bone metabolism remains unclear. In this study, we investigated the function of GDF15 in postmenopausal Chinese women.Methods: We measured serum GDF15 levels, bone mineral density (BMD), and bone turnover markers in 201 postmenopausal Chinese women ranging in age from 47 to 80 years.Results: The concentration of serum GDF15 increased with age. Growth differentiation factor 15 levels displayed a negative correlation with lumbar spine, femoral neck, and total hip BMD. After adjusting for age, this association still existed and was significant. We identified age, GDF15, body mass index (BMI), and estradiol to be associated with BMD. Furthermore, we found that GDF15 levels had a significant negative relationship with bone alkaline phosphatase (BAP) levels; this relationship remained significant after adjustment. However, there was no significant correlation between levels of GDF15 and N-terminal telopeptide of type I collagen (NTX).Conclusions: For postmenopausal Chinese women, GDF15 is a negative predictor of BMD and has a negative correlation with bone formation biomarker BAP. In other words, GDF15 exerts negative regulation on bone mass by inhibiting bone formation.

Prevalence of Non-Responders to Both Oral Bisphosphonate Monotherapy and Intravenous Ibandronate in Patients with Postmenopausal Osteoporosis

Objectives: Although bisphosphonates (BPs) are effective for the majority of patients with osteoporosis, some individuals do not adequately respond to these drugs. The objective of this study was to estimate the prevalence of true BP non-responders who showed insufficient response after both oral BPs and intravenous ibandronate. Methods: Among 146 consecutive patients with postmenopausal osteoporosis who received oral BP monotherapy for more than 12 months, insufficient responders to oral BP monotherapy were switched to intravenous ibandronate injection and followed for more than 12 months. Serum N-terminal telopeptide of type I collagen (NTX) and bone alkaline phosphatase (BAP) concentrations were measured. Patients who also showed insufficient response to intravenous ibandronate were defined as true BP non-responders. Insufficient response to BP therapy was evaluated based on the serum NTX reduction cut-off for minimum significant change. Results: Sixty-one patients (41.8%) were diagnosed as oral BP non-responders. Fourteen patients who switched to intravenous ibandronate and had complete data available were used for final analysis. After switching to intravenous ibandronate, both NTX and BAP decreased significantly (p < 0.05). However, at 6 - 12 months after switching, 57.1% - 64.3% of patients still showed insufficient response of NTX as compared to baseline (before oral BP monotherapy), and 21.4% - 35.7% of patients still showed insufficient response of NTX when compared to data immediately before switching. Conclusion: These results estimated that as few as 9% - 15% (i.e., 21.4% - 35.7% of 41.8%) or as many as 24% - 27% (i.e., 57.1% - 64.3% of 41.8%) of patents might be true BP non-responders.

Effects of vitamin D2-fortified shiitake mushroom on bioavailability and bone structure.

Bioavailability and bone loss inhibitory effects of vitamin D2 derived from UV-irradiated shiitake mushroom were determined in vivo. The effect of the absence of ovaries on the bioavailability of vitamin D2 and bone structure was also investigated. Sham operated (sham) and ovariectomized (OVX) rats were divided in 3 groups according to their diets, i.e. control: only vitamin D-deficient diets; UV(X): vitamin D-deficient diets with non-irradiated mushroom powder; UV(O): vitamin D-deficient diets with irradiated mushroom powder. The obtained results showed that vitamin D2 from shiitake mushroom was able to increase bone mineral density and trabecular bone structure of femur bone as well as its bioavailability. The absence of estrogen induced adverse effects not only on bioavailability of vitamin D2 but also on trabecular bone. In conclusion, vitamin D2-fortified shiitake mushroom might help postmenopausal women increase vitamin D2 bioavailability and retard trabecular bone loss. Abbreviations: OVX: ovariectomized; 25(OH)D: 25-hydroxyvitamin D; 1,25(OH)2D: 1,25-dihydroxyvitamin D; BMD: bone mineral density; micro-CT: micro computed tomography; RSM: response surface methodology; RP-HPLC: Reverse phase-high performance liquid chromatography; MS/MS: tandem mass spectrometry; E2: estradiol; NTx: N-terminal telopeptide of type I collagen; BV/TV: bone volume/total volume; BS/BV: bone surface/bone volume; Tb.Th: trabecular thickness; Tb.Sp: trabecular separation.

Efficacy of 4-year denosumab treatment alone or in combination with teriparatide in Japanese postmenopausal osteoporotic women

Purpose: This extended randomized prospective study aimed to compare the 4-year clinical outcomes of denosumab treatment alone or in combination with teriparatide in treatment-naïve postmenopausal Japanese patients with osteoporosis.Methods: Between July 2013 and December 2016, 30 eligible women from our previous study were enrolled. After newly adding 17 randomly assigned patients, 47 patients were classified into the denosumab alone group (denosumab group, n = 22) or denosumab plus teriparatide group (combination group, n = 25). Serum bone-specific alkaline phosphatase (BAP), serum tartrate-resistant acid phosphatase (TRACP)-5b, urinary cross-linked N-terminal telopeptide of type I collagen (NTX), and bone mineral density (BMD) of the lumbar 1–4 vertebrae (L-BMD) and bilateral total hips (H-BMD) were determined at the first visit and at regular time points up to 48 months of treatment to determine percentage changes.Results: BAP was significantly decreased from baseline in both groups from 24 to 48 months, with significant differences at all time points between the groups. TRACP-5b and urinary NTX were comparably decreased at every time point in both groups versus pretreatment levels. L-BMD was significantly more increased by combination therapy over denosumab alone at 24 and 30 months (21.1% increase vs. 14.2% increase at 48 months). There were no significant differences in H-BMD between the groups, although levels tended to be higher in the combination group throughout the study period (9.7% increase vs. 6.8% increase at 48 months).Conclusion: Long-term denosumab and teriparatide combination therapy represents an effective treatment option for primary osteoporosis patients with low L-BMD.

CD109 deficiency induces osteopenia with an osteoporosis-like phenotype in vivo.

Osteoporosis is a global public health problem that is increasing along with an aging population. A major determinant of osteoporosis is high bone turnover, which results from osteoclast activation. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, a deficiency that leads to a psoriasis-like skin inflammation in mice. Although the expression of CD109 has been reported in mouse pre-osteoclast cells, its function in osteoclasts in vivo remains largely unknown. To investigate the physiological role of CD109 in bone metabolism, we analyzed bones from wild-type and CD109-deficient adult mice. Micro-computed tomography analysis of the femur (thigh bone) showed that bone volume was lower in CD109-deficient mice than in wild-type mice. Bone histomorphometric analysis showed not only a reduction in bone volume but also an increase in bone turnover in CD109-deficient mice as compared with wild-type mice. Additionally, we measured serum levels of several markers of bone turnover and found a significant increase in the N-terminal telopeptide of type I collagen, a bone resorption marker, as well as alkaline phosphatase, a bone formation marker, in CD109-deficient mice. These results indicate that CD109 deficiency induces a high-turnover, osteoporosis-like phenotype, which suggests that CD109 plays a role in bone metabolism in vivo.

Yi Shen Juan Bi Pill Ameliorates Bone Loss and Destruction Induced by Arthritis Through Modulating the Balance of Cytokines Released by Different Subpopulations of T Cells.

The Yi Shen Juan Bi Pill (YSJB), a traditional Chinese compound herbal drug, has been used as an anti-rheumatic drug in clinical practice. Cartilage and bone destruction of inflamed joints is the hallmark of rheumatoid arthritis (RA). Our previous study suggested that YSJB had a protective effect on joint damage in collagen-induced (CIA) rats. However, the role and the mechanism of YSJB in inflammation-induced bone loss are unavailable. The current study aimed to further evaluate the effect of YSJB on the joint destruction and the systemic bone loss, and to clarify the potential mechanism. CIA model was generated by using collagen II and incomplete Freund's adjuvant in Sprague-Dawley rats. After 4 weeks treatment, arthritic index, tissue pathology, micro-computed tomography scanning (μ-CT), and bone mineral density (BMD) analysis were performed. YSJB decreased arthritic scores and bone destruction; improved the BMD of lumbar vertebrae and bone volume fraction of inflamed joints. Moreover, YSJB significantly decreased the production of serum bone resorption markers, including Tartrate-Resistant Acid Phosphatase (TRACP), N-terminal telopeptide of type I collagen and C-terminal telopeptide of type I collagen. Meanwhile, it increased the level of serum bone formation marker type I collagen N-terminal propeptide. These results revealed that YSJB ameliorated bone destruction and reduced bone loss induced by arthritis. We have previously showed that Tregs inhibited osteoclast differentiation and bone resorption in vitro. Furthermore, others suggested that abnormality of Th1, Th17 may contribute to bone destruction. Here, we showed YSJB significantly up-regulated the percentage of Tregs, while also down-regulated the percentage of Th1 and Th17 cells. Our findings provide the evidence that YSJB ameliorates the severity of disease and joint degradation, and reduces systemic bone loss induced by arthritis. We propose YSJB modulates the balance of T cell phenotype, which affects the activation and differentiation of osteoclasts.

Bone turnover markers are associated with bone density, but not with fracture in end stage kidney disease: a cross-sectional study

BackgroundFracture risk is increased in chronic kidney disease (CKD), but assessment of bone fragility remains controversial in these patients. This study investigated the associations between bone turnover markers, bone mineral density (BMD), and prevalent fragility fracture in a cohort of kidney transplantation candidates.MethodsVolumetric BMD of spine and hip was measured by quantitative computed tomography. Parathyroid hormone (PTH), bone-specific alkaline phosphatase, procollagen type-1 N-terminal propeptide, tartrate resistant alkaline phosphatase, and C- and N-terminal telopeptides of type 1 collagen were analyzed from fasting morning blood samples. Fragility fractures included prevalent vertebral fractures and previous low-trauma clinical fractures.ResultsThe fracture prevalence was 18% in 157 adult kidney transplant candidates. Fractured patients had reduced BMD and Z-score at both spine and hip. Levels of bone turnover markers were significantly higher in patients on maintenance dialysis than in pre-dialysis patients; but did not differ between patients with and without fracture. There were strong, positive correlations between PTH and all bone turnover markers. PTH was negatively associated with Z-score at lumbar spine and total hip; in contrast, bone turnover markers were only negatively associated with total hip Z-score.ConclusionsBone turnover markers were negatively associated with bone density, but not associated with prevalent fracture in kidney transplantation candidates. The role of bone turnover markers in assessing bone fragility in CKD will require further investigation.Trial registrationThis study was registered at ClinicalTrials.gov with identifier NCT01344434.

Comparative effects of brown and golden flaxseeds on body composition, inflammation and bone remodelling biomarkers in perimenopausal overweight women

Flaxseed may improve the adverse effects of the lack of oestrogens. This study compared the effects of brown and golden flaxseed intake on body composition, inflammation and bone biomarkers in overweight perimenopausal women. The participants were divided into groups: control, brown, and golden flaxseed and received a calorie-restricted diet plan of 250kcal per day. The brown and golden flaxseed groups consumed 40g of the respective flaxseed per day for 12weeks. Both flaxseeds reduced waist circumference, but the golden flaxseed also reduced body weight, body mass index, and fat mass. Flaxseed supplementation, irrespective to the variety, had no significant effect on pro-inflammatory (TNF-α, IL-1β, and IL-6) and anti-inflammatory (IL-10) biomarkers, hormones (25(OH)D3 and 17β-oestradiol) or on the bone formation (osteocalcin) and resorption (N-terminal telopeptide of type I collagen - NTX-I) biomarkers. Brown flaxseed was less effective than the golden flaxseed in modifying body composition of perimenopausal women.

N-terminal telopeptides of type I collagen and bone mineral density for early diagnosis of nonunion: An experimental study in rabbits.

Background:The diagnosis and treatment of bone nonunion have been studied extensively. Diagnosis and treatment of nonunion are mainly performed based on the interpretation of clinico-radiographic findings, which depend on the clinician's experience and the degree of bone callus formation during the fracture-healing process. However, resolution may be compromised when the bone mineral content is <25%. A feasible method of monitoring bone-healing is therefore needed. We monitored a rabbit model of bone nonunion by regular radiographic examinations, QCT detection, and biomarker concentrations.Materials and Methods:Twenty purebred New Zealand rabbits (10 male and 10 female, 5–6 months of age, 2.5–3.0 kg) were divided into bone defect Group (I) that 10 left radius bones underwent resection of 1.5 cm of mid-radius bone and bone fracture Group (II) that another 10 left radius bones underwent only mid-radius fracture. Quantitative computed tomography detection of bone mineral density (BMD) and serum markers of bone formation (osteocalcin [OC], bone-specific alkaline phosphatase) and bone resorption (C- and N-terminal telopeptides of type I collagen (NTX) and tartrate-resistant acid phosphatase 5b) were assayed. There are twenty rabbits (10 male and 10 females). The age was 5–6 months weighing 2.5–3.0 kg). The defect was created in middle 1/3 radius in 10 rabbits and fracture was created in middle 1/3 radius of 10 rabbits.Results:BMD and NTX concentrations were significantly lower at 5 weeks postoperatively compared to the preoperative values and were significantly different between the two groups. OC showed no significant difference before and after surgery.Conclusions:BMD and NTX concentrations may be useful for early detection of bone nonunion in rabbits.