Telopeptide Of Type Research Articles

706-P: Recreational Soccer Training as a Tool Activity to Prevent Bone Issues in Type 2 Diabetes Patients

Bone formation is suppressed in the diabetic state, being the osteoporotic fractures a serious co-morbidity and complication of diabetes. A better lifestyle with proper diet and exercise have been linked to delay the progression of diabetes and may improve bone metabolism. With diabetes negatively affecting bone health we evaluated the impact of diet and exercise on serum bone markers, hormones and densitometry. This study assessed effects of twelve weeks of recreational soccer training combined with a caloric restricted diet (SO+D) vs. diet alone (D) in markers of bone health of type 2 diabetes (T2D) patients. Training sessions were performed for 40 min, 3 times per week for 12 weeks. We examined the following baseline and postprandial serum bone markers of formation: procollagen type 1 N-terminal propeptide (P1NP), and osteocalcin (OC); and C-terminal telopeptides of type I collagen (CTX) as bone resorption marker. Bone metabolic hormones such as parathyroid hormone (PTH) and 25-hydroxyvitamin D (25[OH]D) were also measured. Results: Compared to baseline levels, the first soccer session for SO+D induced acute increases of osteocalcin (35.0 ± 14.3 to 48.0 ± 26.3 ng/mL, P<0.05) and CTX remained unchanged. Osteocalcin, P1NP and CTX were lower in the D group (P<0.05). Compared to the D group, SO+D group resulted in increased osteocalcin (P<0.05), while P1NP and CTX levels did not alter. After 12 weeks, bone mineral density increased in both SO+D and D groups (P<0.05) and baseline levels of PTH remained unchanged, whereas 25[OH]D increased only in SO+D group (19.1±1.2 to 22.1 ± 1.4 ng/mL, P<0.05). Diet alone or combined with soccer training improved bone health status among T2D patients elicited by suppression on bone resorption marker and increased bone mineral density. However, recreational soccer training enhanced bone formation marker and vitamin D levels decreasing risk factors associated with osteoporosis and osteoporotic fractures in T2D patients better than diet alone. Disclosure M. Vieira de Sousa: None. M.R. da Silva: None. Funding Fundação de Amparo a Pesquisa do Estado de São Paulo (2012/01400-0)

P1430BETA C-TERMINAL TELOPEPTIDE OF TYPE I COLLAGEN: CORRELATIONS WITH MINERAL METABOLISM PARAMETERS AND CARDIAC VALVULAR CALCIFICATIONS IN A COHORT OF HEAMODIALYSIS PATIENTS

Abstract Background and Aims Beta-carboxyterminal telopeptide of type I collagen (beta-CTx) is considered a marker of bone resorption in patients affected by osteoporosis. Nevertheless, its role in mineral bone disorder (MBD) of CKD patients is not clear. The aim of this study was to explore in a group of haemodialysis patients (HDp): 1) The levels of beta-CTx; 2) The correlation between beta-CTx levels and other mineral metabolism (MM) parameters; 3) The association between beta-CTx and CKD-MBD specific therapy 4) The relation between beta-CTx and cardiac valvular calcifications (VC). Method We studied a group of 21 HDp (F/M 9/12, age 68[54-78] years) randomly selected from the HDp actually followed-up in our Department. Dialysis vintage was 52[23-80] months. All HDp were on a three-weekly hemodialysis schedule, with a prescribed dialysate calcium of 1.5 mmol/l. Before the first dialysis session of the week, after the long interdialytic interval, the levels of beta-CTx, total and ionized calcium (tCa and iCa), Phosphorus (P), Magnesium (Mg), intact PTH (iPTH), total and bone isoform of alkaline phosphatase (tALP and bALP), 25-hydroxyvitamin D (25OHVD), 1,25-dihydroxyvitamin D (1,25OH2VD), and other general biochemical parameters were measured (Figure 1). At the same time, data concerning MM therapies were recorded. In all the studied patients, the presence of VC was searched in the the most recent echocardiographic study. Results Beta-CTx levels showed a significant positive correlation with tALP (r 0.92, p <0.0001), bALP (r 0.89, p <0.0001) and iPTH (r 0.87, p<0.0001) and a negative correlation with tCa (r – 0.43, p=0.05) and iCa (r – 0.52, p=0.01). No significant correlation was found with the other MM and general biochemical parameters and with the general features of the studied cohort. 18 patients (85.7%) were taking P binders (72.2% Ca-based and 27.8% Ca-free). In 20 patients (95.2%) vitamin D therapy, either in the natural, active or both natural and active form (35%, 15% and 50%, respectively) was prescribed. 6 patients (28.6%) were in therapy with Cinacalcet. No difference was found in beta-CTx levels according to the presence and the type of each of the above mentioned therapies. Conclusion Taking into account the limitations of this preliminary small size observational study, our data showed that beta-CTx levels are high in HDp. Beta-CTx correlates with iPTH, tALP and bALP. The negative correlation with tCa and iCa probably might be influenced by the negative correlation between iPTH and serum Calcium. Beta-CTx levels are not associated with CKD-MBD specific therapy or with cardiac valvular calcifications. Further prospective and randomized studies, including a higher number of HDp and possibly bone histology are needed to elucidate the possible role of beta-CTx as a marker of bone disease in HDp.

Symbiotic Effects of Kefir and Yacon Flour (Smallanthus sonchifolius) on Bone Remodeling in Rats

Abstract Objectives Kefir is a natural source of probiotics that confer benefits to the host's intestinal health. Yacon (Smallanthus sonchifolius) is a tuberous root originating in the Andes region, rich in prebiotic fructooligosaccharides (FOS), which increases the absorption of minerals. The objective of this study was to evaluate the prebiotic properties of yacon, the probiotic effect of kefir and the symbiotic action of the association between them in bone health in rats. Methods Adult Wistar rats were divided into 4 groups (n = 10): Group C (Control), Y (yacon flour, 51.34% FOS) K (kefir, 10⁷ UFC/mL), and YK (yacon flour + kefir). Group C received AIN-93 M + cow's milk (1 mL/day), group Y received AIN93 diet added by yacon flour to provide 5% FOS + cow's milk, group K received fermented kefir (1 mL/day), and group YK received yacon flour + fermented kefir. Feces and urine were collected for calcium balance in the last week of the experiment. At the end of 6 weeks, the animals were euthanized and the large intestine and blood sample were collected for analysis of intraluminal pH (pH meter Kasvi®) and biomarkers of bone remodeling, respectively. Calcium from diet, feces and urine was analyzed by atomic absorption. Osteocalcin (OC -- EL-R0243), C telopeptide of type I collagen (CTX – EL-R1456) and N telopeptide of type I collagen (NTX – EL-R0276) were analyzed by ELISA, according to manufacture's instructions (Elabscience, TX, USA). The results were analyzed by ANOVA, followed by the Tukey test (p < 0.05), using GENES®. Results No significant differences were observed between groups concerning calcium balance and cecal pH, although pH was slightly lower in the groups fed yacon (Y and YK). Biomarkers of bone formation (OC) and bone resorption (CTX and NTX) were significantly lower in group K (OC = 7.29; CTX = 4.04; NTX = 94.31 ng/mL), compared to the control (OC = 16.33; CTX = 5.68; NTX = 105.97 ng/mL). Groups Y (OC = 13.63; CTX = 5.13; NTX = 114.34 ng/mL) and YK (OC = 15.37; CTX = 5.17; NTX = 132.51 ng/mL) did not differ from the control. Conclusions Prebiotic (Y) and Symbiotic (YK) were more effective than kefir in bone remodeling in rats, although fermentation in the large gut did not reduce pH sufficiently to improve calcium absorption and retention. Funding Sources FAPES; CNPq and CAPES/Brazil.

Vegetable and fruit consumption and its association with bone turnover biomarkers in older adults

Purpose Fruits and vegetables (FVs) are a good source of substances that contributed to bone health. However, the relation of FVs consumption with inflammation and bone biomarkers is inconsistent. Thus, this paper aims to assess the association of FVs intake with inflammation and bone biomarkers in older adults. Design/methodology/approach This cross-sectional study was performed on 178 older adults in Tehran, with a mean age of 67.04. Biochemical measurements including serum osteocalcin, high sensitivity c-reactive protein, 25-hydroxyvitamin D 25(OH) D, parathormone and urine terminal telopeptide of Type I collagen (u-CTx) was done. The intake of FVs was calculated using a validated quantitative food frequency questionnaire. Findings Pearson correlation coefficients showed a positive relation between serum osteocalcin and total vegetables (r = 0.167, p = 0.026), juices group (r = 0.155, p = 0.035), starchy vegetables (r = 0.205, p = 0.006) and other vegetable group (r = 0.161, p = 0.032) even after controlling of potential confounders. Analysis of covariance showed that total vegetable were significantly associated with serum osteocalcin (p = 0.041) and PTH levels (p = 0.028). Additionally, no evidence of a significant relationship between total fruit intake and test variables was observed. However, subgroup analyses demonstrated a significant association between citrus fruits and serum 25(OH) D (p = 0.017). A significant relation between starchy vegetable and urine CTx-I was reported (p = 0.016). Moreover, other vegetable subgroup was strongly associated with serum osteocalcin (p = 0.003). Originality/value The results of this paper may provide insight for clinical interventions and also important to make policy for prevention or easing bone disorders and general inflammation related to fruit and vegetable intake.

The Antiosteoporosis Effects of Yishen Bugu Ye Based on Its Regulation on the Differentiation of Osteoblast and Osteoclast.

Yishen Bugu Ye (YSBGY), a traditional Chinese medicine comprising 12 types of medicinal herbs, is often prescribed in China to increase bone strength. In this study, the antiosteoporotic effects of YSBGY were investigated in C57BL/6 mice afflicted with dexamethasone- (Dex-) induced osteoporosis (OP). The results showed that YSBGY reduced the interstitial edema in the liver and kidney of mice with Dex-induced OP. It also increased the number of trabecular bone elements and chondrocytes in the femur, promoted cortical bone thickness and trabecular bone density, and modulated the OP-related indexes in the femur and tibia of OP mice. It also increased the serum concentrations of type I collagen, osteocalcin, osteopontin, bone morphogenetic protein-2, bone morphogenetic protein receptor type 2, C-terminal telopeptide of type I collagen, and runt-related transcription factor-2 and reduced those of tartrate-resistant acid phosphatase 5 and nuclear factor of activated T cells in these mice, suggesting that it improved osteoblast differentiation and suppressed osteoclast differentiation. The anti-inflammatory effect of YSBGY was confirmed by the increase in the serum concentrations of interleukin- (IL-) 33 and the decrease in concentrations of IL-1, IL-7, and tumor necrosis factor-α in OP mice. Furthermore, YSBGY enhanced the serum concentrations of superoxide dismutase and catalase in these mice, indicating that it also exerted antioxidative effects. This is the first study to confirm the antiosteoporotic effects of YSBGY in mice with Dex-induced OP, and it showed that these effects may be related to the YSBGY-induced modulation of the osteoblast/osteoclast balance and serum concentrations of inflammatory factors. These results provide experimental evidence supporting the use of YSBGY for supporting bone formation in the clinical setting.

Can urinary CTX-II be a biomarker for knee osteoarthritis?

BackgroundEarly diagnosis of knee osteoarthritis (OA) remains a diagnostic challenge. Urinary C-terminal cross-linked telopeptide of type II collagen (urinary CTX-II) is one of the potential OA biomarkers. However, conclusive evidence regarding the use of this biomarker as a tool for early diagnosis is still lacking. The purposes of this study were to compare urinary CTX-II levels in patients with knee OA and in healthy controls, to evaluate the correlation between urinary CTX-II levels, radiographic severity of OA, and patient-reported outcomes and to evaluate the effect of age and gender on urinary CTX-II levels in the Asian populations.MethodsTwo groups were studied. The OA group included 78 patients with knee OA aged > 40 years who met the diagnostic criteria for knee OA described by the American College of Rheumatology (ACR). The control group consisted of 51 healthy participants age > 40 years without clinical or radiographic evidence of knee OA. Bilateral knee radiographs were taken and classified according to the Kellgren and Lawrence (KL) grading system. Urinary CTX-II was measured using a competitive ELISA test and Western Ontario and Mcmaster Universities Arthritis Index (WOMAC) was also recorded in all participants.ResultsUrinary CTX-II was significantly higher in the OA group than in the control group (p < 0.001). The severe knee OA group (KL grade 3 and 4) had higher urinary CTX-II levels than mild knee OA group (KL grade 2) but the difference did not reach statistical significance (p = 0.2). There was a moderate correlation between urinary CTX-II levels and KL grades (r = 0.405, p < 0.001) and a weak correlation between urinary CTX-II levels and WOMAC index scores (r = 0.367, p < 0.001). Multiple regression analysis showed that urinary CTX-II was independently associated with KL grades. Whereas age, gender, and WOMAC index had no statistically significant influence on the urinary CTX-II levels.ConclusionsPatients with knee OA had higher urinary CTX-II levels than healthy controls. Moreover, levels of urinary CTX-II were independently correlated with radiographic severity of knee OA. Age, gender, and patient-reported outcomes exerted no effect on the urinary CTX-II levels.Level of evidenceDiagnostic Level III.

Severely restricting energy intake for 24 h does not affect markers of bone metabolism at rest or in response to re-feeding

PurposeIntermittent energy restriction commonly refers to ad libitum energy intake punctuated with 24 h periods of severe energy restriction. This can improve markers of metabolic health but the effects on bone metabolism are unknown. This study assessed how 24 h severe energy restriction and subsequent refeeding affected markers of bone turnover.MethodsIn a randomised order, 16 lean men and women completed 2, 48 h trials over 3 days. On day 1, participants consumed a 24 h diet providing 100% [EB: 9.27 (1.43) MJ] or 25% [ER: 2.33 (0.34) MJ] of estimated energy requirements. On day 2, participants consumed a standardised breakfast (08:00), followed by an ad libitum lunch (12:00) and dinner (19:30). Participants then fasted overnight, returning on day 3. Plasma concentrations of C-terminal telopeptide of type I collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP) and parathyroid hormone (PTH) were assessed as indices of bone metabolism after an overnight fast on days 1–3, and for 4 h after breakfast on day 2.ResultsThere were no differences between trials in fasting concentrations of CTX, P1NP or PTH on days 1–3 (P > 0.512). During both trials, consuming breakfast reduced CTX between 1 and 4 h (P < 0.001) and PTH between 1 and 2 h (P < 0.05), but did not affect P1NP (P = 0.773) Postprandial responses for CTX (P = 0.157), P1NP (P = 0.148) and PTH (P = 0.575) were not different between trials. Ad libitum energy intake on day 2 was greater on ER [12.62 (2.46) MJ] than EB [11.91 (2.49) MJ].ConclusionsTwenty-four hour severe energy restriction does not affect markers of bone metabolism.

Bone tissue quality in patients with monoclonal gammopathy of uncertain significance.

Monoclonal gammopathy of uncertain significance (MGUS) is highly prevalent in older adults and affects bone structure, with osteoporosis and increased risk of fractures in up to 14% of affected patients. Dual-energy X-ray absorptiometry (DXA), the standard technique for diagnosing osteoporosis, is ineffective to reveal microstructure and bone quality in this disease. We conducted a cross-sectional study of patients with MGUS, recruited consecutively from the Hematology and Internal Medicine Departments of Hospital del Mar, Barcelona, between January 2011 and January 2018. Medical records, clinical results and spinal X-ray images were collected. Bone mineral density (BMD) at hip and spine was measured by DXA and Bone Material Strength index (BMSi) by impact microindentation on the tibial mid-shaft. Thirty-nine patients with MGUS and 65 age-matched controls without previous fractures were included. In the MGUS group, 11 (28.2%) patients had prevalent fractures, nearly half of them vertebral (n = 5, 45.45%). Compared to controls, MGUS patients had significantly lower BMSi, a mean (SD) of 70.72 (9.70) vs. 78.29 (8.70), p = 0.001, and lower spinal BMD values (0.900 [0.159] vs. 1.003 [0.168], respectively, p = 0.012), but no significant differences at femoral neck and total hip. No association was observed between BMSi and DXA. Bone remodeling markers (procollagen type-1 N propeptide, bone-alkaline phosphatase and C-terminal telopeptide of type I collagen) did not differ between the two groups. Spinal BMD and mechanical properties of bone tissue, as measured by impact microindentation, were impaired in patients with MGUS. These changes in bone tissue mechanical resistance were independent of DXA levels.

Consumption of nutrients and insulin resistance suppress markers of bone turnover in subjects with abdominal obesity.

Abdominal obesity and type 2 diabetes are associated with insulin resistance and low bone turnover along with an increased fracture risk. The mode of action is poorly understood. The bone resorption marker, C-terminal telopeptide type 1 collagen (CTX), and to a lesser extent, the bone formation marker, Procollagen type 1 N-terminal propeptide (P1NP) appear to be inhibited by food consumption. The link between food consumption, insulin resistance and bone turnover remains to be clarified. Primarily we aimed to compare the postprandial CTX, P1NP and PTH responses by two frequently applied methods in assessing metabolic health; oral glucose tolerance test (OGTT) and mixed meal tolerance test. Secondly, we explored the effect of insulin resistance on bone marker responses. We enrolled 64 subjects with abdominal obesity. Following 10h of fasting, subjects initially underwent a standard OGTT (300kcal) and approximately one week later a mixed meal tolerance test (1130kcal). Circulating CTX, P1NP and PTH were assessed on both days at time=0, after 30min and after 90min for comparison of the two interventions. We analyzed glucose and insulin levels for the assessment of insulin resistance. Additionally, we measured plasma calcium levels along with the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide 2 (GLP-2) in an attempt to identify possible mediators of the postprandial bone response. CTX, P1NP and PTH were suppressed by OGTT and the mixed meal; the latter induced a more pronounced suppression after 90min. Calcium levels were similar between OGTT and meal. GIP and GLP-2 levels increased after both interventions, although only the meal induced a sustained increase after 90min. Fasting P1NP was inversely associated with insulin resistance. The meal-induced suppression of P1NP (but not CTX or PTH) was inversely associated with level of insulin resistance. The acute postprandial suppression of bone turnover markers is extended after ingestion of a mixed meal compared to an OGTT. The response appears to be independent of gender and prompted by a reduction in PTH. The study additionally indicates a possible link between the development of insulin resistance and low bone turnover - which may be of key essence in the development of the fragile bone structure and increased fracture risk demonstrated in subjects with abdominal obesity and T2D.

Effects of quercetin on the dentin resistance to erosion

Objective To evaluate the effects of quercetin on dentin resistance to erosion and provide evidence-based recommendations for the prevention and therapy of dental erosion. Methods One hundred and twenty-eight dentin samples were prepared from 50 extracted human wisdom teeth (collected from Department of Oral Surgery, School and Hospital of Stomatology). Ninety-six samples were randomly divided into 8 groups using the following different soaking solutions: deionized water, ethanol (control groups), 12.300 mg/L sodium fluoride, 0.120 mg/L chlorhexidine, 0.183 mg/L epigallocatechin gallate (EGCG), and 0.075, 0.150 and 0.300 mg/L quercetin. In each group, twelve specimen was prepared. Before daily acid challenge, the samples were immersed in the respective solutions for 2 min, rinsed with deionized water, and immersed in artificial saliva for 2 h. The samples were then subjected to 4 cycles of in vitro acid challenges. This protocol was applied for 7 d. The surface microhardness (SMH) and surface profiles were measured before and after erosion using the surface microhardness tester and contact profilometry, respectively. The change in surface profiles and reduction in SMH were used to calculate the substance loss and reduction percentage of SMH (SMH%) respectively. Scanning electron microscope (SEM) images were taken to observe the surface morphology of the samples. Additionally, another thirty two samples were divided into 8 groups (n=4) as mentioned above. The specimens were treated with 10% phosphoric acid and desiccated, immersed in the respective solutions for 2 min, rinsed, and immersed in the artificial saliva at 37 ℃ for 7 d. The content of cross-linked carboxyterminal telopeptide of type Ⅰ collagen (ICTP) in the soaking solutions were measure quantitatively. Results Compared with the control groups, the application of chlorhexidine, quercetin, and EGCG were effective in preventing the surface softening and substance loss of human dentin after erosion. More specifically, the specimens treated with 0.300 mg/L quercetin exhibited the lowest SMH% [(8.75±4.95)%], the lowest surface substance loss [(2.26±1.16) μm], and the lowest contents of ICTP in the soaking solution [(5.72±0.88) ng], showing significant differences to the chlorhexidine and EGCG treated samples (P 0.05). However, the specimens treated with 0.300 mg/L quercetin exhibited significantly lower SMH% than those treated with the other two concentrations of quercetin (P<0.05). Conclusions Within the limitations of the current study, immersion in the quercetin solution is effective in improving the dentin resistance to erosion by inhibiting the dentinal MMP. Among all the concentrations tested, 0.300 mg/L quercetin showed the best performance. Key words: Quercetin; Acid etching, dental; Tissue inhibitor of metalloproteinases; Dentin

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.

Combination of Red Clover and Hops Extract Improved Menopause Symptoms in an Ovariectomized Rat Model.

Red clover and hops are already known for their alternative menopausal therapies; however, their combination has not yet been studied. This study aimed to evaluate the efficacy of the combination of red clover and hops extract (RHEC) for treating menopausal symptoms for the first time. A high-performance liquid chromatography (HPLC) method for RHEC was developed and validated for the analysis of biochanin A in red clover extract and xanthohumol in hops extract. An in vivo study was conducted using an ovariectomized rat model treated with RHEC (125, 250, and 500 mg/kg, p.o.) for a 12-week test period. Changes in body weight, tail skin temperature (TST), serum lipid profile, bone metabolism, antioxidants, and markers of vasorelaxation and uterus endometrium were evaluated. RHEC significantly inhibited body weight gain and decreased fat weight. Changes in TST associated with flashes were significantly inhibited in the RHEC groups. Other markers related to menopausal symptoms, such as blood lipid profile (total cholesterol and low-density-lipoprotein cholesterol), bone metabolism (serum alkaline phosphatase, osteocalcin, and c-terminal telopeptide type 1), antioxidants (superoxide dismutase and malondialdehyde), and vasorelaxants (endothelin-1 and nitric oxide), were significantly improved after the administration of RHEC. We also confirmed the safety of RHEC through histopathological observation of the endometrium. Our findings demonstrate that RHEC appears to have high potential for comprehensively improving various symptoms of menopause.

Characteristics of bone turnover markers in women with gestational diabetes mellitus

BackgroundBone turnover markers (BTMs) can be applied to the assessment of bone formation and bone resorption activity. The aim of this study was to investigate the changes in BTMs in women with gestational diabetes mellitus (GDM). MethodsOne hundred and five women with gestational diabetes mellitus defined as the GDM group and 46 healthy pregnant women with normal glucose tolerance selected as the control group were enrolled in this study. Serum samples were collected during regular obstetric examinations and the serum levels of total procollagen type 1 N-terminal propeptide (P1NP), N-terminal midfragment of osteocalcin (N-MID), and β-C-terminal telopeptide of type 1 collagen (β-CTX) were measured. An independent-sample t-test, the Mann–Whitney U test, and a Pearson correlation analysis were performed for data analyses. ResultsSerum β-CTX levels in the GDM group were significantly higher than those in the control group (296.00 [235.00–369.00] pg/mL vs. 218.5 [165.25–292.50] pg/mL, p < 0.05), while P1NP and N-MID levels did not differ between the two groups. The Pearson correlation analysis revealed that β-CTX level was correlated with blood glucose level. ConclusionsThe difference in β-CTX levels indicated that bone resorption in patients with GDM diabetes was higher than that in pregnant women with normal glucose tolerance. No obvious differences in bone formation markers P1NP and N-MID were found between the two groups.

Study protocol: design and rationale for an exploratory phase II randomized controlled trial to determine optimal vitamin D3 supplementation strategies for acute fracture healing

BackgroundObservational studies have found that 75% of healthy adult fracture patients (ages 18–50) have serum 25-hydroxyvitamin D (25(OH)D) levels < 30 ng/mL. Although lower serum 25(OH)D levels have yet to be correlated to fracture healing complications or poor fracture outcomes, many orthopedic surgeons are routinely prescribing vitamin D supplements to improve fracture healing in healthy non-osteoporotic patients. To address this gap in the literature, we propose a phase II exploratory randomized controlled trial comparing three vitamin D3 dosing regimens for early surrogate treatment response.MethodsWe will conduct a 4-arm blinded exploratory phase II trial in 96 adults aged 18–50 years with a closed or low-grade open (Gustilo type I or II) tibial or femoral shaft fracture. Eligible patients will be randomized in equal allocation ratio of 1:1:1:1 to one of the treatment groups: (1) 150,000 IU loading dose vitamin D3 plus daily dose placebo; (2) loading dose placebo plus 4000 IU vitamin D3 per day, (3) loading dose placebo plus 600 IU vitamin D3 per day, or (4) loading dose placebo plus daily dose placebo. The primary outcome is fracture healing, assessed as follows: (1) clinical fracture healing measured using the Function IndeX for Trauma, (2) radiographic fracture healing measured using the Radiographic Union Score for Tibial fractures, and (3) biological fracture healing measured using serum levels of cross-linked C-terminal telopeptides of type I collagen and amino-terminal procollagen propeptides of collagen type I. The main secondary outcome will be assessed by measuring serum 25(OH)D levels. All outcome analyses will be exploratory and adhere to the intention-to-treat principle. Per-protocol sensitivity analyses will also be conducted.DiscussionStudy results will be disseminated through a publication in an academic journal and presentations at orthopedic conferences. Study results will inform dose selection for a large definitive randomized controlled trial and provide preliminary clinical data on which dose may improve acute fracture healing outcomes in healthy adult patients (18–50 years) at 3 months.Trial registrationVita-Shock (A Blinded Exploratory Randomized Controlled Trial to Determine Optimal Vitamin D3 Supplementation Strategies for Acute Fracture Healing) was registered at ClinicalTrials.gov (identifier NCT02786498) prior to enrollment of participants.

Association between serum levels of bone turnover markers and bone mineral density in men and women with type 2 diabetes mellitus.

BackgroundIn patients with type 2 diabetes mellitus (T2DM), higher risks of impaired bone metabolism are widely reported. To evaluate bone metabolism, bone mineral density (BMD) and bone turnover levels should be included. In this article, we analyzed the relationship between them in T2DM.MethodsWe conducted a hospital‐based cross‐sectional study enrolling 1499 patients hospitalized for T2DM between October 2009 and January 2013. Multivariate linear regression models were used to identify the relationship between bone turnover markers (BTMs) and BMD levels. A two‐sided P‐value < .05 was considered statistically significant.ResultsAfter adjusting for confounding factors, osteocalcin (OC) showed a negative relationship with total lumbar, femur neck, and total hip BMD in men and women. N‐terminal propeptides of type I collagen (P1NP) and alkaline phosphatase (ALP) showed a negative association with BMD at three sites in men and total lumbar BMD in women, whereas in the femur neck and total hip in women, the relationship was only found for P1NP with total hip. For β‐C‐terminal telopeptides of type I collagen (β‐CTX), a negative relationship was also found in all three sites for BMD in men and total lumbar BMD in women, whereas β‐CTX was not associated in the femoral neck and total hip in women.ConclusionIn patients with T2DM, serum levels of OC, P1NP, β‐CTX, and ALP were negatively correlated with BMD levels in men in three sites and with total lumbar BMD in women. The relationship varied in femur neck and total hip BMD in women.

Analysis of bio-markers in osteoarthritis early diagnosis

Through analysis and summary of the biological characteristics of various biomarkers, to explore the reliability of different markers for early diagnosis of osteoarthritis. Cartilage oligomeric matrix protein, N-terminal crosslinked telopeptide of type Ⅰ collagen and C-terminal crosslinked telopeptide of type Ⅱ collagen are the possible effective markers in osteoarthritis early diagnosis. Hyaluronic acid and C-terminal crosslinked telopeptide of type I collagen are more suitable for evaluating the ollurrence and derelopment of osteoarthritis. The efficacy of miRNA and lncRNA in osteoarthritis diagnosis and evaluation remains to be proved. Each marker may has two or more biological effect, this paper will focus on finding out an accurate and stable marker with the analysis and summary of present bio-markers. Key words: Biological markers; Osteoarthritis; Early diagnosis

Differential Modulation of Cancellous and Cortical Distal Femur by Fructose and Natural Mineral-Rich Water Consumption in Ovariectomized Female Sprague Dawley Rats

Bone mineral density (BMD) and microstructure depend on estrogens and diet. We assessed the impact of natural mineral-rich water ingestion on distal femur of fructose-fed estrogen-deficient female Sprague Dawley rats. Ovariectomized rats drank tap or mineral-rich waters, with or without 10%-fructose, for 10 weeks. A sham-operated group drinking tap water was included (n = 6/group). Cancellous and cortical bone compartments were analyzed by microcomputed tomography. Circulating bone metabolism markers were measured by enzyme immunoassay/enzyme-linked immunosorbent assay or multiplex bead assay. Ovariectomy significantly worsened cancellous but not cortical bone, significantly increased circulating degradation products from C-terminal telopeptides of type I collagen and receptor activator of nuclear factor-kappaB ligand (RANKL), and significantly decreased circulating osteoprotegerin and osteoprotegerin/RANKL ratio. In ovariectomized rats, in cancellous bone, significant water effect was observed for all microstructural properties, except for the degree of anisotropy, and BMD (neither a significant fructose effect nor a significant interaction between water and fructose ingestion effects were observed). In cortical bone, it was observed a significant (a) water effect for medullary volume and cortical endosteal perimeter; (b) fructose effect for cortical thickness, medullary volume, cross-sectional thickness and cortical endosteal and periosteal perimeters; and (c) interaction effect for mean eccentricity. In blood, significant fructose and interaction effects were found for osteoprotegerin (no significant water effect was seen). For the first time in ovariectomized rats, the positive modulation of cortical but not of cancellous bone by fructose ingestion and of both bone locations by natural mineral-rich water ingestion is described.

The Association between Bone Turnover Markers and Fracture in People with Diabetes: A Systematic Review and Meta-Analysis

Background: The increased fracture risk in persons with diabetes is underestimated by conventional fracture predictors. The aims of this study were to conduct a systematic review and a meta-analysis to compare the levels of bone turnover markers (BTM) in persons with diabetes with and without fractures. Methods: We conducted a systematic literature search. Eligibility criteria were studies investigating BTMs in persons with diabetes with/without fractures. For the meta-analysis, we used the standardised mean difference (SMD) of the markers investigated. Results: We included eight observational studies. Levels of osteocalcin, procollagen type 1 amino terminal propeptide (P1NP), and Insulin-like growth factor-1 (IGF-1) were significantly lower in persons with fracture than in persons without fracture (-0.36 (-0.46, -0.26)) (SMD (95% confidence interval), (-0.57 (-0.75, -0.40)), and (-0.50 (-0.61, -0.39)) respectively. Levels of N-terminal cross-linked telopeptide of type 1 collagen (NTX), sclerostin, and bone-specific alkaline phosphatase (BAP) were significantly higher in persons with fracture (0.24 (0.13, 0.35), (0.47 (0.29, 0.65)), and (0.14 (0.01, 0.27)), respectively, whereas C-terminal cross-linked telopeptide (CTX) showed no difference between the groups. In sensitivity analysis removing one larger study, results were insignificant for osteocalcin, P1NP, NTX, and sclerostin. Conclusions: The results suggest that BTMs may be associated with fracture status in persons with diabetes. Persons with diabetes and fracture have lower levels of formative BTMs and IGF-1, and higher levels of NTX, sclerostin, and BAP compared with no fracture, however, some results were dependent on one larger study.

Correlation Between Serum miR-154-5p and Osteocalcin in Males and Postmenopausal Females of Type 2 Diabetes With Different Urinary Albumin Creatinine Ratios.

Purpose: To investigate the serum levels of miR-154-5p, osteocalcin (OC), and other clinical parameters in male and post-menopausal female type 2 diabetes mellitus (T2DM) patients with different urinary albumin creatinine ratio (UACR) levels and to discuss the relationship between miR-154-5p and glycolipid metabolism, bone metabolism, and different urinary albumin excretion rate in T2DM.Methods: Seven hundred thirty-eight T2DM patients were categorized into six groups, including 374 men and 364 post-menopausal women who were sub-divided into three groups based on albumin excretion that involved normal albuminuria, microalbuminuria, and large amount of albuminuria (138, 127, 109, 135, 125, and 104 cases, UACR<30, 30–300, and >300 mg/g, M1, M2, M3, F1, F2, and F3). Measurement of circulating miR-154-5p, OC, and other biochemical indicators were performed by real-time PCR, ELISA, and chemiluminescence assays in T2DM patients and in 141 M0 and 139 F0 control subjects.Results: There are few differences appeared between groups. Comparing with men, women had higher age, waist-to-hip ratio (WHR), adiponectin (ADPN), connective tissue growth factor (CTGF), UACR, procollagen type 1 N-terminal propeptide (P1NP), β-C-terminal telopeptide of type I collagen (β-CTx), OC, and miR-154-5p, but lower FPG, HOMA-IR, and HbA1c. T2DM patients with albuminuria (micro or macro) had lower bone turnover markers (P1NP, β-CTx, and OC) and adiponectin, but higher HbA1c, CTGF, and miR-154-5p. In addition, after regression analysis, UACR was positively correlated with CTGF, HbA1c, and miR-154-5p, and negatively correlated with ADPN and bone turnover markers (P1NP, β-CTx, and OC). However, OC showed a positive correlation with ADPN and other bone turnover markers (P1NP and β-CTx), but negative correlation with CTGF, UACR, and miR-154-5p in all three groups.Conclusion: These findings suggested that increased serum levels of miR-154-5p and decreased OC levels may influence osteogenesis and proteinuria in T2DM and may identify novel targets for diagnosis and treatment of diabetic kidney disease and osteoporosis.

Zoledronic acid is more efficient than ibandronic acid in the treatment of symptomatic bone marrow lesions of the knee

PurposeThe purpose of this study was to determine the efficacy and tolerability of different antiresorptive therapeutic regimens for treating symptomatic bone marrow lesions (BML) of the knee.MethodsPatient records of 34 patients with radiologically diagnosed, painful BML of the knee treated with either a bisphosphonate (zoledronic, ibandronic, or alendronic acid) or with a human monoclonal antibody (denosumab) were retrospectively evaluated. Response to treatment was assessed, as change in patient-reported pain, by evaluation of BML expansion on MRI using the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and by laboratory analysis of bone turnover markers: C-terminal cross-linking telopeptide (CTx) and procollagen type 1 amino-terminal propeptide (P1NP). Tolerability was evaluated by documentation of adverse reactions.ResultsZoledronic acid was more or at least equally effective as the other treatment regimens with response to treatment in 11 of 12 patients (92%). The highest rate of adverse events was noted in 4 of 12 patients (33%) treated with zoledronic acid. CTx and WORMS differentiated well between responders and non-responders, whereas P1NP failed to do so. Changes in pain correlated moderately with change in WORMS (r = − 0.32), weakly with change in CTx (r = − 0.07), and not at all with change in P1NP.ConclusionZoledronic acid appeared to be more effective than other antiresorptive medications—at the cost of more frequent adverse events. While radiological and laboratory evaluation methods may allow for objective treatment monitoring, they appear to capture different dimensions than patient-reported pain.Level of evidenceIII.