Urinary C-terminal Telopeptide Of Type Research Articles

Bone turnover in pregnancy, measured by urinary CTX, is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial

The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized. We investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices. MAVIDOS (the Maternal Vitamin D Osteoporosis Study) is a randomized, double-blind, placebo-controlled trial of 1000 IU cholecalciferol/d compared with placebo from 14 weeks of gestation to birth. Maternal second-void urinary α- and β-CTX were measured (ELISA) at 14 and 34 weeks of gestation; DXA was performed within 2 wk postpartum. The Mann-Whitney Rank Sum test, Spearman's rank correlation, and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes. In total, 372 women had CTX and 25-hydroxyvitamin D [25(OH)D] measured in early and late pregnancy. CTX at 14 and 34 weeks of gestation were correlated in both placebo (r=0.31) and cholecalciferol (r=0.45) groups (P<0.0001). Median CTX increased from 14 to 34 weeks of gestation in both groups (n=372 total) [placebo (n=188): from 223.6 to 449.7 μg/mmol creatinine; cholecalciferol (n=184): from 222.3 to 419.3 μg/mmol creatinine; P=0.03 for placebo compared with cholecalciferol difference in CTX at 34 weeks of gestation]. The conditional mean±SD increase in CTX [z-score (SD)] from early to late pregnancy was greater in the placebo group (n=188) than in the cholecalciferol group (n=184) (placebo: 0.16±0.92; cholecalciferol: -0.16±1.06; P-difference<0.01). Higher CTX at 34 weeks of gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content and bone mineral density (BMD) (e.g., lumbar spine BMD: β=-0.02g · cm-2 · SD-1 increase in CTX; 95% CI: -0.027, -0.002 g · cm-2 · SD-1; P=0.02, n=283). Maternal urinary CTX, a bone resorption marker, rises through pregnancy, although to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass postpartum.This trial was registered at www.isrctn.com as ISRCTN 82927713 and eudract.ema.europa.eu as EudraCT 2007-001716-23.

Changes in levels of cartilage oligomeric proteinase and urinary C-terminal telopeptide of type II collagen in subjects with knee osteoarthritis after dextrose prolotherapy: A randomized controlled trial.

ObjectiveTo assess the effects of dextrose prolotherapy in patients with knee osteoarthritis on the levels of serum cartilage oligomeric proteinase and urinary C-terminal telopeptide of type II collagen, and on the Western Ontario McMaster Universities Index and numerical rating scale score for pain.MethodsA randomized controlled trial, in which participants were randomly allocated into 2 groups, receiving injections of either hyaluronic acid or dextrose prolotherapy. The hyaluronic acid group received 5 injections, 1 each on weeks 1, 2, 3, 4 and 5, and the dextrose prolotherapy group received 3 injections, 1 each on weeks 1, 5 and 9. Serum cartilage oligomeric proteinase, urinary C-terminal telopeptide of type II collagen, Western Ontario McMaster Universities Index score, and numerical rating scale score for pain were measured at baseline and 3 weeks after the last injection. Comparative analysis was conducted using Wilcoxon test within groups and analysis of covariance (ANCOVA) test between groups.ResultsA total of 47 participants (21 allocated to hyaluronic acid, 26 allocated to dextrose prolotherapy) completed the protocol. Both interventions resulted in significant improvements in numerical rating scale scores for pain, total Western Ontario McMaster Universities Index scores, and its subscales score. However, the dextrose prolotherapy outperformed hyaluronic acid in numerical rating scale score for pain and level of urinary C-terminal telopeptide of type II collagen, with score changes differences of 0.93 (p = 0.042) and 0.34 (p = 0.048), respectively. No significant changes in level of serum cartilage oligomeric proteinase were found in either group.ConclusionDextrose prolotherapy is an alternative injection therapy for knee osteoarthritis, which was found to be associated with a significant reduction in urinary C-terminal telopeptide of type II collagen compared with hyaluronic acid injection. Neither injection method resulted in reduced serum cartilage oligomeric proteinase.LAY ABSTRACTKnee osteoarthritis is a common musculoskeletal disorder, which is one of the most frequent causes of disability in elderly people. To improve patients’ quality of life, prolotherapy has been developed as a non-operative treatment option for osteoarthritis. This study compared the effectiveness of dextrose prolotherapy with that of standard therapy using hyaluronic acid injections. Both interventions were effective in terms of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score improvement and numerical rating scale score changes. Cartilage repair was assessed by measuring levels of specific biomarkers of cartilage breakdown: urinary C-terminal telopeptide of type II collagen (uCTX-II) and serum cartilage oligomeric matrix protein (sCOMP). Dextrose prolotherapy was more effective than hyaluronic acid in reducing these biomarkers and decreasing patients’ pain. Dextrose prolotherapy is therefore recommended for use in patients with knee osteoarthritis, since it gives better results, is cost beneficial, and is suitable for use in low-resource settings. Dextrose prolotherapy may help to repair cartilage in knee OA, as it reduces the uCTX-II level.

Vertebral fracture assessment (VFA) for monitoring vertebral reshaping in children and adolescents with osteogenesis imperfecta treated with intravenous neridronate.

The study was aimed at monitoring vertebral bodies changes with the use of Vertebral Fracture Assessment (VFA) in children and adolescents affected by osteogenesis imperfecta (OI) during treatment with intravenous neridronate. 60 children and adolescents (35 males and 25 females; age 1-16years) with OI type I, III and IV were included in the study. Intravenous neridronate was administered at the dose of 2mg/kg every 3months in all patients. Lumbar spine (LS) bone mineral density (BMD) and VFA by dual X-ray absorptiometry (DXA) were assessed every 6months up to 24months during treatment. VFA with vertebral morphometry (MXA) was used to calculate the three indices of vertebral deformity: wedging, concavity and crushing. Serum calcium, phosphate, parathyroid hormone (PTH), 25-hydroxy-vitamin D [25(OH)D], total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP) and urinary C-terminal telopeptide of type 1 collagen (CTx) were measured at any time point. Mean LS BMD values significantly increased at 24months compared to baseline (p<0.0001); the corresponding Z-score values were -1.28±1.23 at 24months vs -2.46±1.25 at baseline; corresponding mean Bone Mineral Apparent Density (BMAD) values were 0.335±0.206 vs 0.464±0.216. Mean serum levels of ALP, BALP and CTx significantly decreased from baseline to 24months. By MXA, we observed a significant 19.1% reduction of the mean wedging index of vertebral reshaping at 12months, and 38.4% at 24months (p<0.0001) and of the mean concavity index (16.3% at 12months and 35.9% at 24months; p<0.0001). Vertebral reshaping was achieved for 66/88 (75%) wedge fractures and 59/70 (84%) concave fractures, but there were 4 incident mild fractures. Finally, VF rate was reduced at 24months compared to baseline: 37/710 (5.2%) vs 158/710 (22.2%). Our study demonstrates the utility of VFA as a safe and alternative methodology in the follow-up of children and adolescents with OI.

O29 Bone turnover in pregnancy, measured by urinary C-terminal telopeptide of type I collagen (CTX), is influenced by vitamin D supplementation and is associated with maternal bone health: findings from the MAVIDOS trial

Background: the pattern of change in maternal bone turnover throughout pregnancy is poorly characterized.Objective: we investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices. Design: the Maternal Vitamin D Osteoporosis Study (MAVIDOS) is a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol vs placebo from 14 weeks’ gestation to birth. Maternal second void urinary α- and β-CTX were measured (Enzyme Linked Immunosorbent Assay, ELISA) at 14 and 34 weeks’ gestation; DXA was performed within 2 weeks post-partum. Mann-Whitney rank sum, Spearman's rank correlation and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes. Results: 372 women had CTX and 25(OH)-vitamin D measured in early and late pregnancy. CTX at 14 and 34 weeks’ gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P Conclusions: maternal urinary CTX, a bone resorption marker, rises through pregnancy, though to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass post-partum.

Fibulin-3 and other cartilage metabolism biomarkers in relationship to calprotectin (MRP8/14) and disease activity in rheumatoid arthritis patients treated with anti-TNF therapy.

Fibulin-3 (Fib-3) is a new potential biomarker of articular cartilage metabolism. The aim of the study was to evaluate the effect of anti-TNF therapy on serum fibulin-3, cartilage oligomeric matrix protein (COMP), procollagen II C-propeptide (PIICP), and urinary C-terminal telopeptide of type II collagen (CTX-II) levels in relation to calprotectin (MRP8/14) and disease activity in rheumatoid arthritis patients. In the study, 35 female patients with rheumatoid arthritis (RA) were investigated. The concentration of fibulin-3, COMP, PIICP, MRP8/14, and urinary CTX-II in serum was measured before and after anti-TNF therapy. Ten healthy women were investigated as the controls. The concentration of fibulin-3 in RA patients before treatment did not differ significantly from the concentration of fibulin-3 in the control group. A significantly higher concentration of fibulin-3 was noted prior to treatment in the group of women with a worse response to the therapy (non-responders) compared to the concentration of fibulin-3 in the healthy women. During the anti-TNF therapy, the serum fibulin-3 level decreased in patients. The fibulin-3 level correlated with CRP and ESR after anti-TNF treatment. Significant lowering of MRP8/14 was noted in the patients after anti-TNF therapy. No correlation between fibulin-3 and MRP8/14 was observed in the study group or in the control group. During the anti-TNF therapy, the serum fibulin-3 level decreased in RA patients. Serum MRP8/14 concentration also decreased. No correlation between fibulin-3 and MRP8/14 was observed in the study group before and after the treatment. We found a poor correlation between serum fibulin-3 and other cartilage metabolism biomarkers after anti-TNF therapy.

Effect of colchicine treatment on primary knee osteoarthritic patients

Background and Aim: It was hypothesized that cartilage degradation in osteoarthritis (OA) facilitates monosodium urate crystals nucleation which by its turn contribute to progression of OA. The aim of the current study is to assess the efficacy of oral colchicine treatment in patients having primary Knee OA (KOA). Patients and Methods: This clinical trial included 40 patients with KOA. After baseline evaluation, patients received oral colchicine 0.5 mg twice daily for 16-weeks period. The outcome measures (knee pain and WOMAC scale) and human urinary C-terminal telopeptide of type II collagen (uCTX-II) were evaluated at inclusion and at the end of study. Results: Colchicine had significantly improved frequency of knee effusion (from 62.5% to 40.0%, p=0.044), tenderness score (from 1.9 ± 0.8 to 1.3 ± 0.6, p<0.001), VAS-pain score (from 60.2 ± 11.7 to 48.6 ± 11.5, p<0.001) and the total WOMAC score (from 48.2 ± 6.4 to 42.8 ± 9.2, p=0.003). The uCTX-II was reduced from 447.4 ± 63.4 ng/mmol at baseline evaluation to 428.9 ± 106.7 ng/mmol at the end of treatment but this difference was not significant. Only one patient complained of gastrointestinal side effect in the form of diarrhea. Conclusion: Colchicine appears to be an effective and safe option treatment in primary KOA. Colchicine reduced pain and stiffness and improves functionality with good safety profile

Meta-analysis of urinary C-terminal telopeptide of type II collagen as a biomarker in osteoarthritis diagnosis

SummaryObjectiveThis study aims to discover that the urinary C-terminal telopeptide of type II collagen (uCTX-II) levels differ between osteoarthritis (OA) patients and healthy individuals (controls). According to this difference, we may conclude that uCTX-II can be a biomarker for OA diagnosis.MethodsWe searched MEDLINE and EMBASE databases updated to 2014 to find literature on OA biomarkers. We retrieved the publications that met the required criterion. Literature quality was assessed according to the Newcastle–Ottawa Scale. Publication bias was assessed by Begg's test and Egger's test with the software STATA version 12.0. The weighted mean difference (WMD) was calculated, and the subgroup analysis was completed using STATA 12.0.ResultsSix publications were included in our analysis. The WMD for OA patients versus the controls was 83.05, which was within the 95% confidence interval. For subgroup analysis, the WMD of patients with severe OA was 119.92, whereas that of patients with mild OA was 28.07.ConclusionsuCTX-II levels were higher in OA patients than in controls, subgroup analysis revealed that the uCTX-II levels rised with the OA severity, the heterogeneity originated from different levels of OA severity, These results showed that uCTX-II would be a promising clinical biomarker in OA diagnosis.

Urinary C-terminal telopeptide of type II collagen, radiological severity, and functional assessment in knee osteoarthritis: are these related?

Introduction Osteoarthritis (OA) is a chronic, debilitating joint disease characterized by the degeneration of articular cartilage, sclerosis of the subchondral bone, and osteophyte formation. This work aimed at estimating the level of urinary C-terminal telopeptide of type II collagen (CTX-II) as a biomarker of cartilage turnover and to determine its relation with radiological and functional assessment of knee OA. Patients and methods The current study included 40 postmenopausal women with symptomatic knee OA fulfilling the American Rheumatism Association clinical diagnostic criteria for knee OA. A total of 20 healthy volunteers were enrolled as a control group. Patients were assessed radiologically using the Kellgren-Lawrence grading system and functionally using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Urinary CTX-II was measured for the patient and control groups. Results There was no statistically significant difference as regards age and BMI between patients and controls. Disease duration affects both function assessed using the WOMAC and cartilage degradation assessed using urinary CTX-II. There was a statistically significant correlation between the WOMAC and urinary CTX-II, whereas there was no statistically significant correlation between the Kellgren-Lawrence scale and both urinary CTX-II and the WOMAC. Conclusion This study further confirms that urinary CTX-II is an index of early cartilage degradation in knee OA even before radiological changes occurs. The functional assessment using the WOMAC is an easy inexpensive method in reflecting cartilage degradation. Moreover, this work supports the lack of association between the functional status of knee OA patients assessed using the WOMAC and their radiological severity measured using the Kellgren-Lawrence grading scale.

The Optimal Duration of PTH(1-34) Infusion Is One Hour per Day to Increase Bone Mass in Rats.

Parathyroid hormone (PTH) is a potential medicine for osteoporosis, and subcutaneous (s.c.) PTH treatment enhances bone mass; however, continuous infusion of PTH elicits bone resorption and induces bone loss. To clarify this contradictory phenomenon, we examined bone markers and bone mass in rats to assess the optimal duration of PTH(1-34) infusion. Continuous infusion of PTH at 1 µg/kg/h (Css, steady-state concentration ca. 300 pg/mL) for 1-4 h clearly stimulated the expression both of bone formation-related genes (c-fos, Wnt4, EphrinB2) and of bone resorption-related genes (tnfsf11, tnfsf11b, encoding receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG)), but s.c. treatment stimulated these genes only 1-h after the injection. Rats were treated with 1-, 2-, or 4-h infusions of PTH daily using a totally implanted catheter system, and the femoral bone mineral density (BMD) was measured at 4 weeks. The 1-h infusion of PTH significantly stimulated serum bone formation markers (procollagen I N-terminal propeptide (PINP) and osteocalcin) on day 14 and femoral BMD at 2 and 4 weeks, but the 4-h infusion of PTH did not enhance BMD. Since the 4-h infusion increased the levels of both the bone formation markers and a bone resorption marker (urinary C-terminal telopeptide of type 1 collagen (CTx)), the increased bone resorption may predominate over bone formation. The intermittent elevation of plasma PTH to 300 pg/mL for 1-h each day is optimal for increasing bone mass in rats. In osteoporosis therapy in human, using the optimal duration for the clinical dose of PTH may selectively stimulate bone formation.

Biochemical markers of joint tissue damage increase shortly after a joint bleed; an explorative human and canine in vivo study

Evaluation whether biomarkers of joint damage are sensitive to change shortly after a joint bleed in hemophilia patients and in a canine model of blood-induced joint damage. Blood and urine samples were collected from 10 hemophilia patients after they reported a joint bleed: within 2 days, after 3-5 days, and 12-14 days. Additionally, 90 days after the bleed a blood and urine sample was taken and considered to represent baseline condition. Commercial serum and urine biomarker assays were performed: urinary C-terminal telopeptide of type II collagen (uCTX-II), serum cartilage oligomeric matrix protein (sCOMP), serum cartilage cleavage product C1,2C, and serum chondroitin sulfate 846 (sCS846). The same panel of biomarkers was explored in dogs (n=7) after induction of a first joint bleed by intra-articular blood injections. Biosamples were collected at baseline, day 2, 1 and 2 weeks later. In hemophilia patients, levels of uCTX-II and sCS846 increased 5 days after joint bleeding when compared with baseline (+52%; P=0.021 and+14%; P=0.011, respectively). In dogs, uCTX-II increased statistically significant from day 2 to day 7 (from 75% to 155% of baseline; P=0.018), and sCOMP from baseline to day 2 (+46%; P=0.028). This study demonstrates that biochemical markers of joint tissue damage increase shortly after a single joint bleed, both in humans with established hemophilic arthropathy (HA) and in an animal model of joint damage upon a first joint bleed. Biomarkers might be useful in monitoring the impact of a joint bleed and in evaluation of treatment of such bleeds.

Skin pentosidine in very early hip/knee osteoarthritis (CHECK) is not a strong independent predictor of radiographic progression over 5 years follow-up

Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA. The 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed. Both pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R(2) = 0.60-0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R(2) = 0.07-0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis. Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline.

Biomarkers to identify cartilage damage are increased after a joint bleed; an explorative human and canine in vivo study

Purpose: Biomarkers have the capacity to detect cartilage degradation in degenerative joint diseases such as osteoarthritis. They have the potential to detect early, pre-radiographic changes in joints. In haemophilia, a disease accompanied with arthropathy due to spontaneous bleedings in the joint, a panel of four biomarkers for cartilage degradation is associated with overall radiographic joint damage (Jansen et al., A&R 2009). In the present study, we investigated for the first time whether these biochemical markers can detect cartilage degradation immediately after a joint bleed. Methods: Urinary C-terminal telopeptide of type II collagen (CTX-II), serum Cartilage Oligmeric Matrix Protein (COMP), serum C1,2C (cleavage product of both collagen type I and type II), and serum CS846 (the 864 epitope of aggrecan chondroitin sulphate) were measured in samples of patients with haemophilia (n=8). Samples were collected at three different time points: within 2 days, after 3-5 days, and about 90 days after the patient reported a joint bleed (the last time point considered baseline). In parallel, the same biomarkers were measured in an experimental joint bleeding model using 7 dogs at four different time points: before they received an experimental joint bleed (induced by intra-articular autologous blood injections over 5 days), immediately after this bleeding episode, 5 and 90 days later. Results: In haemophilia patients, the levels of all four biomarkers were elevated 3-5 days after a joint bleed when compared to baseline levels, although the increase was not statistically significant for each of the biomarkers individual. A combined score of the four biomarkers 3-5 days after the bleed showed a statistically significant increase when compared to levels directly after the bleed (ratio of 1.01±0.17 at day 1-2 to a ratio of 1.10±0.20 at day 5; p=0.024). In parallel, in dogs, 5 days after the experimentally induced joint bleed, the same panel of biomarkers (except sCOMP) was increased; uCTX-II and the combined biomarker score being statistically significantly different from the time point directly after the bleed (3.81±0.85 vs 2.60±1.41, p=0.007 and a ratio of 1.17±0.42 compared to a ratio of 0.98±0.39; p=0.02 respectively). After 90 days the levels were similar to the pre-bleeding levels. Conclusions: This study demonstrates that biochemical markers of joint tissue damage increase after a single joint bleed, both in haemophilia patients and after an experimentally induced canine joint bleed. Due to the great variation in patients and bleeding characteristics in a small number of patients, these effects were only approaching statistical significance. A combined score could be used to detect cartilage degradation immediately after a joint bleed. Irrespectively, this explorative study clearly warrants further research on the value of biochemical markers to detect the destructive properties of a joint bleed.

Detection of type ii collagen degradation by urinary ctx-ii in patients with minimal lesions of knee cartilage in arthroscopy

Detection of type ii collagen degradation by urinary ctx-ii in patients with minimal lesions of knee cartilage in arthroscopy

Pharmacodynamic Effects on Biochemical Markers of Bone Turnover and Pharmacokinetics of the Cathepsin K Inhibitor, ONO‐5334, in an Ascending Multiple‐Dose, Phase 1 Study

Selective inhibitors of cathepsin K, which has a major role in the degradation of bone collagen, are potential new treatments for osteoporosis. The pharmacokinetics and the pharmacodynamic effects on biochemical markers of bone turnover of the new cathepsin K inhibitor, ONO-5334, were investigated in a multiple ascending dose, phase 1 study. A total of 120 healthy postmenopausal women were enrolled, and doses of 10 to 600 mg once daily and 50 and 300 mg twice daily were evaluated in 15- and 28-day multiple-dosing cohorts. Plasma ONO-5334 concentration reached steady state within 2 days. Twenty-four hours after the last dose in the 15-day multiple-dose cohort, 100, 300, and 600 mg once daily reduced urinary C-terminal telopeptide of type I collagen by a mean (± standard deviation) 44.9% ± 13.6%, 84.5% ± 4.4%, and 92.5% ± 1.3%, respectively. The 28-day cohort showed similar effects. There were far smaller effects on bone-specific alkaline phosphatase (B-ALP), tartrate-resistant acid phosphatase 5b (TRAP5b), or osteocalcin (OC) (measured after 28 days). ONO-5334 was well tolerated up to 600 mg/d and for up to 28 days of multiple dosing. Multiple dosing with ONO-5334 100 mg resulted in considerable suppression of bone resorption markers with no appreciable effects on bone formation markers (B-ALP, OC) or osteoclast number (TRAP5b).

Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transection.

To investigate whether cartilage degeneration is prevented or minimized following intraarticular injections of lubricin derived from human synoviocytes in culture, recombinant human PRG4 (rhPRG4), or human synovial fluid (SF) in a rat model of anterior cruciate ligament (ACL) injury. Unilateral ACL transection (ACLT) was performed in Lewis rats (n = 45). Nine animals were left untreated. The remaining rats were given intraarticular injections (50 microl/injection) of either phosphate buffered saline (PBS) (n = 9), human synoviocyte lubricin (200 microg/ml; n = 9), rhPRG4 (200 microg/ml; n = 9), or human SF lubricin (200 microg/ml; n = 9) twice weekly beginning on day 7 after injury. Joints were harvested on day 32 after injury. Histologic analysis was performed using Safranin O-fast green staining, and articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. Histologic specimens were immunoprobed for lubricin and sulfated glycosaminoglycans. A 24-hour urine collection was performed on days 17 and 29 postinjury, and urinary C-terminal telopeptide of type II collagen (CTX-II) levels were measured. Treatment with human synoviocyte lubricin resulted in significantly lower OARSI scores for cartilage degeneration compared with no treatment or PBS treatment (P < 0.05). Increased immunostaining for lubricin in the superficial zone chondrocytes and on the surface of cartilage was observed in lubricin-treated, but not untreated or PBS-treated, joints. On day 17, urinary CTX-II levels in human synoviocyte lubricin- and human SF lubricin-treated animals were significantly lower than those in untreated animals (P = 0.005 and P = 0.002, respectively) and in PBS-treated animals (P = 0.002 and P < 0.001, respectively). After treatment with any of the 3 types of lubricin evaluated in this study, a reduction in cartilage damage following ACLT was evident, combined with a reduction in type II collagen degradation. Our findings indicate that intraarticular lubricin injection following an ACL injury may be beneficial in retarding the degeneration of cartilage and the development of posttraumatic OA.

Postgraduate Symposium Positive influence of nutritional alkalinity on bone health

There is growing evidence that consumption of a Western diet is a risk factor for osteoporosis through excess acid supply, while fruits and vegetables balance the excess acidity, mostly by providing K-rich bicarbonate-rich foods. Western diets consumed by adults generate approximately 50-100 mEq acid/d; therefore, healthy adults consuming such a diet are at risk of chronic low-grade metabolic acidosis, which worsens with age as a result of declining kidney function. Bone buffers the excess acid by delivering cations and it is considered that with time an overstimulation of this process will lead to the dissolution of the bone mineral content and hence to reduced bone mass. Intakes of K, Mg and fruit and vegetables have been associated with a higher alkaline status and a subsequent beneficial effect on bone health. In healthy male volunteers an acid-forming diet increases urinary Ca excretion by 74% and urinary C-terminal telopeptide of type I collagen (C-telopeptide) excretion by 19% when compared with an alkali (base-forming) diet. Cross-sectional studies have shown that there is a correlation between the nutritional acid load and bone health measured by bone ultrasound or dual-energy X-ray absorptiometry. Few studies have been undertaken in very elderly women (>75 years), whose osteoporosis risk is very pertinent. The EVAluation of Nutrients Intakes and Bone Ultra Sound Study has developed and validated (n 51) an FFQ for use in a very elderly Swiss population (mean age 80.4 (sd 2.99) years), which has shown intakes of key nutrients (energy, fat, carbohydrate, Ca, Mg, vitamin C, D and E) to be low in 401 subjects. A subsequent study to assess net endogenous acid production (NEAP) and bone ultrasound results in 256 women aged > or = 75 years has shown that lower NEAP (P=0.023) and higher K intake (P=0.033) are correlated with higher bone ultrasound results. High acid load may be an important additional risk factor that may be particularly relevant in very elderly patients with an already-high fracture risk. The latter study adds to knowledge by confirming a positive link between dietary alkalinity and bone health indices in the very elderly. In a further study to complement these findings it has also been shown in a group of thirty young women that in Ca sufficiency an acid Ca-rich water has no effect on bone resorption, while an alkaline bicarbonate-rich water leads to a decrease in both serum parathyroid hormone and serum C-telopeptide. Further investigations need to be undertaken to study whether these positive effects on bone loss are maintained over long-term treatment. Mineral-water consumption could be an easy and inexpensive way of helping to prevent osteoporosis and could be of major interest for long-term prevention of bone loss.

The combination of the biomarkers urinary C‐terminal telopeptide of type II collagen, serum cartilage oligomeric matrix protein, and serum chondroitin sulfate 846 reflects cartilage damage in hemophilic arthropathy

Hemophilic arthropathy, with characteristics of inflammatory (rheumatoid arthritis) and degenerative (osteoarthritis) joint damage, occurs at an early age, is associated with minor comorbidity, and is restricted to 3 pairs of large joints. The aim of this study was to determine whether commonly used serum and/or urinary biomarkers of cartilage and bone turnover for which assay kits are commercially available are associated with the severity of joint damage in patients with various degrees of hemophilic arthropathy and, thus, whether this disease could be useful in the identification and evaluation of such biomarkers. Blood and urine samples were collected from 36 patients with various degrees of hemophilic arthropathy. Commercially available assays for the most frequently investigated serum and urine biomarkers were performed: urinary C-terminal telopeptide of type I collagen (CTX-I), urinary CTX-II, serum CTX-I, serum CTX-II, serum cartilage oligomeric matrix protein (COMP), serum cartilage cleavage products C1,2C and C2C, and serum chondroitin sulfate 846 (CS-846). Radiographs of the ankles, knees, and elbows in all patients were evaluated for the degree of joint damage according to the Pettersson score, which is based on cartilage and periarticular bone changes and is specific for hemophilic arthropathy. Urinary CTX-II, serum C1,2C, and serum CS-846 levels correlated with the overall Pettersson score and with the joint space narrowing component. Regression analysis showed that combined indexes of different markers increased the degree of correlation for the combination of urinary CTX-II, serum COMP, and serum CS-846. Bone-specific markers (urinary/serum CTX-I and serum C1,2C) did not correlate with specific bone-related items of the Pettersson score (osteoporosis and erosions). These results support the idea that a combination of biomarkers relates significantly better to the severity of joint damage than do individual biomarkers. The combination of urinary CTX-II, serum COMP, and serum CS-846 correlated best with the degree of arthropathy. Because of its specific characteristics and restricted involvement, hemophilic arthropathy may prove useful in the screening of newly developed biomarkers of joint damage.

Alpha and beta urinary c-terminal telopeptide of type I collagen (CTX) in scholarship from Buenos Aires province (BA), argentine. Preliminary study

Alpha and beta urinary c-terminal telopeptide of type I collagen (CTX) in scholarship from Buenos Aires province (BA), argentine. Preliminary study

Effect of bed rest during pregnancy on bone turnover markers in pregnant and postpartum women

Objective: The aims of our study were to evaluate the changes in bone turnover markers during pregnancy and puerperium as a longitudinal study and to elucidate the effect of bed rest during pregnancy on bone turnover markers in pregnant and postpartum women. Methods: The study population comprised 27 Japanese pregnant women aged 23–40 years. All women were recruited for the longitudinal study from the outpatients clinic of the Department of Obstetrics and Gynecology, Tokushima University Hospital. Concentrations of serum bone-specific alkaline phosphatase (BAP), urinary cross-linked type I collagen N-telopeptides (NTx), serum NTx and urinary C-terminal telopeptide of type I collagen (CTx) were measured at 10, 26, 30 and 36 weeks of pregnancy and at 4 days and 1 month postpartum. In addition, we recruited 15 pregnant women (aged 25–35 years) who were treated by bed rest before 30 weeks of pregnancy for threatened premature delivery and compared bone turnover markers in these women with those in 22 normal pregnant women (aged 22–39 years). Concentrations of serum BAP, serum NTx, urinary NTx and urinary CTx were measured at 30 and 34 weeks of pregnancy and at 4 days and 1 month postpartum. Results: In the longitudinal study, serum BAP concentration at 1 month postpartum was significantly higher than that at any stage of pregnancy and that at 4 days postpartum. Urinary concentration of NTx increased gradually during pregnancy and showed a peak at 36 weeks of pregnancy, followed by a decrease in the postpartum period. Serum NTx concentration and urinary CTx concentration showed the same patterns of change as that of urinary NTx concentration. In the comparison study, urinary concentrations of NTx and CTx at 30 and 34 weeks of pregnancy in women with bed rest were significantly ( p < 0.0001 and p < 0.001, respectively) higher than those in normal pregnant women. Serum NTx concentration at 34 weeks of pregnancy in women with bed rest was also significantly ( p = 0.0029) higher than that in normal pregnant women. Serum BAP concentration at 34 weeks of pregnancy in women with bed rest was significantly ( p = 0.0038) higher than that in normal pregnant women, and these high levels were maintained during puerperium. Serum BAP concentration at 34 weeks of pregnancy was significantly correlated with duration of bed rest ( r = 0.767, p = 0.0041). Conclusion: Immobilization due to bed rest during pregnancy is associated with increases in bone turnover markers in pregnant and postpartum women. Concentrations of bone resorption markers increased rapidly at the start of bed rest, while the concentration of a bone formation marker gradually increased toward puerperium.

Effects of Lowering Food Intake by High Phosphorus Diet on Parathyroid Hormone Actions and Kidney Mineral Concentration in Rats

We investigated whether lowering food intake by high phosphorus (P) diet influenced parathyroid hormone (PTH) actions, bone turnover markers, and kidney mineral concentration in rats. Rats in two of the three groups were respectively given free access to a control diet (C group) and a high P diet (HP group) for 21 days. Rats in another group (PF group) were pair-fed the control diet with the HP group. Compared to the C and PF groups, serum PTH concentration, urinary C-terminal telopeptide of type I collagen excretion, and kidney calcium and P concentrations were significantly higher in the HP group. Urinary excretion of cAMP was significantly lower in the HP group than in the C and PF groups. These results suggested that high P diet decreased PTH action in the kidney and increased bone resorption and kidney mineral concentrations independently of lowering food intake.