Serum CTX Concentrations Research Articles

Preventing OsteoPorosis in Spinal Cord Injury (POPSCI) Study-Early Zoledronic Acid Infusion in Patients with Acute Spinal Cord Injury.

Accelerated sub-lesional bone loss is common in the first 2-3years after traumatic spinal cord injury (TSCI), particularly in the distal femur and proximal tibia. Few studies have explored efficacy of antiresorptives for acute bone loss prevention post-TSCI, with limited data for knee bone mineral density (BMD) or beyond two years follow-up. An open-label non-randomized study was performed at Royal North Shore Hospital and Royal Rehab Centre, Sydney between 2018 and 2023. An 'acute interventional cohort' (n = 11) with TSCI (duration ≤ 12-weeks) received a single infusion of 4mg zoledronic acid (ZOL) at baseline. A 'chronic non-interventional cohort' (n = 9) with TSCI (duration 1-5-years) did not receive ZOL. All participants underwent baseline and 6-monthly blood tests (including CTx and P1NP) and 12-monthly DXA BMD scans (including distal femur and proximal tibia). Participants were predominantly Caucasian and male (mean age 38.4years). At baseline, the 'acute' cohort had higher serum CTx, P1NP and sclerostin concentrations, while the 'chronic' cohort had lower left hip and knee BMD. Majority with acute TSCI experienced an acute phase reaction after ZOL (9/11; 82%). In the acute cohort, left hip BMD fell by mean ~ 15% by 48months. Left distal femoral and proximal tibial BMD declined by mean ~ 6-13% at 12months and ~ 20-23% at 48months, with a tendency towards greater BMD loss in motor-complete TSCI. A single early ZOL infusion in acute TSCI could not attenuate rapidly declining hip and knee BMD. Prospective controlled studies are required to establish the optimal strategy for preventing early bone loss after acute TSCI.

Parathyroidectomy Improves Bone Density in Women With Primary Hyperparathyroidism and Preoperative Osteopenia.

Osteoporosis and/or bone fractures are indications of parathyroidectomy in primary hyperparathyroidism (PHPT), especially in women. However, the benefit of surgery in patients with osteopenia remains unclear. To evaluate bone mineral density (BMD) and bone remodeling biomarkers changes 1 year after parathyroidectomy in women with PHPT. In the prospective, monocentric, observational prospective cohort with primary hyperparathyroidism patients (CoHPT) cohort, women operated for sporadic PHPT since 2016 with ≥1 year follow-up were included. BMD (dual-X ray absorptiometry) and bone remodeling biomarkers [cross-linked C-telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatases] were assessed before and 1 year after parathyroidectomy. Referral center. A total of 177 women with PHPT (62.5 ± 13.3 years, 83.1% menopausal, 43.9% osteopenic, and 45.1% osteoporotic) were included. Parathyroidectomy. BMD change between before and 1 year after parathyroidectomy. Parathyroidectomy resulted in significant increase in BMD and decrease in serum bone remodeling biomarker concentrations. In the 72 patients with baseline osteopenia, mean BMD significantly increased at the lumbar spine [+0.05 g/cm2 (95% confidence interval [CI], 0.03-0.07)], the femoral neck [+0.02 g/cm2 (95% CI 0.00-0.04)], the total hip [+0.02 g/cm2 (95% CI 0.01-0.02)], and the forearm [+0.01 (95% CI 0.00-0.02)], comparable to osteoporotic patients. Among osteopenic patients, those with individual BMD gain (>0.03 g/cm2) at ≥1 site had higher preoperative serum CTX, P1NP, and urine calcium concentrations than those without improvement. Parathyroidectomy significantly improved BMD and remodeling biomarkers in women with osteopenia, thereby supporting the benefit of parathyroidectomy in these patients. Preoperative serum CTX and P1NP concentrations could be useful to predict expected BMD gain.

The influence of sex and age on bone turnover markers in the adult to geriatric Kangal shepherd dogs.

The objective of this research was to learn more about bone metabolism in intact female and male Kangal shepherd dogs during the aging process following skeletal maturity. It also evaluated the potential application of biochemical bone indicators in veterinary clinical practice. Bone markers were determined as bone alkaline phosphatase (BALP), osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), and cross-linked C-telopeptide of type I collagen (ICTP) in this study. Kangal shepherd dogs of different age (adult, senior, and geriatric) and sex (male and female) groups were split into six groups of equal numbers (n=8/group). In this study, the effect of age was observed on serum BALP, OC, CTX, and ICTP concentrations. Specifically, BALP was highest in geriatric female Kangal shepherd dogs, while serum OC, CTX, and ICTP concentrations were highest in geriatric male Kangal shepherd dogs. However, no effects of sex and age-sex interactions were identified. Moreover, the effects of age, sex, and age-sex interactions had no significant effect on serum creatinine, CK, LDH, Mg, and P concentrations or ALT activities. However, only sex was found to affect serum AST activities and gradually decreased with age in females. The effect of age and age-sex interactions on serum Ca concentrations was significant (the lowest serum Ca concentrations were in geriatric females), but the effect of sex was not. These results show the effect of age and sex on bone turnover in Kangal shepherd dogs and provide information about bone biomarkers.

Ambient ozone exposure and bone turnover markers in children: Results from the GINIplus and LISA birth cohorts

BackgroundMultiple environmental factors can regulate bone metabolism, and it is hypothesized that air pollution may be deleteriously involved in this regulation. However, only a few studies considered bone turnover markers (BTMs) - sensitive and specific markers of bone metabolism - as outcomes, and no study investigated the exposure to ambient ozone. Here, we intended to explore the associations between long-term exposure to ambient ozone and concentrations of two BTMs, osteocalcin and β-isomer of C-terminal telopeptide of type I collagen (CTx), amongst 10-year-old children. MethodsBased on the GINIplus and LISA birth cohorts, our cross-sectional analysis included 1848 children aged 10 years from Munich and Wesel. Serum osteocalcin and CTx concentrations were measured. We estimated ozone exposures by optimal interpolation, assessed nitrogen dioxide and particulate matter with an aerodynamic diameter <10 μm concentrations by land use regression models, and assigned the exposures to home addresses. Linear regression models were built and adjusted for covariates as well as co-pollutants. ResultsThe mean concentrations were 93.09 ng/mL and 663.66 ng/L for osteocalcin and CTx, respectively. In general, higher levels of ozone were associated with decreased concentrations of both BTMs. This held true for the two areas and different exposure metrics. The number of days per year with a maximum 8-h average concentration exceeding 120 μg/m³ showed consistent results across different models. Specifically, models adjusted for co-pollutants illustrated that the beta estimates and 95% confidence intervals on osteocalcin and CTx were −2.51 (−3.78, −1.14) and −44.53 (−57.12, −31.93), respectively, for an increase of 10 days. ConclusionsWe found that long-term exposure to ambient ozone was associated with decreased concentrations of BTMs in German children. This association might potentially affect bone metabolism. Nevertheless, unless other prospective studies confirm our results, the detrimental effects of ambient ozone on bone development in children should be interpreted cautiously.

Age-related trends and reference intervals of cross-linked C-telopeptide of type I collagen and procollagen type I N-propeptide from a reference population of Sri Lankan adult women.

This study was performed to establish age-related reference intervals for bone resorption marker; cross-linked C-telopeptide of type I collagen (CTX) and bone formation marker; procollagen type I N-propeptide (PINP) in a group of Sri Lankan adult women. Adult women (n = 347) aged 20-70years were recruited using age-stratified random sampling technique and categorized into age groups by decades. Serum CTX and PINP concentration were measured using enzyme-linked immunosorbent assay (ELISA). The geometric mean (95% confidence interval) and 2.5th and 97.5th percentiles were calculated. ANOVA was used to compare the means between groups. Mean CTX levels were relatively low and remained unchanged between 20 and 49years. After the age of 49years, mean CTXconcentration elevated significantly until the age of 70years (43%, p < 0.001). Mean PINP concentrations were not significantly different between age categories (p > 0.05). Reference intervals of CTX and PINP were based on 2.5th and 97.5th percentile values. Reference intervals of CTX for the age groups of 20-29, 30-39, 40-49, 50-59, and 60-70years were 0.19-0.97ng/mL, 0.18-0.95ng/mL, 0.20-1.29ng/mL, 0.17-2.20ng/mL, and 0.17-2.85ng/mL respectively. Reference intervals of PINP for the same age groups were 118-810pg/mL, 119-772pg/mL, 116-645pg/mL, 108-684pg/mL, and 108-715pg/mL respectively. In Sri Lanka, bone turnover markers are not used in evaluating patients mainly due to lack of normative data. These values can be used as reference data for women in this age group.

Anti-osteoporosis effect of Notopterygium incisum Ting ex H. T. Chang extract in rats

Purpose: To investigate the effect of Notopterygium incisum Ting ex H.T. Chang extract (NICE) on ovariectomy-induced osteoporosis in rats.&#x0D; Methods: Female Sprague-Dawley rats were randomly assigned to a normal group (control) and five ovariectomy (OVX) subgroups: OVX with vehicle (OVX), OVX with positive control drug alendronate sodium tablets (1.8 mg/kg/week), and OVX with varying NICE doses (45, 90, or 180 mg/kg/day). After rats were subjected to ovariectomy for 4 weeks, alendronate or NICE were administered orally daily for 16 weeks. The bone mineral density (BMD) of the L4 vertebrae and right femurs of all rats was estimated. The serum hormones estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and serum alkaline phosphatase (ALP), osteocalcin (OC) and telopeptides of collagen type I (CTx) levels of rats were detrmined.&#x0D; Results: The results show that NICE dose-dependently inhibited bone mineral density (BMD) reduction of L4 vertebrae and femurs (p &lt; 0.05). Compared with OVX group, serum E2, FSH and LH levels was significantly increased in osteoporosis rats (p &lt; 0.01), but serum ALP, CTx, and OC concentrations were significantly lower (p &lt; 0.05). On the other hand, bone trabeculae in the three NICE groups and nilestriol group were all wider, while the space and connections increased.&#x0D; Conclusion: These findings indicate that NICE mitigates OVX-induced osteoporosis in rats, and hence can potentially be developed for the management of osteoporosis.

Comparison of two bone markers with growth evolution in 74 girls with central precocious puberty

BackgroundThe bone markers bone alkaline phosphatase (BAP) and C-terminal telopeptide of type I collagen crosslinks (CTX) are correlated with growth rate during normal puberty. The objective of this study was to evaluate the relationship between the serum concentrations of BAP and CTX and growth evolution in girls with idiopathic central precocious puberty (CPP) to help predict adult height.MethodsA retrospective single-center study was conducted in 74 girls with CPP for whom a serum sample at initial evaluation was available to retrospectively measure BAP and CTX concentrations; 66.2% of them were untreated.ResultsThe serum BAP concentrations showed significant positive correlations with height in standard deviations (SDS) at the initial evaluation (n = 62; r = 0.31; p = 0.015) and with the difference between bone and chronological ages (n = 61; r = 0.39; p = 0.002). BAP was also positively correlated with adult height as measured in both cm and SDS in untreated patients (n = 19; r = 0.58; p = 0.009).The serum CTX concentrations showed significant positive correlations with growth rate the year before the initial evaluation as measured in both cm and SDS (n = 65; r = 0.34; p = 0.006).ConclusionsThis study revealed significant correlations of serum BAP and CTX concentrations with growth evolution in girls with CPP. The high positive correlation between serum BAP and adult height in untreated girls suggests that BAP can possibly be used to optimize models of adult height prediction in girls with CPP.

Effect of &lt;i&gt;Dihuang rougui&lt;/i&gt; decoction on ovariectomyinduced osteoporosis in rats

Purpose: To investigate the effect of Dihuang Rougui Decoction (DRD) on ovariectomy-induced osteoporosis in rats.Methods: Female Sprague-Dawley rats were randomly assigned to a normal group (control) and five ovariectomy (OVX) subgroups: OVX with vehicle (OVX), OVX with positive control drug (alendronate sodium tablets, 1.6 mg/kg/week), and OVX + DRD (75, 150 or 300 mg/kg/day). After the rats were subjected to ovariectomy for 4 weeks, fosamax or DRD were administered daily (orally) for 16 weeks. The bone mineral density (BMD) of the L4 vertebrae and right femurs of the rats was evaluated. Serum hormones estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and serum alkaline phosphatase (ALP), osteocalcin (OC) and telopeptides of collagen type I (CTx) levels of the rats were determined. The bone tissue morphology of the rats was examined by microscopy.Results: The results show that DRD dose-dependently inhibited bone mineral density (BMD) reduction of L4 vertebrae and femurs (both p < 0.05). DRD significantly increased serum E2, FSH and LH levels (p < 0.05) in the osteoporotic rats, and significantly lowered serum ALP, CTx and OC concentrations, compared to OVX group (p < 0.01). Compared with OVX model group, bone trabeculae in all three DRD groups and nilestriol groups were wider, and the space and connections markedly increased. Furthermore, the medullary cavity reduced in size.Conclusion: These findings indicate that DRD mitigates OVX-induced osteoporosis in rats, and thus, the decoction has a potential for clinical management of osteoporosis patients.Keywords: Dihuang Rougui decoction, Osteoporosis, Ovariectomy, Bone mineral density, Serum bone marker, Bone tissue morphology

The relationship among serum lipocalin 2, bone turnover markers, and bone mineral density in outpatient women.

We aimed to investigate associations among serum levels of LCN2, bone resorption marker carboxy-terminal cross-linking telopeptide of type-1 collagen (CTx), bone formation marker osteocalcin (OCN), and bone mineral densities (BMDs) in ambulatory healthy women. This cross-sectional study analyzed 1012 previously enrolled outpatient Han Chinese women. BMDs of the lumbar spine and femoral neck were measured using dual energy X-ray absorptiometry. Serum levels of LCN2, CTx, OCN, and creatinine (Scr) were measured. Circulating LCN2 was inversely correlated with BMDs at the lumbar spine and femoral neck (Spearman's r = -0.08, P = 0.010 and r = -0.14, P < 0.001; respectively). A significant positive correlation between LCN2 and CTx (r = 0.11, P < 0.001), OCN (r = 0.06, P = 0.047), age (r = 0.21, P < 0.001), and Scr (r = 0.24, P < 0.001) was also observed. After adjusting for age and Scr, the correlation among LCN2, BMDs and OCN disappeared, but LCN2 was still positively associated with CTx (r = 0.08, P = 0.010). The circulating concentration of LCN2 showed no significant difference between subjects with and without osteoporotic fractures (43.63 (35.29, 53.66) vs. 42.25 (34.43, 51.46) ng/ml, respectively, P = 0.111). Serum CTx concentrations rose with serum LCN2 increasing from the lowest to the highest quartile (P for trend = 0.005), even after adjusting for age and Scr (P for trend = 0.040). In multivariate regression analysis, LCN2 was one of the main determinants for changes in serum CTx (standard β = 0.061, P = 0.005). In ambulatory healthy women, the relationships among serum LCN2 level, BMDs, and OCN were confounded by age and Scr. Although LCN2 was positively related with CTx, the correlation was very weak and may not be physiologically relevant.

TGF-β1, bone metabolism, osteoprotegerin, and soluble receptor activator of nuclear factor-kB ligand in girls with anorexia nervosa.

Numerous investigations, and especially in vitro studies, indicate that TGF-β1 may act as an important regulator of bone remodelling. Thus, it could be expected that disturbances of this cytokine production observed by several researchers might play a role in the mechanism leading to the development of osteoporosis in girls with anorexia nervosa (AN). The aim of the study was to determine whether 1) girls with AN exhibited a relationship between TGF-β1 and bone metabolism (as assessed based on serum OC and CTx concentrations) and 2) whether OPG and sRANKL might modify the possible relationship between TGF-β1 and bone metabolism. Serum concentrations of TGF-β, OC, CTx, OPG, and its soluble ligand sRANKL were determined by ELISA in 60 girls with AN and in 20 healthy controls (C). All study participants were aged 13 to 17 years. Body weight, BMI, BMI-SDS and the Cole index, serum TGF-β1, OC, CTx, and the OPG/sRANKL ratio were significantly reduced, while OPG and sRANKL levels were significantly increased, in girls with AN compared to healthy participants. BMI and the Cole index correlated negatively and significantly with serum CTx and OPG (AN group) or CTx only (groups C and C + AN). Girls with AN showed a positive and significant correlation between the Cole index and serum TGF-β1. The combination group (C + AN) showed a positive and significant correlation between BMI, the Cole index, and the OPG/sRANKL ratio and TGF-β1 concentration, while TGF-β1 correlated positively and significantly with OC concentrations and the OPG/sRANKL ratio. The Cole index and BMI were identified to be significant and independent predictors of CTx (C, AN, and C+AN groups) and OPG (AN group); the Cole index, BMI, and TGF-β1 independently predicted the OPG/sRANKL ratio (C, AN, and C + AN groups); TGF-β1 was found to be an independent predictor of OC (C + AN group). Changes in bone markers, OPG, and/or OPG/sRANKL ratio observed in girls with AN are associated with changes in serum TGF-β1 concentrations. TGF-β1 suppression in girls with AN might lead to disturbances in the relationship between bone metabolism and the OPG/sRANKL system, which, in turn, might compromise the mechanism compensating for bone remodelling disturbances. (Endokrynol Pol 2016; 67 (5): 493-500).

Serum N-terminal telopeptide of type I collagen as an early marker of fracture nonunion in rabbits.

The aim of the present study was to establish an experimental animal model of fracture nonunion, and to investigate the changes in serum biomarker concentrations in fracture nonunion. A total of 20 purebred New Zealand rabbits were divided into two group: A bone defect group and a bone fracture group. In the bone defect group, a 15-mm section of bone (including the periosteum) was removed from the mid-radius, and the medullary cavities were closed with bone wax. In the bone fracture group, the mid-radius was fractured. X-rays were taken and blood samples were collected preoperatively and at 2, 3, 4, 5, 6, 7, 8, 10 and 12 weeks after the surgical procedure. The serum concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP) served as markers of bone formation, and those of C-terminal telopeptide of type I collagen (CTX), N-terminal telopeptide of type I collagen (NTX) and tartrate-resistant acid phosphatase 5b (TRACP 5b) served as markers of bone resorption. The concentration levels of the markers were measured using a biotin double-antibody sandwich enzyme-linked immunosorbent assay. In the bone defect group, bone callus was observed on X-ray at 2 weeks in three rabbits and the bone calluses stabilized at 5 weeks; however, none of the bones had healed at 8 weeks. In the bone fracture group, the fracture line was distorted at 2 weeks and bone calluses formed at 6–8 weeks. In the bone defect group, the serum BSAP and TRACP 5b concentrations increased following the surgical procedure, peaked at 4 weeks, began to decrease at 5 weeks and stabilized after 6 weeks. The serum OC concentrations did not change significantly following the surgical procedure. The serum CTX concentrations fluctuated during the first 4 weeks, peaked at 5 weeks, then decreased and stabilized after 6 weeks. The serum NTX concentrations fluctuated during the first 4 weeks, were significantly lower at 5 weeks compared with the other time points and stabilized after 6 weeks. These results suggested that a bone nonunion model can be established in New Zealand rabbits by resecting a 15-mm section of bone from the mid-radius prior to bone wax blocking. Measurement of the serum BSAP, CTX, NTX, and TRACP 5b concentrations may be useful for the early detection of bone nonunion. The serum NTX concentrations changed significantly in rabbits with bone nonunion. Further studies are required in order to determine the feasibility of using serum NTX concentrations for the early diagnosis of bone nonunion.

Symptoms of thyrotoxicosis, bone metabolism and occult atrial fibrillation in older women with mild endogenous subclinical hyperthyroidism.

The objective of this study was to evaluate symptoms of thyrotoxicosis, bone turnover, bone mineral density (BMD) and occult atrial fibrillation (AF) in women ≥65 years with mild endogenous subclinical hyperthyroidism (SCH). Cross-sectional and case-control study. Signs and symptoms of thyrotoxicosis, serum carboxyterminal telopeptide (CTx) and procollagen type I N-terminal propeptide (PINP), BMD, resting electrocardiogram (ECG) and 72-h ECG monitoring were evaluated in 180 women ≥65 years, including 90 with mild SCH (TSH between 0·1 and 0·4 mIU/l) and 90 euthyroid controls matched for age and body mass index. Symptom Rating Scale scores did not differ between patients and controls. None of the patients with SCH scored 20 points, a score compatible with clinical thyrotoxicosis. Eighty patients with SCH (89%) obtained seven or fewer points, a score compatible with euthyroidism. No difference in serum CTx or PINP concentrations was observed between patients and controls. There was also no correlation between these markers and TSH, free T4 or total T3 levels. Finally, no difference in femoral neck or lumbar spine BMD was observed between patients with SCH and controls. Three patients with SCH (3·3%) and two euthyroid women (2·2%) had known AF or AF in the resting ECG. ECG monitoring for 72 h revealed episodes of occult AF in 1/87 patients with SCH and in 1/88 euthyroid women (1·1%). Mild endogenous SCH (TSH between 0·1 and 0·4 mIU/l) was not associated with symptoms of thyrotoxicosis, altered bone metabolism or a higher prevalence of occult AF in women ≥65 years.

The role of enteric hormone GLP-2 in the response of bone markers to a mixed meal in postmenopausal women with type 2 diabetes mellitus.

BackgroundType 2 diabetes mellitus (T2D) is a complex disease associated with several chronic complications, including bone fragility and high fracture risk due to mechanisms not yet fully understood. The influence of the gastrointestinal tract and its hormones on bone remodeling has been demonstrated in healthy individuals. Glucagon-like peptide 2 (GLP-2), an enteric hormone secreted in response to nutrient intake, has been implicated as a mediator of nutrient effects on bone remodeling. This study aimed to analyze the dynamics of bone resorption marker C-terminal telopeptide of type I collagen (CTX), bone formation marker osteocalcin, and GLP-2 in response to a mixed meal in diabetic postmenopausal women.MethodsForty-three postmenopausal women with osteopenia or osteoporosis (20 controls – group CO – and 23 diabetic – group T2D) were subjected to a standard mixed meal tolerance test, with determination of serum CTX, plasma osteocalcin and serum GLP-2 concentrations at baseline and 30, 60, 120 and 180 minutes after the meal.ResultsT2D women had higher body mass index as well as higher femoral neck and total hip bone mineral density. At baseline, luteinizing hormone, follicle-stimulating hormone, osteocalcin and CTX levels were lower in group T2D. In response to the mixed meal, CTX and osteocalcin levels decreased and GLP-2 levels increased in both groups. The expected CTX suppression in response to the mixed meal was lower in group T2D.ConclusionsBone turnover markers were significantly reduced in T2D women at baseline. Confirming the role of nutrient intake as a stimulating factor, GLP-2 increased in response to the mixed meal in both groups. Importantly, CTX variation in response to the mixed meal was reduced in T2D women, suggesting abnormal response of bone remodeling to nutrient intake in T2D.

Effect of Kiwifruit on Bone Resorption in Ovariectomized Mice

Kiwifruit is a good source of dietary components and has beneficial effects for health. In this study, we investigated the effects of two types of kiwifruit, green kiwifruit (GRK) and gold kiwifruit (GOK), on bone metabolism in ovariectomized (OVX) mice. Seven-week-old female Balb/c-strain mice were divided into four groups: sham-operated (sham) group, OVX group, and OVX mice that were fed a GRK-supplemented diet or GOK-supplemented diet. Freeze-dried GRK and GOK were prepared and added in the diet at a concentration of 3 g/100 g. After 9 wk, the mice were sacrificed, and the serum, uterus, and femurs were obtained. Final body weight did not differ significantly among the four groups. Compared to the sham group, uterine weight was significantly lower and serum C-terminal telopeptide of type I collagen (CTx) levels and receptor activator of NF-κB ligand (RANKL) mRNA expression of the whole femur were significantly higher in the OVX group. Compared to the OVX group, GRK, but not GOK, reduced serum CTx concentrations and RANKL mRNA expression of the whole femur without changes in uterine weight. These results suggest that the GRK inhibited bone resorption, which might be due to a decrease in RANKL mRNA expression in OVX mice.

Fundamental differences in axial and appendicular bone density in stress fractured and uninjured Royal Marine recruits — A matched case–control study

Stress fracture is a common overuse injury within military training, resulting in significant economic losses to the military worldwide. Studies to date have failed to fully identify the bone density and bone structural differences between stress fractured personnel and controls due to inadequate adjustment for key confounding factors; namely age, body size and physical fitness; and poor sample size. The aim of this study was to investigate bone differences between male Royal Marine recruits who suffered a stress fracture during the 32weeks of training and uninjured control recruits, matched for age, body weight, height and aerobic fitness. A total of 1090 recruits were followed through training and 78 recruits suffered at least one stress fracture. Bone mineral density (BMD) was measured at the lumbar spine (LS), femoral neck (FN) and whole body (WB) using Dual X-ray Absorptiometry in 62 matched pairs; tibial bone parameters were measured using peripheral Quantitative Computer Tomography in 51 matched pairs. Serum C-terminal peptide concentration was measured as a marker of bone resorption at baseline, week-15 and week-32. ANCOVA was used to determine differences between stress fractured recruits and controls. BMD at the LS, WB and FN sites was consistently lower in the stress fracture group (P<0.001). Structural differences between the stress fracture recruits and controls were evident in all slices of the tibia, with the most prominent differences seen at the 38% tibial slice. There was a negative correlation between the bone cross-sectional area and BMD at the 38% tibial slice. There was no difference in serum CTx concentration between stress fracture recruits and matched controls at any stage of training. These results show evidence of fundamental differences in bone mass and structure in stress fracture recruits, and provide useful data on bone risk factor profiles for stress fracture within a healthy military population.

Reference intervals for serum concentrations of three bone turnover markers for men and women

ObjectiveBone turnover markers (BTMs) reflect the metabolic activity of bone tissue and can be used to monitor osteoporosis therapy. To adequately interpret BTMs, method-specific reference intervals are needed. We aimed to determine reference intervals for serum concentrations of intact amino-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BAP) and carboxy-terminal telopeptide of type I collagen (CTX). Material and methodsWe established a healthy reference population of 1107 men as well as 382 pre- and 450 postmenopausal women, who participated in the first follow-up of the Study of Health in Pomerania. Serum PINP, BAP and CTX concentrations were measured on the IDS-iSYS Automated System (Immunodiagnostic Systems, Frankfurt am Main, Germany). The reference interval was defined as the central 95% range. We determined age-specific reference intervals for PINP, BAP, and CTX for men by quantile regression. Reference intervals for women were age-independent. ResultsReference intervals for men for PINP and CTX decreased with age (25–29year-old men: PINP 31.1–95.9ng/mL, CTX 0.12–0.83ng/mL; 75–79year-old men: PINP 15.7–68.1ng/mL, CTX 0.05–0.58ng/mL). The reference interval for men for BAP did not significantly change with age (25–29year-old men: 7.4–27.7ng/mL; 75–79year-old men: 7.6–24.4ng/mL). The reference intervals for 30–54year-old premenopausal women were: PINP 19.3–76.3ng/mL, BAP 6.0–22.7ng/mL, and CTX 0.05–0.67ng/mL. The reference intervals for 50–79year-old postmenopausal women were: PINP 18.2–102.3ng/mL, BAP 8.1–31.6ng/mL, and CTX 0.09–1.05ng/mL. ConclusionAn intensively characterized, large reference population free of bone-related diseases allowed us to determine robust reference intervals for serum concentrations of PINP, BAP and CTX. Our normative data may aid to interpret bone turnover in adult men and pre- and postmenopausal women.

Decreased Bone Turnover Markers in Children on Long‐Term Parenteral Nutrition (PN) for Intestinal Failure (IF)

Metabolic bone disease (MBD) is a well-recognized but poorly understood complication of long-term parenteral nutrition (PN). Bone histomorphometry in adults has provided useful information but does not provide quantitative measures of bone resorption and is to invasive for children. Measurement of bone turnover markers provides an alternative less invasive approach. We therefore aimed to measure bone turnover markers in children on long-term PN for intestinal failure (IF), and to compare them to age- and gender-matched controls. Serum concentrations of osteocalcin (OC), bone-specific alkaline phosphatase (BSAP), and c-telopeptide (CTx) were measured in IF patients treated at a multidisciplinary intestinal rehabilitation and home PN program at the Hospital for Sick Children, Toronto, Canada. Age- and gender-matched control participants were recruited for comparison. A total of 13 IF patients and 20 control participants were recruited. IF patients had lower serum OC and CTx concentrations when compared with controls: 42.43 ± 11.54 vs 68.39 ± 20.95 µg/L (P < .01) and 7.454 ± 2.17 vs 9.246 ± 1.92 (P < .05; mean ± SD) µg/L for OC and CTx, respectively. In a subgroup of 9 IF patients for whom BMD was available, OC and CTx concentration were negatively correlated to BMD (g/cm(2)) and BMD z score. Bone turnover markers may be useful indicators for identifying children on long-term PN at risk of MBD. Further studies are needed to validate the current results and determine the factors that influence the occurrence and evolution of MBD in children on PN.

Measurement of Urinary N-Telopeptides and Serum C-Telopeptides from Type I Collagen Using a Lateral Flow-Based Immunoassay

Measuring bone turnover markers could detect early stages of osteoporosis and early responses to anti-osteoporotic treatments. Currently, commonly used bone turnover markers, N-telopeptides (NTx) and C-telopeptides (CTx), are measured using ELISA tests, which demands time and increases cost. Bone turnover markers need to be measured more easily for general use. Lateral flow-based immunoassay would be an appropriate method for this context. This study was performed to investigate the precision of a newly developed lateral flow-based immunoassay for measuring the urinary NTx and serum CTx, and their correlations with ELISA measurements. Urine NTx and serum CTx concentrations were determined by photoscan of newly developed strips, using a lateral flow-based immunoassay for 36 subjects (mean age 66.2 years, SD 7.5 years; four males and 32 females). Repeated measurement of urinary NTx and serum CTx were performed three times, using this technology for a precision test. The correlation of the lateral flow-based immunoassay with the ELISA measurements was analyzed. Precision of the newly developed lateral flow based immunoassay was 0.974 (ICC, 95% confidence interval, 0.955 to 0.986) and 0.995 (ICC, 95% confidence interval, 0.991 to 0.997) for urinary NTx and serum CTx, respectively. The correlation of lateral flow based immunoassay with ELISA was 0.913 for urinary NTx and 0.872 for serum CTx. These results suggest that measuring the urinary NTx and serum CTx, using a lateral flow-based immunoassay, is a relevant method for point-of-care testing and screening of bone resorption markers.

Antibody-Proteases: Predictive and Preventive Tools

For this purpose, 36 male Wistar growing rats divided into 6 groups (n=6 each) and treated with 0.9% NaCl (control), methylprednisolone 7 mg/kg (MP), MP+ alendronate 20μg/kg, MP+80 mg/kg EPA, MP+160 mg/kg EPA and MP+ 320 mg/kg EPA for 6 weeks. At the end of the experiment, serum CTX, Osteocalcin, Calcium and phosphate concentrations, mineral content of L4 vertebrate and tibia and fibula, trabecular and osteoid widths of femur and cortical widths and marrow area/cortical area ratio of tibial diaphysis determined.

Study of serum ctx in 50 oral surgical patients treated with oral bisphosphonates

Objectives: To determine whether there is a relationship between the total BP dose administered and the variations in serum CTX concentration. Study design: The study included 50 patients requiring dental implant surgery and treated with oral BPs, seen in an Oral Surgery and Implantology Unit between January 2007 and June 2009. The patients were divided into two groups: those in which the medication was not suspended before obtaining the laboratory test sample, and those patients referred from other dental clinics in which BPs was suspended before reporting to our Unit. The total drug dosage administered and the total dose per kilogram body weight were evaluated for comparison with serum CTX. The data obtained were correlated to the osteonecrosis risk table developed by Marx et al. in 2007. Results: There were no significant differences between the two groups in relation to the total administered dose and the dose in mg/kg b.w. Likewise, in both groups no relationship was observed between the serum CTX value and the total administered dose or the dose in mg/kg b.w. No differences were found between the two patient groups regarding chemical osteonecrosis risk based on the criteria of Marx et al. Conclusions: No relationship was observed between the oral BP dose administered (total dose or expressed in mg/kg b.w.) and serum CTX concentration, and suspension of the medication did not influence the serum CTX levels. Key words:Serum CTX, osteonecrosis, oral bisphosphonates.