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Publication
Journal: Journal of endocrinological investigation
April/20/2006
Abstract
Bone remodelling is a process by which bone grows and turns over. This process involves a series of highly regulated steps that depend on the interaction of two cell lineages, the osteoclasts and the osteoblasts. Information on metabolic activity of bone tissue are achieved with the determination, in blood and in urine, of biochemical products derived from the activity of this cells. The ability to determine bone turnover with biochemical markers has been enhanced considerably in recent years with the development of new assays for more sensitive and specific markers. These new markers can now replace the outdated and non-specific markers of bone remodeling such as serum total alkaline phosphatase (ALP) and urinary hydroxyproline (Hyp) determination. Biochemical markers of bone turnover can be classified according to the process that underlie in markers of bone formation, products of the osteoblast activity [bone ALP, osteocalcin (OC), procollagene I C- and N-terminal propeptides] and markers of bone resorption, products of the osteocalst activity [pyridinuim crosslinks, collagen I C- and N-terminal telopeptides (CTX-I and NTX-I), tartrate resistent acid phosphatase (TRACP) isoform 5b]. The interpretation of laboratory results should always include the consideration of potential sources of variability. Variation in the results of biochemical markers of bone metabolism can compromise their ability to characterize disorders of bone metabolism. Variation can be categorized into pre-analytical, analytical and biological sources. However, the determination of biochemical markers of bone turnover offers many advantages in clinical practice, since they are non-invasive, can be repeated often, and major changes occur in a short time.
Publication
Journal: Osteoarthritis and cartilage
October/5/2008
Abstract
OBJECTIVE
To investigate whether early changes in biochemical markers of bone (NTX-I) and cartilage (CTX-II [C-terminal crosslinking telopeptide of type II collagen]) degradation are associated with radiological progression in patients with knee osteoarthritis (OA) receiving risedronate.
METHODS
Two thousand four hundred and eighty three patients with medial compartment knee OA were randomized in two 24-month studies in North America (NA) and European Union (EU). Studies evaluated risedronate 5 mg/day, 35 mg/week (EU), 50 mg/week (NA), and 15 mg/day (NA and EU), compared to placebo in reducing signs and symptoms and in slowing radiographic progression. One thousand eight hundred and eighty five patients from the pooled EU and NA studies with available NTX-I/CTX-II at both baseline and 6 months and radiographs at baseline and at 24 months were analyzed.
RESULTS
Risedronate produced a dose-dependent reduction of <em>NTX</em>-<em>I</em> and CTX-<em>I</em><em>I</em> observed at 6 months which continued up to 24 months. Patients who had CTX-<em>I</em><em>I</em> levels returned to low levels (<150 ng/mmol creatinine) at 6 months had a lower risk of radiographic progression at 24 months than patients whose CTX-<em>I</em><em>I</em> levels were increased both at baseline and 6 months [odds-ratio (95% confidence interval): 0.57 (0.39-0.85) after adjustment for demographics and joint space width]. The lowest risk of progression was observed in patients who had low CTX-<em>I</em><em>I</em> levels both at baseline and at 6 months [odds-ratio 0.36 (0.21-0.63)]. No significant association between <em>NTX</em>-<em>I</em> levels and radiological progression was observed.
CONCLUSIONS
CTX-II decreased with risedronate in patients with knee OA and levels reached after 6 months were associated with radiological progression at 24 months. Monitoring a marker of cartilage degradation 6 months after initiating treatment may be instructive in identifying patients with low progression.
Publication
Journal: Maturitas
July/7/2004
Abstract
OBJECTIVE
Aim of this study was to evaluate increased body mass index (BMI) as an anthropometric factor, predisposing to lower rates of bone turnover or changes in bone balance after menopause.
METHODS
For this purpose, we calculated BMI, and measured spinal (BMD(SP)) and femoral bone mineral density (BMD(FN)) and biochemical markers of bone formation (serum osteocalcin (S-OC), serum procollagen type I C propeptide (S-PICP), serum bone-specific alkaline phosphatase (S-B-ALP)) and resorption (urine N- and C-terminal cross-linking telopeptide of type I collagen (U-NTX-I and U-CTX-I), pyridinoline (U-PYD) and deoxypyridinoline (U-DPD)) in 130 healthy postmenopausal women, aged 46-85 years. Bone balance indices were calculated by subtracting z-scores of resorption markers from z-scores of formation markers, to evaluate bone balance.
RESULTS
S-PICP ( r = -0.297, P = 0.002), S-OC ( r = -0.173, P = 0.05) and bone balance indices (zPICP-zDPD) and (zPICP-zPYD) were negatively correlated with BMI (r = -0.25, P = 0.01 and r = -0.25, P = 0.01 and r = -0.21, P = 0.037) and with BMD(SP) (r = -0.196, P = 0.032 and r = -0.275 and P = 0.022). Women were grouped according to their BMI, in normals (BMI < 25 kg/m2), overweight (BMI = 25-30 kg/m2, and obese (BMI>> 30 kg/m2). Overweight and obese women had approximately 30% lower levels of S-PICP compared to normals (68.11 +/- 24.85 and 66.41 ng/ml versus 97.47 +/- 23.36 ng/ml, respectively; P = 0.0001). zPICP-zDPD, zPICP-zCTX-I and zPICP-zPYD were significantly declined in obese women compared to normals (P = 0.0072, 0.02 and 0.0028).
CONCLUSIONS
We conclude that in postmenopausal women, BMI is inversely associated with levels of collagen I formation marker, serum PICP. In obesity formation of collagen I was reduced, in favor of degradation, but since this finding is not followed by simultaneous decrease in bone mineral density, it seems that increased body weight may have different effects on mature estrogen-deficient bone and extraskeletal tissues containing collagen I.
Publication
Journal: Clinica chimica acta; international journal of clinical chemistry
October/27/2008
Abstract
Bone diseases such as osteoporosis or bone metastases are a continuously growing problem in the ageing populations across the world. In recent years, great efforts have been made to develop specific and sensitive biochemical markers of bone turnover that could help in the assessment and monitoring of bone turnover. The amino- and carboxyterminal cross-linked telopeptides of type I collagen (NTX-I and CTX-I, respectively) are two widely used bone resorption markers that attracted great attention due to their relatively high sensitivity and specificity for the degradation of type I collagen, and their rapid adaptation to automated analyzers. However, the clinical performance of both markers differs significantly depending on the clinical situation. These differences have caused considerable confusion and uncertainty. If used correctly, both markers have great potential to improve the management of many bone diseases. We here review the biochemistry, analytical background and clinical performance of NTX-I and CTX-I, as documented in the accessible literature until March 2008.
Publication
Journal: Bone
October/13/2016
Abstract
While epidemiologic studies suggest that bone turnover biomarkers may predict hip fracture risk, findings are inconsistent and Asian data are lacking. We conducted a matched case-control (1:1) study nested in the Singapore Chinese Health Study, a population-based prospective cohort of Chinese men and women (45-74years) recruited from 1993 to 1998 in Singapore. One hundred cases with incident hip fracture and 100 individually matched controls were randomly selected from 63,257 participants. Serum bone turnover biomarkers, namely bone alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type <em>I</em> N propeptide (P<em>I</em>NP), N-terminal and C-terminal crosslinking telopeptide of type <em>I</em> collagen (<em>NTX</em>-<em>I</em> and CTX-<em>I</em>) were measured using immunoassays. Hip fracture cases had significantly higher serum levels of OC, P<em>I</em>NP, CTX-<em>I</em> and <em>NTX</em>-<em>I</em> than controls (p<0.05). There was a dose-dependent positive relationship between OC, P<em>I</em>NP, CTX-<em>I</em> and <em>NTX</em>-<em>I</em> and risk of hip fracture (all Ps for trend≤0.006), where the risk was significantly increased by 4.32-8.23 folds for the respective BTM [Quartile (Q) 4 vs. Q1]. The odds ratio [OR (95% C<em>I</em>)] at the highest quartile (Q4) was 6.63 (2.02-21.18) for P<em>I</em>NP and 4.92 (1.67-14.51) for CTX-<em>I</em>. The joint effect of P<em>I</em>NP and CTX-<em>I</em> showed a 7-fold increase in risk (OR: 7.36; 95% C<em>I</em>: 2.53-21.41) comparing participants with higher levels of P<em>I</em>NP (Q4) and CTX-<em>I</em> (Q3-Q4) to those with low levels of P<em>I</em>NP (Q1-Q3) and CTX-<em>I</em> (Q1-Q2). Our data demonstrated that higher serum levels of bone turnover biomarkers were associated with increased risk of hip fracture in an Asian population.
Publication
Journal: Arthritis & rheumatology (Hoboken, N.J.)
September/15/2015
Abstract
OBJECTIVE
To prospectively monitor levels of proinflammatory cytokines and aggrecan ARGS neoepitope in synovial fluid and serum as well as levels of C-terminal crosslinking telopeptide of type II collagen (CTX-II) and N-terminal crosslinking telopeptide of type I collagen (NTX-I) in urine after acute anterior cruciate ligament (ACL) rupture.
METHODS
Synovial fluid, serum, and urine were collected from 121 adults on 6 occasions over 5 years after acute ACL injury. Reference samples were obtained from subjects without knee injury. Concentrations of interleukin-6 (IL-6), IL-8, IL-10, interferon-γ (IFNγ), tumor necrosis factor (TNF), aggrecan ARGS neoepitope, CTX-II, and NTX-I were measured by enzyme-linked immunosorbent assay.
RESULTS
Shortly after ACL injury, cytokine concentrations in synovial fluid were elevated 6-fold (TNF) to 1,050-fold (IL-6) compared to reference levels, while concentrations of aggrecan ARGS neoepitope in synovial fluid and serum and CTX-II in urine were elevated 1.4-fold to 8-fold. Thereafter, concentrations of cytokines and aggrecan ARGS neoepitope in synovial fluid decreased with different half-lives (in years: IL-6 0.9, IL-8 2.2, IL-10 2.3, IFNγ 3.1, TNF 3.6, aggrecan ARGS neoepitope 4.0). After 5 years, the TNF concentration in synovial fluid remained higher than the reference level. There was a correlation between the concentrations of aggrecan ARGS neoepitope in synovial fluid and serum (rs = 0.36). Concentrations of aggrecan ARGS neoepitope in synovial fluid and of CTX-II and NTX-I in urine were correlated with concentrations of cytokines in synovial fluid (rs = 0.41-0.49 and rs = 0.21-0.31, respectively).
CONCLUSIONS
Acute ACL injury induced highly increased levels of inflammatory cytokines in the joint, and these were associated with proteolysis of aggrecan and type II collagen. Cytokine levels remained increased up to 5 years after injury, indicative of extended local inflammation in the joint.
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