scholarly journals The Effect of Gonadotropin-Releasing Hormone Agonist on Type I Collagen C-Telopeptide and N-Telopeptide: the Predictive Value of Biochemical Markers of Bone Turnover

1998 ◽  
Vol 83 (2) ◽  
pp. 333-338 ◽  
Author(s):  
Ernest A. Amama ◽  
Michiyoshi Taga ◽  
Hiroshi Minaguchi
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Biochemical Markers ◽  
Type I Collagen ◽  
Type I ◽  
Bone Resorption Markers ◽  
Bone Formation Markers ◽  
Z Scores ◽  
The Mean

To evaluate the clinical utility of recently developed biochemical markers in the assessment of bone metabolism during GnRH agonist (GnRHa) treatment, we compared five bone resorption markers[ C-telopeptide (CTX) and N-telopeptide (NTX) of type I collagen, hydroxyproline (Hpr), pyridinoline (Pyr), and deoxypyridinoline (Dpyr)] and two bone formation markers [total alkaline phosphatase (Alp) and osteocalcin (OC)]. Sixty-eight normally menstruating women were injected with a long-acting GnRHa once a month for 24 weeks for the treatment of endometriosis or leiomyoma. The mean percentage bone loss at the lumbar spine was 3.79% at the end of treatment. Although levels of all markers increased significantly as the treatment progressed, CTX and NTX exhibited the highest correlation coefficients between bone loss at 24 weeks and the seven markers measured at 0, 4, 12, 16, and 24 weeks of treatment. Serum estradiol levels were similarly suppressed during the treatment in both fast losers (whose bone loss was more than the mean) and slow losers (whose bone loss was less than the mean). However, significantly higher z-scores of bone resorption markers, but not of bone formation markers, were observed in the fast losers at 24 weeks of treatment, suggesting a more accelerated bone resorption in this group. Whereas the three highest z-scores at 24 weeks of treatment were CTX, NTX, and Dpyr (in that order), the highest z-score (P < 0.05) was observed for CTX in the fast losers. The subjects in the highest quartile of CTX, the highest, and second highest quartiles of NTX at 24 weeks of treatment experienced 2.1, 2.2, and 1.7 times more bone loss (P < 0.001), respectively, than those in the lowest quartiles. Furthermore, the subjects in the highest quartile of both CTX and NTX experienced 3.6 times more bone loss (P < 0.001) than those in the lowest quartile of both markers. These results indicate that both CTX and NTX are useful and sensitive markers for bone resorption in a hypoestrogenic state induced by GnRHa.

Markers of Bone Formation and Resorption Identify Subgroups of Patients with Clinical Knee Osteoarthritis Who Have Reduced Rates of Cartilage Loss

2010 ◽  
Vol 37 (6) ◽  
pp. 1252-1259 ◽  
Author(s):  
PATRICIA A. BERRY ◽  
ROSE A. MACIEWICZ ◽  
FLAVIA M. CICUTTINI ◽  
MARK D. JONES ◽  
CAROLINE J. HELLAWELL ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Type I Collagen ◽  
Serum Markers ◽  
Cartilage Volume ◽  
Cartilage Loss ◽  
Type I ◽  
Bone Formation Markers ◽  
Markers Of Bone Formation ◽  
Markers Of Bone Resorption

Objective.To determine whether serum markers of bone formation and resorption, used individually or in combination, can be used to identify subgroups who lose cartilage volume at different rates over 2 years within a knee osteoarthritis (OA) population.Methods.Changes in cartilage volume over 2 years were measured in 117 subjects with knee OA using magnetic resonance imaging. We examined relationships between change in cartilage volume and baseline serum markers of bone formation [intact N-terminal propeptide of type I procollagen (PINP) and osteocalcin] and resorption [N-telopeptide of type I collagen (NTX-I), C-telopeptide of type I collagen (CTX-I), and C-telopeptide of type I collagen (ICTP).Results.The baseline markers of bone formation, PINP and osteocalcin (p = 0.02, p = 0.01, respectively), and the baseline markers of bone resorption, CTX-I and NTX-I (p = 0.02 for both), were significantly associated with reduced cartilage loss. There were no significant associations between baseline ratios of bone formation to resorption markers and cartilage loss. However, when subjects were divided into subgroups with high or low bone formation markers (based on levels of marker ≥ mean or < mean for the population, respectively), in the subgroup with high PINP there was a significant association between increasing bone resorption markers CTX-I and NTX-I and reduced cartilage loss (p = 0.02, p = 0.001, respectively). Similarly, in the subgroup with high osteocalcin, there was a significant association between increasing CTX-I and NTX-I and reduced cartilage loss (p = 0.02, p = 0.003, respectively). In contrast, in subgroups with low bone formation markers, no significant associations were obtained between markers of bone resorption and cartilage loss.Conclusion.Overall, the results suggest that higher bone remodeling (i.e., higher serum levels of bone formation and resorption) is associated with reduced cartilage loss. Considering markers of bone formation and resorption together, it is possible to identify subgroups within the OA population who have reduced rates of cartilage loss.

scholarly journals Serum Concentrations of Cross-Linked N-Telopeptides of Type I Collagen: New Marker for Bone Resorption in Hemodialysis Patients

2005 ◽  
Vol 51 (12) ◽  
pp. 2312-2317 ◽  
Author(s):  
Yoshifumi Maeno ◽  
Masaaki Inaba ◽  
Senji Okuno ◽  
Tomoyuki Yamakawa ◽  
Eiji Ishimura ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Type I Collagen ◽  
Bone Alkaline Phosphatase ◽  
Bone Resorption Marker ◽  
Type I ◽  
Serum Concentrations ◽  
Mineral Density ◽  
Intact Osteocalcin ◽  
Bone Formation Markers

Abstract Background: Urinary cross-linked N-telopeptide of type I collagen (NTX) is a reliable bone resorption marker in patients with metabolic bone disease. We assessed a clinically available serum NTX assay suitable for anuric patients on hemodialysis (HD). Methods: Serum concentrations of NTX, C-terminal telopeptide of type I collagen (β-CTX), pyridinoline (PYD), and deoxypyridinoline (DPD) were determined as bone resorption markers, and those of bone alkaline phosphatase (BAP) and intact osteocalcin (OC) as bone formation markers, in 113 male HD patients (mean age, 59.3 years; mean HD duration, 67.7 months). Each patient’s bone mineral density (BMD) in the distal third of the radius was measured twice, with a 2-year interval between measurements, by dual-energy x-ray absorptiometry. Results: Serum NTX correlated significantly with β-CTX, PYD, DPD, BAP, and intact OC. NTX, as well as β-CTX, PYD, DPD, BAP, and intact OC, correlated significantly with BMD at the time of measurement. NTX, β-CTX, and DPD correlated significantly with the annual change in BMD during the 2-year period thereafter, in contrast to PYD, BAP, and intact OC. Patients in the highest quartile of serum NTX concentrations showed the fastest rate of bone loss. The sensitivity and specificity for detecting rapid bone loss were 48% and 83%, respectively, for serum NTX. Conclusion: Serum NTX may provide a clinically relevant serum assay to estimate bone turnover in HD patients.

scholarly journals Comparison of Biochemical Markers of Bone Resorption in Patients with Metabolic and Malignant Bone Diseases

1996 ◽  
Vol 33 (5) ◽  
pp. 421-427 ◽  
Author(s):  
W Withold ◽  
W Friedrich ◽  
H Reinauer
Keyword(s):  
Bone Resorption ◽  
Bone Metastases ◽  
Biochemical Markers ◽  
Type I Collagen ◽  
Bone Diseases ◽  
Type I ◽  
Discriminating Power ◽  
Z Scores ◽  
Cross Links ◽  
Markers Of Bone Resorption

The clinical usefulness of the urinary excretion of three bone resorption markers is compared in patients after renal transplantation and in tumour patients with and without bone metastases. The markers were the 3-hydroxypyridinium derivatives pyridinoline and deoxypyridinoline (pyridinium cross-links; measured by a polyclonal enzyme immunoassay), the cross-linked N-telopeptid-to-helix domain of type I collagen and the destruction products of type I collagen metabolism cross-reacting with a peptide sequence of the α1-chain of the C-terminal telopeptide region of type I collagen (CrossLaps™). In patients receiving renal transplantation the discriminating power of N-telopeptides was superior to that of pyridinium cross-links and CrossLaps™, with Z scores (number of SDs from apparently healthy controls) of 6·61, 2·17 and 1·35, respectively. However, the pyridinium cross-links were the only markers for bone resorption which showed a significant increase with time ( P < 0·001). Receiver operating-characteristic analysis for discriminating patients with bone metastases from those without revealed that the accuracy was 0·81 for pyridinium cross-links, 0·76 for the N-telopeptides and 0·61 for CrossLaps™. The discriminating power for patients with bone metastases was higher for pyridinium cross-links and N-telopeptides than for CrossLaps™, with Z scores (number of SDs from patients without bone metastases) of 4·38, 3·00 and 1·24, respectively. Linear correlation coefficients for the different markers were between + 0·35 and + 0·65 in patients receiving renal transplants, and between + 0·58 and + 0·84 in patients with bone metastases. In conclusion, in patients with metabolic and malignant bone diseases there are marked differences in the diagnostic performance of different biochemical markers of bone resorption. It is suggested that this may reflect the different facets of bone resorption or the different metabolic fates of the marker substances examined.

Different responses of biochemical markers of bone resorption to bisphosphonate therapy in Paget disease

1995 ◽  
Vol 41 (11) ◽  
pp. 1592-1598 ◽  
Author(s):  
A Blumsohn ◽  
K E Naylor ◽  
A M Assiri ◽  
R Eastell
Keyword(s):  
Bone Resorption ◽  
Biochemical Markers ◽  
Type I Collagen ◽  
Bisphosphonate Therapy ◽  
Response To Therapy ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Paget Disease ◽  
Markers Of Bone Resorption ◽  
Total Alkaline

Abstract We examined the response of different biochemical markers of bone resorption to bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The response was somewhat greater for TPyds than for FPyds. We conclude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therapy than do FPyds and may be more sensitive indicators of bone resorption; and (c) as yet no evidence suggests that these markers are substantially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and the clinical utility of these measurements remains uncertain.

scholarly journals Serum Bone Resorption Markers after Parathyroidectomy for Renal Hyperparathyroidism: Correlation Analyses for the Cross-Linked N-telopeptide of Collagen I and Tartrate-Resistant Acid Phosphatase

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kuo-Chin Hung ◽  
Chung-Yu Huang ◽  
Chuan-Chieh Liu ◽  
Chih-Jen Wu ◽  
Shao-Yuan Chen ◽  
...  
Keyword(s):  
Acid Phosphatase ◽  
Bone Resorption ◽  
Type I Collagen ◽  
Bone Alkaline Phosphatase ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Bone Resorption Markers ◽  
Correlation Analyses ◽  
Serum Trap ◽  
The Cross

Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT) with increased serum concentrations of bone resorption markers such as the cross-linked N-telopeptide of type I collagen (NTX) and type-5b tartrate-resistant acid phosphatase (TRAP). When SHPT proves refractory to treatment, parathyroidectomy (PTX) may be needed. Renal patients on maintenance HD who received PTX for refractory SHPT (n=23) or who did not develop refractory SHPT (control subjects;n=25) were followed prospectively for 4 weeks. Serum intact parathyroid hormone (iPTH), NTX, TRAP, and bone alkaline phosphatase (BAP) concentrations were measured serially and correlation analyses were performed. iPTH values decreased rapidly and dramatically. BAP values increased progressively with peak increases observed at 2 weeks after surgery. NTX and TRAP values decreased concurrently and progressively through 4 weeks following PTX. A significant correlation between TRAP and NTX values was observed before PTX but not at 4 weeks after PTX. Additionally, the fractional changes in serum TRAP were larger than those in serum NTX at all times examined after PTX. Serum iPTH, TRAP, and NTX values declined rapidly following PTX for SHPT. Serum TRAP values declined to greater degrees than serum NTX values throughout the 4-week period following PTX.

Iron deficiency and high-intensity running interval training do not impact femoral or tibial bone in young female rats

2021 ◽  
pp. 1-22
Author(s):  
Jonathan M. Scott ◽  
Elizabeth A. Swallow ◽  
Corinne E. Metzger ◽  
Rachel Kohler ◽  
Joseph M. Wallace ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Bone Resorption ◽  
Iron Deficiency ◽  
Bone Formation ◽  
High Intensity ◽  
Female Rats ◽  
Type I ◽  
Bone Resorption Markers ◽  
Iron Deficient ◽  
Tracp 5B

Abstract In the US, as many as 20% of recruits sustain stress fractures during basic training. In addition, approximately one-third of female recruits develop iron deficiency upon completion of training. Iron is a cofactor in bone collagen formation and vitamin D activation, thus we hypothesized iron deficiency may be contributing to altered bone microarchitecture and mechanics during 12-weeks of increased mechanical loading. Three-week old female Sprague Dawley rats were assigned to one of four groups: iron adequate sedentary, iron deficient sedentary, iron adequate exercise, and iron deficient exercise. Exercise consisted of high-intensity treadmill running (54 min 3×/week). After 12-weeks, serum bone turnover markers, femoral geometry and microarchitecture, mechanical properties and fracture toughness, and tibiae mineral composition and morphometry were measured. Iron deficiency increased the bone resorption markers C-terminal telopeptide type I collagen and tartate-resistant acid phosphatase 5b (TRAcP 5b). In exercised rats, iron deficiency further increased bone TRAcP 5b, while in iron adequate rats, exercise increased the bone formation marker procollagen type I N-terminal propeptide. In the femur, exercise increased cortical thickness and maximum load. In the tibia, iron deficiency increased the rate of bone formation, mineral apposition, and zinc content. These data show that the femur and tibia structure and mechanical properties are not negatively impacted by iron deficiency despite a decrease in tibiae iron content and increase in serum bone resorption markers during 12-weeks of high-intensity running in young growing female rats.

scholarly journals Low Dose Estrogen and Calcium Have an Additive Effect on Bone Resorption in Older Women1

1999 ◽  
Vol 84 (1) ◽  
pp. 179-183
Author(s):  
K. M. Prestwood ◽  
D. L. Thompson ◽  
A. M. Kenny ◽  
M. J. Seibel ◽  
C. C. Pilbeam ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Older Women ◽  
Low Dose ◽  
Type I Collagen ◽  
Control Group ◽  
Type I ◽  
Markers Of Bone Formation ◽  
Markers Of Bone Resorption

Previous studies have shown that treatment with estrogen or calcium decreases bone turnover in older women. The mechanisms by which estrogen and calcium exert their effects are probably different. We therefore examined the possibility of an additive or synergistic effect of combined treatment with calcium and low dose estrogen on bone turnover in older women, using biochemical markers. Thirty-one healthy women over 70 yr of age were randomized to 12 weeks of treatment with either micronized 17β-estradiol [0.5 mg/day Estrace (E2)] or 1500 mg/day elemental calcium, given as carbonate plus vitamin D (800 IU/day; Ca+D). At the end of the initial 12-week treatment period, both groups received both Ca+D and E2 for an additional 12 weeks. Eleven older women were followed for 36 weeks without any treatment and served as a control group. Serum and urine were collected at baseline, at 12 and 24 weeks on treatment, and at 12 weeks after treatment was terminated for measurement of biochemical markers of bone turnover. Markers of bone formation were bone alkaline phosphatase, osteocalcin, and type I procollagen peptide; markers of bone resorption were urinary cross-linked C-telopeptides and N-telopeptides of type I collagen, serum cross-linked N-telopeptides of type I collagen, urinary free deoxypyridinoline cross-links, and serum bone sialoprotein. Repeated measures ANOVA was used to determine changes in bone turnover measures over time by group. All markers of bone resorption decreased with initial treatment and decreased further with combination therapy (P &lt; 0.001). Markers of bone formation decreased with Ca+D treatment, but not with E2 alone; there was no additional effect of combination therapy on formation markers compared to Ca+D alone. Neither markers of formation nor resorption changed in the control group. These results suggest that there is an additive effect of low dose estrogen and calcium on bone resorption, but not on bone formation, in older women. Thus, the combination of low dose estrogen plus calcium is likely to be more effective in older women than either treatment alone.

scholarly journals Effects of the Circadian Variation in Serum Cortisol on Markers of Bone Turnover and Calcium Homeostasis in Normal Postmenopausal Women1

1998 ◽  
Vol 83 (3) ◽  
pp. 751-756 ◽  
Author(s):  
Hassan M. Heshmati ◽  
B. Lawrence Riggs ◽  
Mary F. Burritt ◽  
Carol A. McAlister ◽  
Peter C. Wollan ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Type I Collagen ◽  
Serum Cortisol ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Type I ◽  
Serum Osteocalcin ◽  
Circadian Pattern

Bone turnover has a circadian pattern, with bone resorption and, to a lesser extent, bone formation increasing at night. Serum cortisol also has a circadian pattern and is a potential candidate for mediating the circadian changes in bone turnover. Thus, we measured bone formation and resorption markers before (study A) and after (study B) elimination of the morning peak of cortisol. We also assessed effects of the circadian cortisol pattern on serum calcium, PTH, and urinary calcium excretion. Ten normal postmenopausal women, aged 63–75 yr (mean, 69 yr), were studied. Metyrapone was administered to block endogenous cortisol synthesis and either a variable (study A) or a constant (study B) infusion of cortisol was given to reproduce and then abolish the morning cortisol peak. Blood was sampled every 2 h for serum cortisol, ionized calcium, PTH, and bone formation markers[ osteocalcin and carboxyl-terminal propeptide of type I collagen (PICP)], and timed 4-h urine samples were collected for measurement of calcium, phosphorus, sodium, potassium, and bone resorption markers (N-telopeptide of type I collagen and free deoxypyridinoline). During study A, serum osteocalcin had a circadian pattern, with a peak at 0400 h and a nadir at 1400 h. During study B, however, the afternoon nadir of serum osteocalcin was eliminated (P &lt; 0.001 and P &lt; 0.005 for the difference in the patterns of peak and nadir, respectively, on the 2 study days). In contrast, the circadian patterns of serum PICP and urinary N-telopeptide of type I collagen and free deoxypyridinoline were virtually identical during the two studies. Urinary calcium excretion declined after the cortisol peak, without differences between the 2 study days in phosphorus or sodium excretion or in serum PTH. We conclude that the circadian variation in serum cortisol is responsible for the circadian pattern of serum osteocalcin, but not that of PICP or bone resorption markers. The physiological variation in serum cortisol may also reduce urinary calcium excretion.

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