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

Author(s):  
W Withold ◽  
W Friedrich ◽  
H Reinauer

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.

1995 ◽  
Vol 41 (11) ◽  
pp. 1592-1598 ◽  
Author(s):  
A Blumsohn ◽  
K E Naylor ◽  
A M Assiri ◽  
R Eastell

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.


1998 ◽  
Vol 83 (2) ◽  
pp. 333-338 ◽  
Author(s):  
Ernest A. Amama ◽  
Michiyoshi Taga ◽  
Hiroshi Minaguchi

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 &lt; 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 &lt; 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 &lt; 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.


1997 ◽  
pp. 167-171 ◽  
Author(s):  
M Taga ◽  
H Minaguchi

OBJECTIVE: The major side effect of GnRH agonist (GnRHa) therapy is the reduction of bone mass. To analyze bone resorption by GnRHa, we measured the urinary excretion of C-terminal telopeptides of type I collagen (CTX), a new marker of bone resorption. METHODS: We used a new ELISA for CTX (CrossLaps) in a sample of 18 premenopausal women with leiomyoma who were treated with daily administration of 400 micrograms nafarelin or 900 micrograms buserelin for 16 weeks. RESULTS: Urinary CTX excretion increased significantly during GnRHa treatment and then decreased at 12 and 24 weeks after the cessation of GnRHa therapy. Whereas the excretory profile of CTX during GnRHa therapy was almost similar to that of pyridinoline (Pyr) or deoxypyridinoline (D-Pyr), both biochemical markers of bone resorption, the magnitude of the change in CTX was significantly greater than that in Pyr or D-Pyr. CONCLUSIONS: These results indicate that CTX could be a more sensitive marker for bone resorption than the currently used biochemical markers, and that CrossLaps ELISA is useful for therapeutic monitoring during and after GnRHa treatment.


2010 ◽  
Vol 37 (6) ◽  
pp. 1252-1259 ◽  
Author(s):  
PATRICIA A. BERRY ◽  
ROSE A. MACIEWICZ ◽  
FLAVIA M. CICUTTINI ◽  
MARK D. JONES ◽  
CAROLINE J. HELLAWELL ◽  
...  

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.


1995 ◽  
Vol 13 (2) ◽  
pp. 81-86
Author(s):  
Katsuyuki Tomita ◽  
Hideki Kawamura ◽  
Ryosuke Nemoto ◽  
Tomohiro Ohta ◽  
Yoshio Tanabe ◽  
...  

1999 ◽  
Vol 84 (1) ◽  
pp. 179-183
Author(s):  
K. M. Prestwood ◽  
D. L. Thompson ◽  
A. M. Kenny ◽  
M. J. Seibel ◽  
C. C. Pilbeam ◽  
...  

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.


Neurology ◽  
2001 ◽  
Vol 57 (3) ◽  
pp. 445-449 ◽  
Author(s):  
Y. Sato ◽  
I. Kondo ◽  
S. Ishida ◽  
H. Motooka ◽  
K. Takayama ◽  
...  

Background: Bone loss and hypovitaminosis D are reported in patients taking antiepileptic drugs, but little is known about changes in bone and calcium metabolism from valproic acid (VPA).Objective: To assess the relationship of VPA to bone mass and calcium metabolism in 40 adults with epilepsy on long-term VPA monotherapy, 40 age- and sex-matched epileptic patients taking phenytoin (PHT), and 40 healthy control subjects. Bone mineral density (BMD) of the second metacarpal was determined as T- and Z-scores.Results: BMD reduction from control values was 14% (12% in men, 16% in women) with VPA and 13% (12% in men, 15% in women) with PHT. Among patients on VPA, nine (23%) had T-scores below −2.5 SD, suggesting osteoporosis; 15 (37%) had T-scores between −1 and −2.5 SD, suggesting osteopenia. Serum concentrations of calcium were significantly higher with VPA than in PHT or control groups. Serum concentrations of bone Gla protein (a bone formation marker) and pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a bone resorption marker) associated with either drug significantly exceeded control values. Z-scores for BMD in the VPA group correlated negatively with calcium and ICTP. High ICTP correlated positively with ionized calcium, implying that increased bone resorption caused the latter.Conclusion: Long-term VPA monotherapy can increase bone resorption, leading to decreased BMD.


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