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.

Evidence that serum NTx (collagen-type I N-telopeptides) can act as an immunochemical marker of bone resorption

1997 ◽  
Vol 43 (11) ◽  
pp. 2058-2063 ◽  
Author(s):  
J Daniel Clemens ◽  
Michael V Herrick ◽  
Frederick R Singer ◽  
David R Eyre
Keyword(s):  
Bone Resorption ◽  
Type I Collagen ◽  
Collagen Type I ◽  
Bisphosphonate Therapy ◽  
Bone Collagen ◽  
Type I ◽  
Blood Samples ◽  
Paget Disease ◽  
Liver And Kidney ◽  
Serum And Urine

Abstract Previous studies have shown that immunoassay of urinary NTx (cross-linked N-telopeptides of type I collagen) provides a responsive index of human bone resorption. Here we report by a sensitive immunoassay that NTx is present in serum and is suppressed appropriately in patients with Paget disease of bone by bisphosphonate antiresorptive therapy. The monoclonal antibody (1H11) developed against urinary NTx was applied in a sensitive chemiluminescence format. Results for human serum and urine showed parallel inhibition curves. The NTx concentrations in paired serum and urine samples from individual patients correlated well when urinary concentrations were normalized to creatinine concentrations (in premenopausal and postmenopausal women and Paget disease patients, r = 0.90, n = 60). The percentage of NTx suppression from baseline values for Paget disease patients on bisphosphonate therapy was similar for serum and urine. Blood samples drawn from bone marrow at the site of Pagetic lesions in three patients with active disease had as much as 10-fold higher concentrations of NTx than did peripheral blood samples drawn at the same time. The latter finding is consistent with other evidence showing that immunoreactive NTx originates directly during the proteolytic cleavage of bone collagen by osteoclasts rather than, e.g., by degradative processes occurring later in the liver and kidney.

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.

Change in C-terminal cross-linking domain of type I collagen in urine, a new marker of bone resorption, during and after gonadotropin-releasing hormone agonist administration

1997 ◽  
pp. 167-171 ◽  
Author(s):  
M Taga ◽  
H Minaguchi
Keyword(s):  
Bone Resorption ◽  
Biochemical Markers ◽  
Type I Collagen ◽  
Premenopausal Women ◽  
Therapeutic Monitoring ◽  
Type I ◽  
Major Side Effect ◽  
Gonadotropin Releasing Hormone Agonist ◽  
Markers Of Bone Resorption ◽  
Sensitive Marker

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.

Bortezomib Reduces Serum Dickkopf-1 and RANKL Concentrations and Normalizes Indices of Bone Remodeling in Patients with Relapsed Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 506-506
Author(s):  
Evangelos Terpos ◽  
Deborah Heath ◽  
Amin Rahemtulla ◽  
Kostas Zervas ◽  
Andrew Chantry ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Remodeling ◽  
Serum Levels ◽  
Response To Therapy ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Lytic Lesions ◽  
Tracp 5B ◽  
Dickkopf 1

Abstract Bortezomib is a proteasome inhibitor, which is currently indicated for the treatment of relapsed/refractory myeloma (MM). Although the anti-myeloma effect of bortezomib has been clearly demonstrated, its effect on bone metabolism is still unclear. There are recent reports that bortezomib increases serum alkaline phosphatase (ALP) activity, which is consistent with enhanced osteoblast function. The aim of this study was to evaluate the effect of bortezomib on bone turnover in 34 patients with relapsed MM. Bortezomib was given alone at a dose of 1.3 mg/m2 on days 1, 4, 8, and 11 of a 3-week cycle for 4 cycles. Responders could continue for 4 more cycles, while non-responders could continue therapy with the addition of dexamethasone. The following serum indices were measured on day 1 of cycle 1, and then on day 21 of cycles 4 and 8: osteoblast inhibitor dickkopf-1 (DKK-1); osteoclast regulators: soluble RANKL (sRANKL) and osteoprotegerin (OPG); bone resorption markers: C-telopeptide of collagen type-I (CTX) and tartrate-resistant acid phosphatase type-5b (TRACP-5b); and bone formation markers: bone-specific ALP (bALP) and osteocalcin (OC). We also studied 33 healthy controls of similar gender and age. The objective response rate after 4 cycles of therapy was 66%: CR 8% and PR 58%. Sixteen responders and 3 non-responders continued on therapy for 4 more cycles. Myeloma patients at baseline had increased values of DKK-1 (p=0.007), sRANKL, sRANKL/OPG ratio, and both markers of bone resorption (p&lt;0.0001) when compared to controls. In contrast, bone formation as assessed by serum bALP and OC was significantly reduced (p&lt;0.001). There was a strong correlation between bone lytic disease and serum CTX (r=0.59, p&lt;0.01), and sRANKL (r=0.4, p=0.03). Patients with severe bone disease (&gt;9 lytic lesions, n=7) had elevated values of DKK-1 compared with all others (mean±SD: 223.4±264.4 ng/mL vs. 84±62.4 ng/mL; p=0.01). Moreover, serum levels of DKK-1 correlated with CTX levels (r=0.39, p=0.04), and weakly with bALP concentrations (r=−0.32, p=0.09). The administration of bortezomib produced a significant reduction of DKK-1 (p=0.035), sRANKL (p=0.01), CTX and TRACP-5b (p&lt;0.001) after 4 cycles, which was still seen after 8 cycles of treatment (p&lt;0.01). Bortezomib also produced a dramatic increase in both markers of bone formation, bALP and OC, after 4 and 8 cycles of therapy (p&lt;0.01). Responders tended to have lower initial levels of DKK-1 compared with non-responders. Patients who achieved a CR or vgPR after 4 cycles of bortezomib had greater elevation of bALP than all others: mean±SD of increase: 306.3%±556.9% vs. 45.8%±56.5%; p=0.02. It is of interest that 3/4 non responders also had an increase in bALP (mean: 39.6%) after 4 cycles of bortezomib. There was no other correlation between response to therapy and alteration of bone markers. No healing of the lytic lesions was observed even in CR patients. This study suggests that bortezomib reduces serum levels of DKK-1 and RANKL, irrespective of response to therapy, in patients with relapsed myeloma and thus leads to normalization of abnormal bone remodeling through the increase of bone formation and reduction of bone resorption.

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 The Role of PINP in Diagnosis and Management of Metabolic Bone Disease

2021 ◽  
Vol 42 (1) ◽  
pp. 3-10
Author(s):  
Melissa Gillet ◽  
Samuel Vasikaran ◽  
Charles Inderjeeth
Keyword(s):  
Fracture Risk ◽  
Bone Disease ◽  
Type I Collagen ◽  
Metabolic Bone Disease ◽  
Bisphosphonate Therapy ◽  
Response To Therapy ◽  
Type I ◽  
Reference Marker ◽  
Monitoring Therapy ◽  
Metabolic Bone

Abstract Serum procollagen type I N-propeptide (PINP) is designated the reference marker of bone formation in osteoporosis; the reference marker for resorption is C-terminal telopeptide of type I collagen (CTX). PINP has very low circadian and biological variation, is not affected by food intake, and is very stable in serum after venepuncture. The two automated commercial assays for PINP provide similar results in subjects with normal renal function, allowing reference intervals to be used interchangeably. Bone turnover markers (BTM) are currently not recommended for fracture risk assessment and therefore not included in fracture risk calculators. In the management of osteoporosis, the main utility of BTM including PINP is for monitoring therapy, both antiresorptive as well as anabolic agents; monitoring is thought to help improve adherence. PINP as well as CTX may also be used in assessing offset of drug action following a pause in bisphosphonate therapy, to help decide when to re-instate therapy, or following cessation of denosumab therapy to assess efficacy of follow-on bisphosphonate therapy. PINP may also be used in the diagnosis of Paget’s disease of bone as well as in monitoring response to therapy and for recurrence. Although BTM other than bone alkaline phosphatase are currently not recommended for use in metabolic bone disease of chronic kidney disease, PINP measured by assays specific to the intact molecule has potential in this condition. Further studies are needed to examine this area, as well as in malignant bone disease.

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.

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