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Does urinary deoxipyridinoline improve the diagnostic accuracy of urinary pyridinoline as a bone resorption marker in Paget's disease?
100
Abstracts
Bone Vol. 17, No. 1 July 1995:97-103
USEFULNESS OF BIOCHEMICAL MARKERS OF BONE FORMATION (TOTAL AND BONE ALKALINE PHOSPHATASE) AND BONE RESORPTION (HYDROXYPROLINE AND TELOPEPTIDE) IN PAGET'S DISEASE OF BONE. M.A. Dlizz Martin, C. de la Piedra, A. Rapado. Unidad Metabblica. Fundacibn Jim6nez Dlaz. Avda. Reyes Catblicos 2, 28040 Madrid SPAIN. The aim of this work has been to compare the usefulness of serum alkaline phosphatase CAP) and its bone isoenzyme (bAP), biochemical markers of bone formation and serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and urinary hydroxyprollne/creatinine (Hp/Cr), biochemical markers of bone resorption, in the study of patients with disease paget of bone (PD6). patients: Serum samples from 27 patients with active PD8 (11 males, 16 females, age 69 + 6.6 years) and 26 age and sex paired controls were drawn after overnight fasting. 24 hours urine samples were also collected. M(~thods: AP: Hydrolisis of 4-nitrophenilphosphate, ph=10.5; bAP: IRMA, TANDEM R-OSTASE (Hybritech Europe, Belgium). Hp: Kivirikko method; Cr: Jaff6 reaction; ICTP: RIA Telopeptide (Orion Diagnostic, Finland). Ftesults: AP and bAP levels were significantly higher in PDB patients then in control subjetcs: AP (KAU): PDB 30.2 ± 19.4, C 6.6 ± 1.4, p < 0,001 ; bAP (ng/mL): PDB 116 + 115, C 12.7 + 3.4, p < 0.001 .A 96.15% of patients showed levels of AP and bAP higher than the upper limit of normality. ICTP and Hp/Cr levels were also significantly higher in PDB patients than in control subjetcs. ICTP (#g/L): PDB 4.62 ± 2.94, C 2.07 ±0.58, p<0.001; Hp/Cr (both in mg/dL): PDB 0.087¢0.045, C 0,025±0.09, p<0.001. A 92.3% and a 66.6% of patients showed respectivelly levels of ICTP and Hp/Cr higher than the upper limit of normality. Conclusions: bAP determination does not improve significantly AP quantitation in PDB. bAP would be the elected marker only in the cases in which an hepatic affectation is present. With respect to the studied biochemical markers of bone resorption, the classical hydroxyproline seems to be more sensitive than ICTP in the study of PDB.
CROSSLAPS TM : A NOVEL BONE RESORPTION MARKER AND ITS ~ IN BONE DISORDER DIAGNOSIS M. Bond~ (1). M.Y. Ri~ault (2) Osteometer, Ballerup , Denmark (1), CIS bio international, Gif sur Yvette, France (2) We used a new ELISA method to measure peptides released during degradation of type 1 collagen ( C r o s s L a p s TM, CIS bio international). The assay uses an immobilised synthetic peptide with a specific sequence of a fragment located at the (~-1 chain of the C-telopeptide of type 1 collagen containing Lysine, site of Pyridinoline erosslinking. During the incubation with an antibody raised against this sequence, a competition occurs with the fragment contained in the urine sample. The results obtained by the eolorimetric measurement are expressed in ~g/l~mo] of urine creatinine. We assay with C r o s s L a p s TM several urine samples from patients with Paget disease of the Bone before and after treatment. The corrected mean values are as follows: I Mean value (~l~/~tmol) S. D. (F~/~mol)
I Paget Pre'treatedi Paget post'treated i 0.62 0.05 0.25 0.02
C r o s s L a p s TM showed a good correlation with Pyridinoline values in HPLC but its sensitivity and easiness to use were higher. Results showed clearly that this new specific marker of bone resorption opens a new view of the follow-up of Paget patients. In conclusion, we have a new performance tool for diagnosis monitoring the treatment of bone diseases. Because of its high sensitivity this assay could measure bone turnover after menopause and be used as an important bone marker in the management of osteoporosis.
Does urinary deoxipyridinoline improve the diagnostic accuracy of urinary pyridinoline as a bone resorption marker in Paget's disease? Alvarez L, Guafiabens N, Peris P, Monegal A, Bedini JL, Aibar C, MuSozG(~mez J and Bellesta AM. Metabolic Bone Diseases Unit, Services of Clinical Biochemistry, Rheumatology and Hormonology. Hospital Clinic. University of Barcelona, School of Medicine. Spain. Objectives: To investigate the diagnostic accuracy of urinary deoxipyridinoline (D-PYR) and urinary pyridinoline (PYR) in patients with Paget's disease of bone and to analyze their variations according to the Paget's disease activity evaluated by serum alkaline phosphatase (AP). Patients and Methods: We measured urinary D-PYR and PYR in 42 patients aged 39 to 84 years (mean + SD, 66± 11 years) with Paget's disease. Patients were classified into three groups based on serum AP: group I in = 14) AP<250 U/L; group II (n = 10) AP between 251 U/L and 500 U/L and group III (n = 18) AP> 501 U/L. Results were compared with those obtained in a sample of healthy subjects matched for age and sex. Results: With a specificity of 100 %, the sensitivity of urinary D-PYR was of .59.5 % and 73 % for urinary PYR. Mean values (±SEM) for D-PYR and PYR in the three groups of pagetic ~atients are shown in the Table. Marker
Controls
Group I
Group II
Group III
PYR nM/mM
33±4.06
56±6,1 #
77± 15 #
121 ± 14# &
D-PYR 4.2±0.36 5.9±0.44# 9.9±1.6#* 18±2.4#& nM/mM # differences from controls p'
B E H A V I O U R O F B O N E R E M O D E L I N G M A R K E R S IN P A G E T ' S D I S E A S E . B. Suqufa, R. Querol, M.T. Brefias, T. Arroyo, L. Morales, B. Aparicio, M.V. Rodriguez, J. Dominguez, J. del Pino, J.M. G-Buitrago, J.A. Navajo. Hospital Universitado de Salamanca. Spain. Background: Biochemical markers of b o n e remodeling have been s h o w n to be useful in diagnosis and follow-up of Paget's disease. Objectives: To determine the capacity of discrimination and correlation degree in Paget's disease of total serum alkaline p h o s p h a t a s e activity (ALP), A L P b o n e i s o e n z y m e (ISO), t y p e I collagen C propeptide terminal (CICP), tartrate resistant acid p h o s p h a t a s e (TrACP), crosslink's pyridinium (PYR) and urinary hydroxyproline excretion (HYP). P a t i e n t s a n d m e t h o d s : L e v e l s of A L P a n d I S O (Autoanalizar Hitachi 717), C I C P and PYR (ELISA), T r A C P and PYR (colorimetric), were determined in 40 patients with Paget's disease and in 34 healthy subjects. Student's "t" test, S p e a r m a n ' s correlation test and R O C curves, w e r e used in statisca] analysis.
Results • Descriptive: ALP ISO (~IC,_,P HY_~P TrACP PYFI x 724.6 547.1 193 54.5 16.4 74.6 sd 730.3 737.2 136 83.3 8.69 506 p .001 .01 .01 .01 .001 .01 Spearman's correlation: ALP-ISO IS.O-(~I(~P HYP-TrACP HYP-PYR TrACP-PYR r .99 .93 58 .84 .5 p .0001 O001 .001 .0001 .01 R O C areas: AL._.~P ~ ClC_P HY__~P T r A C P PY__RR .88 .94 .79 .88 .86 .71 Conclusions: Given their high degree of correlation, PYR and H Y P can replace one another in Paget's disease. ISO i m p r o v e s the capacity of discrimination of ALP. As C I C P c o r r e l a t e s well with ISO, C I C P could be u s e d as an alternative index of osteoblastic activity in this bone disorder.
Abstracts
Bone Vol. 17, No. 1 July 1995:97-103
USEFULNESS OF BIOCHEMICAL MARKERS OF BONE FORMATION (TOTAL AND BONE ALKALINE PHOSPHATASE) AND BONE RESORPTION (HYDROXYPROLINE AND TELOPEPTIDE) IN PAGET'S DISEASE OF BONE. M.A. Dlizz Martin, C. de la Piedra, A. Rapado. Unidad Metabblica. Fundacibn Jim6nez Dlaz. Avda. Reyes Catblicos 2, 28040 Madrid SPAIN. The aim of this work has been to compare the usefulness of serum alkaline phosphatase CAP) and its bone isoenzyme (bAP), biochemical markers of bone formation and serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and urinary hydroxyprollne/creatinine (Hp/Cr), biochemical markers of bone resorption, in the study of patients with disease paget of bone (PD6). patients: Serum samples from 27 patients with active PD8 (11 males, 16 females, age 69 + 6.6 years) and 26 age and sex paired controls were drawn after overnight fasting. 24 hours urine samples were also collected. M(~thods: AP: Hydrolisis of 4-nitrophenilphosphate, ph=10.5; bAP: IRMA, TANDEM R-OSTASE (Hybritech Europe, Belgium). Hp: Kivirikko method; Cr: Jaff6 reaction; ICTP: RIA Telopeptide (Orion Diagnostic, Finland). Ftesults: AP and bAP levels were significantly higher in PDB patients then in control subjetcs: AP (KAU): PDB 30.2 ± 19.4, C 6.6 ± 1.4, p < 0,001 ; bAP (ng/mL): PDB 116 + 115, C 12.7 + 3.4, p < 0.001 .A 96.15% of patients showed levels of AP and bAP higher than the upper limit of normality. ICTP and Hp/Cr levels were also significantly higher in PDB patients than in control subjetcs. ICTP (#g/L): PDB 4.62 ± 2.94, C 2.07 ±0.58, p<0.001; Hp/Cr (both in mg/dL): PDB 0.087¢0.045, C 0,025±0.09, p<0.001. A 92.3% and a 66.6% of patients showed respectivelly levels of ICTP and Hp/Cr higher than the upper limit of normality. Conclusions: bAP determination does not improve significantly AP quantitation in PDB. bAP would be the elected marker only in the cases in which an hepatic affectation is present. With respect to the studied biochemical markers of bone resorption, the classical hydroxyproline seems to be more sensitive than ICTP in the study of PDB.
CROSSLAPS TM : A NOVEL BONE RESORPTION MARKER AND ITS ~ IN BONE DISORDER DIAGNOSIS M. Bond~ (1). M.Y. Ri~ault (2) Osteometer, Ballerup , Denmark (1), CIS bio international, Gif sur Yvette, France (2) We used a new ELISA method to measure peptides released during degradation of type 1 collagen ( C r o s s L a p s TM, CIS bio international). The assay uses an immobilised synthetic peptide with a specific sequence of a fragment located at the (~-1 chain of the C-telopeptide of type 1 collagen containing Lysine, site of Pyridinoline erosslinking. During the incubation with an antibody raised against this sequence, a competition occurs with the fragment contained in the urine sample. The results obtained by the eolorimetric measurement are expressed in ~g/l~mo] of urine creatinine. We assay with C r o s s L a p s TM several urine samples from patients with Paget disease of the Bone before and after treatment. The corrected mean values are as follows: I Mean value (~l~/~tmol) S. D. (F~/~mol)
I Paget Pre'treatedi Paget post'treated i 0.62 0.05 0.25 0.02
C r o s s L a p s TM showed a good correlation with Pyridinoline values in HPLC but its sensitivity and easiness to use were higher. Results showed clearly that this new specific marker of bone resorption opens a new view of the follow-up of Paget patients. In conclusion, we have a new performance tool for diagnosis monitoring the treatment of bone diseases. Because of its high sensitivity this assay could measure bone turnover after menopause and be used as an important bone marker in the management of osteoporosis.
Does urinary deoxipyridinoline improve the diagnostic accuracy of urinary pyridinoline as a bone resorption marker in Paget's disease? Alvarez L, Guafiabens N, Peris P, Monegal A, Bedini JL, Aibar C, MuSozG(~mez J and Bellesta AM. Metabolic Bone Diseases Unit, Services of Clinical Biochemistry, Rheumatology and Hormonology. Hospital Clinic. University of Barcelona, School of Medicine. Spain. Objectives: To investigate the diagnostic accuracy of urinary deoxipyridinoline (D-PYR) and urinary pyridinoline (PYR) in patients with Paget's disease of bone and to analyze their variations according to the Paget's disease activity evaluated by serum alkaline phosphatase (AP). Patients and Methods: We measured urinary D-PYR and PYR in 42 patients aged 39 to 84 years (mean + SD, 66± 11 years) with Paget's disease. Patients were classified into three groups based on serum AP: group I in = 14) AP<250 U/L; group II (n = 10) AP between 251 U/L and 500 U/L and group III (n = 18) AP> 501 U/L. Results were compared with those obtained in a sample of healthy subjects matched for age and sex. Results: With a specificity of 100 %, the sensitivity of urinary D-PYR was of .59.5 % and 73 % for urinary PYR. Mean values (±SEM) for D-PYR and PYR in the three groups of pagetic ~atients are shown in the Table. Marker
Controls
Group I
Group II
Group III
PYR nM/mM
33±4.06
56±6,1 #
77± 15 #
121 ± 14# &
D-PYR 4.2±0.36 5.9±0.44# 9.9±1.6#* 18±2.4#& nM/mM # differences from controls p'
B E H A V I O U R O F B O N E R E M O D E L I N G M A R K E R S IN P A G E T ' S D I S E A S E . B. Suqufa, R. Querol, M.T. Brefias, T. Arroyo, L. Morales, B. Aparicio, M.V. Rodriguez, J. Dominguez, J. del Pino, J.M. G-Buitrago, J.A. Navajo. Hospital Universitado de Salamanca. Spain. Background: Biochemical markers of b o n e remodeling have been s h o w n to be useful in diagnosis and follow-up of Paget's disease. Objectives: To determine the capacity of discrimination and correlation degree in Paget's disease of total serum alkaline p h o s p h a t a s e activity (ALP), A L P b o n e i s o e n z y m e (ISO), t y p e I collagen C propeptide terminal (CICP), tartrate resistant acid p h o s p h a t a s e (TrACP), crosslink's pyridinium (PYR) and urinary hydroxyproline excretion (HYP). P a t i e n t s a n d m e t h o d s : L e v e l s of A L P a n d I S O (Autoanalizar Hitachi 717), C I C P and PYR (ELISA), T r A C P and PYR (colorimetric), were determined in 40 patients with Paget's disease and in 34 healthy subjects. Student's "t" test, S p e a r m a n ' s correlation test and R O C curves, w e r e used in statisca] analysis.
Results • Descriptive: ALP ISO (~IC,_,P HY_~P TrACP PYFI x 724.6 547.1 193 54.5 16.4 74.6 sd 730.3 737.2 136 83.3 8.69 506 p .001 .01 .01 .01 .001 .01 Spearman's correlation: ALP-ISO IS.O-(~I(~P HYP-TrACP HYP-PYR TrACP-PYR r .99 .93 58 .84 .5 p .0001 O001 .001 .0001 .01 R O C areas: AL._.~P ~ ClC_P HY__~P T r A C P PY__RR .88 .94 .79 .88 .86 .71 Conclusions: Given their high degree of correlation, PYR and H Y P can replace one another in Paget's disease. ISO i m p r o v e s the capacity of discrimination of ALP. As C I C P c o r r e l a t e s well with ISO, C I C P could be u s e d as an alternative index of osteoblastic activity in this bone disorder.