Bone resorption in post-menopausal women with normal and low BMD assessed with biochemical markers specific for telopeptide derived degradation products of collagen type I
Osteoporosis; Diagnosis; Antiresorptive therapies; Collagen type I; Bone turnover; Biochemical markers
Abstract :
[en] Biochemical markers of bone resorption can be used clinically to predict the risk of osteoporosis-related fractures (prognostic tool) and to assess the response of an osteoporotic patient to an antiresorptive therapy (monitoring tool). Our aim was to assess the ability of four currently marketed biochemical markers of bone resorption, based on the measurement of degradation products from collage type I telopeptides to monitor the elevated resorption associated with menopause. Women (846) were stratified for menopause, age, and bone mineral density and the following markers were measured: urinary cross-linked N-telopeptides of type I collagen (NTx), the levels of breakdown products of type I collagen C-telopeptides in serum (S-CTx), and in urine, by ELISA (U-CTx-E), and RIA (U-CTx-R). Furthermore, the ratio (a/b) between the aL form of CTx measured in the CTx RIA and the bL form measured in the ELISA was calculated. The mean difference was calculated for each marker in women with osteopenia (Op) or osteoporosis (PMO) (WHO definition) compared with healthy premenopausal (Pre) women and postmenopausal (N Post) women with normal bone mass. Serum CTx showed the highest elevation in post- compared with premenopausal women. All marker values were significantly higher in Op and PMO subjects compared with both Pre and to N Post women. Compared with premenopausal values, the largest elevation in both Op and PMO women was observed for serum CTx. Compared with N Post, urine NTx showed the highest increase in OP subjects. The a/b CTx ratio was elevated in post- compared with Pre women, but there was no difference in the ratio among N Post, Op, or PMO women. In conclusion, postmenopausal women showed elevated turnover with all bone resorption markers, but with substantial individual variation in resorption levels. Furthermore, the turnover process in postmenopausal women appears to be quantitatively different from the premenopausal stage, apparent as altered a/b CTx ratios.
Disciplines :
General & internal medicine Public health, health care sciences & services
Author, co-author :
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Henrotin, Yves ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.) - Didactique des sciences de la santé - Pathologie générale et physiopathologie
Christiansen, C.
Gamwell-Henriksen, E.
Bruyère, Olivier ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Collette, Julien ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Christgau, S.
Language :
English
Title :
Bone resorption in post-menopausal women with normal and low BMD assessed with biochemical markers specific for telopeptide derived degradation products of collagen type I
Publication date :
2001
Journal title :
Calcified Tissue International
ISSN :
0171-967X
eISSN :
1432-0827
Publisher :
Springer Verlag, New York, United States - New York
Watts N.B. (1999) Clinical utility of biochemical markers of bone remodelling. Clin Chem 45:1359-1368.
Christenson R.H. (1997) Biochemical markers of bone metabolism: An overview. Clin Biochem 30:573-593.
Eastell R., Blumshohn A. (1997) The value of biochemical markers of bone turnover in osteoporosis. J Rheum 24:1215-1217.
Lindsay R. (1999) Clinical utility of biochemical markers. Osteoporosis Int 2.
Christgau S., Bitsch-Jensen O., Hannover Bjarnasson N., Gamwell Henriksen E., Qvist P., Alexandersen P., Bang Henriksen D. (2000) Serum CrossLaps for monitoring the response in individuals undergoing antiresorptive therapy. Bone 26:505-511.
Hesley R.P., Shepard K.A., Jenkins D.K., Riggs B.L. (1998) Monitoring estrogen replacement therapy and identifying rapid bone losers with an imnmnoassay for deoxypyridinoline. Osteoporosis Int 8:159-164.
Chen J.T., Hosoda K., Hasumi K., Ogata E., Shiraki M. (1996) Serum N-terminal osteocalcin is a good indicator for estimating responders to hormone replacement therapy in postmenopausal women. J Bone Miner Res 11:1784-1792.
Bonde M., Qvist P., Fledelius C., Riis B., Christiansen C. (1995) Applications of an enzyme immunoassay for a new marker of bone resorption (CrossLaps): Follow-up on hormone replacement therapy and osteoporosis risk assessment. J Clin Endocrinol Metab 80:864-868.
Riggs B.L., Melton L.J., O'Fallon W. (1996) Drug therapy for vertebral fractures in osteoporosis: Evidence that decreases in bone turnover and increases in bone mass both determine anti-fracture efficacy. Bone 18:197-201.
Greenspan S.L., Parker R.A., Ferguson L., Rosen H.N., Maitland-Ramsey L., Karpf D.B. (1998) Early changes in biochemical markers of bone turnover predict the long-term response to alendronate therapy in representative elderly women: A randomised clinical trial. J Bone Miner Res 13:1431-1438.
Seibel M.J., Cosman F., Shen V., Gordon S., Dempster D.W., Ratcliffe A., Lindsay R. (1993) Urinary hydroxypyridinium crosslinks of collagen as markers of bone resorption and estrogen efficacy in postmenopausal osteoporosis. J Bone Miner Res 8:881-889.
Rosen C.J., Chesnut C.H., Mallinak N.J. (1997) The predictive value of biochemical markers of bone turnover for bone mineral density in early postmenopausal women treated with hormone replacement or calcium supplementation. J Clin Endocrinol Metab 82:1904-1910.
Chesnut C.H., Bell H.H., Clark G.S., Drinkwater B.L., English S.C., Johnson C.C., Notelovitz M., Rosen C., Cain D.F., Flessland K.A., Mallinak N.J. (1997) Hormone replacement therapy in postmenopausal women: Urinary N-telopeptide of type I collagen monitors therapeutic effect and predicts response of bone mineral density. Am J Med 102:29-37.
Riis B.J., Overgaard K., Christiansen C. (1995) Biochemical markers of bone turnover to monitor the bone response to postmenopausal hormone replacement therapy. Osteoporosis Int 5:276-280.
Overgaard K., Christiansen C. (1996) A new biochemical marker of bone resorption for follow-up on treatment with nasal salmon calcitonin. Calcif Tissue Int 59:12-16.
Ross P.D., Knowlton W. (1998) Rapid bone loss is associated with increased levels of biochemical markers. J Bone Miner Res 13:297-302.
Garnero P., Somay-Rendu E., Chapuy M.C., Delmas P.D. (1996) Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 11:337-349.
Van Daelle P.L.A., Seibel M.J., Burger H., Hofman A., Grobee D.E., Van Leeuwen J.P., Birkenhager J.C., Pols H.A. (1996) Case-control analysis of bone resorption markers, disability and hip fracture risk: The Rotterdam study. Br Med J 312:1045.
Ravn P., Rix M., Andreassen H., Clemmensen B., Bidstrup M., Gunnes M. (1997) High bone turnover is associated with low bone mass and spinal fracture in postmenopausal women. Calcif Tissue Int 60:255-260.
Melton L.J., Khosla S., Atkinson E.J., O'Fallon W.M., Riggs B.L. (1997) Relationship of bone turnover to bone density and fractures. J Bone Miner Res 12:1083-1091.
Keen R.W., Nguyen T., Sobnack R., Perry L.A., Thompson P.W., Spector T.D. (1996) Can biochemical markers predict bone loss at the hip and spine? A 4-year prospective study of 141 early postmenopausal women. Osteoporosis Int 6:399-406.
Garnero P., Hausnerr E., Chapuy M.C., Marcelli C., Grandjean H., Muller C., Cormier C., Breart G., Meunier P.J., Delmas P.D. (1996) Markers of bone resorption predict hip fracture in elderly women: The EPIDOS prospective study. J Bone Miner Res 11:1531-1538.
Garnero P., Dargent-Molina P., Hans D., Schott A.M., Breart G., Meunier P.J., Delmas P.D. (1998) Do markers of bone resorption add to bone mineral density and ultrasonographic heel measurement for the prediction of hip fracture in elderly women? The EPIDOS prospective study. Osteoporosis Int 8:563-569.
Schneider D.L., Barrett-Connor E.L. (1997) Urinary N-telopeptide levels discriminate normal, osteopenic, and osteoporotic bone mineral density. Arch Intern Med 157:1241-1245.
Woitge H.W., Pecherstorfer M., Li Y., Keck A.V., Horn E., Ziegler R., Seibel M.J. (1999) Novel serum markers of bone resorption: Clinical assessment and comparison with established urinary indices. J Bone Miner Res 14:792-801.
Hanson D.A., Weis M.A., Bollen A.M., Maslan S.L., Singer F.R., Eyre D.R. (1992) A specific immunoassay for monitoring human bone resorption: Quantitation of type I collagen cross-linked N-telopeptides in urine. J Bone Miner Res 7:1251-1258.
Rosen H.N., Moses A.C., Garber J., Iloputaife I.D., Ross D.S., Lee S.L., Greenspan S.L. (2000) Serum CTx: A new marker of bone resorption that shows treatment effect more often than other markers because of low coefficient of variability and large changes with bisphosphonate therapy. Calcif Tissue Int 66:100-103.
Clemmens J.D., Herrick M.W., Singer F.R., Eyre D.R. (1997) Evidence that serum NTx (collagen type I N-telopeptides) can act as an immunochemical marker of bone resorption. Clin Chem 43:2058-2063.
Christgau S., Rosenquist C., Alexandersen P., Bjarnason N.H., Ravn P., Fledelius C., Herling C., Qvist P., Christiansen C. (1998) Clinical evaluation of the serum CrossLaps one step ELISA, a new assay measuring the serum concentration of bone-derived degradation products of type I collagen C-telopeptides. Clin Chem 44:2290-2300.
Rosenquist C., Fledelius C., Christgau S., Pedersen B.J., Bonde M., Qvist P., Christiansen C. (1998) The serum CrossLaps one step ELISA. The first quantitative determination in serum of degradation products from C-terminal telopeptides of type I collagen from bone using monoclonal antibodies. Clin Chem 44:2293-2301.
Bonde M., Qvist P., Fledelius C., Riis B.J., Christiansen C. (1994) Immunoassay for quantifying type I collagen degradation products in urine evaluated. Clin Chem 40:2022-2025.
Blumsohn A., Eastell R. (1997) The performance and utility of biochemical markers of bone turnover: Do we know enough to use them in clinical practice?. Ann Clin Biochem 34:449-459.
Christgau S., Bjarnason N.H., Rigault M.Y., Pedersen B.J., Littau M., Heelsberg M., Rosenquist C. (1998) Intra-individual variation and response to antiresorptive therapy assessed by bone resorption measurements with the serum CrossLaps one step ELISA. Ligand Assay 3:200-205.
Fledelius C., Johnsen A.H., Cloos P., Bonde M., Qvist P. (1997) Characterization of urinary degradation products derived from type I collagen. J Biol Chem 272:9755-9763.
Cloos P., Fledelius C. (2000) Collagen fragments in urine derived from bone resorption are highly racemized and isomerized: A biological clock of protein ageing with clinical potential. Biochem J 345:473-480.
Fledelius C., Kolding I., Qvist P., Bonde M., Hassager C., Reginster J.Y., Hejgaard J., Frookiaer H., Christiansen C. (1997) Development of a monoclonal antibody to urinary degradation products from the C-terminal telopeptide α1 chain of type I collagen. Application in an enzyme immunoassay and comparison to CrossLaps ELISA. Scand J Clin Lab Invest 57:73-83.
Gineyts E., Cloos P., Borel O., Grimaud L., Delmas P.D., Garnero P. (2000) Racemization and isomerization of type I collagen C-telopeptides in human bone and soft tissue: Assessment of tissue turnover. Biochem J 345:481-485.
(1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. WHO Technical Report Series, Geneva, n° 843, ISBN 9241208430; .
Jaffe M. (1886) Ueber den niederschlag, welchen pricrinsaure in normalen ham erzeugt und eine neue reaction des kreatinins. Hoppe Seylers Z Phys Chem 10:391-400.
Garnero P., Fledelius C., Gineyts E., Serre C.-M., Vignot E., Delmas P.D. (1997) Decreased β-isomerization of the C-terminal telopeptide of type I collagen α1 chain in Pagets disease of bone. J Bone Miner Res 12:1407-1415.
Kelly P.J., Pocock N.A., Sambrook P.N., Eisman J.A. (1989) Age and menopause-related changes in indices of bone turnover. J Clin Endocrinol Metab 69:1160-1165.
Riis B.J. (1993) Biochemical markers of bone turnover II: Diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 95:17-21.
Del Campo M.T., Gonzalez-Casaus M.L., Aguado P., Bernard M., Carrera F., Martinez M.E. (1999) Effects of age, menopause and osteoporosis on free, peptide-bound and total pyridinium crosslink excretion. Osteoporosis Int 9:449-454.
Fledelius C., Riis B.J., Overgaard K., Christiansen C. (1994) The diagnostic validity of urinary-free pyridinolines to identify women at risk of osteoporosis. Calcif Tissue Int 54:381-384.
Hassager C., Risteli J., Risteli L., Christiansen C. (1994) Effect of the menopause and hormone replacement therapy on the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen. Osteoporosis Int 4:349-352.
Garnero P., Gineyts E., Riou J.P., Delmas P.D. (1994) Assessment of bone resorption with a new marker of collagen degradation in patients with metabolic bone disease. J Clin Endocrinol Metab 79:780-785.
McLaren A.M., Hordon L.D., Bord H.A., Robins S.P. (1992) Urinary excretion of pyridinium crosslinks of collagen in patients with osteoporosis and the effects of bone fracture. Ann Rheum Dis 51:648-651.
Hoshimo H., Takahashi M., Kushida K., Ohishi T., Inoue T. (1998) Urinary excretion of type I collagen degradation products in healthy women and osteoporotic patients with vertebral and hip fractures. Calcif Tissue Int 62:36-39.
Eastell R., Robins S.P., Colwell T., Assiri A.M.A., Riggs B.L., Russell R.G.G. (1993) Evaluation of bone turnover in type I osteoporosis using biochemical markers specific for both bone formation and bone resorption. Osteoporosis Int 3:255-260.
Earnshaw S.A., Cawte S.A., Worley A., Hosking D.J. (1998) Colles' fracture of the wrist as an indicator of underlying osteoporosis in postmenopausal women: A prospective study of bone mineral density and bone turnover rate. Osteoporosis Int 8:53-60.
