Collagen abnormalities in the skin and spinal cord have been reported in amyotrophic lateral sclerosis (ALS) patients. Serum carboxyterminal propeptide of type I procollagen (PICP) and the carboxyterminal cross-linked telopeptide of type I collagen (ICTP) reflect type I collagen synthesis and degradation, respectively. However, there has been no study concerning PICP or ICTP in ALS. We studied collagen contents of the skin and measured serum levels of PICP and ICTP in patients with ALS and control subjects. Serum PICP levels were significantly lower in ALS patients than in controls. Serum ICTP levels were significantly higher in ALS patients than in controls, and there was an appreciable positive correlation between serum ICTP levels and the duration of illness in ALS patients. In ALS patients, the collagen content of the skin was significantly smaller than in controls and indicated a progressive decrease in relation to illness. In addition, there was a significant negative correlation between serum ICTP concentrations and the collagen content of the skin in ALS patients. These data suggest that increased ICTP levels and decreased serum PICP levels may reflect unique changes in the skin, with a predominance of degradation compared to the synthesis of type I collagen in ALS.

1.
Ono S, Toyokura Y, Mannen T, Ishibashi Y: Amyotrophic lateral sclerosis: Histological, histochemical, and ultrastructural abnormalities of skin. Neurology 1986;36:948–956.
2.
Ono S, Imai T, Takahashi K, Jinnin K, Yamano T, Nagao K, Shimizu N, Yamauchi M: Decreased type IV collagen of skin and serum in patients with amyotrophic lateral sclerosis. Neurology 1998;51:114–120.
3.
Ono S, Yamauchi M: Collagen cross-linking of skin in patients with amyotrophic lateral sclerosis. Ann Neurol 1992;31:305–310.
4.
Ono S, Yamauchi M: Amyotrophic lateral sclerosis: Increased solubility of skin collagen. Neurology 1992;42:1535–1539.
5.
Ono S, Imai T, Munakata S, Takahashi K, Kanda F, Hashimoto K, Yamano T, Shimizu N, Nagao K, Yamauchi M: Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis. J Neurol Sci 1998;160:140–147.
6.
Triffitt JT: The special proteins of the bone tissue. Clin Sci 1987;72:399–408.
7.
Hunzelmann N, Risteli J, Risteli L, Sacher C, Vancheeswaran R, Black C, Krieg T: Circulating type I collagen degradation products: A new serum marker for clinical severity in patients with scleroderma. Br J Dermatol 1998;139:1020–1025.
8.
Prockop DJ, Kivirikko KI, Tuderman L, Guzman NA: The bio-synthesis of collagen and its disorders (first of two parts). N Engl J Med 1979;301:13–23.
9.
Miyahara M, Njieha FK, Prockop DJ: Formation of collagen fibrils in vitro by cleavage of procollagen with procollagen proteinases. J Biol Chem 1982;257:8442–8448.
10.
Melkko J, Niemi S, Risteli L, Risteli J: Radioimmunoassay of the carboxyterminal propeptide of human type I procollagen. Clin Chem 1990;36:1328–1332.
11.
Risteli J, Elomaa I, Niemi S, Novamo A, Risteli L: Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: A new serum marker of bone collagen degradation. Clin Chem 1993;39:635–640.
12.
Parfitt AM, Simon LS, Villanueva AR, Krane SM: Procollagen type I carboxy-terminal extension peptide in serum as a marker of collagen biosynthesis in bone. Correlation with iliac bone formation rates and comparison with total alkaline phosphatase. J Bone Miner Res 1987;2:427–436.
13.
Brooks BR: El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. J Neurol Sci 1994;124(suppl):96–107.
14.
Caroscio JT, Cohen JA, Zawodniak J, Takai V, Shapiro A, Blaustein S, Mulvihill MN, Loucas SP, Gudesblatt M, Rube D: A double-blind, placebo-controlled trial of TRH in amyotrophic lateral sclerosis. Neurology 1986;36:141–145.
15.
Patten BM, Harati Y, Acosta L, Jung SS, Feimus MT: Free amino acid levels in amyotrophic lateral sclerosis. Ann Neurol 1978;3:305–309.
16.
Minor RR: Collagen metabolism: A comparison of diseases of collagen and diseases affecting collagen. Am J Pathol 1980;98:225–280.
17.
Streuyer L: Biochemistry. New York, Freedman, 1988.
18.
Yamauchi M, Woodley DT, Mechanic GL: Aging and cross-linking of skin collagen. Biochem Biophys Res Commun 1988;152:898–903.
19.
Ono S, Mechanic GL, Yamauchi M: Amyotrophic lateral sclerosis: Unusually low content of collagen in skin. J Neurol Sci 1990;100:234–237.
20.
Smedsrød B, Melkko J, Risteli L, Risteli J: Circulating C-terminal propeptide of type I procollagen is cleared mainly via the mannose receptor in liver endothelial cells. Biochem J 1990;271:345–350.
21.
Hassager C, Jensen LT, Johansen JS, Riis BJ, Melkko J, Podenphant J, Risteli L, Christiansen C, Risteli J: The carboxy-terminal propeptide of type I procollagen in serum as a marker of bone formation: The effect of nandrolone decanoate and female sex hormones. Metabolism 1991;40:205–208.
22.
Akimoto S, Akakura K, Shimazaki J: Clinical usefulness of serum carboxyterminal propeptide of type I procollagen and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen in patients with prostate cancer. Jpn J Clin Oncol 1996;26:157–163.
23.
Joerring S, Jensen LT, Andersen GR, Johansen JS: Types I and III procollagen extension peptides in serum respond to fracture in humans. Arch Orthop Trauma Surg 1992;111:265–267.
24.
Li F, Iqbal J, Wassif W, Kaddam I, Moniz C: Carboxyterminal propeptide of type I procollagen in osteomalacia. Calcif Tissue Int 1994;55:90–93.
25.
Simon LS, Krane SM, Wortman PD, Krane IM, Kovitz KL: Serum levels of type I and III procollagen fragments in Paget’s disease of bone. J Clin Endocrinol Metab 1984;58:110–120.
26.
Guañabens N, Parés A, Alvarez L, Martinez de Osaba MJ, Monegal A, Perris P, Ballesta AM, Rodes J: Collagen-related markers of bone turnover reflect the severity of liver fibrosis in patients with primary biliary cirrhosis. J Bone Miner Res 1998;13:731–738.
27.
Savolainen ER, Goldberg B, Leo MA, Velez M, Lieber CS: Diagnostic value of serum procollagen peptide measurements in alcoholic liver disease. Alcohol Clin Exp Res 1984;8:384–389.
28.
Kikuchi K, Ihn H, Sato S, Igarashi A, Soma Y, Ishibashi Y, Takehara K: Serum concentration of procollagen type I carboxyterminal propeptide in systemic sclerosis. Arch Dermatol Res 1994;286:77–80.
29.
Kikuchi K, Sato S, Kadono T, Ihn H, Takehara K: Serum concentration of procollagen type I carboxyterminal propeptide in localized scleroderma. Arch Dermatol 1994;130:1269–1272.
30.
Díez J, Laviades C, Mayor G, Gil MJ, Monreal I: Increased serum concentrations of procollagen peptides in essential hypertension. Relation to cardiac alterations. Circulation 1995;91:1450–1456.
31.
Saggese G, Bertelloni S, Baroncelli GI, Nero GD: Serum levels of carboxyterminal propeptide of type I procollagen in healthy children from 1st year of life to adulthood and in metabolic bone diseases. Eur J Pediatr 1992;151:764–768.
32.
Tähtelä R, Thölix E: Serum concentrations of type I collagen carboxyterminal telopeptide (ICTP) and type I procollagen carboxy- and aminoterminal propeptides (PICP, PINP) as markers of metastatic bone disease in breast cancer. Anticancer Res 1996;16:2289–2293.
33.
Legovini P, De Menis E, Da Rin G, Roiter I, Breda F, Artuso V, Divirgilio R, Conte N: Increased serum levels of carboxyterminal propeptide of type I collagen (PICP) in hyperthyroidism. Horm Metab Res 1994;26:334–337.
34.
Oikarinen A, Autio P, Vuori J, Vaananen K, Risteli L, Kiistala V, Risteli J: Systemic glucocorticoid treatment decreases serum concentrations of carboxyterminal propeptide of type I procollagen and aminoterminal propeptide of type III procollagen. Br J Dermatol 1992;126:172–178.
35.
Miyakawa M, Tsushima T, Demura H: Carboxy-terminal propeptide of type 1 procollagen (P1CP) and carboxy-terminal telopeptide of type 1 collagen (1CTP) as sensitive markers of bone metabolism in thyroid disease. Endocr J 1996;43:701–708.
36.
Elomaa I, Virkkunen P, Risteli L, Risteli J: Serum concentration of the cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a useful prognostic indicator in multiple myeloma. Br J Cancer 1992;66:337–341.
37.
Hansen M, Hørslev-Petersen K, Stoltenberg M, Lorenzen I, Risteli L, Risteli J: Type I collagen metabolism in rheumatoid arthritis. Effect of a single pulse of methylprednisolone. Br J Rheumatol 1992;31(suppl 2):129.
38.
Hakala M, Risteli L, Manelius J, Nieminen P, Risteli J: Increased type I collagen degradation correlates with disease severity in rheumatoid arthritis. Ann Rheum Dis 1993;52:866–869.
39.
Heickendorff L, Zachariae H, Bjerring P, Hallkier-Sorensen L, Sondergaard K: The use of serologic markers for collagen synthesis and degradation in systemic sclerosis. J Am Acad Dermatol 1995;32:584–588.
40.
Kylmälä T, Tammela T, Risteli L, Risteli J, Tsube T, Elomaa I: Evaluation of the effect of oral clodronate on skeletal metastases with type I collagen metabolites. A controlled trial of the Finnish Prostate Cancer Group. Eur J Cancer 1993;29A:821–825.
41.
Ricard-Blum S, Chossegros P, Guerret S, Trepo C, Grimaud JA, Chevallier M: The carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) is a potential serum marker of ongoing liver fibrosis. Clin Chim Acta 1996;248:187–195.
42.
Wenisch C, Bankl HC, Schönthal E, Myskiw D, Presterl E, Runpold H, Graninger W: Serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen and laminin are elevated in Graves’ disease but not in toxic nodular goiter. Clin Immunol Immunopathol 1995;75:225–230.
43.
Katagiri M, Ohtawa T, Fukunaga M, Harada T: Evaluation of bone loss and the serum markers of bone metabolism in patients with hyperparathyroidism. Jpn J Surg 1995;25:598–604.
44.
Kahaleh MB, Sultany GL, Smith EA, Huffstutter JE, Loadholt CB, LeRoy EC: A modified scleroderma skin scoring method. Clin Exp Rheumatol 1986;4:367–369.
45.
Ono S, Imai T, Takahashi K, Jinnai K, Kanda F, Fukuoka Y, Hashimoto K, Shimizu N, Nagao K: Alteration in amino acids in motor neurons of the spinal cord in amyotrophic lateral sclerosis. J Neurol Sci 1999;167:121–126.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.