[Skip to Content]
[Skip to Content Landing]
December 1966

Hydroxyproline Excretion in Malignant Neoplastic Disease

Author Affiliations


From the Department of Medicine, Albany Medical College of Union University, Albany.

Arch Intern Med. 1966;118(6):565-571. doi:10.1001/archinte.1966.00290180041008

THE HE URINARY excretion of peptide bound hydroxyproline reflects the rate of bone collagen metabolism 1-3 being elevated in disorders affecting bone such as hyperthyroidism,1,3-5 hyperparathyroidism,1,3,6 acromegaly,1,3 Paget's disease of bone,1,3,5,7 Marfan's syndrome,8 Hurler's syndrome,9 malabsorption states (with secondary osteomalacia,7 and rheumatoid arthritis.10 The immediate derivation of urinary hydroxyproline, whether from catabolism of mature bone 2,8 or from synthesis of soluble collagen fractions 2,5,6 or from both is disputed.

Elevated hydroxyproline with normal skeletal radiographs has been reported in pregnancy and postpartum involution,11 psoriasis (with and without arthritis),12,13 thermal burns,14 and mental deficiency states.15,16

Since 1956, hydroxyproline excretion rates have been reported in 80 cases of malignancy with and without bone involvement.5,9,10,17-21 The present communication reports the observations in 117 additional adult patients with malignant neoplastic disease.

Methods  Normal adults and adult patients with cancer in various primary sites and stages were studied. Whenever possible, patients were studied prior to

Dull, T.A., and Henneman, P.H.:  Urinary Hydroxyproline as an Index of Collagen Turnover in Bone ,  New Eng J Med 268:132, 1963.Crossref
Smiley, J.D., and Ziff, M.:  Urinary Hydroxyproline Excretion and Growth ,  Ann Rev Physiol 44: 30, 1964.
Benoit, F.L.; Thiel, G.B.; and Watten, R.H.:  Hydroxyproline Excretion in Endocrine Disease ,  Metabolism 12:1072, 1963.
Kivirikko, K.I., et al:  Hydroxyproline in the Serum and Urine of Patients With Hyperthyroidism ,  J Clin Endocr 24:222, 1964.Crossref
Klein, L., et al:  Correlation of Urinary Hydroxyproline, Serum Alkaline Phosphatase, and Skeletal Calcium Turnover ,  Metabolism 13:272, 1964.Crossref
Klein, L.; Albertsen, K.; and Curtiss, P.H., Jr.:  Urinary Hydroxyproline in Hyperparathyroidism ,  Metabolism 11:1023, 1962.
Crabbe, P., and Isselbacher, K.J.:  Urinary Hydroxyproline Excretion in Malabsorption States ,  Gastroenterology 48:307, 1965.
Prockop, D.J., and Sjoerdsma, A.:  The Significance of Urinary Hydroxyproline in Man ,  J Clin Invest 40:843, 1960.Crossref
Nakagawa, M., and Tamaki, T.:  Urinary Hydroxyproline Excretion in Orthopedic Disease ,  Nagoya J Med Sci 27:228, 1965.
Ziff, M., et al:  Excretion of Hydroxyproline in Patients With Rheumatic and Nonrheumatic Diseases ,  J Clin Invest 35:579, 1956.Crossref
Klein, L.:  Urinary Hydroxyproline During Late Pregnancy and Postpartum Involution ,  Metabolism 13:386, 1964.Crossref
Korting, G.W., and Holzmann, H.:  Zur Hydroxyprolin-Ausscheidung im Harn von Hautkranken ,  Klin Wschr 43:361, 1965.Crossref
Brunish, R., and Sorensen, B.:  Urinary Ex- cretion of Acid Mucopolysaccharides and Hydroxyproline in Psoriasis ,  Dermatologica 130:165, 1965.Crossref
Klein, L.; Curtiss, P.H., Jr.; and Davis, J.H.:  Collagen Breakdown in Thermal Burns ,  Surg Forum 13:459, 1962.
Seakins, J.W.T.:  Peptiduria in an Unusual Bone Disorder ,  Biochem J 84:115P, 1962.
Efron, M.L., et al:  Hydroxyprolinemia Associated With Mental Deficiency ,  New Eng J Med 267:1193, 1962.Crossref
Rubegni, M.; Ravenni, G.; and Del Giovane, L.:  Aumento Dell'Eliminazione Urinaria Dell'Idrosiprolina nei Processi Osetolitici ,  Boll Soc Ital Biol Sper 38:877, 1962.
Bentzel, C.J.; Carbone, P.P.; and Rosenberg, L.:  The Effect of Prednisone on Calcium Metabolism and Ca47 Kinetics in Patients With Multiple Myeloma and Hypercalcemia ,  J Clin Invest 43:2132, 1964.Crossref
Platt, W.D.; Doolittle, L.H.; and Hartshorn, J.W.S.:  Urinary Hydroxyproline in Metastatic Cancer of Bone ,  New Eng J Med 271:287, 1964.Crossref
Mitoma, C., et al:  Improvements in Methods for Measuring Hydroxyproline: Application to Human Urine ,  J Lab Clin Med 53:970, 1959.
Leroy, E.C.; Carbone, P.P.; and Sjoerdsma, A.::  Elevated Plasma Levels of a Hydroxyproline Containing Protein in Hodgkin's Disease and Their Relation to Disease Activity ,  J Lab Clin Med 67:891, 1966.
Prockop, D.J., and Udenfriend, S.:  A Specific Method for the Analysis of Hydroxyproline in Tissues and Urine ,  Anal Biochem 1:228, 1960.Crossref
Jones, C.R., et al:  Urinary Hydroxyproline Excretion in Normal Children and Adolescents ,  Proc Soc Exp Biol Med 115:85, 1964.Crossref
Lenzi, F., et al:  The Significance of Urinary Hydroxyproline in Osteoporosis ,  Panminerva Med 5:155, 1963.
Moskowitz, R.W.; Klein, L.; and Katz, D.:  Urinary Hydroxyproline Levels in an Aged Population: A Study of Non-osteoporotic and Osteoporotic Patients ,  Arthritis Rheum 8:61, 1965.Crossref
Bonadonna, G.; Sonenberg, M.; and Merlino, S.:  Total Urinary Hydroxyproline Excretion in Diabetics Before and After Hypophysectomy and After Growth Hormone in Adult Hypopituitarism ,  Metabolism 14:832, 1965.Crossref
Theil, G.B.; Benoit, F.L.; and Watten, R.H.:  An Oral Gelatin-Xylose Test for Estimating Pancreatic Proteolytic Activity ,  Amer J Dig Dis 8:1008, 1963.Crossref
Sjoerdsma, A., et al:  Hydroxyproline and Collagen Metabolism: Clinical Implications ,  Ann Intern Med 63:672, 1965.Crossref
Prockop, D.J.:  Isotopic Studies on Collagen Degradation and the Urinary Excretion of Hydroxyproline ,  J Clin Invest 43:453, 1964.Crossref
Ginsburg, J.:  Hypertrophic Pulmonary Osteoarthropathy ,  Postgrad Med J 39:639, 1963.Crossref
Scriver, C.R.; Efron, M.L.; and Schafer, I.A.:  Renal Tubular Transport of Proline, Hydroxyproline, and Glycine in Health and Familial Hyperprolinemia ,  J Clin Invest 43:374, 1964.Crossref
Dubovsky, J.; Pacovsky, V.; and Dubovska, E.:  Plasma Hydroxyproline and Proline in Primary Hyperparathyroidism and in Chronic Uremia ,  Clin Chim Acta 12:230, 1965.Crossref