Influence of Growth Hormone on a New Marker of Cartilage Metabolism (Chondrex) G. Radetti, 1 M. Bozzola, 2 V. Braga, 3 C. Paganini, 1 C. Moretti, 2 S. Adami 3 1 Department of Paediatrics, Regional Hospital of Bolzano, via L Boehler n° 5, 39100 Bolzano, Italy 2 Department of Paediatrics, Pavia, Italy 3 Rheumatologic Department, Ospedale di Valeggio, Italy Received: 19 March 1999 / Accepted: 3 February 2000 Abstract. The aim of this study was to evaluate the useful- ness of a major secretory protein of human chondrocytes (chondrex) as a potential serum marker of bone responsive- ness to growth hormone (GH). The study included 18 chil- dren (10 F, 8 M), aged 10.9 ± 2.3 years, bone age 8.8 ± 2.7 years, height -2.3 ± 0.22 SDS, affected by isolated idio- pathic GH deficiency (GHD). Serum samples for evaluation of chondrex, total, and bone alkaline phosphatase were taken before and 3 and 6 months following treatment with rhGH. The basal serum level of chondrex did not differ between patients (37 ± 22 ng/ml) and controls (33 ± 9.8 ng/ml). Following 6 months of treatment with rhGH, a sig- nificant increase of height velocity SDS (from -2.8 ± 0.5 to 1.3 ± 0.7), total (from 195 ± 47 to 264 ± 79 U/liter) and bone alkaline phosphatase (from 81 ± 21 to 108 ± 30 U/li- ter) was observed, while chondrex serum level remained unchanged (from 37 ± 22 to 36 ± 29 ng/ml). It was con- cluded that chondrex cannot be considered a reliable marker of bone responsiveness to GH in the growing child. Key words: Growth hormone — Growth — Chondrex — XKL-40. Growth hormone (GH) is a crucial factor during the period of growth in children and adolescents, allowing longitudinal bone growth, buildup, and maintenance of the peak bone mass. Clear evidence of the role played by GH also comes from treatment of GH-deficient children where a normal growth pattern is resumed and bone mineralization is nor- malized following therapy [1, 2]. GH acts directly by stimu- lating the prechondrocytes in the growth plate followed by clonal expansion due to both GH-induced local production of insulin-like growth factor I (IGF-I) and to a GH-induced increase in circulating levels of IGF-I [3]. The aim of our study was to evaluate the value of a major secretory protein of human condrocytes and synovial fibroblasts (chondrex) [4, 5] as a new potential serum marker of bone responsive- ness to GH. Material and Methods Patients We examined 18 children (10 F, 8 M), chronological age 10.9 ± 2.3 years, bone age 8.8 ± 2.7 years, affected by isolated idiopathic GH-deficiency (GHD). The diagnosis of GHD was based on the following criteria: height <2 SDS and/or height velocity (HV) <10th percentile for chronological age when measured for more than 6 months; bone age delay >2 years compared with chrono- logical age; peak GH <10 ng/ml after at least two consecutive conventional pharmacological tests, together with a mean 12-hour nocturnal GH concentration of less than 3.3 ng/ml. All children had normal pituitary features on magnetic resonance imaging (MRI); were free from any cardiovascular, respiratory, renal, or rheumatic diseases; and were not affected by any other endocrine disorders. Controls were 41 healthy children (24 F, 17 M), age 5.9 ± 4.7 years, assessed during routine medical examination. In GHD patients, blood was taken after an overnight fast, be- tween 8 and 9 a.m., before starting GH therapy and after 3 and 6 months to evaluate circulating chondrex and total and bone alka- line phosphatase. In controls, serum samples were taken only once. Auxology All patients were measured by a wall-mounted Harpenden stadi- ometer by the same observer before and after 6 months treatment. Height and height velocity were evaluated and expressed as height velocity-SDS, according to Tanner et al. [6]. Serum Markers The total alkaline phosphatase (T-ALP) was measured by standard automated procedures (Cobas Integra Roche analyzer; F. Hoff- man-La Roche Ltd. Basilea, Switzerland). The intra- and interas- say coefficients of variation (CVs) were below 1.6%. Serum bone alkaline phosphatase (B-ALP) was measured by ELISA (Alkphase-B, Metra Biosystems, CA, USA). The intra- and interassay CVs were 3.9% and 7.6%, respectively. Chondrex (YKL-40) was assayed in serum specimens by ELISA (Chon- drex, Metra Biosystems, CA, USA) by sandwich immunoassay. Intra-and interassay CVs were 5.6% and 7%, respectively. Chon- drex (also known as YKL-40) is a glycoprotein secreted by cul- tured human chondrocytes, synovial cells, and the osteosarcoma cell line, MG-63. Chondrex mRNA is undetectable in normal hu- man articular cartilage, but is prominent in patients with rheuma- toid arthritis. Its level in synovial fluid is approximately 15-fold higher than in serum. Chondrex appears to play a role in cartilage remodeling, perhaps as a glycosidic bond hydrolase with polysac- charide specificity. Statistical Analysis One-way analysis of variance with the Bonferroni correction as Correspondence to: G. Radetti Calcif Tissue Int (2000) 67:45–46 DOI: 10.1007/s00223001095 © 2000 Springer-Verlag New York Inc.