Differential enhancement of collagen crosslink excretion in cases of osteosarcoma and chondrosarcoma

Abstract

Hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are markers of collagen absorption and LP is specific for collagen type I in bone. In the present study we evaluated the concentration of HP and LP in urine of patients with osteosarcoma ( n=20; age range 16-49 years) and chondrosarcoma ( n=15; age range 18-70 years). The values were compared with those obtained from 74 healthy controls (age range 16-83 years). The range and upper limit of normal values (HP(max) and LP(max)) were measured in our control group. High performance liquid chromatography (HPLC) was used to determine concentrations of HP and LP (nmol/mmol creatinine). The average urinary HP concentrations were significantly increased in patients with osteosarcoma ( p=0.001) and chondrosarcoma ( p<0.001), whereas HP remained within the normal range in approximately half of the patients. The average urinary LP concentrations were not increased in osteosarcoma and chondrosarcoma patients as compared with the control group. Further studies in a large group of patients are necessary to evaluate whether HP might be a valuable marker of prognosis, and if its urinary concentration can be correlated to tumour burden.

The post-translational phenotype of collagen synthesized by SAOS-2 osteosarcoma cells

“…Although elevated levels of LH1 have not yet been associated with any form of human disease, high levels of hydroxylysine and of glycatedhydroxylysine residues have been found in osteoporotic bone collagen, diabetic bone and skin collagen (reviewed in [57]), and osteosarcoma bone collagen [21,22]. Resorption of bone collagen with a high degree of lysine hydroxylation can explain the high HP:LP ratio in urine of osteosarcoma patients (25,26). Upregulation of LH1 activity in osteosarcoma cells can explain this.…”

“…The overall content of hydroxylysine in human bone collagen has been shown to vary greatly with stage of bone maturity [20], being higher, for example, in osteosarcoma bone [21,22], osteoporotic cancellous bone [23] and woven repair bone [24] than in normal mature bone. Elevated levels of hydroxylysyl pyridinoline (a marker of bone degradation) and a high HP:LP ratio in the urine of osteosarcoma patients [25,26] is likely to be due to the degradation of bone collagen with a high degree of lysine hydroxylation.…”