2.2. Effect of Nitisinone Treatment on the ECM Biomarkers
PRO-C1, ill
None of the studied biomarkers showed a significant difference after nitisinone treatment (end of study), but CTX-II/Creat levels increased significantly in the urine of controls and not that of treated patients (However, analysing the trajectories over time, levels of the biomarkers of bone remodelling (CTX-I and PRO-C1) increased significantly in patients treated with nitisinone compared to controls after one year of treatment (19% (95% CI [5%, 36%]) and 40% (95% CI [19%, 65%]), respectively), returning to levels like the control group at later time points (It was then investigated whether the trajectories of the ECM biomarkers and ALP were different in patients stratified by sex, age (≤55 or >55 years), cAKUSSI (above or below the median), and concomitant antiresorptive treatment at baseline (When stratifying by age, the lowering of CTX-II/Creat at Year 1, 3, and 4 in the nitisinone-treated patients was significant only in the younger patients. Further, the lowering in CTX-II/Creat at Year 4 was only significant in males. When looking at C2M, the difference in the levels of the biomarker at Year 4 in the nitisinone-treated group was significant only in males and in patients with cAKUSSI below the median, i.e., the less severely ill patients. There was no significant interaction of the concomitant use of antiresorptive treatment for any of the biomarkers, and there was no significant interaction between treatment and age, sex, or cAKUSSI at baseline for the biomarkers of type I collagen turnover.