M TIONG 1,2, S HOLT 1,2,3,4, N TOUSSAINT 1,2, H AL-KHAYYAT 1, E SMITH 1,2
1Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia, 2Department of Medicine (RMH), University of Melbourne, Parkville, Australia, 3SEHA Kidney Care, Abu Dhabi Health Services Company, Abu Dhabi, United Arab Emirates, 4Khalifa University, Abu Dhabi, United Arab Emirates
Aim: To examine the relationship between serum calciprotein particles (CPP) and bone turnover in patients with chronic inflammatory disease (CID) receiving infliximab.
Background: Patients with chronic kidney disease (CKD) and CID experience accelerated vascular calcification and loss of bone mineral density. CPP are circulating colloidal aggregates of calcium and phosphate with the mineral-binding protein fetuin-A, which have emerged as potential mediators of vascular calcification in CKD, and are elevated in CID. The precise origins of CPP in these settings is unclear, but bone turnover may be an important source.
Methods: We studied ten patients with active CID undergoing induction treatment with infliximab and three patients with quiescent CID receiving maintenance infliximab. Using validated disease activity scores, patients were grouped according to therapeutic response, and the dynamic relationship between bone turnover and serum CPP was compared between groups over 8 weeks.
Results: Patients with active CID had elevated bone resorption markers and suppressed bone formation markers as well as higher calciprotein monomers (CPM) and primary CPP (CPP-I) compared to those with quiescent CID. Patients who responded to induction treatment had an early but transient reduction in resorption markers by week 1, but a more sustained increase in bone formation markers compared to non-responders at week 8. This was accompanied by reductions in CPM (= -6.5×103 AU [95%CI -11.1, -1.8], p=0.006) and CPP-I (= -23.4×104 particles/ml [95%CI -34.8, -11.9], p<0.001). No significant change in any marker was observed in non-responders or those receiving maintenance therapy.
Conclusions: CPP have a dynamic association with changes in bone turnover in response to infliximab therapy, adding to accumulating evidence of the role of bone as a determinant of systemic levels
Dr Mark Tiong completed his RACP fellowship in nephrology in 2019 and currently works as a fellow in the Department of Nephrology at The Royal Melbourne Hospital. He is also currently undertaking his PhD in the area of Chronic Kidney Disease – Mineral and Bone Disorder (CKD-MBD) within the Department of Medicine (RMH) at The University of Melbourne.