#1552 The role of osteocytes in bone remodeling: comparison between biopsies from patients with osteitis fibrosa and mixed uremic osteodystrophy disease
Authors: Chaer Juliana , Nunes Lucas A , Guapyassu Hanna K , Wagner Carolina S , de Oliveira Ivone Braga , Silva Cleonice , Dominguez Wagner Vasques , Martin Rita C T , Moyses Rosa M A , Dos Reis Luciene M , Jorgetti Vanda 
Published: May 2024

Abstract

Background and Aims
Osteocytes represent about 95% of bone cells. They are located in mineralized bone tissue and connect with each other, with osteoblasts, osteoclasts, blood vessels and bone marrow cells. These cells express several proteins that regulate phosphorus-calcium metabolism and bone remodeling. Disorders of mineral metabolism resulting from chronic kidney disease – mineral bone disorder (CKD-MBD) alter tissue function leading to histological changes known as renal osteodystrophy (ROD). ROD is classified: in high turnover – osteitis fibrosa (OF) and mixed uremic osteodystrophy (MUO) and low turnover – adynamic bone disease and osteomalacia. The participation of osteocytes proteins in ROD pathogenesis is not fully explained.
The aim of this study was to evaluate the expression of osteocytic proteins in bone biopsies from patients with OF and MUO and analyze clinical, biochemical and bone histomorphometric results.

Method
We evaluated patients with CKD on hemodialysis, who underwent bone biopsy to elucidate the diagnosis of ROD. Static and dynamic parameters by histomorphometry, including quantification of osteocytes, and the expression of proteins by immunohistochemistry (Sclerostin; Nuclear factor Kappa B ligand – RANKL; Osteoprotegerin – OPG; Dickkopf-related protein 1 - DKK1; Fibroblast growth factor 23 - FGF23; Dentin matrix protein 1 - DMP1; Matrix extracellular phosphoglycoprotein – MEPE; Phosphate regulatory gene with homologies to endopeptidases on the X chromosome – PHEX; podoplanin - E11; and CD44).

Results
We included 47 patients (24 with OF and 23 with MUO). Table 1 describes the results from the comparison between both groups. Patients with MUO were older and had lower serum P levels compared to patients with OF. Histomorphometric results showed that the structural parameter trabecular number was greater in patients with OF. The formation parameters, as osteoid volume, thickness and surface were greater in patients with MUO. Regarding mineralization, these patients also have lower bone formation rate, and mineralizing surface and a longer mineralization lag time. The expression of osteocytic proteins in both groups showed that DMP-1 was approximately 50% lower, near to statistical significance (p = 0.07) and RANKL was 23% lower in patients with MUO. In Table 2 are described the association found between proteins and histomorphometric parameters. The majority of the proteins involved in bone remodeling are negatively associated with histomorphometric parameters.

Conclusion
The clinical symptoms of CKD-BMD in patients with OF and MD are similar, and, except for serum P levels, other biochemical parameters did not contribute to differentiate Of and MUO. Bone biopsy, despite being an invasive procedure, revealed differences between the two pathologies, which could better guide clinical treatment, such as, vitamin D supplementation and VD analogs in patients with MUO who present an increase in osteoid parameters, which could improve bone mineralization. Regarding the expression of proteins in osteocytes, we found few differences between the two groups. However, several associations were observed between the expression of these proteins and structural, formation, reabsorption and mineralization parameters in high turnover bone disease.