Burosumab treatment in a child with cutaneous skeletal hypophosphatemia syndrome: A case report

Manal Khadora, Zulf Mughal
2021 Bone Reports  
Background/Introduction: Osteoarthrosis (OA) of the hip leads to destruction of cartilage and bone tissue, requiring arthroplasty. Immune and stromal cells were found to be important in OA-affected synovial fluid, while cell compartments of bone marrow (BM) involved in OA are not revealed. Purpose: We investigated BM populations of acetabulum and proximal femur obtained from patients at different OA stages. Methods: BM reaming samples, 71 acetabulum (age 63,83±12,09 years) and 21 matched
more » ... l femur (age 63±12,09 years), were obtained from patients undergoing total hip arthroplasty. Patients underwent radiographic imaging and were scored in accordance with the Kellgren and Lawrence classification. The study was approved by local ethical committee (No. 187/18). Cells were analyzed combining ex vivo and in vitro assays, using flow cytometry, RT-PCR and histochemical staining. Normal distribution of data was analyzed using the D'Agostino & Pearson test. Correlations were calculated using Spearman's rank correlation (r). Results: The frequency of CD45 + CD3 + CD4 + T-lymphocytes was higher in acetabular (3,67±0,98%) BM when compared to femur (2,34± 0,37%), and increased with age (r=0,448; p=0,008). Frequencies of examined B-lineage cells were significantly lower in acetabulum, where acetabular CD45 + CD3 + CD4 + CD25 + T-lymphocytes (2,98±1,07%) positively correlated with CD19 + B-lymphocytes (1,57±0,97%) frequency. The incidence of CD45 -CD34 -CD13 + CD73 + stromal cells was higher in acetabulum (0,0019±0,00065%) than in femur (0,0005± 0,0001%) (p=0,056), showing certain positive correlation with presence of clonogenic cells. A higher proliferation rate in acetabular mesenchymal stromal cells (MSCs) was also associated with increased β-galactosidase activity and expression of genes involved in the regulation of cell cycle and survival (p16, p53, HiF1α, Survivin), and immunomodulatory activity (ll-7, Il-6, Ido-1, Ptgs2, Tgf-β1). Acetabular MSCs displayed higher osteogenic and chondrogenic, but weaker adipogenic potential than their femoral counterparts. Conclusion(s): Our findings suggest that hip OA severity and associated risk factors may correlate with marrow cell frequency and functionality, indicating the possible skeletal site-dependent behavior of marrow cells in OA.
doi:10.1016/j.bonr.2021.100846 fatcat:gnxipue2ibcatg43lct6vmjqwa