Calcitriol Modulates Both the Vitamin D Receptor and the Calcium-Sensing Receptor in Blood Mononuclear Cells in Elderly Female Patients with Hip Osteoporotic Fractures.

INTRODUCTION

Peripheral blood mononuclear cells (PBMCs) constitute a diverse population of cells involved in adaptive and innate immunity, playing an essential role in pathogen recognition, immune signaling, and immune response modulation. Vitamin D deficiency through the regulation of vitamin D receptor (VDR) and calcium-sensing receptor (CaSR) gene expression could influence the apoptotic functioning of PBMCs, which, despite its importance in the immune response, has not been sufficiently explored.

OBJECTIVES

This research aimed to detect differences in the mRNA expression of CaSR, VDR, and apoptosis of PBMcs between elderly women with hip fractures and vitamin D deficiency and healthy young women, as well as in older women both at baseline and after administration of calcitriol.

METHODS

A case-control study involving 44 women (22 and 20, respectively) was conducted. The case group (hip fracture) was administered 2 µg/day of calcitriol for two weeks and a before-and-after comparison was made. The baseline gene expression of VDR and CaSR in PBMCs, as well as the effects of calcitriol on both the VDR/CaSR regulation and PBMC apoptosis, were studied in both groups. Serum bone biomarkers were also assessed.

RESULTS

No differences were observed in creatinine and calcium serum levels between the young and elderly osteoporotic women studied. Serum phosphorus and 25-hydroxyvitamin D (25(OH)D) were low in osteoporotic fractured women with vitamin D deficiency. In contrast, intact parathyroid hormone (PTH1-84) and alkaline phosphatase were high, while no significant difference in calcitriol [l,25(OH)2D3] serum levels was observed. In elderly women, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D, and calcitriol remained unchanged after intravenous calcitriol therapy; however, PTH1-84 decreased after the treatment. In comparison to the young women, the elderly women showed decreased VDR and increased CaSR mRNA expression in PBMCs, as well as higher monocyte apoptosis.

CONCLUSIONS

Calcitriol administration increased both VDR and CaSR mRNA expression in PBMCs and decreased PBMC apoptosis.

CONCLUSIONS

The results obtained support the role of the vitamin D endocrine system as a regulator of the immune response and thus may contribute to explaining certain aspects of the immune dysfunction reported in individuals with vitamin D insufficiency.