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

## TL;DR

This study shows that calcitriol affects immune cell receptors and reduces cell death in elderly women with hip fractures and vitamin D deficiency.

## Contribution

The novel finding is that calcitriol modulates both VDR and CaSR in PBMCs, reducing apoptosis in elderly patients with osteoporotic fractures.

## Key findings

- Elderly women with hip fractures showed decreased VDR and increased CaSR mRNA expression in PBMCs compared to young women.
- Calcitriol treatment increased VDR and CaSR mRNA expression and decreased PBMC apoptosis in elderly patients.
- PTH1–84 levels decreased in elderly women after calcitriol therapy, while other serum markers remained unchanged.

## Abstract

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.