The Imbalance of Cytokines and Lower Levels of Tregs in Elderly Male Primary Osteoporosis

Abstract

Introduction: Osteoporosis (OP) is a debilitating disease that brings a heavy burden to individuals and society with reduced quality of life and lifespan. However, it's frequently overlooked and poorly studied in elderly male patients. Worse still, few anti-osteoporosis drugs are effective at the prevention and treatment of osteoporosis in men. It has been reported that the cells of bone and the immune system share common progenitors, cytokines and growth factors, and that reciprocal interactions occur during health and disease. Nevertheless, the role of immune system in OP is not fully understood, especially in male patients. Therefore, this study aimed to investigate molecular alterations in immune cells in men with OP and to identify immunomodulatory strategies with potential therapeutic value.

Materials and methods: A population of 121 men aged between 51 and 80 years old was recruited. Bone mineral density (BMD) was measured at the lumbar spine L1-4 and femoral neck using dual-energy X-ray absorptiometry (DXA). Twenty people were healthy, 66 people had osteopenia and 35 people had OP. Bone metabolic markers, Th1, Th2, Tregs and immune molecules were evaluated at the time of enrollment.

Results: Smoking was a risk factor for OP. C-terminal crosslinking of type I collagen (β-CTX) and the ratio of receptor activator of nuclear factor-κB ligand (RANKL) to osteoprotegerin (OPG) were higher in OP group, which had lower 25-hydroxyvitamin D [25(OH)D] levels. OP had the higher levels of IL-6 and TNF-α and lower levels of IFN-γ and IL-10. CD4⁺CD25⁺CD127^-/low Tregs were significantly lower in the OP group. The imbalance of Th1/Th2 cells may play an important role in the development of OP. 25(OH)D may play essential roles in maintaining bone health. The low level of Tregs is also one of the underlying immune mechanism that leads to male primary OP.

Conclusion: The active function of osteoclasts and the decline in osteoblasts were characteristics of OP, and the imbalance in cytokines and lower levels of Tregs were observed in elderly male patients with primary OP.

Keywords: Treg cells; bone mineral density; bone turnover markers; cytokines; male primary osteoporosis.

Figure 1

Characteristics of the studied groups. (A) Spine L1-4 BMD and Femoral neck BMD. (B) Bone metabolic markers [25(OH)VD, β-CTX, RANKL/OPG]. (C) Plasma levels of TNF-α and IFN-γ secreted by Th1. (D) Plasma levels of IL-6 and IL-10 secreted by Th2. (E) CD4⁺CD25⁺CD127^-/low Treg cells. *p < 0.05, **p < 0.01, ^# p < 0.017 (^# p < 0.017, was considered significant, the test level needed to be adjusted for multiple pairwise comparisons of data, inspection level α’= inspection level α/times of comparison). NS, No statistical differences. Data are Mean± SD or Mean ± Q.

Figure 2

The correlation between clinical indicators and the incidence of OP. (A) 25(OH)D, CD4⁺CD25⁺ Treg cell and CD4⁺CD25⁺CD127^-/low Treg cell were found to decrease after the occurrence of OP. (B) RANKL/OPG, CD4/CD8, TNF-α and IL-6 were found to increase after the occurrence of OP.