Potential diagnostic value of PD-1 in peripheral blood mononuclear cells of postmenopausal osteoporosis patients.

Xiu‐Ping Cai,Zhi‐Xiang Chen,Shao‐Jun Lin,Zhao‐Di Guo,Min‐Yuan Chen,Qing Zhao,Lei Zheng,Ke‐Wei Zhao

doi:10.1002/jcla.23223

Abstract

BackgroundPostmenopausal osteoporosis (PMOP) is an estrogen deficiency‐induced skeletal disorder. Bone mineral density (BMD) testing is the gold standard for diagnosing osteoporosis. However, its sensitivity for fracture risk assessment is low. Programmed cell death protein 1 (PD‐1) is a key immune checkpoint molecule implicated in the pathophysiology of bone remodeling, but its role in osteoporosis has not yet been explored. Thus, this study aimed to assess the expression and diagnostic utility of PD‐1 in PMOP.MethodsA total of 56 patients with PMOP and 37 postmenopausal healthy controls (NC) were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll density gradient centrifugation, and PD‐1 expression was measured by quantitative polymerase chain reaction (qPCR). Pearson's correlation test was performed to explore the associations between PD‐1 level and clinical variables, while receiver operating characteristic (ROC) curve analysis was used to evaluate the potential diagnostic value of PD‐1 in patients with PMOP.ResultsWe found that PD‐1 level was significantly upregulated in the PBMCs of PMOP patients than those of NC (P = .016). PD‐1 expression was positively correlated with C‐reactive protein (CRP) levels. ROC curve analysis showed that PD‐1 had certain diagnostic value for PMOP (area under the curve = 0.65, standard error = 0.06, 95% confidence interval [0.53,0.76], P = .016), with a sensitivity and specificity of 44.64% and 81.08%, respectively.ConclusionProgrammed cell death protein 1 is significantly upregulated in the PBMCs of PMOP patients and has certain diagnostic value for PMOP.

Highlights

Postmenopausal osteoporosis (PMOP) is a systemic, metabolic bone disorder resulting from decreased ovarian estrogen production after menopause[1] and disrupted balance between bone resorption and bone formation
The diagnostic value of PD-1 was assessed by receiver operating characteristic (ROC) curve analysis, in which the postmenopausal osteoporosis (PMOP) patients and healthy controls served as true positives and true negatives, respectively
To determine whether PD-1 in the Peripheral blood mononuclear cells (PBMCs) of PMOP patients could serve as a biomarker for the severity of PMOP, we evaluated the correlations between PMOP-related clinical features and PD-1 expression in PMOP patients

Summary

| INTRODUCTION

Postmenopausal osteoporosis (PMOP) is a systemic, metabolic bone disorder resulting from decreased ovarian estrogen production after menopause[1] and disrupted balance between bone resorption (mediated by osteoclasts) and bone formation (mediated by osteoblasts). Measurement of bone turnover markers (BTMs) is useful in differential diagnosis, distinguishing the different types of osteoporosis, and early assessment of patient response to treatment, but it cannot be used to diagnose osteoporosis. The recent advances in osteoimmunology, an interdisciplinary research field that explores the interaction between bone and immune system, revealed that bone remodeling is under strict immunological control.[3] it is of vital clinical importance to identify the specific immune molecules involved, as they could serve as potential targets for the diagnosis and treatment of osteoporosis. Programmed cell death protein-1 (PD-1) is an inhibitory immune receptor that is mainly expressed on active T cells, B cells, monocytes, dendritic cells, and natural killer cells. We explored PD-1 expression, and its association with clinical and laboratory parameters, in PMOP patients

| Ethical approval

Findings

| DISCUSSION