DHEA prevents bone loss by suppressing the expansion of CD4⁺ T cells and TNFa production in the OVX-mouse model for postmenopausal osteoporosis

Abstract

Recent studies have suggested that dehydroepiandrosterone (DHEA) might serve as a form of immunomodulatory therapy for postmenopausal osteoporosis (PMO). The current study investigated the effects of DHEA administration on ovariectomy (OVX)-induced bone loss and its corresponding immunological changes. Adult OVX mice were treated with DHEA or 17-β-estradiol (E2) for 12 weeks, with or without the aromatase inhibitor letrozole. DHEA improved bone mass after OVX and displayed action like that of E2 with regard to decreasing osteoclast-related parameters. DHEA also suppressed an OVX-induced increase in CD4⁺ T cell subsets and TNF-α production. However, DHEA elevated serum E2 levels to a lesser extent than E2. Although letrozole decreased serum E2 levels in OVX mice treated with DHEA, it did not alter DHEA's effects on corresponding immunological changes due to OVX. In conclusion, DHEA may prevent bone loss by suppressing the OVX-induced expansion of CD4⁺ T cells and TNF-α production in mice, independent of E2.