Suppression of Experimental Arthritis and Associated Bone Loss by a Tissue-Selective Estrogen Complex

Abstract

In addition to the systemic inflammation present in rheumatoid arthritis (RA), decreased estradiol levels in postmenopausal RA patients further accelerate bone loss in these patients. The tissue-selective estrogen complex (TSEC), an estrogen combined with a selective estrogen receptor modulator, is a new hormone replacement therapy option. The first approved TSEC, containing conjugated estrogens and bazedoxifene (BZA), reduces menopausal symptoms and prevents osteoporosis with an improved safety profile compared with conventional hormone replacement therapy. Previous studies have shown that estrogens strongly inhibit experimental arthritis whereas BZA is mildly suppressive. In this study the antiarthritic potential of combined BZA and estradiol is explored for the first time. Female ovariectomized DBA/1 mice were subjected to collagen-induced arthritis, an experimental postmenopausal RA model, and treated with BZA, 17β-estradiol (E2), combined BZA and E2 (BZA/E2), or vehicle. BZA/E2 suppressed arthritis severity and frequency, synovitis, and joint destruction, equally efficient as E2 alone. Unwanted estrogenic proliferative effects on the endometrium were blocked by the addition of BZA, determined by collecting uterine weights. Bone mineral density was measured by peripheral quantitative computed tomography, and all treatments protected collagen-induced arthritis mice from both trabecular and cortical bone loss. Moreover, BZA/E2, but not E2 alone, inhibited preosteoclast formation and reduced serum anticollagen type II antibodies. In conclusion, a TSEC, herein combined BZA/E2, suppresses experimental arthritis and prevents associated bone loss as efficiently as E2 alone but with minimal uterine effects, highlighting the need for clinical trials that evaluate the addition of a TSEC to conventional postmenopausal RA treatment.

Estrogen attenuates the spondyloarthritis manifestations of the SKG arthritis model

“…Therefore, selective estrogen receptor modulators (SERMs) were developed to prevent their side effects. Recent studies reported that SERMs inhibit joint inflammation and osteoporosis in female CIA animal models [ 43 , 44 ]. Further experiments are needed to evaluate the effects of SERMs in the SpA mouse model.…”

Association of blood neutrophil lymphocyte ratio in the patients with postmenopausal osteoporosis

“…Postmenopausal osteoporosis is a disease characterized by bone loss and microarchitectural deterioration leading to bone fragility and an increased risk of fracture. 1 The latest data 2 suggests that inflammation plays a critical role in bone remodeling and in pathogenesis of osteoporosis. The present study 3 describes the neutrophil as a cell that acquires roles beyond that of a prototypic inflammatory cell, directly capable of activating osteoclasts.…”

Application of Bone Marrow-Derived Mesenchymal Stem Cells in the Treatment of Intrauterine Adhesions in Rats

“…ER and PR are critical factors mediating the reproductive activity [29]. These two factors are extensively expressed in whole layers of uterus.…”