Lasofoxifene

The third generation selective estrogen receptor modulators lasofoxifene (las) and bazedoxifene (bza) are indicated for treatment of postmenopausal osteoporosis. 17β-Estradiol (E2) and the second generation SERM raloxifene (ral) have major effects on the immune system, particularly on B cells. Treatment with E2 or ral inhibits B lymphopoiesis and treatment with E2, but not ral, stimulates antibody production. The effects of las and bza on the immune system have not been studied. Therefore, the aim of this study was to investigate their role in B cell development, maturation, and function. C57BL/6 mice were sham-operated or ovariectomized (ovx) and treated with vehicle, E2, ral, las, or bza. All substances increased total bone mineral density in ovx mice, as measured by peripheral quantitative computed tomography. In uterus, bza alone lacked agonistic effect in ovx mice and even acted as an antagonist in sham mice. As expected, E2 decreased B cell numbers at all developmental stages from pre-BI cells (in bone marrow) to transitional 1 (T1) B cells (in spleen) and increased marginal zone (MZ) B cells as determined by flow cytometry.

OBJECTIVE: RA predominantly affects post-menopausal women and is strongly associated with development of generalised osteoporosis. To find treatments that target both joint manifestations and osteoporosis in RA is desirable. The third generation of selective oestrogen receptor modulators (SERMs) [lasofoxifene (LAS) and bazedoxifene (BZA)] are new treatment options for post-menopausal osteoporosis. The aim of this study was to investigate the effects of LAS and BZA on arthritic disease and inflammation-associated bone loss using CIA in mice.