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Effects of lasofoxifene and bazedoxifene on B cell development and function
Angelina I Bernardi1, Annica Andersson1, Louise Grahnemo1
1Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, University of Gothenburg Sweden.
Immunity, Inflammation and Disease
|April 14, 2015
Summary
Third-generation SERMs lasofoxifene and bazedoxifene preserve B cell numbers during development and do not increase antibody production, unlike estradiol. These findings highlight their distinct immune effects.
Area of Science:
- Immunology
- Endocrinology
- Pharmacology
Background:
- Selective estrogen receptor modulators (SERMs) like lasofoxifene (las) and bazedoxifene (bza) treat osteoporosis.
- Estradiol (E2) and raloxifene (ral) impact B cells, affecting lymphopoiesis and antibody production.
- Immune effects of las and bza remain largely unstudied.
Purpose of the Study:
- To investigate the effects of las and bza on B cell development, maturation, and function.
- To compare the immunomodulatory effects of las and bza with E2 and ral.
Main Methods:
- Ovariectomized (ovx) and sham-operated C57BL/6 mice were treated with vehicle, E2, ral, las, or bza.
- Bone mineral density was measured using peripheral quantitative computed tomography.
- B cell populations and antibody-producing cells were analyzed by flow cytometry and ELISPOT.
Main Results:
- All treatments increased bone mineral density in ovx mice.
- E2 decreased B cell numbers across developmental stages and increased marginal zone (MZ) B cells.
- Las and bza reduced late-stage B cell development and splenic T1 B cells but did not affect MZ B cells or antibody production.
Conclusions:
- Lasofoxifene and bazedoxifene differ from estradiol in their effects on B cell lymphopoiesis and maturation.
- Unlike estradiol, las and bza do not increase the number of antibody-producing cells.
- These findings suggest distinct immunomodulatory profiles for third-generation SERMs compared to estradiol.
