Osteoporosis in murine SLE - Treatment with a tissue-selective estrogen complex
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease
affecting mainly young women. Almost every organ in the body can be
affected and SLE patients often suffer from co-morbidities such as
cardiovascular disease and osteoporosis. Postmenopausal women with
SLE have a three-fold increase in fractures compared with the healthy
population. Treatment with bisphosphonates is associated with side effects
and newer anti-osteoporotic treatments need to be tested in SLE patients.
MRL/lpr mice spontaneously develop lupus-like symptoms. We show that
ovariectomized MRL/lpr mice also develop an osteoporotic bone phenotype
and can be used as a model for osteoporosis in postmenopausal SLE.
Estrogen has been known to worsen SLE, however there are also
contradictory findings available. A tissue-selective estrogen complex
(TSEC) comprising estrogen and a selective estrogen receptor modulator
(SERM) facilitates the positive effects by estrogen on for example bone,
while the negative estrogenic effects on for example the endometrium is
blocked by the SERM. The TSEC consisting of conjugated estrogens and
the SERM Bazedoxifene (Bza) is approved for treatment of vasomotor
symptoms and prevention of postmenopausal osteoporosis. In this thesis
we show that treatment with TSEC and Bza protects from trabecular bone
loss in ovariectomized MRL/lpr mice, without affecting uterus or lupusassociated
disease parameters.
B lymphopoiesis and antibody production are regulated by estrogens. We
show that TSEC share the estrogenic inhibitory effect on B lymphopoiesis
and stimulatory effect on antibody production in healthy mice.
These findings have increased the knowledge regarding TSEC as a
potential future drug for treating osteoporosis in postmenopausal SLE
patients.
Date
2021-10Author
Nordqvist, Jauquline
Keywords
Tissue-Selective Estrogen Complex
Osteoporosis
MRL/lpr
Systemic Lupus Erythematosus
Selective Estrogen Receptor Modulator
Publication type
licentiate thesis
ISBN
978-91-8009-492-4
978-91-8009-493-1
Language
eng