Role of raloxifene as a potent inhibitor of experimental postmenopausal polyarthritis and osteoporosis

Jochéms, Caroline; Islander, Ulrika; Kallkopf, Anna; Lagerquist, Marie K; Ohlsson, Claes; Carlsten, Hans

doi:10.1002/art.22873

Cited by 40 publications

(49 citation statements)

References 34 publications

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“…It has repeatedly been shown that treatment with E2 improves disease development in experimental models of arthritis (Jansson and Holmdahl, 1989;Nandakumar et al, 2003;Engdahl et al, 2014) shown that the second generation SERM ral inhibits experimental postmenopausal arthritis (Jochems et al, 2007). Interestingly, preliminary data from our lab show that also las and bza have beneficial effects on disease development and associated bone loss in postmenopausal collagen-induced arthritis (Andersson et al, submitted).…”

Section: Introductionmentioning

confidence: 82%

“…Conversely, hormone replacement therapy including E2 ameliorates rheumatoid arthritis and multiple sclerosis (D'Elia et al, 2003;El-Etr et al, 2011) and treatment with E2 inhibits experimental models of arthritis and multiple sclerosis (Jansson and Holmdahl, 1989;Nandakumar et al, 2003;Engdahl et al, 2014). Our group has previously demonstrated that ral ameliorates arthritis and protects against bone loss in experimental collagen-induced arthritis (CIA) (Jochems et al, 2007). Interestingly, preliminary data show that also las and bza Fig.…”

Section: Discussionmentioning

confidence: 98%

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Selective estrogen receptor modulators in T cell development and T cell dependent inflammation

et al. 2015

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Lasofoxifene (las) and bazedoxifene (bza) are third generation selective estrogen receptor modulators (SERMs) with minimal estrogenic side effects, approved for treatment of postmenopausal osteoporosis. T cells are involved in the pathology of postmenopausal osteoporosis and previous studies have established an important role for 17β-estradiol (E2) in T cell development and function. E2 causes a drastic thymic atrophy, alters the composition of thymic T cell populations, and inhibits T cell dependent inflammation. In contrast, the second generation SERM raloxifene (ral) lacks these properties. Although las and bza are drugs approved for treatment of postmenopausal bone loss, it is of importance to study their effects on other biological aspects in order to extend the potential use of these compounds. Therefore, the aim of this study was to investigate if treatment with las and bza affects T lymphopoiesis and T cell dependent inflammation. C57Bl6 mice were ovariectomized (ovx) and treated with vehicle, E2, ral, las or bza. As expected, E2 reduced both thymus weight and decreased the proportion of early T cell progenitors while increasing more mature T cell populations in the thymus. E2 also suppressed the T cell dependent delayed-type hypersensitivity (DTH) reaction to oxazolone (OXA). Ral and las, but not bza, decreased thymus weight, while none of the SERMs had any effects on T cell populations in the thymus or on inflammation in DTH. In conclusion, this study shows that treatment with las or bza does not affect T lymphopoiesis or T cell dependent inflammation.

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Section: Introductionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 98%

Selective estrogen receptor modulators in T cell development and T cell dependent inflammation

et al. 2015

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“…In addition, an epidemiological study showed that HRT users had decreased risk of developing seropositive RA (in this case having antibodies against citrullinated peptides)-compared with nonusers (10). Estradiol is undoubtedly protective in mice with experimental arthritis (11,12). We have previously demonstrated that the SERMs, raloxifene, lasofoxifene, and BZA, inhibit joint inflammation and protect from bone loss in experimental arthritis (11,12).…”

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confidence: 99%

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

et al. 2016

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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.

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“…Treatment with aromatase inhibitor has decreased trabecular bone mass but has minimal effect on cortical bone area in intact male rats [30,51]. Selective estradiol receptor modulators (SERMs) increase cortical and trabecular bone mass in orchiectomized rats and increases trabecular bone mass in intact males [52,53]. DHEA and androstenedione increase trabecular bone formation in ovariectomized rats.…”

Section: ) Epidemiology Of Osteopenia and Osteoporosismentioning

confidence: 99%

Low Testosterone—An Important Predictor of Low Mineral Bone Density in Young Men—Our Own Experience and a Review of Literature

Funaro¹,

Bolyakov²,

Gimenez³

et al. 2013

ASM

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Urologists and reproductive endocrinologists have become the first contact physicians for young men of reproductive age and have the unique opportunity to positively affect men's health and quality of life. Growing evidence indicates that a significant proportion of men presenting with infertility or sexual dysfunction are hypogonadal. One hundred ninety nine men were enrolled in our center, and mean total testosterone was <300 ng/dl. Patients were divided into three groups based on their DEXA scan results; normal bone density (n = 122, 57%), osteopenia (n = 69, 39%) and osteoporosis (n = 8, 4%). There were no differences in the mean age (p < 0.64), height (p < 0.99) and weight (p < 0.06) among the three groups (ANOVA), but men with osteopenia had statistically significant lower weights (p < 0.02). Our results indicate that hypogonadism is one of the main risk factors for osteopenia and osteoporosis which can be found in 8% of hypogonadal men younger than 50 years of age. Testosterone replacement therapy may be indicated in most men with hypogonadism and low bone mineral density (BMD); however the benefits of testosterone treatment in eugonadal men are unproven. Selective estradiol and androgen receptor modulators expand our treatment modalities in men of reproductive age when suppression of gonadotropins may interfere with reproductive plans. Early detection of hypogonadism and osteoporosis may lower the risk of hip and vertebral fractures in some men. Further prospective RCTs are needed to prove cost-effectiveness of detection and the best treatment of osteoporosis in hypogonadal men of reproductive age. Urologists have the opportunity to be at the forefront of greater awareness of this clinical problem due to their frequent contact with this population of patients.

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Role of raloxifene as a potent inhibitor of experimental postmenopausal polyarthritis and osteoporosis

Cited by 40 publications

References 34 publications

Selective estrogen receptor modulators in T cell development and T cell dependent inflammation

Selective estrogen receptor modulators in T cell development and T cell dependent inflammation

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

Low Testosterone—An Important Predictor of Low Mineral Bone Density in Young Men—Our Own Experience and a Review of Literature

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