Raloxifene: Mechanism of Action, Effects on Bone Tissue, and Applicability in Clinical Traumatology Practice

Abstract

Raloxifene, a member of the class of selective estrogen receptor modulators (SERM), reproduces the beneficial effects of estrogens on the skeletal systems, without the negative effects estrogens on breast and endometrium. This is a review article summarizing its mechanism, effects on bone and its applicability in traumatology clinical practice. In postmenopausal osteoporosis, this drug has been proven to decrease accelerated bone turnover, increase bone mineral density (BMD), and to structurally recover bone, decreasing the risk of vertebral fractures and the risk of non-vertebral fractures in patients with previous, severe vertebral fractures. Moreover, raloxifene appears to lower the risk of invasive breast cancer. Raloxifene would be efficacious in the prevention and treatment of postmenopausal osteoporosis.We can therefore conclude that raloxifene would be efficacious in the prevention and treatment of postmenopausal osteoporosis, while reducing the risk of breast cancer when used at the indicated dose of 60 mg/day and with a low incidence of side effects.

Association Between Hormone-Modulating Breast Cancer Therapies and Incidence of Neurodegenerative Outcomes for Women With Breast Cancer

“…More specifically, the steroidal aromatase inhibitor (exemestane) had a greater association than nonsteroidal aromatase inhibitors (anastrozole and letrozole) with reduced RR of neurodegenerative disease outcomes. divergent actions in uterine tissue [48][49][50][51] and brain tissue. 52,53 Aromatase inhibitors are known to act systemically to decrease the amount of estrogen.…”

Osteoporosis: Therapeutic Options

“…This drug has been extensively studied and data support its estrogen agonist profi le in the skeletal system. 47 The molecular mechanisms of action of SERM include: 1) differential binding activity to ER-α receptors (selective partial agonist / antagonist) and ER-β receptors (selective antagonist); 2) direct reduction of resorbing activity by inhibiting the production of interleukin 6, tumor necrosis factor α and inhibition of RANKL and increased production of transforming growth factor -β3. 47 SERM are shown for the prevention of vertebral fractures and treatment of osteoporosis in postmenopausal women.…”

“…47 The molecular mechanisms of action of SERM include: 1) differential binding activity to ER-α receptors (selective partial agonist / antagonist) and ER-β receptors (selective antagonist); 2) direct reduction of resorbing activity by inhibiting the production of interleukin 6, tumor necrosis factor α and inhibition of RANKL and increased production of transforming growth factor -β3. 47 SERM are shown for the prevention of vertebral fractures and treatment of osteoporosis in postmenopausal women. 47 PHYTOESTROGENS Phytoestrogens are polyphenolic plant metabolites: fl avonoids, fl avonols: kaempferol, quercetin, rutin, icariin; fl avanols: catechin, epicatechin of Camellia sinensis L.; polymeric fl avanols proanthocyanidins; fl avanones: hesperidin; isofl avones: daidzein, genistein, glycitein, kalita formononetin, biochanin A and coumestans, coumestrol, 4'-O-methylcoumestrol; isofl avones: equiol; polyphenols: oleuropein, oleocanthin; lignans: enterolactone, enterodiol; stilbenes: resveratrol.…”

“…47 SERM are shown for the prevention of vertebral fractures and treatment of osteoporosis in postmenopausal women. 47 PHYTOESTROGENS Phytoestrogens are polyphenolic plant metabolites: fl avonoids, fl avonols: kaempferol, quercetin, rutin, icariin; fl avanols: catechin, epicatechin of Camellia sinensis L.; polymeric fl avanols proanthocyanidins; fl avanones: hesperidin; isofl avones: daidzein, genistein, glycitein, kalita formononetin, biochanin A and coumestans, coumestrol, 4'-O-methylcoumestrol; isofl avones: equiol; polyphenols: oleuropein, oleocanthin; lignans: enterolactone, enterodiol; stilbenes: resveratrol. 48 Phytoestrogens possess estrogenic activity and show a higher affi nity for β-estrogen receptor, due to structural similarity with 17β-oestradiol stimulate osteoblast differentiation and inhibiting osteoclastogenesis.…”

Raloxifene modulates regulators of osteoclastogenesis and angiogenesis in an oestrogen deficiency periapical lesion model

“…Raloxifene (RLX) mimics the beneficial effects of oestrogen without stimulating tissues, such as those of the breast and endometrium (Lewis & Jordan ), once it binds to different receptors (Rey et al . ). RLX influences bone remodelling cells, such as osteoblasts and osteoclasts, and inflammatory mediators (Mencej‐Bedrač et al .…”