Bazedoxifene Acetate: Indications, Mechanism of Action and Side Effects

Bazedoxifene Acetate (BZA) is an oral, nonsteroidal, indole, FDA-approved third-generation selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women. In addition, BZA has been found to be a myelin restorative in multiple sclerosis and a potential anti-coronavirus drug. BZA inhibits infection by the original SARS-CoV-2, Delta variant, Omicron variant, and pseudovirus of SARS-CoV.

Mechanism of Action

Bazedoxifene Acetate, as a selective estrogen receptor modulator (SERM), has high affinity for both α and β estrogen receptors, but has a significantly superior binding affinity to α receptors. In women, osteoporosis and fractures occur primarily due to postmenopausal estrogen deficiency. BZA binds to estrogen receptors (ERα and ERβ), which in turn leads to activation (estrogen agonism) and blockade (estrogen antagonism) of estrogen pathways in tissues expressing estrogen receptors. This helps reduce bone resorption and lowers biochemical markers of bone turnover to the premenopausal range. These effects on bone remodeling lead to increased bone mineral density (BMD), which in turn helps reduce the risk of fractures.

Side effects

The most common adverse reactions of Bazedoxifene Acetate include:

• Abdominal pain

• Headache

• Influenza syndrome

• Venous thromboembolism

The combination of estrogen and bazedoxifene may cause nausea, diarrhea, muscle cramps, indigestion, oropharyngeal pain, joint pain, neck pain and dizziness, and severe cases may lead to thrombosis, stroke, heart attack, endometrium, cancer, dementia, gallbladder problems, vision loss, liver problems and thyroid problems. Serious adverse reactions are rare and manifest as swelling of the eyes, face, mouth, tongue or throat, hoarseness, and difficulty breathing or swallowing.

References:

[1] SZMYD M, ZANIB A, BEHLOW V, et al. Modulation of Estrogen Receptor Alpha (ERα) and Tumor Suppressor Gene BRCA1 in Breast Cancer Cells by Bazedoxifene Acetate (BZA)[J]. Cancers, 2024. DOI:10.3390/cancers16040699.

[2] PALACIOS S. Bazedoxifene acetate for the management of postmenopausal osteoporosis.[J]. Drugs of today, 2011. DOI:10.1358/dot.2011.47.3.1587026.

[3] GEN MIAO. Antiviral efficacy of selective estrogen receptor modulators against SARS-CoV-2 infection in vitro and in vivo reveals bazedoxifene acetate as an entry inhibitor[J]. Journal of Medical Virology, 2022. DOI:10.1002/jmv.27951.

[4] FIGHERA T, KULAK C M, JÚNIOR J K. Safety, Efficacy and Patient Acceptability of Bazedoxifene Acetate in the Management of Postmenopausal Osteoporosis[C]. 2012. DOI:10.4137/CMWH.S7308.

[5] ANNIE W C KUNG; Ling X; Eva Y W Chu. Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis.[J]. Expert Opinion on Pharmacotherapy, 2009. DOI:10.1517/14656560902980228.

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