Conjugated Estrogens-Bazedoxifene Combination Reduces Postmenopausal Bone Loss

NEW YORK (Reuters Health) - The combination of conjugated estrogens with bazedoxifene (CE/BZA) significantly improves bone mineral density (BMD) and bone turnover, according to pooled results from the SMART-1 and SMART-5 trials.

"This combination prevents postmenopausal bone loss, has no side effects, and is safer than PremPro (estrogen plus medroxyprogesterone acetate)," Dr. J. Christopher Gallagher from Creighton University School of Medicine in Omaha, Nebraska told Reuters Health by email.

Hormone therapy with estrogen and progestogen prevents postmenopausal bone loss and fractures, but there are safety concerns associated with the use of the progestin medroxyprogesterone acetate. Bazedoxifene, a third-generation selective estrogen-receptor modulator (SERM), has been shown to maintain or increase bone mass and to reduce the incidence of new vertebral fractures in postmenopausal women.

Dr. Gallagher's team pooled data for BMD and bone marker results from 1,172 women in SMART-1 and SMART-2, two of five phase 3 clinical trials that demonstrated the efficacy and safety of CE/BZA for prevention of osteoporosis and treatment of vasomotor symptoms associated with menopause.

Treatment of postmenopausal women with CE/BZA significantly increased lumbar spine, total hip, and femoral neck BMD through month 12 compared with placebo, which was associated with significant declines in BMD at all three sites, the researchers report in Menopause, online July 11.

CE/BZA treatment was also associated with significantly reduced levels of the bone formation marker osteocalcin and of the bone resorption marker C-telopeptide.

Efficacy did not differ based on age, body mass index, fracture risk score, or geographic region.

The overall incidence of treatment-emergent adverse events was similar for CE/BZA and placebo, the most frequent being headache, nasopharyngitis, back pain, and arthralgia.

"CE/BZA provides another option to relieve menopausal symptoms and prevent postmenopausal bone loss," the researchers conclude. "As with traditional hormone therapy, extended use of CE/BZA for prevention of postmenopausal bone loss may also be a useful option for women who are not candidates for or cannot tolerate other antiresorptive therapies, and this decision should be based on individual assessment of risks and benefits."

"The effect of estrogen (Premarin) on bone is similar to previous data," Dr. Gallagher added. "Bazedoxifene antagonizes the estrogen receptor, so what was important was that this dose of bazedoxifene does not block the estrogen effect on bone. A higher dose of bazedoxifene would impair the estrogen effect on bone."

Dr. Yasuo Terauchi from Yokohama City University in Japan, who has also studied the effects of bazedoxifene on bone, glucose, and lipid metabolism, cautioned, "This study showed that conjugated estrogen/bazedoxifene increased BMD, but did not show that conjugated estrogen/bazedoxifene prevent new vertebral and non-vertebral fractures. Therefore, it is necessary to prove their efficacy to prevent fractures in the long term."

"It is also important to evaluate the adverse events such as breast cancer, uterine cancer, and thrombosis," Dr. Terauchi told Reuters Health by email.

The study was funded by Pfizer, which also provided writing support for the report. Several authors disclosed ties to the company, including employment.

Menopause 2016.


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