What is the role of estrogen therapy in bone loss prevention?

Updated: Oct 16, 2018
  • Author: Janice L Bacon, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Existing evidence largely supports the efficacy of hormone therapy in reducing loss of bone mineral density and decreasing the risk of fracture. The mechanism is via inhibiting osteoclast bone resorption and bone remodeling. A meta-analysis of 22 randomized trials showed a significant reduction of 35% in nonvertebral fractures among women who began hormone therapy before the age of 60 years, with a possible attenuation of the benefit when hormone therapy is started after age 60 years. [53] The WHI investigators also reported significant decreases in the fracture risk with estrogen therapy and EPT. [54, 55]

In fact, all of the systemic hormone therapy preparations (estrogen, estrogen and progestogen and estrogen with bazedoxifene) in standard doses are indicated for the prevention of osteoporosis. Bone mineral density preservation is dose related with less protection of bone at lower doses.  Low dose oral (CEE 0.3 mg, estradiol < or=0.5 mg), low dose transdermal estrogens (estradiol patch 0.025mg) and ultralow-dose estrogen transdermal therapy (patch 0.014 mg) have not been shown to reduce fracture risk however but current evidence is limited. The estrogen protection of bone lasts only while in use and bone density rapidly decreases when discontinued. [113]

The stance adopted by the ACOG is that the use of hormone therapy for osteoporosis prevention or treatment needs to be individualized and needs to include the woman’s need for treatment of vasomotor symptoms. Although other medications are available, such as bisphosphonates and selective estrogen receptor modulators, women with vasomotor symptoms may benefit from hormone therapy. [58] . Women with premature menopause may be better served using combined hormonal contraceptive regimens instead of menopausal hormone therapy when considering preservation of bone density.

The combination product of bazedoxifene, a SERM, and conjugated estrogens (CEs) was approved by the FDA in October 2013. Combining a SERM with CEs lowers the risk of uterine hyperplasia caused by estrogens. This eliminates the need for a progestin and its associated risks (eg, breast cancer, MI, VTE). In clinical trials, this combination decreased bone turnover and bone loss in postmenopausal women at risk for osteoporosis. Bone mineral density increased significantly more with all bazedoxifene/CE doses compared with placebo at the lumbar spine and total hip and with most bazedoxifene/CE doses compared with raloxifene at the lumbar spine. [59] Bazedoxifene/CE is FDA-approved for prevention of osteoporosis and treatment of vasomotor symptoms in postmenopausal women.

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