UPDATE: MENOPAUSE
We’re learning more about the long-term risks and benefits of hormone therapy, how to assess and treat osteoporosis, and the need for vitamin D
IN THIS ARTICLE
In the absence of these risk factors, BMD assessment should begin at 65 years of age.
Once initiated, treatment is usually long-term
The NAMS statement indicates that drug therapy—using bisphosphonates as first-line agents—is appropriate in postmenopausal women who have any of the following:
- a history of osteoporotic hip or vertebral fracture
- DXA-defined T-score lower than –2.5, indicating osteoporosis
- T-score from –1.0 to –2.5 (low bone mass) plus either a FRAX score that indicates a 10-year risk of hip fracture of at least 3% or a 10-year overall risk of osteoporotic fracture of at least 20%.
The World Health Organization (WHO) Fracture Risk Algorithm (FRAX) was developed to calculate the 10-year risk of hip fracture and the 10-year overall risk of osteoporotic fracture (online at https://www.shef.ac.uk/FRAX/). (For a description of two menopausal cases in which this Web site was used to determine appropriate clinical management, see the article by Kaunitz and colleagues cited above. Also, be aware that use of the FRAX Web site is inappropriate for making clinical decisions about women who are already using prescription antifracture therapy.)
NAMS points out that 1) treatment should usually span a period of years and 2) the risk of fracture after discontinuation of treatment has not been adequately studied.
Lasofoxifene seems unlikely to offer net benefits greater than what women obtain from existing therapies
Clinicians and menopausal women would welcome any agent that can prevent osteoporotic fracture with minimal adverse outcomes. Lasofoxifene appears to fulfill the first half of this equation, but its potential risks and questionable long-term effects cast doubt on its overall utility.
In a manufacturer-sponsored international trial, investigators randomized 8,556 women (mean age, 67 years) who met BMD criteria for osteoporosis to the selective estrogen-receptor modulator (SERM) lasofoxifene (0.25 mg daily or 0.5 mg daily) or placebo for 5 years. Women who received 0.5 mg daily of lasofoxifene had a substantially lower risk of vertebral (HR, 0.58) and nonvertebral (HR, 0.76) fracture than did women who received placebo.1
This dosage of lasofoxifene was also associated with a lower risk of estrogen-receptor–positive breast cancer (HR, 0.19), CAD events (HR, 0.68), and stroke (HR, 0.64), but a twofold higher risk of venous thromboembolic events overall and more than fourfold higher risk of pulmonary embolism. The incidence of endometrial cancer and endometrial hyperplasia was low (fewer than three women in each group), but endometrial polyps and hypertrophy were substantially more common among women who received either dosage of lasofoxifene.1
At 3 years, questionable benefit
Although these findings indicate that lasofoxifene lowers the risk of radiologically confirmed vertebral fracture, data submitted to the FDA reveal that the risk of clinical vertebral fracture was not reduced at 3 years.
Both raloxifene and lasofoxifene are associated with a heightened risk of venous thromboembolic events. Although lasofoxifene did not raise the risk of endometrial neoplasia or hyperplasia in the trial just described, the rates of other endometrial outcomes suggest that this agent has a proliferative effect on the endometrium.1
The reduced risk of estrogen-receptor–positive breast cancer and CAD events is intriguing. However, as an editorial writer points out, a clinician would need to treat 492 women for 1 year to prevent one major CAD event.2
Lasofoxifene does not seem to offer any clinically important benefit over existing SERMs. Moreover, alendronate, a generic bisphosphonate proven to prevent clinical vertebral and nonvertebral fracture, often fills the bill for the prevention of osteoporotic fracture in menopausal women.
References
1. Cummings SR, Ensrud K, Delmas PF, et al. Lasofoxifene in postmenopausal women with osteoporosis. N Engl J Med. 2010;362(8):686-696.
2. Becker C. Another selective estrogen-receptor modulator for osteoporosis. N Engl J Med. 2010;362(8):752-754.
BMD reassessment should be minimal
BMD assessment by means of DXA imaging to monitor the effects of therapy is appropriate after 1 or 2 years of treatment. Thereafter, repeat measurement is of little value in women whose BMD has stabilized or increased on therapy. A follow-up DXA scan is of limited use in predicting the effectiveness of antiresorptive therapy in lowering the risk of fracture. Moreover, changes in BMD can lag behind actual therapeutic benefits (i.e., fracture prevention).
In menopausal women who are not taking prescription antifracture therapy, the follow-up measurement of BMD is not useful until 2 to 5 years after initial testing. Although BMD may be lost rapidly in the initial years after menopause (or after discontinuation of HT), subsequently it plateaus or declines slowly.
If a woman is not using prescription antifracture therapy and is within 2 or 3 years of menopause (or if she has discontinued menopausal HT in the past 2 to 3 years), retesting in 2 years is prudent. However, if the same woman were 5 or more years post-menopausal and had not recently discontinued HT, follow-up BMD assessment can be deferred for 3 to 5 years.
