UPDATE: OSTEOPOROSIS
A roundup of medical and other interventions that make a difference (or don’t, in some cases)
IN THIS ARTICLE
Most of our patients believe that weight-bearing exercise “builds bone.” Although the importance of maintaining adequate flexibility, agility, mobility, and strength is obvious in terms of fall prevention, its role in increasing bone mass has been unclear. As early as 2006, Martyn-St. James reported that a high-intensity progressive resistance training program in premenopausal women significantly increased absolute BMD at the lumbar spine, but not at the femoral neck.
Earlier this year Bemben and Bemben reported their findings in regard to 45 men and 79 women 55 to 74 years old who undertook either high-intensity or low-intensity resistance training either 2 or 3 days a week.4 Regardless of intensity and frequency, resistance training improved BMD of the proximal femur and lumbar spine but not the total body. Men and women responded similarly at the hip, but men had a greater response at the lumbar spine than women did.
Last, Almstedt and colleagues explored changes in BMD in response to 24 weeks of resistance training among college-aged men and women.5 Men had significantly greater increases in BMD at the lateral spine and femoral neck.
Overall, male exercisers experienced an increase in BMD of 2.7% to 7.7%, whereas women experienced an increase of 0.8% to 1.5%, depending on the bone site. In the control group, both men and women experienced an increase of approximately 1% at any bone site. These findings indicate that 24 weeks of resistance training, including squat and dead-lift exercises, is effective in increasing BMD in young, healthy men. Similar benefits were not obtained by women who followed the same protocol.
Although it appears that resistance exercise has much more effect on BMD in men than it does in women, and may not actually build bone in women, its importance in our patients cannot be stressed enough. Fall prevention through strength and increased balance is an essential component of bone health. For this reason, patients should be encouraged to maintain flexibility, agility, mobility, and strength (what I have called FAMS).
Lasofoxifene gets the nod—in Europe, not the United States
Cummings SR, Ensrud K, Delmas PD, et al; for PEARL Study Investigators. Lasofoxifene in post-menopausal women with osteoporosis. N Engl J Med. 2010;362(8):686–696.
Goldstein SR, Neven P, Cummings S, et al. Postmenopausal evaluation and risk reduction with lasofoxifene trial: 5-year gynecological outcomes [published online ahead of print August 3, 2010]. Menopause. doi:10.1097/gme.0b013e3181e84bb4.
On September 8, 2008, an FDA advisory panel voted 9–3 in support of this statement: “There is a population of postmenopausal women with osteoporosis in which the benefits of lasofoxifene likely outweigh the risks.” However, the FDA decided against approval of lasofoxifene, a new SERM developed for the treatment of osteoporosis in postmenopausal women. The drug has been approved outside the United States, most notably in the European Union.
The reasoning behind the FDA’s failure to approve the SERM is unclear. As Cummings and associates report in the PEARL trial (Postmenopausal Evaluation and Risk Reduction with Laxofoxifene), an international, randomized, placebo-controlled study of 8,556 postmenopausal women who had T-scores worse than –2.5, the drug had a favorable therapeutic profile.
In that study, participants were randomized to a daily dosage of 0.25 mg of lasofoxifene, 0.5 mg of lasofoxifene, or placebo. For the first 3 years of this trial, which took place at 113 sites in 32 countries, the primary endpoint was vertebral fracture. For the first 5 years of the trial, co-primary endpoints were nonvertebral fracture and breast cancer. Mean age of participants was 67 years (age range, 59 to 80 years), and 28% had at least one baseline vertebral fracture, as defined by radiograph.
At the 0.5-mg dosage (the one suggested to the FDA), lasofoxifene reduced the rate of nonvertebral fracture by 24% (P =.002). It reduced vertebral fracture by 42% (P < .001). And it reduced estrogen-receptor–positive breast cancer (P < .001) and all invasive breast cancer (P < .001) by 81% and 85%, respectively. As for major coronary heart disease events (P < .02) and stroke (P =.04), lasofoxifene reduced them by 32% and 36%, respectively.
Lasofoxifene is the first SERM to reduce nonvertebral fracture. Although no significant reduction in hip fracture was observed in this trial, the small number of cases may have been a factor (incidence <1%).
As it does with other SERMs and estrogen, the risk of thromboembolic events increased significantly (HR, 2.06), as did pulmonary embolism (HR, 4.49). Fatal stroke, for which raloxifene was given a boxed warning by the FDA, did not increase significantly with lasofoxifene.
