New options in osteoporosis therapy: Combination and sequential treatment
Perhaps the biggest medical question to emerge from the WHI study is how to best treat postmenopausal osteoporotic women. Could the answer lie in combining 2 current monotherapies?
The mechanism of PTH action is fundamentally different than that of antiresorptive agents such as alendronate, risedronate, raloxifene, and estrogen. Although combinations of PTH plus an antiresorptive agent have not yet been studied directly, it is likely that additive effects would be demonstrated.
- Rittmaster et al.10 In 1 study of sequential treatment of postmenopausal women with PTH followed by alendronate, each for 1 year, investigators demonstrated that after 1 year of PTH therapy, alendronate treatment resulted in additional BMD increases much greater than those previously reported for alendronate or estrogen alone.10
Sequential treatment
Estrogen followed by a bisphosphonate. Because premenopause, perimenopause, and postmenopause are dynamic physiological states, specific osteoporosis treatments may need to target different stages. For example, in premenopausal and perimenopausal women with osteoporosis, estrogen replacement therapy (ERT) may be indicated.11-13 In early postmenopause, ERT may be warranted to treat both vasomotor symptoms and osteoporosis. Estrogen-progestin therapy is clearly effective in the treatment of osteoporosis. In the WHI study, the risk of osteoporotic fracture was reduced at both the hip (5 fewer hip fractures per 10,000 woman-years with a relative risk of 0.66; 95% CI, 0.45 to 0.98) and in the vertebral spine (relative risk 0.66; 95% CI, 0.44 to 0.98) for women receiving estrogen-progestin therapy compared to placebo.
The results of the WHI study have caused many women to discontinue estrogen therapy, but bone loss is significant in postmenopausal women in the first few years after discontinuing estrogen therapy.14 Once the patient enters later stages of postmenopause, therefore, many authorities recommend switching from estrogen to a bisphosphonate, since bisphosphonates are not associated with a known risk of breast cancer or cardiovascular disease.
Calcitonin followed by a bisphosphonate. After an osteoporotic fracture, some women experience intense pain for 1 to 2 months. Calcitonin has been demonstrated to decrease pain associated with osteoporotic fractures significantly more than placebo.15 One possible solution, therefore, is to use calcitonin (200 IU by nasal administration daily) for the first month after a painful osteoporotic fracture, followed by treatment with a bisphosphonate.
Looking ahead
In the next 12 months approximately 1.5 million new osteoporotic fractures will occur in American women. Given the data that indicate the life expectancy of a 65-year-old American woman is 20 years, it is likely that there will be a significant increase in the number of osteoporotic fractures in the next decade. According to community-based population studies, however, the majority of women with osteoporotic fractures do not receive adequate treatment for the disease.16 Gynecologists play an important role in helping to increase the effectiveness of the prevention and treatment of osteoporosis.
Dr. Barbieri reports no financial relationship with any companies whose products are mentioned in this article.
