As 2007 draws to a close, we are still awaiting the World Health Organization’s fracture risk-assessment tool. The much-anticipated instrument will calculate 5- and 10-year fracture risks using an individual’s femoral neck T-score, age, history of low-trauma fracture, body mass index, steroid exposure, family history of hip fracture, smoking status, and alcohol intake. Once it is implemented, the tool will eliminate much of the confusion that arises when the T-score is the only variable used to determine the need for pharmacotherapy.
Why is the ability to stratify risk important? Although the incidence of fragility fractures is highest in osteoporotic women (as defined by the T-score), the absolute number of fractures is greater in those who have osteopenia. All clinicians should realize that the current definitions of normal bone density, osteopenia, and osteoporosis apply to the postmenopausal population only:
- normal – T-score above -1.0
- osteopenia – T-score below -1.0 but above -2.5
- osteoporosis – T-score below -2.5.
Indications added for raloxifene
The year did bring new indications for raloxifene, based on data from the RUTH and STAR trials,1,2 which were mentioned in this Update 1 year ago. On September 14, the Food and Drug Administration approved two new indications:
- reduction of risk of invasive breast cancer in postmenopausal women with osteoporosis
- reduction of risk of invasive breast cancer in postmenopausal women at high risk of breast cancer.
These new indications are very important for clinicians who prescribe agents to prevent fragility fractures. Raloxifene should be considered for breast cancer risk reduction when deciding which agent to prescribe.
Silverman SL, Watts NB, Delmas PD, et al. Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study. Osteoporos Int. 2007;18(1):25–34.
Patients who take risedronate have lower rates of hip and nonvertebral fracture during their first year of therapy than do those who take alendronate. That is the finding of the RisedronatE and ALendronate (REAL) cohort study, a retrospective observation of the records of health-care utilization among women in the United States. Silverman and colleagues analyzed data sets for women older than age 65 who had ever used once-weekly dosing of risedronate or alendronate. The risedronate cohort included 12,215 women who were followed for a mean of 226 days of therapy. The alendronate cohort included 21,615 women followed for a mean of 238 days of therapy.
Risedronate group had more risk factors for fracture
At baseline, women taking risedronate had a statistically greater incidence of:
- advanced age
- use of concomitant medications
- glucocorticoid use
- rheumatoid arthritis.
Each of these characteristics might have been expected to increase the risk of fragility fracture. However, through 1 year of therapy, women using risedronate had an incidence of nonvertebral fractures 18% lower than those using alendronate (2.0% versus 2.3%; 95% confidence interval [CI], 0.02–0.32). They also had an incidence of hip fracture 43% lower than those using alendronate (0.4% versus 0.6%; 95% CI, 0.13–0.63). Overall, there were 507 nonvertebral fractures and 109 hip fractures.
Footnote: Large database analyses complement randomized trials
Randomized clinical trials (RCTs) are, of course, the gold standard for determining drug safety and efficacy and the key requisite for regulatory approval of new drugs. By design, RCTs have strict inclusion and exclusion criteria to meet the regulatory standard for evaluating drug efficacy and safety and to exclude internal bias. Often, the majority of patients are deemed ineligible for entry into an RCT because of comorbidity, concomitant medication use, age, or severity of disease. Therefore, database analyses are often more “real world” than RCTs.
As clinical practice data accumulate over time, observational, or outcomes, studies can be conducted to complement the data that have been generated by RCTs. For example, over the past decade, large databases of health-care utilization claims have become available in the United States and are being tapped to conduct effectiveness studies. These observational studies can supplement the efficacy measures obtained from the carefully controlled environment of a placebo-controlled RCT. They also provide a measure of effectiveness over a wide range of patients and health-care practices. Data generated from the REAL study are just another piece of the huge puzzle we must grapple with as we seek good information about agents to treat osteoporosis and prevent fragility fractures.