A drug for the treatment of osteoporosis dramatically reduced the risk of spine and hip fractures by almost half and the risk of other painful fractures by 30 percent among women with osteoporosis, according to a study by University of California San Francisco researchers.
The drug, called alendronate, is a bisphosphonate that binds to bones and protects against bone loss. During a four-year study of 4432 postmenopausal women, 2214 participants received alendronate. New results from the study, part of the landmark Fracture Intervention Trial (FIT), are published in the December 23 issue of the Journal of American Medical Association (JAMA).
"Our study demonstrates that women who are concerned about osteoporosis or are over 60 or 65 years of age should have a bone density test so that they can be proactive about bone fracture prevention," said Steven R. Cummings, MD, UCSF professor of medicine and epidemiology and lead author of the study. "Women who do test positive for osteoporosis are at a very high risk of suffering a fracture, and should talk with their doctors about alendronate or other therapy for osteoporosis."
FIT, which included 6,000 patients, had two arms: the Vertebral Fracture Arm, which was previously reported at the 1997 American Society for Bone and Mineral Research Meeting and that included women who had a spinal fracture, and the Clinical Fracture Arm, which is the subject of this current study being reported in JAMA and that included women without spinal fractures.
Because 10 to 15 percent of postmenopausal women have spinal fractures, UCSF researchers aimed to determine in this Clinical Fracture Arm of the study whether four years of treatment with alendronate would reduce the risk of fractures in the large number of postmenopausal women who have a low bone mineral density (BMD), and therefore thin bones, but no spinal fractures. Cummings reported that the effect of alendronate on fractures depended on a woman's initial hip bone density measured at the beginning of the study, an indicator of whether or not she had osteoporosis. Those with the lowest BMD--and therefore the thinnest, most fragile bones, who are at the highest risk of fractures--benefited the most from alendronate. Women with osteoporosis were defined as those having a hip BMD 2.5 standard deviations below the normal mean.
The women in the study with a low enough BMD to qualify as osteoporotic experienced dramatic benefits from alendronate. However, those who did not have a low enough BMD to be classified as having osteoporosis, did not experience a reduction in the risk of fractures from taking the drug. All the women who received the drug during the four-year study did have a significant increase in BMD at the hip and spine, Cummings said.
During the four-year study, a total of 4432 women were randomized: 2214 to alendronate and 2218 to placebo (an inactive pill with no medical benefits). Participants were postmenopausal, between 54 to 81 years old (mean age 68 years), 97 percent Caucasian, and had a low neck BMD, but no spinal fractures. Women in the alendronate group were randomly assigned to 5 mg of the drug daily for the first two years followed by 10 mg daily for the remainder of the study.
Key findings of the FIT study include:
- Alendronate reduced clinical fractures 36 percent among women with
osteoporosis, and 22 percent among women whose BMD was equal to or less than 2.0
standard deviations below the normal mean. The drug did not reduce the risk of
fractures among those with a higher BMD.
- Alendronate reduced the risk of hip fractures by 56 percent among women with
osteoporosis compared to osteoporotic women in the placebo group.
- Alendronate reduced the risk of new spinal fractures by 44 percent: 78 women
in the placebo group developed at least one new spinal fracture compared to 43
in the alendronate group.
- Alendronate significantly increased the BMD of all women, both those with and
without osteoporosis, who received the drug during the study.
- After four years of treatment, compared to women who received a placebo and
lost .8 percent of BMD at the neck, women who received alendronate gained almost
4 percent of BMD.
- The placebo group lost an average of 1.6 percent of BMD at the hip, while the
alendronate group gained 3.4 percent.
- In the spine, the placebo group gained 1.5 percent, versus an 8.3 percent gain
in the alendronate group.
- Alendronate was well tolerated. Upper gastrointestinal (GI) disease is very common among older women, and the incidence of GI disease among postmenopausal women in FIT was the same regardless of whether they received alendronate or placebo.
In fact, osteoporosis results in 1.5 million fractures each year, over 400,000 hospital admissions, more than 44 million patient days in nursing homes, and $13.8 billion in health care expenditures among women and men in the U.S. FIT is a collaborative effort of the University of California San Francisco and 11 other academic centers.
The first arm of the study (Vertebral Fracture Arm) included 2,027 postmenopausal women between the ages of 55 and 82 who had osteoporosis and previous spine fractures, as detected by x-ray. Researchers found that alendronate reduced the risk of hip fractures by 51 percent, spine fractures by 47 percent, and all clinical fractures by 28 percent.
Alendronate, which is available as FOSAMAX in 72 countries including the United States, was developed by Merck & Co. Inc., USA, which operates in many countries as Merck Sharp & Dohme.
Other researchers include Dennis M. Black, PhD, Lisa Palermo, Susan M. Rubin, MPH, University of California San Francisco Department of Epidemiology and Biostatistics; A. John Yates, MD, Desmond E. Thompson, PhD, Thomas A. Musliner, MD, Merck Research Labs, Rathway, New Jersey; William B. Applegate, MD, Department of Preventive Medicine, University of Tennessee; Elizabeth Barrett-Connor, MD, University of California San Diego; Andrea Z. La Croix, MD, Center for Health Studies, Group Health Cooperative, Seattle, Washington; Ronald Prineas, MD, University of Miami, Florida; Jean C. Scott, DrPH, University of Maryland, Baltimore; Thomas Vogt, MD, MPH, Cancer Research Center of Hawaii, Honolulu; Robert Wallace, MD, University of Iowa, Iowa City, Iowa.
Journal
JAMA