Safety and Efficacy of Risedronate in Reducing Fracture Risk
Objectives: To determine the efficacy of risedronate in reducing vertebral fracture risk in women aged 80 and older with osteoporosis.
Design: Pooled analysis of data from three randomized, double-blind, controlled, 3-year-fracture-endpoint trials conducted from November 1993 to April 1998: Hip Intervention Program (HIP), Vertebral Efficacy with Risedronate Therapy–Multinational (VERT-MN), and VERT-North America (NA).
Setting: Office-based practices, research centers, and osteoporosis clinics in Europe, North America, and Australia.
Participants: Osteoporotic (femoral neck bone mineral density T-score <–2.5 standard deviations or at least one prevalent vertebral fracture) women aged 80 and older.
Intervention: Patients received placebo (n=688) or risedronate 5 mg/d (n=704) for up to 3 years. All patients received 1,000 mg/d calcium and, if baseline levels were low, up to 500 IU/d vitamin D.
Measurements: Cumulative incidence of new vertebral fractures.
Results: After 1 year, the risk of new vertebral fractures in the risedronate group was 81% lower than with placebo (95% confidence interval=60–91%; P<.001). The number of women who needed to be treated to prevent one new vertebral fracture after 1 year was 12. This early onset of efficacy was consistent across the clinical programs, and antifracture efficacy was confirmed over 3 years. Risedronate was well tolerated, with a safety profile comparable with that of placebo.
Conclusion: These findings provide the first evidence that, even in the very old, reducing bone resorption rate remains an effective treatment strategy for osteoporosis. Because each therapeutic agent used for the treatment of osteoporosis may have unique characteristics, the observations made in this study should not be assumed to apply to other bisphosphonates.
Vertebral fractures are the most common serious complication of osteoporosis, and their incidence increases steadily with age. The prevalence of vertebral deformities, which is 5% to 10% in women aged 50 to 54, increases to about 45% to 55% in women aged 80 to 89. Because the elderly are the fastest-growing segment of the population, the number of individuals affected with vertebral fractures can be expected to increase dramatically in coming decades.
Although hip fractures are considered to be the most severe and economically important osteoporotic fracture, vertebral fractures also lead to adverse health outcomes, including back pain, height loss, and kyphosis. These changes may result in significant declines in physical performance and function and ultimately loss of independence. Vertebral fractures frequently require hospitalization or prolongation of hospital stays, particularly in elderly individuals. Each additional vertebral fracture leads to further functional limitation and substantially increases the risk of additional vertebral and hip fractures. Vertebral fractures are even associated with an excess rate of mortality, and relative survival rates after fracture decline with age at the time of fracture.
Despite the debilitating effects of vertebral fractures and the availability of therapies to reduce fracture occurrence, only a small percentage of women with osteoporotic fractures receive treatment, and this percentage decreases with age. One explanation for this decrease is that clinicians presume that it is too late to alter the course of disease in its late stage. Treatment of very elderly women with combined calcium and vitamin D supplements has been shown to reduce the risk of fracture, but there is no published evidence in persons aged 80 and older that further reducing bone turnover by adding an antiresorptive agent provides protection against osteoporotic fractures in addition to that provided by calcium and vitamin D.
The effectiveness of risedronate, a pyridinyl bisphosphonate, in reducing the risk of vertebral and nonvertebral fractures in osteoporotic women is well established across a wide range of ages. The risedronate database includes almost 1,400 individuals aged 80 and older with confirmed osteoporosis and thus provides a unique opportunity to study the antifracture effect of antiresorptive treatment from a geriatric perspective. Given the high prevalence of osteoporosis in elderly women, the underuse of antiresorptive treatment in these patients, and the paucity of information about antiresorptive treatment of osteoporosis in the very old, a retrospective analysis was conducted to determine the efficacy and safety of risedronate in reducing the risk of vertebral fractures in women aged 80 and older with osteoporosis. To this end, data from three large clinical trials with fracture as the primary endpoint were evaluated.
Objectives: To determine the efficacy of risedronate in reducing vertebral fracture risk in women aged 80 and older with osteoporosis.
Design: Pooled analysis of data from three randomized, double-blind, controlled, 3-year-fracture-endpoint trials conducted from November 1993 to April 1998: Hip Intervention Program (HIP), Vertebral Efficacy with Risedronate Therapy–Multinational (VERT-MN), and VERT-North America (NA).
Setting: Office-based practices, research centers, and osteoporosis clinics in Europe, North America, and Australia.
Participants: Osteoporotic (femoral neck bone mineral density T-score <–2.5 standard deviations or at least one prevalent vertebral fracture) women aged 80 and older.
Intervention: Patients received placebo (n=688) or risedronate 5 mg/d (n=704) for up to 3 years. All patients received 1,000 mg/d calcium and, if baseline levels were low, up to 500 IU/d vitamin D.
Measurements: Cumulative incidence of new vertebral fractures.
Results: After 1 year, the risk of new vertebral fractures in the risedronate group was 81% lower than with placebo (95% confidence interval=60–91%; P<.001). The number of women who needed to be treated to prevent one new vertebral fracture after 1 year was 12. This early onset of efficacy was consistent across the clinical programs, and antifracture efficacy was confirmed over 3 years. Risedronate was well tolerated, with a safety profile comparable with that of placebo.
Conclusion: These findings provide the first evidence that, even in the very old, reducing bone resorption rate remains an effective treatment strategy for osteoporosis. Because each therapeutic agent used for the treatment of osteoporosis may have unique characteristics, the observations made in this study should not be assumed to apply to other bisphosphonates.
Vertebral fractures are the most common serious complication of osteoporosis, and their incidence increases steadily with age. The prevalence of vertebral deformities, which is 5% to 10% in women aged 50 to 54, increases to about 45% to 55% in women aged 80 to 89. Because the elderly are the fastest-growing segment of the population, the number of individuals affected with vertebral fractures can be expected to increase dramatically in coming decades.
Although hip fractures are considered to be the most severe and economically important osteoporotic fracture, vertebral fractures also lead to adverse health outcomes, including back pain, height loss, and kyphosis. These changes may result in significant declines in physical performance and function and ultimately loss of independence. Vertebral fractures frequently require hospitalization or prolongation of hospital stays, particularly in elderly individuals. Each additional vertebral fracture leads to further functional limitation and substantially increases the risk of additional vertebral and hip fractures. Vertebral fractures are even associated with an excess rate of mortality, and relative survival rates after fracture decline with age at the time of fracture.
Despite the debilitating effects of vertebral fractures and the availability of therapies to reduce fracture occurrence, only a small percentage of women with osteoporotic fractures receive treatment, and this percentage decreases with age. One explanation for this decrease is that clinicians presume that it is too late to alter the course of disease in its late stage. Treatment of very elderly women with combined calcium and vitamin D supplements has been shown to reduce the risk of fracture, but there is no published evidence in persons aged 80 and older that further reducing bone turnover by adding an antiresorptive agent provides protection against osteoporotic fractures in addition to that provided by calcium and vitamin D.
The effectiveness of risedronate, a pyridinyl bisphosphonate, in reducing the risk of vertebral and nonvertebral fractures in osteoporotic women is well established across a wide range of ages. The risedronate database includes almost 1,400 individuals aged 80 and older with confirmed osteoporosis and thus provides a unique opportunity to study the antifracture effect of antiresorptive treatment from a geriatric perspective. Given the high prevalence of osteoporosis in elderly women, the underuse of antiresorptive treatment in these patients, and the paucity of information about antiresorptive treatment of osteoporosis in the very old, a retrospective analysis was conducted to determine the efficacy and safety of risedronate in reducing the risk of vertebral fractures in women aged 80 and older with osteoporosis. To this end, data from three large clinical trials with fracture as the primary endpoint were evaluated.