Seven Years of Treatment with Risedronate in Women with Postmenopausal Osteoporosis

Abstract

The effects of 7 years of risedronate treatment were evaluated in a second 2-year extension of a 3-year vertebral fracture study in women with osteoporosis. For the first 5 years of the study, women received risedronate 5 mg/day or placebo according to the original randomization, with maintenance of blinding. All the women who entered into the 6-7 years extension study received risedronate 5 mg/day. Endpoints included vertebral and nonvertebral fracture assessments, changes in biochemical markers of bone turnover, and bone mineral density (BMD) measurements. A total of 164 women (placebo/risedronate group, 81; risedronate group, 83) entered the 6-7 years extension study and 136 (83%) completed the study. Annualized incidence of new vertebral fractures during the 6-7 years was similar between the 2 treatment groups (3.8%). The incidence of vertebral fractures did not change in the 7-year risedronate group during the 6-7 years as compared to 4-5 years, while a significant reduction was observed in the placebo group that switched to risedronate treatment during years 6-7. The incidence of nonvertebral fractures was 7.4% and 6.0% in the placebo/risedronate and risedronate groups, respectively, during years 6-7. Urinary N-telopeptide decreased from baseline by 54% and 63% at 3 months and 7 years, respectively, in the risedronate group. The increases in BMD from baseline after 5 years of risedronate treatment were maintained or increased further during years 6-7; lumbar spine BMD after 5 and 7 years of risedronate treatment increased from baseline by 8.8% and 11.5%, respectively, for this extension study population. Risedronate was well tolerated and the occurrence of upper gastrointestinal adverse events was low. After 7 years of continuous risedronate treatment there were significant increases in BMD and decreases in bone turnover to within premenopausal levels and there was no indication of any loss of anti-fracture efficacy.

Effect of Pre- and Post-Surgery Treatment with Risedronate on Trabecular Bone Loss in Ovariectomized Rats

“…Recently, however, it has been reported that suppressed bone turnover by long-term treatment with high-dose risedronate increased microdamage accumulation in the dog rib [11], suggesting long-term and/or high-dose risedronate treatment may deteriorate bone quality through microdamage accumulation. Thus, long-term treatment with risedronate in postmenopausal women with osteoporosis may potentially deteriorate bone quality, although the 7-year effect of risedronate in preventing vertebral fractures has been reported [12]. Strategies to avoid the potential complications of long-term risedronate treatment need to be established.…”

Canadian Consensus Conference on Osteoporosis, 2006 Update

“…The mean increase from baseline in lumbar spine BMD over 7 years was 11.5% (P < 0.05). 109 In a large RCT designed to determine hip fracture efficacy, risedronate was shown to reduce hip fracture rates in those with low femoral neck BMD by 40% (P = 0.009) and prior vertebral fractures by 60% (P = 0.003). 110 Nonskeletal clinical risk factors (other than low BMD) did not identify a population that benefited from treatment, although it did identify a population at increased risk of hip fracture.…”

Atypical subtrochanteric and diaphyseal femoral fractures: Report of a task force of the american society for bone and mineral Research

“…Based on studies with alendronate (162) and risedronate, (163,164) patients with osteoporosis will have an antifracture benefit for at least 5 years. However, continued use of BP therapy beyond that time should be reevaluated annually, assessing factors such as BMD, particularly in the hip region, fracture history, newly diagnosed underlying conditions or initiation of other medications known to affect skeletal status, and new research findings in a rapidly evolving field.…”

“…With regard to risedronate, 7 years of therapy did not further reduce the incidence of vertebral fractures below that observed with 3 and 5 years of therapy. (163) Models to help determine absolute risk of fracture in patients who have already been treated for 4 to 5 years are needed to help guide these decisions.…”