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Risedronate; Placebo; cancer surgery

Introduction

The results presented here were unaffected by excluding these women from sensitivity analyses (data not shown). The withdrawal from the primary IBIS-II study due to anastrozole-related adverse events was the primary cause of missing DXA data. Symptoms related to the joints, such as arthralgia, joint stiffness, and pain, were the most frequently mentioned side effects. Within the first two years after randomization, most of these incidents were reported. The development of breast cancer (the primary endpoint of the main trial), other types of cancer, and death were additional reasons for non-compliance in the bone substudy [1]. This analysis did not include any women who died or developed breast cancer.

Method

Calcium and vitamin D supplements were recommended to all women, but no specific doses were specified or required in accordance with the protocol. Throughout the five-year treatment period, 68% of women took these supplements. Regardless of treatment allocation, we observed no differences in BMD changes between those taking supplements and those not. All BMD measurements were available for 127 osteopenic women in the main trial who were randomly assigned to anastrozole [2]. These women were followed for 5 years. 68 of these were also randomly assigned to risedronate, while 59 were given the placebo. Those taking risedronate had a significant (0.4%) difference in the mean percentage of BMD change at the lumbar region [3].

Osteopenic women who received anastrozole and placebo had a linear decrease in lumbar spine BMD over the course of the five years of follow-up, whereas those who received risedronate had an initial increase in lumbar spine BMD that stabilized within the five years of follow-up. Risedronate did not prevent anastrozole-induced bone loss at the total hip. When compared to women who did not receive risedronate, women who did received a mean BMD decrease of 3.8% at the total hip (Difference: −1.3% (95% CI -3.2 to 0.5); P = 0.2) [4- 6]. Anastrozole and risedronate caused a BMD decrease of 2.5% at the total hip, which was very similar to the 2.7% seen in osteopenia-free women.

Result

Over the course of five years of follow-up, osteoporosis patients who were randomly assigned to risedronate or placebo (N = 74) experienced a mean BMD increase of 3.9% (95% CI, 2.2 to 5.6) at the lumbar spine (Fig. 2). When compared to those who received placebo (N = 57), those who maintained their mean BMD at the lumbar spine over the course of five years showed a highly significant difference (P = 0.0001). At the total hip, a picture that was similar but less striking was observed. After three years, women taking risedronate (N = 72) had a mean BMD of 1.8% (95% CI 1.0 to 2.7), but after five years, it fell to 0.9% (95% CI -0.3 to 2.1). However, these BMD changes were significantly different in 55 placebo-only participants (2.7%; 95 percent confidence interval (CI): -3.4 to 2.0); P < 0.0001). According to a BMD loss of more than 6% since baseline, the majority of rapid bone loss occurred in year one (N = 17). A bisphosphonate was given to these women, who were forced to withdraw from the trial. At year 5, one woman had rapid bone loss, which was defined as a change in BMD of more than 16% from baseline. At 12 months and 60 months, women taking anastrozole and risedronate had a mean decrease in PINP of 27%, while women not taking risedronate had a mean increase of 16% and 3% [7].

Discussion

Women taking risedronate only saw a mean decrease in PINP of 48% at 12 months and 30% at 60 months, while those not taking risedronate saw a mean decrease of 6% at 12 months and 4% at 60 months. (P 0.001), all differences were statistically significant. There was a correlation between the risedronate group's 12-month change in PINP and the total hip's 12-month change (r = 0.21, P = 0.03) and lumbar spine BMD (r = 0.33, P = 0.0003), respectively.

In the risedronate group, the 60-month change in PINP was correlated with the 60-month change in total hip (r = 0.29, P = 0.003) and lumbar spine BMD (r = 0.26, P = 0.008). In the groups that did not receive risedronate, there was no significant correlation found between the change in PINP and the BMD.

In the five years of follow-up, pre-defined side effects like abdominal pain, bloating, diarrhea, and constipation were not statistically different between risedronate treatment allocations (data not shown). In addition, during the five years of risedronate treatment, we did not observe any jaw osteonecrosis. In the bone sub-study, 97 osteopenia patients reported fractures, but there was no significant difference between anastrozole and placebo (RR = 0.98; 95 percent CI 0.61–1.56); P = 0.7). There was no difference in the number of fractures that were reported by women who took risedronate and those who did not.

Conclusion

This study demonstrated that oral risedronate taken once per week for five years can prevent anastrozole-induced hip bone loss in postmenopausal women with osteopenia. During the five years that Risedronate was being used, no serious side effects, like jaw osteonecrosis, were reported. Risedronate was well-received, and excluding women who did not comply had no effect on BMD changes. The majority of evidence that AIs have a negative effect on BMD comes from adjuvant trials in women with early breast cancer, with the exception of the MAP.3 trial. The tamoxifen comparator, which has been demonstrated to have a positive impact on bone, was the common factor in all of these trials, which all demonstrated significant BMD loss with an AI.

In a similar vein, treatment trials are the source of all other reports examining the effect of a bisphosphonate on BMD in women taking anastrozole. Greenspan and others found that postmenopausal women with hormone receptor positive breast cancer who received an AI for two years showed improvements in BMD and decreased markers of bone turnover when taking risedronate on a weekly basis. They demonstrated that measurements of bone markers (C-telopeptide crosslinks type I collagen (CTX) and N-Terminal Propeptide of Type I Collagen (PINP)) can predict changes in BMD, despite the fact that this was a small study with a relatively short follow-up period. We observed very similar correlations between the 12-month change in PINP and BMD.

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