Treatment of aromatase inhibitor-induced bone loss
As in other forms of increased bone loss, the bisphosphonates are the preferred treatment for aromatase inhibitor-induced bone loss. The results of several intervention studies with zoledronic acid have been published recently; there are also ongoing studies with a number of oral bisphosphonates, such as anastrozole and risedronate in the SABRE trial, and anastrozole and ibandronate in the ARIBON trial. In SABRE, 138 women receiving anastrozole who were osteopaenic at baseline were randomised to risedronate 35 mg weekly or placebo. Risedronate led to a mean increase of 1.7% in BMD at 12 months compared with a 0.41% loss in the placebo arm. In this study, risedronate also improved BMD in a cohort of women with osteoporosis at baseline.76 In ARIBON, 50 osteopaenic women were randomized to monthly oral ibandronate 150 mg monthly or placebo during treatment with anastrozole. As expected, ibandronate prevented the bone loss observed in the placebo group. BMD changes at 12 months were +2.78% at the spine and +1.35% at the hip versus -2.61% at the spine and -2.34% at the hip for ibandronate and placebo treated patients, respectively (p<0.001).
These two studies suggest that bisphosphonates at the dose and schedule used in postmenopausal osteoporosis are effective in the setting of aromatase inhibitor bone loss.
The Austrian Breast Cancer Study Group (ABCSG) reported on 400 patients with early breast cancer undergoing ovarian suppression with goserelin plus either anastrozole or tamoxifen, with or without bone-protecting therapy comprising a 6-monthly schedule of zoledronic acid 4 mg.21 Without zoledronic acid, clinically important and significant bone loss occurred; the mean reductions in BMD at 3 years were 8% and 16% with tamoxifen and anastrozole, respectively. However, the addition of zoledronic acid prevented bone loss with either endocrine strategy. The effects of zoledronic acid on bone turnover and fracture rates have not been reported.
The Zometa-Femara Adjuvant Synergy Trials (Z-FAST [US)]/ (ZO-FAST [Europe]) (n=1668) recruited postmenopausal breast cancer patients with normal bone density or osteopaenia (T-score of >–2). Patients were treated with adjuvant letrozole and randomised either to immediate intravenous zoledronic acid (4 mg by intravenous infusion every 6 months) or to a delayed phase of treatment based on changes in BMD. In the Z-FAST study, the mean difference in BMD between the immediate and delayed groups at 12 months was 5.1% and 3.6% at the spine and hip, respectively (p≤0.001). Bone turnover was increased in the delayed group but reduced with zoledronic acid therapy. Similar results were seen in the ZO-FAST study.79 Follow-up is currently too short for a reliable assessment of the effect of prophylactic zoledronic acid on the incidence of fragility fractures, but the increase in BMD coupled with reduced bone turnover would be expected to prevent any increase in fractures associated with aromatase inhibitor use.
Raloxifene is an effective treatment for the prevention of osteoporosis. Unlike HRT, it does not increase the risk of recurrent breast cancer. However, in view of the interaction between tamoxifen and anastrozole, with the combination behaving like tamoxifen alone,the addition of raloxifene to an aromatase inhibitor cannot be recommended in the adjuvant treatment setting.
Strontium ranelate is licensed in most of the world for the treatment of postmenopausal osteoporosis. However, there is currently no research using this agent in cancer treatment-induced bone loss and so we cannot recommend its use.
As in other forms of increased bone loss, the bisphosphonates are the preferred treatment for aromatase inhibitor-induced bone loss. The results of several intervention studies with zoledronic acid have been published recently; there are also ongoing studies with a number of oral bisphosphonates, such as anastrozole and risedronate in the SABRE trial, and anastrozole and ibandronate in the ARIBON trial. In SABRE, 138 women receiving anastrozole who were osteopaenic at baseline were randomised to risedronate 35 mg weekly or placebo. Risedronate led to a mean increase of 1.7% in BMD at 12 months compared with a 0.41% loss in the placebo arm. In this study, risedronate also improved BMD in a cohort of women with osteoporosis at baseline.76 In ARIBON, 50 osteopaenic women were randomized to monthly oral ibandronate 150 mg monthly or placebo during treatment with anastrozole. As expected, ibandronate prevented the bone loss observed in the placebo group. BMD changes at 12 months were +2.78% at the spine and +1.35% at the hip versus -2.61% at the spine and -2.34% at the hip for ibandronate and placebo treated patients, respectively (p<0.001).
These two studies suggest that bisphosphonates at the dose and schedule used in postmenopausal osteoporosis are effective in the setting of aromatase inhibitor bone loss.
The Austrian Breast Cancer Study Group (ABCSG) reported on 400 patients with early breast cancer undergoing ovarian suppression with goserelin plus either anastrozole or tamoxifen, with or without bone-protecting therapy comprising a 6-monthly schedule of zoledronic acid 4 mg.21 Without zoledronic acid, clinically important and significant bone loss occurred; the mean reductions in BMD at 3 years were 8% and 16% with tamoxifen and anastrozole, respectively. However, the addition of zoledronic acid prevented bone loss with either endocrine strategy. The effects of zoledronic acid on bone turnover and fracture rates have not been reported.
The Zometa-Femara Adjuvant Synergy Trials (Z-FAST [US)]/ (ZO-FAST [Europe]) (n=1668) recruited postmenopausal breast cancer patients with normal bone density or osteopaenia (T-score of >–2). Patients were treated with adjuvant letrozole and randomised either to immediate intravenous zoledronic acid (4 mg by intravenous infusion every 6 months) or to a delayed phase of treatment based on changes in BMD. In the Z-FAST study, the mean difference in BMD between the immediate and delayed groups at 12 months was 5.1% and 3.6% at the spine and hip, respectively (p≤0.001). Bone turnover was increased in the delayed group but reduced with zoledronic acid therapy. Similar results were seen in the ZO-FAST study.79 Follow-up is currently too short for a reliable assessment of the effect of prophylactic zoledronic acid on the incidence of fragility fractures, but the increase in BMD coupled with reduced bone turnover would be expected to prevent any increase in fractures associated with aromatase inhibitor use.
Raloxifene is an effective treatment for the prevention of osteoporosis. Unlike HRT, it does not increase the risk of recurrent breast cancer. However, in view of the interaction between tamoxifen and anastrozole, with the combination behaving like tamoxifen alone,the addition of raloxifene to an aromatase inhibitor cannot be recommended in the adjuvant treatment setting.
Strontium ranelate is licensed in most of the world for the treatment of postmenopausal osteoporosis. However, there is currently no research using this agent in cancer treatment-induced bone loss and so we cannot recommend its use.
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