Management of anastrozole-induced bone loss in breast cancer patients with oral risedronate: results from the ARBI prospective clinical trial

Abstract

IntroductionThe aim of this multicenter, phase III, prospective open label clinical trial was to investigate the effect of risedronate (R) on bone mineral density (BMD) in postmenopausal, early breast cancer (BC) patients scheduled to receive anastrozole (A).MethodsPre-treatment BMD of 213 patients with hormone receptor-positive BC was evaluated at lumbar spine (LS) and hip (HP). Patients were categorized according to their baseline BMD T-score as being at low, moderate and high risk of osteoporosis. Low risk patients received anastrozole only (A), moderate risk were randomized to anastrozole +/- risedronate (A+/-R) administration and high risk patients received anastrozole + risedronate (A+R). Anastrozole was given at a dosage of 1 mg/day while oral risedronate was given at 35 mg/week. BMD was then assessed at 12 and 24 months. All patients received daily supplements of calcium (1000 mg/day) and vitamin D (400 IU/day).ResultsAt 24 months, in the moderate risk group, treatment with A+R resulted in a significant increase in BMD at LS and HP compared to treatment with A only (5.7% v -1.5%, Wilcoxon test P = 0.006, and 1.6% v -3.9% Wilcoxon test P = 0.037, respectively), while no significant difference was found at 12 months; 24.3% of the patients moved to normal BMD region. In the high risk group, a significant increase for LS was detected both at 12 and 24 months (6.3% and 6.6%, P < 0.001) but not for HP; BMD in 14% of patients improved to the osteopenic region. In the low risk group, a significant decrease of BMD was detected at 12 months for LS and HP (-5.3% P < 0.001 and -2.4% P < 0.001, respectively,); at 24 months, a significant decrease of BMD was detected only for LS (-2.5%, P < 0.001). However, 22% of patients became osteopenic and only 4% became osteoporotic.ConclusionsThe addition of oral risedronate in post-menopausal breast cancer patients receiving anastrozole has a favorable effect on BMD. Patients with pre-treatment osteopenic to osteoporotic status should be treated with a combination of both therapies in order to avoid bone loss induced by aromatase inhibition. Patients with normal BMD before starting treatment with anastrozole have a very low risk to develop osteoporosis.Trial registrationClinicalTrials.gov Identifier NCT00809484.

Preventive effect of risedronate on bone loss and frailty fractures in elderly women treated with anastrozole for early breast cancer

“…The BMD of these patients increased by 3.0% in the lumbar spine after 1 year and by 4.5% after 2 years, whereas their femoral BMD remained unchanged. These results confirm the positive effect of risedronate in protecting lumbar bone, confirming the findings of previous studies on postmenopausal women treated with AIs [20,22]. In patients in the SABRE study with T-scores \ -2 [20] treated with anastrozole and risedronate, lumbar BMD increased by 3% (P \ 0.0001) after 24 months: this increase is lower than the 6% observed after 2 years in elderly women with osteoporosis in the VERT trial [18] who were treated with risedronate alone.…”

“…These and other studies [21,22] indicate that AIs affect BMD in postmenopausal women, particularly at the lumbar spine level.…”

AI-related BMD variation in actual practice conditions: A prospective cohort study

“…Extensive data strongly recommend that individuals who are at low risk for fractures and not candidates for BP treatment should receive calcium and 25(OH) vitD supplements (Markopoulos et al 2010). Patients in the current study receive much higher 25(OH)vitD supplementation than the amount recommended in the Institute of Medicine report: 25(OH) vitD levels improved significantly in our cohort with the proposed regimen, reaching an average >55 ng/mL, and persisting up to 3 years beyond (Prieto-Alhambra et al 2012).…”

A Retrospective Study on Screening and Management of Osteoporosis in Breast Cancer Women Treated With Aromatase Inhibitors in Libya

“…Bone mineral density rapidly decreases resulting in increased risk of skeletal fragility. For the prevention of this adverse event, antiresorptive agents such bisphosphonates are used in combination with AI (11)(12)(13)(14)(15)(16)(17)(18). Recently, also denosumab, a human monoclonal antibody anti RANK-L, is being investigated as an alternative treatment to bisphosphonates for the long-term management of bone loss in women with breast cancer (19,20).…”

“…Recently, also denosumab, a human monoclonal antibody anti RANK-L, is being investigated as an alternative treatment to bisphosphonates for the long-term management of bone loss in women with breast cancer (19,20). Due to the association of AI and decreased BMD, practical guidelines have been developed for the management of these important side effects (16). Firstly, it is well accepted that all postmenopausal women initiating therapy with AI should receive calcium and vitamin D supplements.…”