Background

Prevention of letrozole–induced bone loss using oral risedronate has not been proved in the Japanese women. The aim of this study was to assess the effect of risedronate 17.5mg/week on bone mineral density (BMD) in postmenopausal, early breast cancer patients scheduled to receive adjuvant letrozole.

Patients and Methods

Postmenopausal women with hormone receptor–positive early breast cancer were assigned to one of two strata according to their baseline BMD T-score as being at low and high risk of osteoporosis. Patients with low risk (-2.5 ≤ T score) were randomly assigned to letrozole and risedronate (L+R) or to letrozole alone (L). Patients with high risk (-2.5 > T score) received letrozole and risedronate (L+R). Letrozole was given at a dosage of 2.5 mg/day while oral risedronate was given at 17.5mg/week. The primary end point was the change in lumbar spine (LS) BMD at 12 months. The secondary end points included change in total hip (HP) BMD and bone turnover markers.

Results

In the low risk group (N=103), treatment with L+R resulted in a significant increase in BMD at LS and at HP compared to treatment with L only at 12 months (1.8% vs -2.2%, P < 0.001, and -0.3% vs -2.9%, P = 0.001, respectively). In the L+R group, significant decreases in bone turnover makers, NTX and PINP, were recognized compared with L only at 12months (-11.1% vs. 27.5%, P<0.001, -42.3% vs. 15.2%, P<0.001, respectively). In the high risk group (N=28), treatment with L+R resulted in a significant increase in BMD at LS and prevention of decrease in BMD at HP (3.6%; 95%CI, 1.8% to 5.3%, p=0.003, 0.3%; 95%CI, -1.3% to 1.8%, p=0.47, respectively).

Estimated Percentage Change From Baseline to 6 and 12 Months in Lumbar Spine and Total Hip BMD

      From Baseline to 6 Months From Baseline to 12 Months 
BMD area Risk Group Treatment Change in BMD (%), 95% CI Change in BMD (%), 95% CI 
Lumbar spine Low risk L+R 1.7 (-1.3 to 4.7) <0.001 1.8 (-2.1 to 5.7) <0.001 
    -1.6 (-4.3 to 1.1)   -2.2 (-5.7 to 1.3)   
  High risk L+R 1.8 (0.4 to 3.2) 0.04 3.6 (1.8 to 5.3) 0.003 
Total hip Low risk L+R -0.2 (-2.7 to 2.3) 0.001 -0.3 (-3.2 to 2.6) 0.001 
    -2.2 (-5.4 to 1.0)   -2.9 (-7.2 to 1.4)   
  High risk L+R 0.1 (-1.3 to 1.6) 0.61 0.3 (-1.3 to 1.8) 0.47 
      From Baseline to 6 Months From Baseline to 12 Months 
BMD area Risk Group Treatment Change in BMD (%), 95% CI Change in BMD (%), 95% CI 
Lumbar spine Low risk L+R 1.7 (-1.3 to 4.7) <0.001 1.8 (-2.1 to 5.7) <0.001 
    -1.6 (-4.3 to 1.1)   -2.2 (-5.7 to 1.3)   
  High risk L+R 1.8 (0.4 to 3.2) 0.04 3.6 (1.8 to 5.3) 0.003 
Total hip Low risk L+R -0.2 (-2.7 to 2.3) 0.001 -0.3 (-3.2 to 2.6) 0.001 
    -2.2 (-5.4 to 1.0)   -2.9 (-7.2 to 1.4)   
  High risk L+R 0.1 (-1.3 to 1.6) 0.61 0.3 (-1.3 to 1.8) 0.47 

BMD: bone mineral density, L: Letrozole, R: risedronate

Four patients (14.3%) improved from osteoporotic region to the osteopenic region with L+R treatment. Letrozole and risedronate were well tolerable and there was no serious adeverse event including osteonecrosis of jaw.

Conclusions

At 12 months, 17.5mg/week risedronate therapy prevented bone loss in postmenopausal women with breast cancer who were receiving adjuvant letrozole, of which results were compatible with previous findings of western populations.

Citation Format: Kadoya T, Masumoto N, Shigematsu H, Emi A, Kajitani K, Kobayashi Y, Funakoshi M, Kawabuchi Y, Ohara M, Matsuura K, Noma M, Sasada T, Okada M. Prevention of letrozole–induced bone loss using risedronate in postmenopausal women with hormone receptor positive breast cancer: A multicenter randomized clinical trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-15-03.