Abstract P5-15-06: Open-label randomized parallel controlled study comparing bone mineral density between alendronate plus alfacalcidol combination and single administration of alfacalcidol in postmenopausal women receiving aromatase inhibitor as adjuvant therapy
Authors: Saito Mitsue , Matsuoka Joe 
Published: May 2015

Abstract
&lt;Background&gt;
One of the most worrisome side effects of endocrine therapy is loss of bone mineral density. Optimized bone therapy is thus warranted.
&lt;Objectives&gt;
The primary endpoint of this study was to assess the difference in bone mineral density between aromatase inhibitor-treated breast cancer patients receiving alfacalcidol alone versus also prescribed alendronate.
Secondary endpoints were measured levels of surrogate markers for bone health and adverse events associated with bone-preserving therapies.
&lt;Material and method&gt;
Postmenopausal breast cancer patients (stage I-III) receiving any form of aromatase inhibitor (anastrozole (ANA), exemestane (EXE) or letrozole (LTZ)) whose bone mineral density as measured by DEXA (Dual-energy X-ray absorptiometry) was lower than the adult mean and from whom written informed consent had been obtained between March in 2008 and September in 2010 were studied. The study period was 2 years after enrollment. This study was approved by our institutional review board.
Patients were randomized into two arms stratified by age (&lt;70 or not), use of an aromatase inhibitor (ANA, EXE or LTZ) and T score on DEXA (&lt;-1.0 or not). Patients enrolled in arm A were treated with 35mg of oral alendronate weekly and 1µ g of alfacalcidol daily. Patients in arm D were given 1µ g of alfacalcidol daily.
Patients underwent DEXA (L2,3,4) every 6 months and blood tests for 1CTP (carboxyterminal telopeptide of type I collagen), BAP (bone alkaline phosphatase) and urine testing for NTX (type I collagen cross-linked N-telopeptide) every 3 months. Adverse events were monitored by physicians every 3 months.
&lt;Results&gt;
We enrolled 58 patients. Nine out of the 29 patients in arm D dropped out due to adverse events caused by alfacalcidol (2), caused by the aromatase inhibitor (2), metastasis (3) and severe bone loss (1). Six out of the 29 patients in arm A dropped out due to adverse events caused by alendronate plus alfacalcidol (1), caused by the aromatase inhibitor (2), metastasis (2) and financial difficulties (1). Improvement from the DEXA baseline in arm A was significantly better (p&lt;0.0001) than that in arm D by analysis of covariance. NTX and BAP Improved significantly in arm A (p&lt;0.0001), but 1CTP did not (p=0.0382).
&lt;Considerations&gt;
Strict indications for and durations of bone therapy require further investigation. The dosage of alendronate was lower in this study than the international recommendation because the dosage approved by the Japanese government is half that in other countries and this applies to all the oral bisphosphonates because of the ethnic differences in absorption rate demonstrated in phase II studies.
&lt;Conclusions&gt;
Co-administration of alendronate and alfacalcidol contributed to preserving bone mineral density during adjuvant aromatase inhibitor treatment without producing severe adverse events. NTX and BAP are possible surrogate markers for bone therapy.
Citation Format: Mitsue Saito, Joe Matsuoka. Open-label randomized parallel controlled study comparing bone mineral density between alendronate plus alfacalcidol combination and single administration of alfacalcidol in postmenopausal women receiving aromatase inhibitor as adjuvant therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-06.