healthmedicinet

Anastrozole is superior to tamoxifen in terms of disease-free survival, time to recurrence,
and the incidence of contralateral breast cancer in postmenopausal woman with early
breast cancer (Baum et al. 2003]). However, AIs are definitely associated with the reduction of BMD (Eastell et al.
2008]; Zaman et al. 2011]). The reduction of plasma estrogen due to AIs has been associated with an accelerated
rate of bone mineral loss and an increased risk of bone fracture. However, there is
little data on the association between changes of BMD and bone fractures especially
for Asian women.

Fractures are related to increased mortality among elderly patients. The mortality
after hip fracture is most marked in the first year and thereafter tails off, but
always exceeds the mortality of the general population (Johnell and Kanis 2004]). Therefore, the prevention of bone loss is important for postmenopausal women in
order to preclude a fracture.

Oral Bis therapy increased BMD at clinically important skeletal sites in postmenopausal
osteoporosis, and decreased the incidence of bone lumbar and non-lumbar fractures
(Harris et al. 1999]). The SABRE trial demonstrated that the effect of Bis appeared to be manageable with
the use of established practices for maintaining bone health in postmenopausal women
treated with AIs (Van Poznak et al. 2010]). MA.27B is the largest prospective bone study to assess the role of oral Bis treatment
for women with a T-score ?2.0 with concomitant AIs (Goss et al. 2014]). These data indicate that Bis prevented AI-induced bone loss in Caucasian women
for at least two years.

Our data demonstrated that the Bis (risedronate or alendronate) could control BMD
at the LS. However, the effect of Bis at the FN was restricted. In the SABRE trial,
the effect of risedronate was demonstrated at the FN (Van Poznak et al. 2010]). The effect of Bis at the FN was relatively weak in MA27B. Discordance between these
studies is seen regarding the response to Bis at the FN. One reason is that the effect
of Bis is essentially larger in LS than FN (Harris et al. 1999]). Secondly, the measurement error might be larger at the FN than LS. Furthermore,
ethnic difference might influence the response to Bis at the FN. In any case, no femoral
fracture was observed in our study. There will be no problem even if BMD of FN does
not rise unless the incidence of femoral fractures increases.

Although the observation period of only two studies on AI and Bis in breast cancer
(SABLE and MA-27B) is 2 years (Van Poznak et al. 2010]; Baum et al. 2003]), our study is the result of 5 years’ observation. Our results showed that the BMD
of the group receiving Bis at the LS increased during the first 4 years, and afterward
decreased. However, the BMD after 5 years increased by 1.9% at the LS from baseline.
Our data demonstrated that Bis could control BMD of LS in patients treated with anastrozole
for 5 years. Thus, it is not necessary to exclude osteoporotic patients from the treatment
of anastrozole.

Which is better, upfront use of Bis for the prevention of osteoporosis or delayed
use of Bis after reduction of BMD? Bisphosphonate-related osteonecrosis of the jaw
(BRONJ) is a rare, but serious toxicity of Bis. Therefore, we want to avoid the use
of Bis as much as possible. This study indicated that BMD of LS increased from baseline
at month 60, in patients with both upfront and delayed use of Bis. BMD of FS increased
at month 60 in those with upfront Bis; however, it decreased in those with delayed
Bis. Thus, it is suggested that upfront use of Bis is recommended for the prevention
of decreases in BMD of FN.

Although some data have shown that continuous treatment with Bis for 5 years maintained
or increased BMD (Black et al. 2006]; Sorensen et al. 2003]) in Caucasian postmenopausal women, the BMD decreased from 4 years later in this
study. There is a report of the BMD receiving Bis in postmenopausal Asian women. It
showed that the pattern of the changes of BMD in Singaporean women was similar to
that in Japanese women (Ang et al. 2011]).

A review article provided some insights into the potential difference in osteoporosis-related
phenotypes between Asians and Caucasians (Lei et al. 2006]). These phenotypic differences may partially be the result of different genetic backgrounds,
and included the pattern of bone loss and response to treatment.

Bone fractures were observed in 4 patients (7.3%), and 1 patient (1.8%) had a fragility
fracture in this study. The annual incidence of vertebral fracture for all Japanese
women in their 70 s was 4% per year, and 8.4% per year for those in their 80 s (Fujiwara
et al. 2003]). The annual bone fracture rate was 1.6% per year in this study, suggesting that
Bis would prevent fractures for Japanese women treated with AI. In the ATAC trial,
bone fractures were observed in 7.1% of patients over 4 years (Baum et al. 2003]). In the BIG 1-98 trial, bone fractures were observed in 9.3% over 5 years (Rabaglio
et al. 2009]). In view of bone fracture, our results were similar to the results for Caucasians.

This is the first report on changes of BMD in more than 50 patients treated with anastrozole
for 5 years including osteoporotic patients receiving Bis.