Osteoporosis in Breast and Prostate Cancer Survivors: Page 2 of 2
Osteoporosis in Breast and Prostate Cancer Survivors: Page 2 of 2
Prostate Cancer and Bone Loss
Prostate cancer is one of the most
common malignancies in men. It has
been estimated that in 2005 there will
be 232,000 new cases of prostate cancer
causing approximately 30,000
deaths. Androgen-deprivation therapy
(ADT) is the primary treatment for
patients with metastatic disease; this
therapy results in reduced morbidity
and improved survival when combined
with radiation therapy.
Despite the fact that it can ameliorate
survival, ADT is a palliative rather
than curative treatment. More
recently androgen-deprivation therapy
has been used in patients presenting
with locally advanced or locally
recurrent disease. As these patients
survive longer than patients with widespread
metastatic disease, they are
exposed longer to ADT and are at a
higher risk to manifest the complications
of chronic androgen deprivation.
includes all treatments that will result
in a reduction of testosterone level or
blockade of testosterone action. These
include bilateral orchiectomy, gonadotropin-
releasing hormone (GnRH)
agonists, antiandrogen therapy (androgen
receptor blockers), and combined
androgen blockade (GnRH agonist with antiandrogens). Androgen-
deprivation therapy can result in
loss of libido, erectile dysfunction,
gynecomastia, loss of muscle, and loss
of bone mass. In bone, testosterone
deficiency results in increased bone
turnover; osteoclast resorption exceeds
bone formation resulting in a
net loss of bone.
Several prospective studies have
investigated the effects of ADT on
bone mass (Table 4). Despite the small
number of patients enrolled in these
studies, they clearly demonstrate sub-
stantial bone loss.[7,8,32-34]
Maillefert and colleagues evaluated
BMD in six patients undergoing ADT;
within 18 months they observed a
7.1% and 6.6% reduction in bone mass
of the lumbar spine and femoral neck,
respectively. Mittan and colleagues
evaluated BMD at baseline
and at 6 and 12 months after initiating
ADT (15 patients), and compared the
results to 13 sex-matched controls
without prostate cancer. While no
bone loss was observed in the control
group, patients receiving ADT lost a
significant amount of bone in the hips
and distal radius. Another study by
Daniell showed a 10% decrease in
BMD 2 years following orchiectomy
(10 patients) and a 6.5% reduction in
bone mass in 16 men receiving GnRH
agonist alone or in combination with
In summary, the observed rates of
bone loss during ADT are higher than
those associated with menopause. The
rates observed vary by study population
and by the type of ADT, but
ranged from 2% to 8% in the lumbar
spine and from 1.8% to 6.5% in the
femoral neck after 12 months of continuous
ADT.[32,35] The fracture risk
in these patients has been retrospectively
reviewed (Table 5). Fractures
start to occur within 2 years of treatment
and increase in frequency with
longer durations of ADT.
Melton and colleagues reported a
fracture prevalence of 40% in a group
of patients on ADT (bilateral orchiectomy)
for a mean of 15 years. In a
recent study, Shahinian and colleagues
evaluated the records of 50,613 men
with prostate cancer who were listed
in the linked database of the Surveillance,
Epidemiology, and End Results
(SEER) program and Medicare from
1992 and 1997 and found that ADT
was associated with an increase in
risk of fracture; the risk was proportional
to the number of doses of GnRH
agonist administered in the first year
How to Prevent or Treat Bone
Loss in Cancer Patients
Early screening and identification
of patients at increased risk for bone
loss is a key element of management
of bone health in breast and prostate
cancer patients. The American Society
of Clinical Oncology has published
guidelines for the identification and
management of bone loss in breast
cancer patients. These guidelines
recommend that any patient at risk
for osteoporosis undergo a DXA scan
to evaluate the bone mineral density
followed by appropriate treatment.
High-risk patients include women older
than 65 years of age, postmenopausal
women receiving aromatase
inhibitors, women who develop premature
menopause as a result of the
breast cancer treatment, and patients
with other known risk factors for osteoporosis
(Table 6). All patients with
breast cancer, including the ones not
at risk for osteoporosis, should be
counseled on lifestyle changes and
appropriate calcium and vitamin D
supplementation. All patients with
natural or drug-induced estrogen deficiency
should have periodic evaluation
of their bone mass in addition to
calcium/vitamin D supplementation
and exercise; patients with osteoporosis
or significant bone loss over time
should be started on therapy.
The American Society of Clinical
Oncology has not yet provided guidelines
for maintenance of bone health
in prostate cancer patients. However,
several authors have published recommendations
for this group of patients.
In a recent publication, Diamond
and colleagues recommended
that patients with risk factors for fractures
(on ADT, previous fracture) undergo
assessment of their bone mass
by using DXA or QCT. Patients
with osteoporosis should be started
on treatment, patients with osteopenia
should have a repeat BMD evaluation
in 6 to 12 months, and patients
with normal BMD should be reassessed
in 2 years. Patients with osteoporotic
fractures confirmed by
imaging studies should also be started
While these guidelines are an important
first step, there are compelling
reasons for being more proactive.
Current guidelines from several bone
clinical.htm), endocrine, and rheumatologic[
39] societies recommend
prevention of bone loss rather than
the more passive approach of waiting
until it happens suggested by oncologic
guidelines. Current therapies for
osteoporosis make it difficult to increase
bone mass by more than 10%,
arguing persuasively for a strategy
focused on prevention. Oncologists
should be mindful of these guidelines.
There are several drugs approved
or under investigation for treatment
of osteoporosis.[40-44] The two classes
of drugs available include bone
resorption inhibitors and anabolic
agents. The bone resorption inhibitors
include estrogen, selective estrogen
receptor modulators (SERMS),
nasal calcitonin (Miacalcin), bisphosphonates,
and the RANKL monoclonal
only anabolic agent currently approved
for use in osteoporosis is teriparatide
human parathyroid hormone (hPTH
1-34)-a potent enhancer of bone formation
that results in significant improvement
of bone mineral density in
women with postmenopausal osteoporosis
and in men with osteoporosis.[
42] Teriparatide has not yet been
investigated in breast or prostate cancer
patients; therefore the risks and
benefits of this agent should be carefully
considered before using it in this
group of patients.
There is a fully humanized monoclonal
antibody against RANKL (AMG 162) that has been under investigation
and is a promising bone
resorption inhibitor. AMG 162 has
been investigated in postmenopausal
osteoporosis in phase I and II studies.
A single subcutaneous dose of AMG
162 (1 mg/kg or 60 mg) resulted in
suppression of bone resorption for
more than 6 months and increase in
bone mineral density. Studies with
AMG 162 in breast cancer patients
for control of bone loss as well as for
bone metastatic disease are currently
Bisphosphonates are potent inhibitors
of osteoclast differentiation and
activity. This class of drugs is widely
used for treatment of postmenopausal,
steroid-induced, and male osteoporosis.
In breast cancer patients,
several studies have addressed the role
of bisphosphonates in preventing bone
loss after chemotherapy-induced premature
menopause. Clodronate and
risedronate (Actonel), both oral bisphosphonates,
have been investigated
and were shown to be effective in
reducing the rate of bone loss.[45,46]
The use of intravenous bisphosphonates
in these patients is still under
investigation, but preliminary data
from a study that has evaluated the
effect of zoledronic acid (Zometa) in
patients receiving tamoxifen or anastrozole
have indicated that zoledronic
acid is able to counteract the bone
loss induced by anastrozole in these
In prostate cancer patients, intravenous
bisphosphonates have proven to
reduce bone loss in at least two studies.
Smith and colleagues have investigated
the effects of both intravenous pamidronate
(Aredia) and zoledronic acid
on bone mass in patients receiving androgen
therapy and compared their
bone mineral densities to individuals
who received androgen-deprivation
therapy alone.[48,49] In the pamidronate
study, 47 patients who were
being treated with androgen-deprivation
therapy were randomized to receive
pamidronate at 60 mg or placebo
every 3 months. Pamidronate treatment
protected patients from developing the
bone loss associated with ADT.
Another study investigated the use
of zoledronic acid vs placebo in patients
undergoing androgen deprivation
therapy. Zoledronic acid was
given at a dose of 4 mg every 3 months
for 12 months. Patients who received
zoledronic acid were not only protected
against bone loss, but gained a
significant amount of bone mass.
Diamond and colleagues investigated
the effect of an oral bisphosphonate
(etidronate [Didronel]) in patients undergoing
ADT. Despite the small number
of patients included in the study,
they were able to show a gain of bone
mass at the lumbar spine in patients
treated with etidronate.
As estrogen plays an important role
in male bone metabolism and can be
used in patients with prostate cancer,
it has been studied as a potential treatment
for ADT-induced bone loss. Taxel
and colleagues investigated the
effects of micronized estradiol on bone
turnover in prostate cancer patients
on ADT; they observed a significant
reduction in bone turnover markers.[
51] Subsequently, two studies
have addressed the question of whether
estrogen or a SERM is a potential
treatment for prevention or treatment
of osteoporosis associated with ADT.
Smith and colleagues have studied the
effects of raloxifene (Evista), a SERM,
in patients with nonmetastatic prostate
cancer being treated with
ADT. A total of 48 patients were
randomized to receive raloxifene or
placebo. At 12 months, patients on
raloxifene maintained their bone mass
at the spine and hips while patients
receiving placebo suffered a reduction
in BMD. Ockrim et al investigated
transdermal estradiol in
patients with prostate cancer and also
noted a significant improvement in
bone mass with this agent.
In conclusion, gonadal insufficiency
caused by cancer treatment can
cause rapid bone loss in women with
breast cancer or men with prostate
cancer. Therefore, high-risk patients
should be assessed by bone mineral
density testing. Patients with severe
osteopenia or osteoporosis should undergo
early treatment to prevent fractures,
pain, and deformities associated
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