NcXHF

BONE HEALTH AND ENDOCRINE THERAPY IN BREAST OR PROSTATE CANCER
cancer chemotherapy. Women were randomly assigned to
treatment with zoledronic acid, to be given up front or in the
second year of the study. Women were serially monitored for
ovarian function and BMD. A total of 150 women met the
study defınition for chemotherapy-induced ovarian failure
and completed lumbar spine BMD assessments at baseline
and 1 year; 80 women in the delay zoledronic acid arm and 70
women in the up-front zoledronic acid arm. Women who
were treated with zoledronic acid gained 1.2% in lumbar
spine BMD whereas the untreated group lost 6.7% of lumbar
spine BMD at 1 year (p 0.001). 36
Prostate Cancer Endocrine Therapies
The androgen receptor is expressed on prostate cancer 37 and
the majority of prostate cancers are androgen-dependent and
respond to endocrine therapy. 38 Androgen deprivation therapy
(ADT) may be permanently induced with bilateral orchiectomy
or temporarily induced by chemical ablation with
GnRH agonists (leuprolide, goserlin, triporeline, or histrelin)
or GnRH antagonists (degarelix).
ADT may be used in earlier stage prostate cancers that are
deemed to be at high risk of recurrence. ADT may be used as
neoadjuvant therapy, concurrently with radiation therapy, or
as adjuvant therapy following radiation. In addition, ADT
may be used in the setting of biochemical recurrence. This
discussion will not cover metastatic disease or combined androgen
blockage.
The hypogonadal state induced by ADT is associated with
an accelerated rate of bone resorption. In general, in an older
man the normal rate of loss of BMD is approximately 0.5 to
1.0% per year. With bilateral orchiectomy the rate of loss in
BMD is estimated at approximately 8% to 10% over the fırst 1
to 2 years, 39 whereas the rate of BMD loss with ADT is 3% to
7% per year. 26 The rate of BMD loss is greatest when fırst
starting ADT and decreases over time.
ADT is associated with an increased risk for fracture. An
analysis of SEER-Medicare records of more than 50,000 men
with a diagnosis of prostate cancer demonstrated a dosedependent
association between the use of GnRH agonists
and the risk of fracture. 40 Nineteen percent of men who received
ADT for 12 to 60 months experienced a fracture
whereas only 12.6% without ADT had fractures in the same
time period (p 0.001). Men treated with one to four doses
of GnRH had a fracture risk similar to those with no ADT,
and those treated with nine or more doses had a fracture risk
similar to that of men who underwent orchiectomy, which
was associated with the highest rate of fractures. This study
could not rule out pathologic fractures; however, the risk of
fracture with ADT was not signifıcantly altered when the
analysis was restricted to early-stage disease. Similarly, another
large database analysis of men with prostate cancer
treated with or without GnRH demonstrated a signifıcantly
increased risk for fracture in those treated with GnRH; the
relative risk for hip fracture with ADT was 1.76 (95% CI, 1.33
to 2.33). 41
BONE HEALTH CARE IN THE SETTING OF
ENDOCRINE THERAPY FOR BREAST OR PROSTATE
CANCER
Low bone mass may be a pre-existing comorbid condition
when breast or prostate cancer is diagnosed or may be induced
secondary to cancer therapies. When prescribing cancer
therapies that might increase the risk of fracture,
counseling on the potential bone toxicity and means to mitigate
that risk should be provided. Universal counseling on
bone health includes providing advice on calcium and vitamin
D intake, exercise, behavior (no tobacco, limit alcohol),
the risk of falling, and certain medications such as steroids.
These risk factors can be modifıed in many situations and
should not be neglected as they are opportunities to optimize
bone health. The management of bone health can be shared
with the patient’s primary care provider, as well as other
medical providers such as endocrinologists. Bone health
guidelines for the general public and for those affected by
cancer have been published and serve as references. Examples
of such guidelines include documents produced by the
USPSTF, 42 National Osteoporosis Foundation, 11 American
College of Physicians, 43 and European Society of Medical
Oncology. 44
Screening for risk of fracture includes obtaining a bone
health history, assessing loss in height as an indicator of prior
vertebral compression fractures, obtaining a personal and
family history of fragility fractures, assessing calcium and
vitamin D intake, and reviewing prior BMD assessments.
Using information obtained by history and physical examination,
the clinical team may consult the free online World
Health Organization Fracture Risk Assessment Tool (FRAX),
which can be used with or without BMD data. 45 This tool has
similarities to Adjuvant! OnLine in that it calculates estimated
risk of specifıc outcomes, but it does not replace additional
evaluations and clinical judgment. The outcomes
estimated by FRAX are the 10-year risk of either a major osteoporotic
fracture or a hip fracture. Suggested thresholds for
pharmacologic intervention include a 20% or greater risk of
major osteoporotic fracture risk in 10 years or a 3% or greater
risk of hip fracture in 10 years; however, treatment decisions
must be made based on the individual’s situation. FRAX is
not applicable to patients on antiresorptive therapy.
The result of BMD testing may provide the diagnosis of
osteoporosis or osteopenia. A low BMD is associated with a
high risk of fracture and DXA is the gold standard for measuring
BMD. If low bone mass is identifıed, consideration
should be given to secondary causes of osteoporosis such as
primary hyperparathyroidism or vitamin D defıciency,
which may be common in women with breast cancer. 46 It is
estimated that for each standard deviation drop in BMD the
risk of fracture increases by 1.5- to 2.5-fold, thus making the
measurement of BMD for fracture risk assessment similar to
that of blood pressure for stroke. 13 DXA results can be serially
monitored in treated or untreated patients. The interval between
DXA scans is typically 1 to 2 years 13,26 although a longer
duration may be appropriate, particularly for those on
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