Trial Information

A Pilot Study to Determine the Prevalence of Osteoporosis in Patients With Advanced Prostate Cancer Treated With Hormonal Manipulation

INTRODUCTION - Osteoporosis is a common disorder with many predisposing factors including
hypogonadism from a variety of causes. Prostate cancer is the second most common malignancy
in men. The standard treatment for men with advanced prostate cancer is hormonal
manipulation in order to decrease testosterone levels which renders a man hypogonadal. There
is an increasing body of literature that suggests men with prostate cancer treated with
hormonal manipulation develop osteoporosis and associated complications more commonly than
aged matched controls. With the increasing incidence of prostate cancer and the increasing
indications with hormonal therapy use in advanced prostate cancer, osteoporosis in these men
is a major health concern.Hormonal manipulation in order to obtain castrate levels of
testosterone can be achieved with bilateral orchiectomy, Luteinizing Hormone Releasing
Hormone agonists (LHRHA) and steroidal antiandrogens combined with mini doses of estrogen
based therapy. Nonsteroidal antiandrogens are also used in the management of advanced
prostate cancer however, on their own, are not enough to suppress testosterone. The data on
exactly how common and severe a problem osteoporosis is in men treated with different forms
of hormonal manipulation is sparse and because of the lack of data, there is currently no
accepted standard of care in the investigation and management of osteoporosis in these men.
The researchers propose to start with a pilot study to first determine the prevalence of
osteoporosis in 6 different populations of men with advanced prostate cancer, (1) newly
diagnosed, (2) treated with orchiectomy, (3) treated with an LHRHA, (4) treated with
steroidal antiandrogen therapy, (5) treated with nonsteroidal antiandrogen based therapy,
(6) treated with complete androgen blockade (LHRHA plus a nonsteroidal antiandrogen).

OBJECTIVES - To determine, in the above populations, the bone mineral density as measured by
Dual Energy X-ray Absorptiometry (DEXA) of the lumbar spine, proximal hip (total hip,
femoral neck and trochanter), and non-dominant distal radius, to document biochemical
markers of bone turnover, to document vertebral fractures and body height, to document other
aspects of body composition including adipose tissue and muscle mass as measured by whole
body composition densitometry, and to document other potential confounding factors
predisposing prostate cancer patients to osteoporosis.

STUDY DESIGN - This primarily will be a descriptive, exploratory study describing the
prevalence of osteoporosis in each of the 6 groups defined above. The diagnosis of
osteoporosis will be based on bone densitometry studies. There are accepted densitometric
criteria for the assessment of normal and abnormal bone mass. The criteria were largely
developed in postmenopausal Caucasian women but reference values are also available for
Caucasian, Black and Hispanic men. Normal bone density is described as a T-score less than
-1. T-scores between -1 and -2.5 are indicative of osteopenia, and T-scores of less than
-2.5 are indicative of osteoporosis. The prevalence of osteoporosis (T value less than 2.5)
in each of the groups will be reported. Information on biochemical markers of bone turnover,
vertebral fractures, and other risk factors will also be described.

PATIENT SELECTION - Patients with biopsy proven advanced prostate cancer, no known prior
clinical or radiographic history of osteoporosis, minimum of 1 year of hormonal therapy in
arms 2, 3, 4, 5 and 6, and an ability and willingness to give informed consent. Exclusion
criteria - Patients with known bone disorders other than metastatic disease such as
hyperparathyroidism, Paget's disease, renal osteodystrophy, and documented osteomalacia as
well as osteoporosis, patients who have received a bisphosphonate, systemic fluoride,
pharmacological doses of calcium (less than 1500 mg/day) or Vitamin D (less than 1000
IU/day), or calcitonin, patients with known abnormal thyroid function, and patients with
marked renal impairment (creatinine less than 2.0 X normal).

MANAGEMENT OF PATIENTS - This will be an outpatient study. All patients will initially be
assessed by a research nurse and/or physician at the Cross Cancer Institute with a prostate
cancer specific history, blood and urine tests. Patients will be referred to a single
endocrinologist for a more detailed osteoporosis history and physical exam. On the same day,
they will have a densitometry study, whole body composition study, and plain radiographs
taken. Patients will then be seen at the Cross Cancer Institute to discuss their results.
Should a diagnosis of osteoporosis be made, a letter indicating this will be sent to the
patient's family physician.

ENDPOINTS - The primary endpoint will be bone mineral density. Osteoporosis will be
diagnosed if the T value is less than -2.5. The secondary endpoints will be - biochemical
markers of bone turnover, vertebral fractures, vertebral body height, body composition of
fat, body composition of adipose tissue.

DATA ANALYSIS - The data will be entered into a computerized database. Descriptive
statistics will be tabulated for all 5 arms being studied with respect to demographic
variables, baseline characteristics, and test results.