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Atypical angiomyolipoma of the kidney A distinct morphologic variant that is easily confused with a variety of malignant neoplasms

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1561
The Effect of Combined Androgen Blockade on Bone
Turnover and Bone Mineral Densities in Men Treated
for Prostate Carcinoma
Longitudinal Evaluation and Response to Intermittent Cyclic Etidronate Therapy
Terrence Diamond1
Joanne Campbell1
Carl Bryant1
William Lynch2
1
Metabolic Bone Unit, St. George Hospital, Kogarah, Sydney, Australia.
2
Urology Department, St George Hospital, Kogarah, Sydney, Australia.
Address for reprints: Terrence Diamond, St.
George Hospital, Department of Endocrinology, 32
Belgrave Street, Kogarah, Sydney 2217, Australia.
Received December 19, 1997; revision received
March 25, 1998; accepted March 25, 1998.
© 1998 American Cancer Society
BACKGROUND. Androgen receptor blocking agents have become an established
form of therapy for men with disseminated prostate carcinoma. The purpose of
this study was to evaluate markers of bone turnover and to measure bone mineral
densities (BMD) in men with disseminated prostate carcinoma treated with combined androgen blockade prior to and after 6 months of intermittent cyclic etidronate therapy.
METHODS. Twelve consecutive men with disseminated prostate carcinoma were
evaluated at 0, 6, and 12 months after treatment with a long acting gonadotropinreleasing hormone agonist (goserelin acetate) and an androgen antagonist (flutamide). During the 6 –12 month period, patients were treated with adjuvant intermittent cyclic etidronate therapy and calcium supplementation. Lumbar spine
BMD was measured by spinal quantitative computed tomography (QCT) and
femoral neck BMD by dual energy X-ray absorptiometry (DXA).
RESULTS. Combined androgen blockade resulted in all men achieving serum
free testosterone concentrations of ,2.2 pmol/L (normal range, 38 –114 pmol/
L). The mean serum prostate specific antigen activities decreased from 130.8 6
46 to 6.9 6 4.4 ng/mL (P , 0.05). Although serum calcium, parathyroid hormone, and 25-hydroxyvitamin D measurements remained unchanged, serum
bone Gla-protein concentrations and urinary deoxypyridinolene excretion rates
increased significantly (P , 0.01, respectively). Mean lumbar spine QCT decreased by 6.6 6 1.5% from 76.5 mg/cm3 (95% confidence interval [95% CI],
57–96 mg/cm3) to 73.9 mg/cm3 (95% CI, 55–93 mg/cm3) (P , 0.001) and mean
femoral neck DXA decreased by 6.5 6 1.3% from 0.94 g/cm2 (95% CI, 0.81–1.07
g/cm2) to 0.91 g/cm2 (95% CI, 0.79 –1.04 g/cm2) (P , 0.001). After treatment
with adjuvant intermittent cyclic etidronate, mean lumbar spine QCT increased
by 7.8 6 3.7% to a final value of 75 mg/cm3 (95% CI, 48.7–101 mg/cm3) (P 5
0.001 compared with the initial 6 months without intermittent cyclic etidronate
therapy). Significant increases in BMD also were observed in the femoral neck
and Ward’s triangle.
CONCLUSIONS. Androgen receptor blocking agents have an established role in the
treatment of disseminated prostate carcinoma. However, combined androgen
blockade in elderly men with disseminated prostate carcinoma results in high bone
turnover with significant cancellous bone loss. The results of this study show that
adjuvant therapy with intermittent cyclic etidronate may prevent these changes
and decrease the risk of spinal fractures. Cancer 1998;83:1561– 6.
© 1998 American Cancer Society.
KEYWORDS: prostate carcinoma, combined androgen blockade, osteoporosis, disseminated.
1562
CANCER October 15, 1998 / Volume 83 / Number 8
R
ecent data have demonstrated increased survival
in men with disseminated prostate carcinoma
treated with androgen receptor blocking agents.1,2
These agents cause significant hypogonadism and
bone loss in premenopausal women3 and elderly
men.4 Although osteoporosis and spinal fractures have
been reported in men with prostate carcinoma treated
by orchiectomy,5–10 limited data are available regarding bone turnover studies and bone mineral densities
(BMD) in men treated with androgen receptor blocking agents.11–14 To our knowledge, to date there are no
data regarding the treatment or prevention of osteoporosis in men with prostate carcinoma.
MATERIALS AND METHODS
We studied 12 consecutive men with a mean age of
78.2 years (range, 60 – 89 years) referred with prostate
carcinoma over a 12-month period. All men had histologic evidence of adenocarcinoma, an elevated prostate specific antigen level, and radioisotopic evidence
of metastatic bone disease. Patients were studied at 0,
6, and 12 months after commencing treatment with a
long-acting gonadotropin-releasing hormone (GnRH)
agonist (goserelin acetate, 3.6 mg subcutaneously
monthly) and an androgen antagonist (flutamide, 750
mg daily). During the second 6-month period they
were treated with intermittent cyclic etidronate therapy (Procter & Gamble Pharmaceuticals, Cincinnati,
OH) (400 mg at bedtime for 2 weeks of every 3 months)
and with daily calcium supplements (equivalent to 600
mg elemental calcium per day).15 No patient had thyroid, renal, or liver disease and none had received
calcium, calcitriol, bisphosphonates, or calcitonin
prior to entering the study. Two men had well controlled type II diabetes that was managed with oral
hypoglycemic agents.
Data on 113 healthy community dwelling men
ages 70 –92 years residing in the same metropolitan
area as the men presenting with prostate carcinoma
were used as normal controls for baseline biochemistry and densitometry assessment. These men were
recruited for a study on Muscle Mass Determinants in
the Elderly (unpublished data). Longitudinal changes
in bone densitometry performed in a subset of 12 of
these men was used as comparative data for the longitudinal studies.
After informed consent was obtained venous
blood and an early morning fasting 2-hour urine sample were collected from all men for biochemical and
hormonal measurements. Serum and urinary calcium
and creatinine levels and serum alkaline phosphatase
activities were determined by routine autoAnalyser
methods.
Serum parathyroid hormone, serum bone Gla-
protein (a serologic marker of bone formation), and
serum 25 hydroxyvitamin D were measured by immunoradiometric assay (Nichols Institute, San Clemente,
CA). Serum free testosterone was measured by radioimmunoassay (Diagnostic Products Corporation,
Santa Barbara, CA) and serum prostate specific antigen by microparticle enzyme immunoassay (Abbott
Laboratories, Abbott Park, IL). Serum follicle-stimulating and luteinizing hormone and urinary deoxypyridinolene (a marker of bone resorption) were measured
by chemiluminescence (Ciba Corning, Medfield, MA).
A lateral thoracolumbar spine X-ray performed
prior to commencing combined androgen blockade
was used to assess for metastatic bone disease, vertebral crush fractures, and spondyloarthropathy. The
BMD of the lumbar spine (anteroposterior; L2 to L4)
and femoral neck was measured by dual energy X-ray
absorptiometry (DXA) (Lunar DPX-L; Lunar Corporation, Madison, WI). The in vivo precision was 1.7% for
measurements of the lumbar spine, 3.6% for measurements of the femoral neck, 3.3% for measurements of
Ward’s triangle, and 2.2% for measurements of the
femoral trochanter.16 BMD measurements were expressed in absolute terms as g/cm2 and as a percentage of the initial value. Osteoporosis was defined as a
BMD measurement .2.5 standard deviations below
the mean for a healthy population group ages 20 – 40
years. Longitudinal changes in BMD were expressed as
percentage change and were calculated by subtracting
the final BMD from the initial BMD and dividing this
difference by the initial BMD. Percentage changes in
BMD were calculated for each individual and the
mean 6 standard error of the mean (SEM) derived for
the groups.
Lumbar spine BMD also was measured by quantitative computed tomography (QCT)17 using a General Electric Hi Speed scanner (General Electric Co.,
Milwaukee, WI). A lateral scout radiograph of the lumbar spine was obtained to permit precise positioning
of the scanner. Baseline and follow-up measurements
were performed by obtaining scans through lumbar
vertebrae L2, L3, and L4. A mean lumbar spine QCT
value was calculated for the three vertebral bodies and
expressed as mg/cm3. The precision for this technique
was 2.8%.
All values were reported as the mean 6 SEM and,
where appropriate, 95% confidence intervals (CI) were
cited. Data were compared by the Student’s t test for
paired data and analysis of variance. Statistical significance was assigned as P , 0.05.
RESULTS
Results of serum biochemistry, markers of bone turnover and bone densitometry performed at 0, 6, and 12
Bone Changes in Prostate Carcinoma/Diamond et al.
1563
TABLE 1
Serum Biochemistry, Markers of Bone Turnover, and Bone Mineral Density Measurements in Men with Prostate Carcinoma at 0, 6, and 12
Months after Therapy with Combined Androgen Blockade
Patients (no)
Calcium (2.40 6 0.02 mmol/L)a
Phosphate (1.18 6 0.04 mmol/L)
Creatinine (0.11 6 0.01 mmol/L)
PTH (3.8 6 0.5 pmol/L)
Free testosterone (38 6 1.2 pmol/L)
PSA (,4 ng/mL)
SAP (94 6 12 u/L)
BGP (5.7 6 0.2 ng/mL)
Urinary Ca/Cr (0.41 6 0.05 mmol/mmol)
Urinary DPYD/Cr (0.54 6 0.05 nmol/mmol)
Spinal QCT (99 6 6.2 mg/cm3)
Femoral Neck DXA (0.94 6 0.03 g/cm2)
Ward’s triangle DXA (0.73 6 0.03 g/cm2)
Trochanter DXA (0.89 6 0.03 g/cm2)
0 mos (baseline)
6 mos (without etidronate)
12 mos (with etidronate)
12
2.45 6 0.03
1.17 6 0.04
0.11 6 0.01
4.2 6 0.4
43.7 6 3.5
130.8 6 46c
98.6 6 13
4.4 6 0.5
0.32 6 0.03
5.6 6 0.4
76.5 6 8.8f
0.94 6 0.06
0.67 6 0.05f
0.88 6 0.07
11
2.42 6 0.07
1.25 6 0.04
0.10 6 0.01
3.5 6 0.4
2.3 6 0.6b,c
8 6 5.6d
92 6 9.6
5.9 6 0.3e
0.69 6 0.2e
7.9 6 0.5b,f
73.9 6 8.5b,f
0.91 6 0.03b,f
0.63 6 0.05e,f
0.84 6 0.04f
8
2.39 6 0.03
1.27 6 0.07
0.11 6 0.01
3.0 6 0.4
3.0 6 0.7b,c
6.8 6 4.4d
127 6 4.9
6.1 6 0.5e
0.60 6 0.1e
6.9 6 0.2b,f
75 6 11.1e,f
0.92 6 0.03e
0.65 6 0.06f,g
0.90 6 0.07
PTH: parathyroid hormone; PSA: prostate specific antigen; SAP: serum alkaline phosphatase; BGP: bone Gla-protein; Ca/Cr: calcium/creatinine ratio; DPYD/Cr: deoxypyridinolene/creatinine ratio; QCT: bone density
measured by quantitative computed tomography; DXA: bone density measured by dual energy X-ray absorptiometry.
Values are presented as the mean 6 the standard error of the mean.
a
Data in parentheses are the normal reference range for 113 age-matched healthy controls.
b
P , 0.001 compared with value at 0 months.
c
P , 0.001 versus controls.
d
P , 0.05 compared with value at 0 months.
e
P , 0.01 compared with value at 0 months.
f
P , 0.01 versus controls.
g
P , 0.05 compared with value at 6 months.
months are recorded in Table 1. One man died during
the initial 6 months of the study and an additional 3
men died during the final 6 months of the study.
Combined androgen blockade resulted in all men
achieving serum free testosterone concentrations of
,2.2 pmol/L (normal range, 38 –114 pmol/L) and serum gonadotrophin measurements of ,5 mu/L (normal range, 5–21 mu/L). The mean serum prostate
specific antigen activities decreased from 130.8 6 46
ng/mL to 6.8 6 4.4 ng/mL (P , 0.05) after 12 months
of therapy. Individual serum prostate specific antigen
activities normalized in 9 of the 11 men after 6 months
of therapy and remained within the normal reference
range in 6 of the 8 men after 12 months of therapy.
Serum calcium, phosphate, and parathyroid hormone
measurements remained unchanged during the study.
No man had evidence of subclinical vitamin D deficiency.
Serum bone Gla-protein, a marker of bone formation, increased after combined androgen blockade by
approximately 34% from 4.4 6 0.5 to 5.9 6 0.3 ng/mL
(P , 0.01) and remained persistently elevated in 5
men despite intermittent cyclic etidronate therapy.
Conversely, urinary deoxypyridinoline excretion, a
marker of bone resorption, increased after combined
androgen blockade by approximately 41% from 5.6 6
0.4 to 7.9 6 0.5 nmol/mmol of creatinine (P , 0.001).
However, after intermittent cyclical etidronate therapy, urinary deoxypyridinoline excretion rates decreased to a mean value of 6.9 6 0.2 nmol/mmol of
creatinine, but still remained above the normal reference range in 6 men.
Spinal radiography performed prior to commencing combined androgen blockade demonstrated vertebral fractures (T12 and L1) in two men with prostate
carcinoma. There was no evidence of lumbar spine
metastases or osteosclerosis secondary to prostate
carcinoma in any patient. Lumbar spine BMD measured by DXA was pseudoelevated and uninterpretable in 9 of the 12 men (75%). This was due to significant lumbar spine disk degeneration and facet joint
hypertrophy.18 Figure 1 shows the individual lumbar
spine QCT and femoral neck DXA measurements performed at 0, 6, and 12 months after therapy. Osteoporosis of the lumbar spine (QCT) and femoral neck
(DXA) was present in 9 (75%) and 4 (33%), respectively, of the 12 men prior to commencing therapy.
After 6 months of combined androgen blockade,
mean lumbar spine QCT decreased by 6.6% from 76.5
mg/cm3 (95% CI, 57–96) to 73.9 mg/cm3 (95% CI,
1564
CANCER October 15, 1998 / Volume 83 / Number 8
FIGURE 1. Individual lumbar spine (squares) and femoral neck (circles) bone
mineral density (BMD) values in men with disseminated prostate carcinoma.
Lumbar spine BMD was measured by quantitative computed tomography (QCT)
and expressed as mg/cm3. Femoral neck BMD was measured using dual
energy X-ray absorptiometry (DXA) and expressed as g/cm2. Closed symbols:
densities recorded at 0 months after combined androgen blockade; open
symbols: densities recorded at 6 months after combined androgen blockade;
shaded symbols: densities recorded at 12 months after combined androgen
blockade and intermittent cyclic etidronate therapy. The shaded area in the
figure represents the normal bone mineral density reference range. The
horizontal bars represent mean bone mineral density values. The P value
represents a comparison between bone mineral density values at 0 – 6 months
and 6 –12 months (Student’s t test for paired data).
55–93) (P , 0.001); the mean femoral neck DXA decreased by 6.5% from 0.94 g/cm2 (95% CI, 0.81–1.07) to
0.91 g/cm2 (95% CI, 0.79 –1.04) (P , 0.001) and the
mean Ward’s triangle DXA decreased by 7.5% from
0.67 g/cm2 (95% CI, 0.55– 0.78) to 0.63 g/cm2 (95% CI,
0.53– 0.74) (P , 0.001). These changes in BMD were
significantly greater than that recorded in the 12
healthy age-matched men without prostate carcinoma
who were assessed over the same period. Their mean
spinal QCT decreased by 2.5% per year, mean femoral
neck DXA by 0.9% per year, and mean Ward’s triangle
DXA by 0.7% per year (P , 0.001, respectively, compared with BMD changes in men with prostate carcinoma receiving combined androgen blockade).
Table 2 shows the percent change in BMD measurements (95% CI) in men treated with combined
androgen blockade, prior to and after 6 months of
intermittent cyclic etidronate therapy. The mean lumbar spine QCT increased by 7.8% (95% CI, 20.8 –16.6)
and the mean Ward’s triangle DXA increased by 1.9%
(95% CI, 24 –7.9) after intermittent cyclic etidronate
therapy (P 5 0.01 and P 5 0.04, respectively, compared with the initial 6 months without intermittent
cyclic etidronate therapy).
DISCUSSION
Recent case studies and short reports have demonstrated that elderly men with disseminated prostate
carcinoma treated by either orchiectomy or with androgen blockade will experience hypogonadal symptoms and may be at risk for developing high turnover
osteoporosis and skeletal fractures.5–14 In this longitudinal study we recorded a 6.6% reduction in lumbar
spine and a 6.5% reduction in femoral neck BMD after
6 months of therapy with a long-acting GnRH agonist
(goserelin acetate) and an androgen antagonist (flutamide). The decrease in BMD was similar to that previously reported in premenopausal women3 and elderly men4 treated with GnRH agonists and was much
greater than expected in an age-matched control
group.19 This significant bone loss is of major clinical
relevance because many of the men presenting with
prostate carcinoma are elderly with preexisting osteoporosis. In our study 75% of men had spinal QCT
evidence of osteoporosis and two already had preexisting spinal fractures prior to commencing treatment
with combined androgen blockade.
Hypogonadism remains an important cause of
male osteoporosis and skeletal fractures.20 –24 Both
cortical and cancellous bone loss have been reported
to occur within 6 months of developing hypogonadism after either GnRH agonist therapy or orchiectomy.
Rates of bone loss vary from 2–7% depending on the
methods of BMD assessment.4,6 In this study, lumbar
spine DXA measurements were confounded by coexisting spondyloarthropathy and hence spinal QCT, a
more sensitive method of BMD analysis,18,25 was used
to determine cancellous bone loss. On average, a
6 –7% loss in BMD was recorded from the lumbar
spine and the majority of regions of the femoral neck
within 6 months of combined androgen blockade.
This data is similar to the bone loss reported by Eriksson et al.6 who performed dual photon absorptiometry
of the distal forearm and the femoral neck on 11 men,
prior to and 12 months after orchiectomy for prostate
carcinoma.
The histomorphometric changes of hypogonadism include high bone turnover,22 trabecular plate
perforation, and osteoclast activation.23 These findings often are reflected by increases in the noninvasive
markers of bone turnover.24 As demonstrated in this
study, combined androgen blockade resulted in all
men achieving castrate levels of serum free testosterone concentrations accompanied by significant increases in serum bone Gla-protein concentrations and
urinary deoxypyridinolene excretion rates. Similar
findings have been noted by Percival et al.,9 who investigated 28 men with disseminated prostate carcinoma treated by orchiectomy. They found significant
increases in serum alkaline phosphatase activities and
urinary hydroxyproline excretion rates, associated
with histologic evidence of active erosion surfaces.
Bone Changes in Prostate Carcinoma/Diamond et al.
1565
TABLE 2
Percentage Change in Bone Mineral Density in Men with Prostate Carcinoma Treated with Combined
Androgen Blockade, prior to and after 6 Months of Intermittent Cyclic Etidronate Therapy
Combined androgen blockade
a
BMD
Without ICT
Spinal QCT
Femoral neck
Ward’s triangle
Trochanter
26.6% (210 to 23.2)
26.5% (29.5 to 23.5)
27.5% (212.4 to 22.7)
26.2% (210.5 to 22)
With ICTb
P value
7.8% (20.8 to 16.6)
22.4% (26.6 to 1.7)
1.9% (24 to 7.9)
0.6% (26.4 to 7.7)
P 5 0.01
P 5 0.02
P 5 0.04
P 5 0.08
BMD: bone mineral density; ICT: intermittent cyclic etidronate therapy; QCT: bone density measured by quantitative computed tomography.
Values are the mean percentage change in bone mineral density after 6 months of therapy (95% confidence interval).
P values were established using the Student’s t test for paired data.
a
Mean values calculated for 11 of the 12 mean at 0–6 months on combined androgen blockade (1 man died).
b
Mean values calculated for 8 of the 12 men at 6–12 months on combination of combined androgen blockade and intermittent cyclic etidronate therapy (4 men
died).
Although combined androgen blockade has been
demonstrated to improve long term survival in elderly
men with disseminated prostate carcinoma,1,2 the
prolonged effects of hypogonadism and osteoporosis
may result in an increase risk for skeletal fractures. A
recent report by Daniell10 recorded a significant increase in osteoporotic fractures in men with prostate
carcinoma treated with orchiectomy. By 9 years, men
treated with orchiectomy had a 50% greater risk of
having a first osteoporotic fracture than men treated
without orchiectomy (P , 0.001). A similar finding has
been reported in men with disseminated prostate carcinoma treated with GnRH agonists alone. In a retrospective chart and telephone interview, Townsend et
al.14 recorded a history of bone fractures in 20 of 224
men (9%) with prostate carcinoma treated for up to 96
months with GnRH agonists, with 5% being attributable to osteoporosis. These data emphasize the importance of differentiating between hypogonadal osteoporosis and metastatic bone disease as a cause for
fractures in men treated for disseminated prostate
carcinoma.
Recent studies have emphasized the role of
bisphosphonates in the treatment of cancer and related metabolic bone disorders.26 These antiresorptive
agents include drugs such as clodronate, etidronate,
and pamidronate, which have been shown to inhibit
osteoclastogenesis and to cause apoptosis of active
osteoclasts.27 Clodronate has been used effectively for
the management of bone pain associated with metastatic prostate carcinoma,28 and intermittent cyclic
etidronate has been demonstrated to prevent bone
loss in women treated with GnRH agonists,29 whereas
pamidronate routinely is used for lytic bone diseases
and hypercalcemia of malignancy.30 In this study we
evaluated the role of adjuvant intermittent cyclic
etidronate therapy for the prevention of high turnover
osteoporosis in men with disseminated prostate carcinoma treated for 6 months with combined androgen
blockade. During the 6 months of therapy with intermittent cyclic etidronate, the spinal bone loss observed with combined androgen blockade nearly completely reversed, whereas the femoral neck bone loss
was retarded. These findings were associated with a
tendency for normalization in bone turnover as reflected by decreases in serum bone Gla-protein concentrations and urinary deoxypyridinolene excretion
rates. In a previous study by Clarke et al.5 intravenous
pamidronate administered weekly for 4 weeks then
alternate weekly for 6 months, prevented the high
bone turnover changes accompanying orchiectomy
without significantly affecting tumor burden. Recent
data suggest that the role of bisphosphonates also may
reside in their ability to delay the progression of prostatic skeletal metastases.31
The limitation of this study includes its small sample size with power limitations, lack of appropriate
controls, and the study design. Nevertheless, our data
demonstrate that combined androgen blockade in elderly men with disseminated prostate carcinoma may
result in high bone turnover associated with significant cancellous bone loss. Adjuvant therapy with intermittent cyclic etidronate partially prevented these
changes and hence decreased the risk of spinal fractures. We eagerly await randomized clinical trials assessing the role of the more potent bisphosphonates
for the prevention of osteoporosis and metastatic
bone disease in men with disseminated prostate carcinoma treated with either orchiectomy or GnRH agonist therapy.
REFERENCES
1.
McLeod DG. Hormonal therapy in the treatment of carcinoma of the prostate. Cancer 1995;75:1914.
1566
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
CANCER October 15, 1998 / Volume 83 / Number 8
Garnick MB. Hormonal therapy in the management of prostate cancer: from Huggins to the present. Urology 1997;
49(Suppl 3a):5–15.
Bianchi S, Fedele L, Vignali M, Galbiati E, Cherubini R,
Ortolani S. Effects on bone mineral density of 12-month
goserelin treatment in over 40-year old women with uterine
myomas. Calcif Tissue Int 1995;57:78 – 80.
Goldray D, Weisman Y, Jaccard N, Merdler C, Chen J, Matzkin H. Decreased bone density in elderly men treated with
the gonadotropin-releasing hormone agonist decapeptyl
(D-Trp6-GnRH). J Clin Endocrinol Metab 1993;76:288 –90.
Clarke NW, McLure J, George NJR. The effects of orchiectomy on skeletal metabolism in metastatic prostate cancer.
Scand J Urol Nephrol 1993;27:475– 83.
Eriksson S, Eriksson A, Stege R, Carlstrom K. Bone mineral
density in patients with prostatic cancer treated with orchiectomy and with estrogen. Calcif Tissue Int 1995;57:97–9.
Mc Grath SA, Diamond T. Osteoporosis as a complication of
orchiectomy in two elderly men with prostatic cancer. J Urol
1995;154:535– 6.
Carlstrom K, Stege R, Henriksson P, Pousette A. Effects of
endocrine treatment on bone mineral markers in patients
with prostatic cancer [abstract]. Scand J Urol Nephrol 1994;
161:28 –9.
Percival RC, Urwin GH, Harris S, Yates AJ, Williams JL,
Beneton M, et al. Biochemical and histological evidence that
carcinoma of the prostate is associated with increased bone
resorption. Eur J Surg Oncol 1987;13:41– 6.
Daniell HW. Osteoporosis after orchiectomy for prostate
cancer. J Urol 1997;157:439 – 44.
Collinson MP, Tyrell CJ, Hutton C. Osteoporosis occurring
in two patients receiving LHRH analogs for carcinoma of the
prostate. Calcif Tissue Int 1994;54:327– 8.
Maillefert JF, Sibilia J, Kuntz JL, Tavernier C. Gonadotrophin-releasing hormone agonists induce osteoporosis. Br J
Rheumatol 1994;33:1199 –200.
Horan AH. Fractures ascribable to osteoporosis following
LHRH antagonism for carcinoma of the prostate: a preliminary survey. J Bone Miner Res 1993;8:763 [abstract].
Townsend M, Sanders WH, Northway RO, Graham SD. Bone
fractures associated with luteinizing hormone-releasing
hormone agonists used in the treatment of prostate carcinoma. Cancer 1997;79:545–50.
Watts NB, Harris ST, Genant HK, et al. Intermittent cyclical
etidronate treatment of postmenopausal osteoporosis.
N Engl J Med 1990;323:73–9.
Larnach TA, Boyd SJ, Smart RC, Butler SP, Rohl PG, Diamond T. Reproducibility of lateral spine scans using dual
energy Xray absorptiometry. Calcif Tissue Int 1992;51:255– 8.
Diamond T, McGuigan L, Barbagallo S, Bryant C. Cyclical
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
etidronate plus ergocalciferol prevents glucocorticoid-induced bone loss in postmenopausal women. Am J Med
1995;98:459 – 63.
Orwoll ES, Oviatt SK, Mann T. The impact of osteophytic
and vascular calcifications on vertebral bone mineral density measurements in men. J Clin Endocrinol Metab 1990;
70:1202–7.
Jones G, Nguyen T, Sambrook P, Kelly PJ, Eisman JA. Progressive loss of bone in the femoral neck in elderly people:
longitudinal findings from the Dubbo osteoporosis epidemiology study. BMJ 1994;309:691–5.
Jackson JA, Kleerekoper M. Osteoporosis in men: diagnosis,
pathophysiology and prevention. Medicine 1990;69:137–52.
Vermeulen A, Kaufman JM. Role of the hypothalamo-pituitary function in the hypoandrodrogenism of healthy aging.
J Clin Endocrinol Metab 1992;75:704 – 6.
Jackson JA, Kleerekoper M, Parfitt AM, Rao DS, Villanaueva
AR, Frame B. Bone histomorphometry in hypogonadal and
eugonadal men with spinal osteoporosis. J Clin Endocrinol
Metab 1987;65:53– 8.
Manolagas SC, Jilka RL. Bone marrow, cytokines and bone
remodelling. N Engl J Med 1995;332:305–11.
Stepan JJ, Lachman M, Zverina J, Pacovsky V, Baylink D.
Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling. J Clin
Endocrinol Metab 1989;69:523–7.
Reinbold WD, Genant HK, Reiser UJ, et al. Bone mineral
content in early postmenopausal and postmenopausal osteoporotic women: comparison of measurement methods.
Radiology 1986;160:469 –78.
Delmas P. Bisphosphonates in the treatment of bone disease. N Engl J Med 1996;24:1836 –7.
Rodan GA, Fleisch HA. Bisphosphonates: mechanism of action. J Clin Invest 1996;12:2692– 6.
Vorreuther R. Bisphosphonates as an adjunct to palliative
therapy of bone metastases from prostate cancer. A pilot
study on clodronate. Br J Urol 1993;72:792–5.
Mukherjee T, Barad D, Yurk R, Freeman R. A randomized,
placebo-controlled study on the effect of cyclic intermittent
etidronate therapy on the bone mineral density changes
associated with six months of gonadotropin-releasing hormone agonist treatment. Am J Obstet Gynecol 1996;175:
105–9.
Hortobagyi GN, Theriault RL, Porter L, et al. Efficacy of
pamidronate in reducing skeletal complications in patients
with breast cancer and lytic bone disease. N Engl J Med
1996;335:1785–91.
Yu-cheng S, Geldoff AA, Newling DWW, Rao BR. Progression
delay of prostate tumor skeletal metastasis effects by
bisphosphonates. J Urol 1995;148:1270.
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neoplasms, variety, distinct, variant, atypical, malignant, kidney, easily, morphological, confused, angiomyolipoma
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