goserelin and Osteoporosis

Treatment for cancer may cause gonadal dysfunction and bone loss (cancer treatment-induced bone loss ; CTIBL) . Especially, endocrine therapies for breast cancer or prostate cancer carry a significant risk of CTIBL. Therapy-induced premature menopause in premenopausal breast cancer patients, aromatase inhibitor in postmenopausal breast cancer patients, and LHRH agonist with or without anti-androgen in prostate cancer patients may cause bone loss of 5% or more. RANKL (receptor activator of nuclear factor-κB ligand) antibody (denosumab) is effective for prevention of CTIBL and it may prevent CTIBL-induced fracture. During cancer treatment with gonadal dysfunction, bone mineral density should be carefully followed to avoid QOL impairment due to osoteoporosis.

Topics: Androgen Antagonists; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Aromatase Inhibitors; Denosumab; Fractures, Bone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Osteoporosis; RANK Ligand; Selective Estrogen Receptor Modulators

The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones are breast cell mitogens. By reducing exposure to these ovarian hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to suppress ovarian function may prove useful in cancer prevention. To prevent deleterious effects of hypoestrogenemia, the addition of low-dose hormone replacement to the LHRH agonist appears necessary. Pilot data with such an approach indicates it is feasible and reduces mammographic densities.

Topics: Breast; Breast Neoplasms; Clinical Trials as Topic; Endometrium; Epithelial Cells; Estrogen Replacement Therapy; Estrogens; Feasibility Studies; Female; Forecasting; Gonadotropin-Releasing Hormone; Goserelin; Humans; Incidence; Mammography; Methyltestosterone; Multicenter Studies as Topic; Neoplasms, Second Primary; Osteoporosis; Ovariectomy; Ovary; Pilot Projects; Premenopause; Progesterone; Progestins; Risk; Secretory Rate

To assess the effects of timing and schedule of zoledronic acid (ZA) administration on bone mineral density (BMD) in patients beginning androgen deprivation therapy (ADT) for the treatment of recurrent prostate cancer.. In this randomized, 3-arm trial, we evaluated changes in BMD after 3 different ZA administration schedules in men with recurrent prostate cancer who were beginning ADT. Forty-four patients were enrolled and randomized to receive a single dose of ZA given 1 week before beginning ADT (arm 1), a single dose of ZA given 6 months after beginning ADT (arm 2), or monthly administration of ZA starting 6 months after beginning ADT, for a total of 6 doses (arm 3).. Patients who received ZA before ADT had a significant improvement in BMD at the total proximal femur and trochanter after 6 months compared with the other groups. In addition, only patients in the arm that received multiple doses improved lumbar spine BMD while on ADT, with these findings persisting to 24 months. However, this group also experienced more grade 1 adverse events.. Analysis of these data suggests that ZA administration before initiation of ADT was superior to treatment 6 months after starting ADT in maintaining BMD. In addition, monthly ZA administration can increase BMD above baseline but is associated with more adverse events. Further study is needed to examine whether the timing and frequency of ZA therapy in patients on ADT can reduce fracture risk.

Topics: Aged; Alkaline Phosphatase; Androgen Antagonists; Bone Density; Bone Density Conservation Agents; Cell Proliferation; Diphosphonates; Drug Administration Schedule; Goserelin; Humans; Imidazoles; Leuprolide; Lymphocyte Count; Male; Middle Aged; Osteoporosis; Prostate-Specific Antigen; Prostatic Neoplasms; T-Lymphocytes; Zoledronic Acid

The assessment of the impact aerobic exercises on bone mineral density in breast cancer women during endocrine therapy (ET).. The study included 53 women (mean 44.3 ±SD 4.9) during breast cancer treatment. This was a nonrandomized, prospective clinical study. The following examinations of the assessment of bone in the DEXA were measured: the bone mineral density of the neck of a femur (FN), lumbar region L₁-L₄, and total body (TB) as well as defining of T-score and Z-score. The examinations were conducted for all the patients according to the schedule: before the beginning of ET, after 6 months of ET and after 12 months of ET (after 6 month aerobic training).. After the first 6 months of ET without regular physical exercise the following results were noted: the BMD mean value of FN, in the L₁-L₄ spine region and in TB were significant lower than the initial value. After 6 month aerobic training, in the 12th month of the follow up, the BMD mean value of FN was 1.1% (p>0.05) lower, while in the L₁-L₄ spine region it was 5.6% (p<0.05) lower, and in TB 2.7% (p<0.05) lower in comparison to the values in the sixth month of the observation.. That even short course of ET is related to changes in bone mineral density. The introduction of aerobic exercises caused a slowdown in negative changes in bones.

Topics: Adolescent; Adult; Bone Density; Breast Neoplasms; Drug Administration Schedule; Exercise; Exercise Therapy; Female; Goserelin; Humans; Middle Aged; Osteoporosis; Prospective Studies; Tamoxifen; Young Adult

The Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) bone substudy assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density (BMD) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid. The aim of this substudy is to gain insight into bone health in this setting.. ABCSG-12 is a randomised, open-label, phase III, 4-arm trial comparing tamoxifen (20 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days) versus anastrozole (1 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days), both with or without zoledronic acid (4 mg intravenously every 6 months) for 3 years in premenopausal women with endocrine-responsive breast cancer. This prospective bone subprotocol measured BMD at 0, 6, 12, 36, and 60 months. The primary endpoint of the bone substudy (secondary endpoint in the main trial) was change in BMD at 12 months, assessed by dual-energy X-ray absorptiometry in assessable patients. Analyses were intention to treat. Statistical significance was assessed by t tests. The ABCSG-12 trial is registered on the ClinicalTrials.gov website, number NCT00295646.. 404 patients were prospectively included in the bone substudy and randomly assigned to endocrine therapy alone (goserelin and anastrozole or goserelin and tamoxifen; n=199) or endocrine therapy concurrent with zoledronic acid (goserelin, anastrozole, and zoledronic acid or goserelin, tamoxifen, and zoledronic acid; n=205). After 3 years of treatment, endocrine therapy alone caused significant loss of BMD at the lumbar spine (-11.3%, mean difference -0.119 g/cm(2) [95% CI -0.146 to -0.091], p<0.0001) and trochanter (-7.3%, mean difference -0.053 g/cm(2) [-0.076 to -0.030], p<0.0001). In patients who did not receive zoledronic acid, anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine (-13.6%, mean difference -0.141 g/cm(2) [-0.179 to -0.102] vs -9.0%, mean difference -0.095 g/cm(2) [-0.134 to -0.057], p<0.0001 for both). 2 years after the completion of treatment (median follow-up 60 months [range 15.5-96.6]), patients not receiving zoledronic acid still had decreased BMD at both sites compared with baseline (lumbar spine -6.3%, mean difference -0.067 g/cm(2) [-0.106 to -0.027], p=0.001; trochanter -4.1%, mean difference -0.03 g/cm(2) [-0.062 to 0.001], p=0.058). Patients who received zoledronic acid had stable BMD at 36 months (lumbar spine +0.4%, mean difference 0.004 g/cm(2) [-0.024 to 0.032]; trochanter +0.8%, mean difference 0.006 g/cm(2) [-0.018 to 0.028]) and increased BMD at 60 months at both sites (lumbar spine +4.0%, mean difference 0.039 g/cm(2) [0.005-0.075], p=0.02; trochanter +3.9%, mean difference 0.028 g/cm(2) [0.003-0.058], p=0.07) compared with baseline.. Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss. Although there was partial recovery 2 years after completing treatment, patients receiving endocrine therapy alone did not recover their baseline BMD levels. Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years.

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Bone Density Conservation Agents; Bone Diseases, Metabolic; Breast Neoplasms; Chemotherapy, Adjuvant; Diphosphonates; Female; Goserelin; Humans; Imidazoles; Linear Models; Nitriles; Osteoporosis; Premenopause; Prospective Studies; Tamoxifen; Triazoles; Zoledronic Acid

It is known that bone mineral density (BMD) is low in men who are hypogonadal. However, the rate and sites of bone loss following testosterone deficiency are not known. The resulting hypogonadism after GnRH analog therapy for the treatment of prostate cancer allows us to examine bone loss and bone resorption immediately after testosterone withdrawal. Therefore, we examined the effects of GnRH analog treatment on bone loss and bone resorption in men with prostate cancer. BMD and serum and urine concentrations of markers of bone turnover were determined in men with prostate cancer and in age-matched controls. Measurements were taken before GnRH therapy and 6 and 12 months after instituting therapy. After 12 months of GnRH therapy, the BMD of the total hip and ultra distal radius decreased significantly (P < 0.001) in men with prostate cancer compared with the controls. The mean bone loss was 3.3% and 5.3%, respectively. The observed reduction in BMD in the spine (2.8%) and the femoral neck (2.3%) did not reach statistical significance. No significant bone loss was observed in the control subjects. The concentration of the urine marker of bone resorption, N-telopeptide, was significantly increased from baseline and from controls at both 6 and 12 months in patients treated with GnRH analog therapy compared with control subjects (P < 0.05). The concentration of a serum marker of bone formation, bone-specific alkaline phosphatase, was not significantly different from baseline or from controls at 6 and 12 months. Thus, the decreased total hip and ultra distal radius BMD and increased urinary N-telopeptide concentration after testosterone withdrawal demonstrate an increase in trabecular bone loss and enhanced bone resorption. These findings demonstrate a significant loss of bone in men with prostate cancer after receiving GnRH therapy and suggest that the total hip and radius are the preferred sites for monitoring bone loss in older men. In addition, markers of bone resorption may be helpful.

Topics: Absorptiometry, Photon; Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Bone Density; Femur Neck; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hypogonadism; Male; Osteoporosis; Prospective Studies; Prostatic Neoplasms; Radius

Prostate carcinoma therapy with combined androgen blockade may result in high bone-turnover with significant bone loss. This study was undertaken to evaluate the antiosteoporotic efficacy of intravenous pamidronate in a double blind, randomized, placebo-controlled, crossover study.. Twenty-one consecutive men with metastatic prostate carcinoma who were receiving combined androgen blockade with a long-acting gonadotropin-releasing hormone agonist (gosarelin acetate) and an androgen antagonist (flutamide or bicalutamide) were evaluated at baseline and at 6 and 12 months after therapy. They were randomly assigned to receive a single intravenous infusion of 500 mL of normal saline solution diluted with either pamidronate (90 mg) or placebo at baseline and with a crossover at 6 months. Lumbar-spine bone-mineral densities (BMDs) were measured by spinal quantitative computed tomography (QCT), femoral neck BMDs were measured by dual-energy X-ray absorptiometry (DXA), and markers of bone turnover were measured by noninvasive methods. Data on 10 men with localized prostate carcinoma who were treated with radiotherapy alone, over the same period, was collected for comparison studies.. The mean age of the men was 75.1 years +/- 1.6 years. One man withdrew from the study because of deteriorating health, and two died from metastatic disease within the first 6 months. Combined androgen blockade normalized serum prostate-specific antigen activities (from an initial mean value of 86.2 ng/mL +/- 10.1 ng/mL) and maintained serum free testosterone concentrations in the hypogonadal range (< 2.2 pmol/L) in all men throughout the study. Treatment with pamidronate resulted in a 7.8% +/- 1.5% increase in mean lumbar spine QCT from 79.4 mg/cm(3) (95% confidence interval [CI], 64-94 mg/cm(3)) to 85.6 mg/cm(3) (95% CI, 70-101 mg/cm(3)) (P = 0.0005) and a 2% +/- 0.9% increase in mean total femoral neck DXA from 0.98 g/cm(2) (95% CI, 0.90 -1.05 g/cm(2)) to 1.0 mg/cm(2) (95% CI, 0.91-1.08 g/cm(2)) (P = 0.02). Conversely, treatment with placebo, resulted in a 5.7% +/- 1.6% decrease in mean lumbar spine QCT and a 2.3% +/- 0.7% decrease in mean total femoral neck DXA (P = 0.0001 and P = 0.0007 for the comparison of percentage change between the pamidronate and placebo treatments). After pamidronate therapy, serum bone Gla-protein concentrations decreased by 16.8% +/- 5.9%, and urinary deoxypyridinoline excretion rates decreased by 18.5% +/- 12.8% (P < 0.01 respectively for the comparison between pamidronate and placebo treatment).. This study demonstrated that a single intravenous infusion of pamidronate (90 mg) significantly reduced the high bone turnover and bone loss (for at least 6 mos) in men with prostate carcinoma who had been rendered hypogonadal with combined androgen blockade therapy.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Bone Density; Cross-Over Studies; Diphosphonates; Double-Blind Method; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Injections, Intravenous; Male; Osteoporosis; Pamidronate; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

To investigate the effect of medrogestone on bone mineral density (BMD) and bone turnover under conditions of estrogen withdrawal, premenopausal women with endometriosis were treated with goserelin (Zoladex), combined with either placebo (group A, n = 12) or 10 mg medrogestone (Prothil, group B, n = 11) for six months, and followed for an additional six months. Lumbar spine BMD was measured at 0 and 6 month. Markers of bone turnover were serum bone alkaline phosphatase (sBAP) and osteocalcin (sOC) by ELISA, and urinary total pyridinoline (uPYD) and deoxypyridinoline crosslinks (uDPD) by HPLC. Patients in both groups had a similar and significant decrease in BMD after 6 months (4%, p < 0.01). The time course of changes in bone turnover, in contrast, was different in both groups. In group A, crosslink excretion increased from one month onwards, while no changes were seen in group B. In group A, sBAP levels rose during treatment, while in group B, this rise was delayed until treatment was terminated. Additionally, group B showed an initial suppression of sBAP and sOC. In both groups, sOC increased after treatment was discontinued. Medrogestone at 10 mg/d does not prevent lumbar bone loss in premenopausal women under estrogen deprivation. In the medrogestone add back group, the changes in bone turnover are compatible with low turnover bone loss,as ooposed to a state of high turnover seen in the unopposed goserelin group. This effect may be due to glucocorticoid receptor mediated actions of medrogestone on bone.

Topics: Adult; Alkaline Phosphatase; Amino Acids; Bone and Bones; Bone Density; Bone Remodeling; Double-Blind Method; Endometriosis; Female; Goserelin; Humans; Kinetics; Medrogestone; Osteocalcin; Osteoporosis; Placebos; Premenopause; Progesterone Congeners

To investigate the efficacy and safety of tibolone on hypoestrogenic vasomotor symptoms and bone parameters in patients treated with goserelin acetate.. Prospective, randomized placebo controlled double-blind study.. Human volunteers in a university-based fertility clinic.. Twenty-nine women of mean age 29.2 +/- 4.8 years with mild to severe endometriosis undergoing 6 months of treatment with 3.6 mg goserelin acetate in an SC depot formulation were studied.. The patients were allocated randomly to either 2.5 mg/d tibolone (n = 15) or an iron pill (n = 14) in a double-blinded fashion beginning in the third cycle.. Frequency and severity of hot flushes, sweating, irritability, loss of libido, nervousness, and sleeplessness were assessed by the patients using 0 to 6 point scoring system and compared. Samples of urine were obtained for calcium and creatinine (Ca:Cr) ratios at the start of treatment and monthly there after. The vasomotor scoring for each symptom and Ca:Cr ratios before the treatment and at the end of 6th month were analyzed by parametric and nonparametric tests.. The mean age, weight, vasomotor scores, pelvic scores, and urine Ca:Cr ratios were similar in both placebo and tibolone group (28.7 +/- 4.8 versus 27.6 +/- 6.3 years, 50.9 +/- 5.3 versus 53.1 +/- 7.1 kg, 4.7 +/- 1.1 versus 4.2 +/- 0.8, and 0.056 +/- 0.008 versus 0.059 +/- 0.006, respectively). The decreases in vasomotor scoring as regards to hot flushing, sweating, and other associated symptoms were statistically significant in tibolone group compared with placebo (10.4 +/- 1.6 versus 24.6 +/- 4.9). During the study significant reductions in urine Ca:Cr ratio was obtained in the tibolone patients compared with placebo (0.031 +/- 0.006 versus 0.0055 +/- 0.007). The incidence of side effects (weight change, vaginal bleeding) was low and did not differ from the placebo group.. Considering the beneficial effects of tibolone on vasomotor symptoms and bone loss, our data suggest that this synthetic steroid is an effective and safe option in relieving symptoms induced by GnRH-analogue.

Topics: Adult; Anabolic Agents; Double-Blind Method; Endometriosis; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Norpregnenes; Osteoporosis; Prospective Studies

To verify if a 6-month period of hypoestrogenism due to chronic treatment with GnRH analogue (GnRH-a) causes irreversible bone loss in young women.. Controlled clinical study in volunteer women.. Department of Obstetrics and Gynecology, University of Cagliari, Cagliari, Italy.. Twenty-eight women (mean age +/- SE 81.1 +/- 0.99 years) with endometriosis diagnosed by laparoscopy and 25 healthy, normally cycling women of the same age (28.3 +/- 1.14 years).. In women with endometriosis, six SC implants of the GnRH-a compound, 3.6 mg goserelin acetate depot, were administered every 28 days starting within 15 days of laparoscopy. Compounds interfering with bone metabolism or hormonal formulations were not taken by control women during the entire period of the study.. Evaluation of lumbar bone mineral density at the start of the study and 6, 12, and 30 months later.. At the onset of the study, lumbar bone mineral density did not differ in women with endometriosis and control women. Lumbar bone mineral density values significantly decreased after 6 months of GnRH-a treatment. This reduction was still evident 6 months after GnRH-a interruption. However, 24 months after treatment withdrawal, bone mineral density reduction disappeared and bone mineral density values were completely superimposable (+/- O.4 percent) to those observed before treatment. In contrast, control women lumbar bone mineral density values did not change during the entire period of observation.. These data suggest that GnRH-a treatment for 6 months is not associated with long-term effects on lumbar bone density.

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Density; Drug Implants; Endometriosis; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Osteoporosis; Time Factors

Topics: Administration, Oral; Bone Density; Double-Blind Method; Endometriosis; Estrogen Replacement Therapy; Female; Goserelin; Humans; Medroxyprogesterone Acetate; Osteoporosis; Prospective Studies

To determine whether the addition of a low dose of oral estrogen replacement therapy (ERT) taken daily can prevent the bone loss associated with continuous GnRH analogue use.. In a double-blind, placebo-controlled study, 60 women aged 21-45 years were randomized to one of three treatment groups: placebo implant every 4 weeks plus placebo ERT tablets daily, Zoladex (goserelin 3.6 mg) implant every 4 weeks plus placebo ERT tablets daily, or Zoladex (3.6 mg) implant every 4 weeks plus estradiol valerate, 2 mg/day, with norethisterone 5 mg from days 22-28. A dual x-ray bone density scan was performed before treatment and again after six treatment cycles. The percentage bone change with respect to the initial bone density was calculated.. There was a significant loss of bone density at both the lumbar spine and proximal femur in the group receiving Zoladex plus placebo after 6 months compared with both pre-treatment values and with the group receiving placebo plus placebo. The addition of estrogen "add-back" therapy to GnRH analogue treatment (Zoladex plus ERT) resulted in no significant change in bone density compared with either pre-treatment values or the group receiving placebo plus placebo. The study had a dropout rate of 32%.. The addition of "add-back" estrogen therapy to continuous GnRH analogue use can prevent bone loss.

Topics: Administration, Oral; Adult; Bone Density; Double-Blind Method; Drug Implants; Estradiol; Estrogens; Female; Goserelin; Humans; Middle Aged; Norethindrone; Osteoporosis; Premenstrual Syndrome

To identify whether veterans receiving androgen-deprivation therapy (ADT) are screened at any time by bone mass measurement.. Cross-sectional study.. Veterans Administration Tennessee Valley Healthcare System (VA-TVHS).. All male veterans who received at least one dose of goserelin or leuprolide within the fiscal years October 1, 2005, through September 30, 2009.. Data from patients' charts were extracted for demographic information (race, age, and weight prior to the initial injection); date of initiation of therapy; the use of calcium, vitamin D, bisphosphonate, or calcitonin therapy; and documented bone-mineral density testing.. To determine whether veterans receiving ADT with goserelin or leuprolide for prostate cancer were screened at any time for BMD more or less than rates as documented in previous literature.. 22.8% of veterans were screened for BMD, which was statistically significant when compared with results found in previous literature.. Although rates of BMD testing were higher at VA-TVHS compared with previous literature, this rate is still low given the well-known risk of accelerated osteoporosis associated with ADT.

Topics: Aged; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Bone Density; Cross-Sectional Studies; Goserelin; Humans; Leuprolide; Male; Osteoporosis; Prostatic Neoplasms; Risk Assessment; Veterans

Topics: Aged; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Diphosphonates; Goserelin; Humans; Imidazoles; Male; Osteoporosis; Uveitis, Anterior; Zoledronic Acid

Topics: Absorptiometry, Photon; Anastrozole; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Bone Density; Breast Neoplasms; Diphosphonates; Female; Fractures, Bone; Goserelin; Humans; Imidazoles; Nitriles; Osteoporosis; Randomized Controlled Trials as Topic; Tamoxifen; Triazoles; Zoledronic Acid

Androgen deprivation therapy (ADT) is a strong risk factor for osteoporosis. The current study identified physician practices in preventing or treating osteoporosis during ADT. The practices of interest are the uses of dual-energy X-ray absorptiometry (DXA) scans, bisphosphonates, calcium or vitamin D supplement, calcitonin, or estrogen.. A retrospective medical record review was conducted. Patients were included if they had received ADT with goserelin injection for >/= 1 year. Multivariable logistic regression analysis was performed to identify independent predictors of receiving at least one intervention.. Analyses included 184 patients. Most were the elderly with multiple risk factors for osteoporosis. Only 8.7% (95% confidence interval [CI], 4.6-13.0%) of patients received a DXA scan at least once during the past 3 years. Oral and intravenous bisphosphonates were prescribed in 4.9% (95%CI, 1.8-8.0%) and 0.5% (95%CI, 0-2.0%) of patients, respectively, during the past year. Overall, 14.7% of patients (95%CI, 9.5-20.0%) received at least one intervention. Concurrent risk factors for osteoporosis, including smoking, alcoholism, advanced age, low body mass index, long duration of ADT, multiple comorbidities, history of fractures, and steroid use, were not independent predictors of having received interventions. However, bone metastasis was, with a hazard ratio of 5.6 (95%CI, 1.99-15.6%). Primary care physicians provided the greatest number of interventions and cancer-related specialists provided the fewest.. The majority of patients with prostate carcinoma undergoing ADT did not receive interventions to prevent or treat osteoporosis. Having other concurrent risk factors for osteoporosis was not predictive of receiving these few interventions.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Androgen Antagonists; Attitude of Health Personnel; Bone Density; Confidence Intervals; Diphosphonates; Drug Utilization; Follow-Up Studies; Goserelin; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Osteoporosis; Practice Patterns, Physicians'; Probability; Prognosis; Proportional Hazards Models; Prostatic Neoplasms; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome

To investigate the rate of testosterone recovery and changes in bone mineral density in patients found to be osteoporotic while receiving luteinizing hormone-releasing hormone (LHRH) analogues after changing to antiandrogen monotherapy in an attempt to reduce further demineralization.. Fifteen patients receiving LHRH analogue therapy for > or = 1 year were identified as osteoporotic by distal forearm dual X-ray densitometry. They were then converted to antiandrogen monotherapy, and prostate specific-antigen (PSA) and total testosterone monitored at 3-monthly intervals. The forearm densitometry was repeated at 1 year.. All patients had some testosterone recovery; the mean (range) duration to initial detectable testosterone was 12.8 (6-22) months. Six patients had a normal testosterone level after a mean of 17.5 (14-30) months. In the year after stopping LHRH analogue therapy the mean bone mineral density (t-score) decreased by 7.2%.. Osteoporotic patients, after stopping LHRH analogues, continue to have suppressed levels of testosterone which have a detrimental effect on bone mineral density. We therefore would not advocate conversion to antiandrogen monotherapy to improve bone density, and suggest alternative therapeutic intervention e.g. bisphosphonate therapy, for these patients.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Density; Goserelin; Humans; Male; Middle Aged; Osteoporosis; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

To better understand bone metabolism and predict bone loss in treatment using gonadotropin-releasing hormone agonist for patients with prostate cancer.. The changes in bone mineral density and blood levels of bone metabolism markers and the level of pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen, a specific marker of bone resorption, and carboxy-terminal pro-peptide of human type I procollagen, a specific marker of bone formation, were examined in 27 consecutive patients with prostate cancer without bone metastasis.. After 2 years of gonadotropin-releasing hormone treatment, the bone mineral density was significantly lower (median 0.937 g/cm2) than before treatment. Pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen began to increase significantly 6 months after the start of treatment (3.0 to 8.3 ng/mL, median 4.6, at baseline versus 3.4 to 8.2 ng/mL, median 5.2, after 6 months). Carboxy-terminal pro-peptide of human type I procollagen began to show a significant rise 1 year after the start of treatment (from 72.8 to 221.5 ng/mL, median 102.0, at baseline to 82.7 to 293.4 ng/mL, median 132.0, at 1 year).. Functional coupling between bone resorption and formation was noted, and a decrease in bone mass, even in men, owing to androgen deficiency, was biochemically demonstrated. Fluctuations in these two bone metabolism markers preceded the decrease of bone mineral density. Therefore, these markers might be a predictor of bone loss.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Bone Density; Bone Remodeling; Bone Resorption; Collagen Type I; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Peptide Fragments; Peptides; Procollagen; Prostatic Neoplasms; Testosterone

We determined the risk factors for osteoporosis and spinal fractures in men with prostate cancer receiving androgen deprivation therapy.. We performed a retrospective analysis of 87 consecutive men with prostate cancer receiving androgen deprivation therapy referred for evaluation of osteoporosis. Data were comprised of lateral thoracolumbar radiographs, bone densitometry, serum biochemistry and a detailed assessment of osteoporotic risk factors. Multivariate regression analysis was used to determine the major risk factors for osteoporosis and spinal fractures.. There were 38 (44%) men who were 74.5 years old with radiographic evidence of spinal fractures. They had an initial mean prostate specific antigen of 52.8 ng/ml and had received androgen deprivation therapy for a mean of 39.6 months (95% confidence interval 28.7 to 50.4). Mean spinal (quantitative computerized tomography t-score -4.2) and femoral neck bone mineral densities (dual energy x-ray absorptiometry t-score -2.1) were significantly lower than in men without spinal fractures (p < 0.001 for all measurements). In the regression analysis the duration of androgen deprivation therapy (p = 0.002), serum 25-hydroxyvitamin D levels (p = 0.003) and a history of alcohol excess (defined as more than 4 standard drinks daily, p = 0.04) were the main determinants of spinal fractures.. Prolonged androgen deprivation therapy, low serum 25-hydroxyvitamin D levels and a history of alcohol excess are important risk factors for osteoporosis and spinal fractures in men with prostate cancer.

Topics: Aged; Alcohol Drinking; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Comorbidity; Flutamide; Goserelin; Humans; Male; Multivariate Analysis; Nitriles; Osteoporosis; Prostatic Neoplasms; Retrospective Studies; Risk Factors; Spinal Fractures; Time Factors; Tosyl Compounds; Vitamin D

We report 3 patients referred to the bone clinic after spinal fractures. Dual energy X-ray absorptiometry showed severe osteoporosis. Each patient was found to have a history of prostatic carcinoma and long-term treatment with goserelin. We suggest that all patients who have received androgen deprivation therapy for more than 1 year should be evaluated by bone densitometry.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Carcinoma; Densitometry; Femoral Fractures; Follow-Up Studies; Fractures, Spontaneous; Goserelin; Humans; Male; Osteoporosis; Prostatic Neoplasms; Risk Assessment; Severity of Illness Index; Spinal Fractures; Thoracic Vertebrae

The objective of this work was to determine the effect of androgen deprivation therapy (ADT) on rates of bone mineral density (BMD) loss in men with prostate cancer. It was a prospective study comparing men receiving ADT to age matched controls for 2 y. Subjects received a history, physical exam, bone mineral density measurement, and laboratory evaluation every 6 months. Thirty-nine subjects receiving continuous ADT for prostate cancer (subjects) were compared to 39 age-matched controls not receiving ADT (controls). Twenty-three subjects and 30 controls completed the study through 24 months. Men in the ADT group demonstrated greater rates of bone mineral density loss than men in the control group at every site except the lumbar spine. Twenty-four month per cent of bone mineral density loss is presented as mean+/-standard error (s.e.). At the distal forearm, the ADT group value was -9.4%+/-1.0% and -4.4%+/-0.3% for controls (P<0.0005). The ADT group femoral neck values were -1.9%+/-0.7% and 0.6%+/-0.5% in the control group (P=0.0016). The ADT group total hip value was -1.5%+/-1.0% and 0.8%+/-0.5% in the control group (P=0.0018). The ADT group trochanter value was -2.0%+/-1.3% and -0.1%+/-0.5% in the control group (P=0.0019). The ADT group lumbar spine value was -0.2%+/-0.8 % and 1.1%+/-0.6% in the control group (P=0.079). Our data demonstrate greater rates of bone mineral density loss in men receiving androgen deprivation therapy for prostate cancer.

Topics: Absorptiometry, Photon; Adenocarcinoma; Aged; Amino Acids; Androgen Antagonists; Androgens; Anilides; Antineoplastic Agents, Hormonal; Biomarkers; Bone Density; Bone Remodeling; Calcium; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Neoplasms, Hormone-Dependent; Nitriles; Orchiectomy; Osteoporosis; Prospective Studies; Prostatic Neoplasms; Testosterone; Tosyl Compounds

Luteinizing hormone-releasing hormone (LHRH) agonists are popularly used drugs in the treatment of prostatic cancer. However, it has been reported that continuation of a low testosterone level following a longterm administration of these drugs reduces the bone mineral density and makes for osteoporosis, which is accountable for fracture, we measured the bone mineral density and bone metabolic markers in the cases who suffered fracture receiving LHRH agonists for prostatic cancer.. Between 1994 and 1998, 196 patients (mean age 78.1 years) were treated with LHRH agonists for prostatic cancer. Of these patients, 13(7%) who had bone fracture during treated with LHRH agonists were divided into fracture group, and 70 patients who had not bone fracture divided into non-fracture group. Fracture by traffic accident was excluded. The bone density in the third lumbar vertebra was measured using quantitative computed tomography (QCT). Osteocalcin, 1, 25- (OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone (PTH) and calcitonin were measured as bone metabolic markers.. The mean age of fractured cases was 78 years. The period from the start of treatment to fracture was 11 to 45 months (mean 27 months). No case of fracture at the site of metastasis of prostatic cancer was found. The bone density was significantly low in the fracture group compared with that of non-fracture group. Of the bone metabolic markers, NTx showed high values in the fracture group.. There is a need to measure bone mineral density and bone metabolic markers periodically and to evaluate secondary osteoporosis in the patients receiving LHRH agonists for prostatic cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Density; Fractures, Bone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Osteoporosis; Prostatic Neoplasms; Spine

It is well known that androgens play an important role in bone metabolism and male hypogonadism induce osteoporosis. Luteinizing hormone-releasing hormone analogue (LHRH-a) which is essential for conservative therapy of prostatic carcinoma (CaP) ultimately reduces circulating testosterone to castration levels. The purpose of this study was to determine the risk of decrease of bone mineral density in men receiving LHRH-a for CaP.. Fifty-three man with CaP aged 63 to 95 years (mean 75.5 years) were included in this study. Seven patients received LHRH-a with estrogen drug, forty-six patients received LHRH-a with or without anti androgen drug. To estimate patient's bone density we use the second metacarpal bone density using a microdensitometry method.. Blood level of sex hormone of the forty-six patients who were received LHRH-a without estrogen, was the same as that of castration. Patients who were treated more than twelve months had less bone density than patients who were treated less than eleven months. As the duration of medical castration period was prolonged, patients bone density were reduced. Whereas seven patients who received estrogen drug did not find a decrease of bone density regardless of duration of treatment period.. Hypogonadism induced LHRH-a also reduce bone density, so there is a risk of iatrogenic osteoporosis caused by therapy for CaP with LHRH-a. Patients with osteoporosis easily suffer from a much complicated and pernicious bone fracture, so we should measure bone density of male patients same as female treated with LHRH-a for a long-term.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Density; Estrogens; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Prostatic Neoplasms; Risk

In the design of clinical trials, sample size determination is usually undertaken by statisticians and clinicians. It is rare for health economists to be involved in this aspect of trial design. However, there are a number of outcome changes that are of 'economic significance', and it is important for trial designers and funders to be aware of these before planning, funding and mounting a trial. In this paper we demonstrate through the use of three examples (prevention of osteoporosis, management of infertility, and endometriosis) how economics can be used to influence the size of a clinical trial. Trials that are too small or too large waste research resources; health economics can lead to more efficient trial designs.

Topics: Adult; Aged; Clinical Trials as Topic; Cost-Benefit Analysis; Danazol; Endometriosis; Female; Goserelin; Humans; Hydrochlorothiazide; Infertility, Female; Osteoporosis; Research Design; Sample Size; Treatment Outcome

Topics: Adenocarcinoma; Aged; Goserelin; Humans; Male; Middle Aged; Osteoporosis; Prostatic Neoplasms

The skeletal effects of two therapies for endometriosis that produce hypo-oestrogenism in 23 premenopausal women have been studied. Eleven women received goserelin 3.6 mg monthly by subcutaneous implant and 12 women received danazol 600 mg daily, orally, both for 6 months. Goserelin causes a small decline in spinal bone density, but a greater loss of density in the proximal femur. Preliminary results show no evidence that bone loss is reversible after stopping therapy. Danazol treatment is not associated with loss of bone. Prolonged or repeated courses of treatment with goserelin alone could lead to a clinically significant adverse effect on the skeleton.

Topics: Adult; Bone Density; Buserelin; Danazol; Endometriosis; Female; Goserelin; Humans; Osteoporosis; Pregnadienes