Osteoporosis in men with prostate carcinoma receiving androgen-deprivation therapy: recommendations for diagnosis and therapies

BACKGROUND: Androgen-deprivation therapy (ADT) is prescribed with increasing frequency for men with prostate carcinoma. There is growing concern about the effects of such therapy on the skeleton. In the current review, the authors addressed the current research, diagnostic methods, and treatment recommendations for bone loss and osteoporosis in men with prostate carcinoma who received ADT. METHODS: Data were obtained from electronic literature searches (for the years 1986 through 2002) and from abstracts and meeting proceedings. All randomized and nonrandomized clinical trials, retrospective studies, and cross-sectional studies of osteoporosis in men with prostate carcinoma who received ADT with or without other therapies were reviewed. RESULTS: The findings confirmed that ADT resulted in significant bone loss in men with prostate carcinoma. Bone mineral density (BMD) of the hip, as measured by dual-energy X-ray absorptiometry (DXA), is considered the preferred site of assessment in older men. Spinal BMD is equally important, although careful interpretation of spinal DXA values is required, because of coexisting facet joint disease and extravertebral calcification. Osteoporosis is diagnosed when BMD is > 2.5 standard deviations below a reference mean. Men with prostate carcinoma who were treated with ADT had average BMD measurements below those of eugonadal men. Rates of bone loss ranged from 2% to 8% in the lumbar spine and from 1.8% to 6.5% in the femoral neck during the initial 12 months of continuous ADT. Retrospective data indicated an increased risk of fracture in men with prostate carcinoma who were treated with ADT. CONCLUSIONS: For men with prostate carcinoma who are at high risk for osteoporosis and fractures, clinical management should be dictated by the results of radiographic and DXA skeletal assessment.     

Single infusion of zoledronic acid to prevent androgen deprivation therapy‐induced bone loss in men with hormone‐naive prostate carcinoma

BACKGROUND:

Androgen‐deprivation therapy (ADT) decreases bone mineral density (BMD) and increases fracture risk in patients with prostate carcinoma. The authors investigated the effectiveness of a single infusion of zoledronic acid initiated subsequent to ADT on BMD with hormone‐naive prostate carcinoma.

METHODS:

Forty men received either a single infusion of zoledronic acid (4 mg intravenously on Day 1) or no infusion during ADT. BMD of the proximal femur and posteroanterior lumbar spine was measured by dual‐energy x‐ray absorptiometry and urinary N‐telopeptide (u‐NTx) at 6 and 12 months.

RESULTS:

At baseline, the overall BMDs demonstrated no significant difference in lumbar spine and hip regions. At 6months, mean (±standard error) BMD of the posteroanterior lumbar spine decreased 4.6% ± 1.0% in control patients and increased 5.1% ± 1.2% in patients receiving zoledronic acid, a significant difference (P = .0002). At 12 months, the change in BMD between the 2 groups was statistically significantly different at the lumbar region (P = .0004), indicating that zoledronate preserved BMD. For u‐NTx, bone turnover was statistically significantly decreased in the zoledronate group compared with controls at 6 months (P < .0001), but returned to pretreatment levels at 12 months in the zoledronate group.

CONCLUSIONS:

Bone loss begins at 6 months with ADT. A single infusion of zoledronic acid in patients receiving ADT reduces bone mineral loss and maintains BMD at least at 12 months during ADT. Further study is needed to determine the best dosing schedule to prevent ADT‐induced bone loss in men with hormone‐naive prostate carcinoma. Cancer 2009. © 2009 American Cancer Society.     

Natural history of bone complications in men with prostate carcinoma initiating androgen deprivation therapy

BACKGROUND: As evidence accumulates in favor of androgen deprivation therapy (ADT) in patients with recurrent or metastatic prostate carcinoma, concern has increased regarding bone loss associated with therapeutic hypogonadism. The current study described the natural history of bone complications in men with prostate carcinoma who have initiated ADT. METHODS: Using 1992-2001 claims data from a 5% national random sample of Medicare beneficiaries, the authors identified men with prostate carcinoma who initiated ADT between 1992 and 1994. They analyzed inpatient, outpatient, and physician claims for bone complications over 7 subsequent years. They stratified the quartile of patients who survived longest into 2 cohorts: those who had received ADT for longer than and those who had received ADT for shorter than the median of 697 days. They evaluated the cumulative proportions of patients in each cohort with claims for pathologic fractures, osteoporosis/osteopenia, and nonpathologic fractures. RESULTS: In the 1992-1994 sample, 4494 men with prostate carcinoma initiated ADT. Of these, 1126 survived > 2028 days (5.5 years). During the first 3 years of evaluation, the proportion of bone events was similar for men with shorter durations of ADT and men with longer durations of ADT. However, by 7 years, more men in the longer ADT cohort (45%) had sustained at least 1 pathologic or nonpathologic fracture compared with men in the shorter ADT cohort (40%). CONCLUSIONS: In the current study, men with prostate carcinoma were found to be at risk for adverse bone effects from both the disease and the treatment. These longitudinal data revealed that fractures are common in this patient population and appear to be linked to the duration of ADT.     

Bone density testing among prostate cancer survivors treated with androgen‐deprivation therapy

BACKGROUND.

Androgen‐deprivation therapy (ADT) causes bone loss and fractures. Guidelines recommend bone density testing before and during ADT to characterize fracture risk. The authors of the current report assessed bone density testing among men who received ADT for ≥ 1 year.

METHODS.

Surveillance, Epidemiology, and End Results/Medicare data were used to identify 28,960 men aged > 65 years with local/regional prostate cancer diagnosed from 2001 to 2007 who were followed through 2009 and who received ≥ 1 year of continuous ADT. Bone density testing was documented in the 18‐month period beginning 6 months before ADT initiation. Logistic regression was used to identify the factors associated with bone density testing.

RESULTS.

Among men who received ≥ 1 year of ADT, 10.2% had a bone density assessment from 6 months before starting ADT through 1 year after. Bone density testing increased over time (14.5% of men who initiated ADT in 2007‐2008 vs 6% of men who initiated ADT in 2001‐2002; odds ratio for 2007‐2008 vs 2001‐2002, 2.29; 95% confidence interval, 1.83‐2.85). Less bone density testing was observed among men aged ≥ 85 years versus men ages 66 to 69 years (odds ratio, 0.76; 95% confidence interval, 0.65‐0.89), among black men versus white men (odds ratio, 0.72; 95% confidence interval, 0.61‐0.86), and among men in areas with lower educational attainment (P < .001). Men who visited a medical oncologist and/or a primary care provider in addition to a urologist had higher odds of testing than men who only consulted a urologist (P < .001).

CONCLUSIONS.

Few men who received ADT for prostate cancer underwent bone density testing, particularly older men, black men, and those living in areas with low educational attainment. Visiting a medical oncologist was associated with increased odds of testing. Interventions are needed to increase bone density testing among men who receive long‐term ADT. Data on bone density testing for nonmilitary populations of prostate cancer survivors in the United States who have received long‐term androgen‐deprivation therapy (ADT) have not been published. The current analysis of Surveillance, Epidemiology, and End Results/Medicare data suggests that few prostate cancer survivors who receive long‐term ADT undergo bone density testing; and several key populations, including African Americans and older men, have considerably lower rates of bone density screening. Cancer 2013. © 2012 American Cancer Society.     

Bone mineral density in Jamaican men on androgen deprivation therapy for prostate cancer

Background

Androgen deprivation therapy (ADT) has been reported to reduce the bone mineral density (BMD) in men with prostate cancer (CaP). However, Afro-Caribbeans are under-represented in most studies. The aim was to determine the effect of androgen deprivation therapy (ADT) on the bone mineral density (BMD) of men with prostate cancer in Jamaica.

Methods

The study consisted of 346 Jamaican men, over 40 years of age: 133 ADT treated CaP cases (group 1), 43 hormone-naïve CaP controls (group 2) and 170 hormone naïve controls without CaP (group 3). Exclusion criteria included metastatic disease, bisphosphonate therapy or metabolic disease affecting BMD. BMD was measured with a calcaneal ultrasound and expressed in S.D. units relative to young adult men (T score), according to the World Health Organization definition. Patient weight, height and BMI were assessed.

Results

Mean ± sd, age of patients in group 1 (75± 7.4 yrs) was significantly greater than groups 2 and 3 (67 ± 8.1 yrs; 65±12.0 yrs). There was no significant difference in weight and BMI between the 3 groups. . The types of ADT (% of cases, median duration in months with IQR) included LHRH (Luteinizing hormone releasing hormone) analogues (28.6%, 17.9, IQR 20.4), oestrogens (9.8%, 60.5, IQR 45.6) anti-androgens (11.3%, 3.3, IQR 15.2) and orchiectomy (15.7%, 43.4, IQR 63.9). Unadjusted t score of group 1, mean ± sd, (-1.6± 1.5) was significantly less than group 2 (-0.9±1.1) and group 3 (-0.7±1.4), p <0.001. Ninety three (69.9%), 20 (45%) and 75 (42%) of patients in groups 1, 2 and 3 respectively were classified as either osteopenic or osteoporotic (p<0.001). Adjusting for age, there was a significant difference in t scores between groups 1 and 2 as well as between groups 1 and 3 (p<0.001). Compared with oestrogen therapy and adjusting for duration of therapy, the odds of low bone mineral density (osteopenia or osteoporosis) with LHRH analogue was 4.5 (95%CI, 14.3 to 3.4); with anti-androgens was 5.9 (95%CI, 32.7 to 5); with orchiectomy was 7.3 (95%CI, 30 to 5.8) and multiple drugs was 9.2 ((95%CI, 31 to 7.1).

Conclusions

ADT is associated with lower BMD in Jamaican men on hormonal therapy for prostate cancer.

     

Factors affecting bone mineral density in patients with prostate carcinoma before and after orchidectomy

BACKGROUND: Orchidectomy is an accepted form of androgen-deprivation therapy (ADT) for prostate carcinoma. Osteoporosis is common in elderly individuals and is accelerated by ADT. The authors studied changes in bone mineral density (BMD) after ADT and factors that affected those changes. METHODS: Fifty patients with prostatic adenocarcinoma who opted to undergo orchidectomy were studied prospectively. All patients completed 6 months of follow-up, and 20 of those patients completed 12 months of follow-up. Patients' age, weight, height, body mass index (BMI), physical activity, addiction (smoking, alcohol), dietary calcium intake, and lactose tolerance status were noted. Lumbar spinal (L1-L3) trabecular BMD was measured with quantitative computed tomography (QCT) at baseline and every 6 months for 1 year and was compared with preoperative values. The effects of various patient characteristics on preoperative BMD and changes in BMD also were analyzed. RESULTS: The mean +/- standard deviation (SD) age of the patients was 69.5 +/- 8.1 years, BMI was 23.5 +/- 3.9 kg/m2, dietary calcium intake was 1066.1 +/- 443.3 mg per day. Thirty-eight percent of patients were lactose intolerant. Sixty-two percent of patients were in the light weight-bearing activity group. The mean +/- SD preoperative BMD was 119.2 +/- 34.9 mg/cc, with T-scores of - 1.77 +/- 1.22 and Z-scores of 0.43 +/- 1.27. A decrease in BMD during the first 6 months ( approximately 13%) was statistically significant (P = 0.0001) and continued further during next 6 months (BMD loss of approximately 18% at 12 months). Patients with osteoporosis, as defined by T-scores < or = - 2.5, increased from 24% at baseline to 48% at 6 months. Nonsmokers, nonalcoholics, patients with higher physical activity, and patients with a BMI > 25 kg/m2 had statistically significant higher BMD compared with their counterparts (P < 0.05). Body weight < 60 kg and BMI < 25 kg/m2 were significant risk factors for loss of BMD (P < 0.05). Dietary calcium had a discernible but statistically insignificant effect on BMD (P = 0.16). Lactose intolerance had no significant effect on BMD or bone loss. CONCLUSIONS: Osteoporosis was common in the population affected by prostate carcinoma. Orchidectomy led to accelerated bone loss. Periodic measurement of BMD after ADT would help in the early detection of osteoporosis. Maintenance of high BMI, weight-bearing physical activity, avoidance of alcohol and smoking, and possibly high dietary calcium intake help in maintaining bone mass.     

A Randomized Phase II Trial Evaluating Different Schedules of Zoledronic Acid on Bone Mineral Density in Patients With Prostate Cancer Beginning Androgen Deprivation Therapy

ObjectiveTo 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.Patients and MethodsIn 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).ResultsPatients 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.ConclusionsAnalysis 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.     

Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate carcinoma

BACKGROUND: Initial treatment with a gonadotropin-releasing hormone (GnRH) agonist increases fat mass, decreases lean body mass, and decreases bone mineral density (BMD) in men with prostate carcinoma. To the authors' knowledge, little is known regarding either the long-term effects of treatment or predictors of treatment-related changes in BMD and body composition. METHODS: The authors analyzed prospective 12-month data from 65 men during initial and long-term GnRH agonist treatment for prostate carcinoma. Relationships between baseline characteristics (age, treatment duration, body mass index, and baseline values for outcome of interest) and changes in lean mass, fat mass, and BMD were assessed using univariate and multivariate regression models. RESULTS: Mean BMD of total hip decreased by 1.9 +/- 2.7%, lean body mass decreased by 2.0 +/- 3.3%, and fat mass increased by 6.6 +/- 9.4% at 12 months (P < 0.001 for each comparison). Twenty-three men (35%) had received treatment with a GnRH agonist before study entry, and the mean (+/- standard deviation) duration of previous treatment was 35 +/- 41 months. Longer duration of previous GnRH agonist treatment was found to independently predict less fat accumulation and less loss of lean body mass in multivariate models. In contrast, the duration of GnRH agonist treatment did not significantly predict changes in BMD. Other covariates did not appear to predict changes in body composition or BMD consistently. CONCLUSIONS: The results of the current study showed that fat mass increased and lean body mass decreased mostly during initial GnRH agonist therapy whereas BMD decreased steadily during initial and long-term treatment.     

Androgen deprivation therapy increases cardiovascular morbidity in men with prostate cancer

BACKGROUND: The use of androgen deprivation therapy (ADT) in the treatment of men with prostate cancer has risen sharply. Although cardiovascular disease is the most common reason for death among men with prostate cancer who do not die of the disease itself, data regarding the effect of ADT on cardiovascular morbidity and mortality in men with prostate cancer are limited. In the current study, the authors attempted to measure the risk for subsequent cardiovascular morbidity in men with prostate cancer who received ADT. METHODS: A cohort of newly diagnosed men in a population-based registry who were diagnosed between 1992 and 1996 were identified retrospectively. A total of 22,816 subjects were identified after exclusion criteria were applied. Using a multivariate model, the authors calculated the risk of subsequent cardiovascular morbidity in men with prostate cancer who were treated with ADT, as defined using Medicare claims. RESULTS: Newly diagnosed prostate cancer patients who received ADT for at least 1 year were found to have a 20% higher risk of serious cardiovascular morbidity compared with similar men who did not receive ADT. Subjects began incurring this higher risk within 12 months of treatment. However, Hispanic men were found to have a lowered risk for cardiovascular morbidity. CONCLUSIONS: ADT is associated with significantly increased cardiovascular morbidity in men with prostate cancer and may lower overall survival in men with low-risk disease. These data have particular relevance to decisions regarding the use of ADT in men with prostate cancer in settings in which the benefit has not been clearly established. For men with metastatic disease, focused efforts to reduce cardiac risk factors through diet, exercise, or the use of lipid-lowering agents may mitigate some of the risks of ADT.     

High bone density is associated with prostate cancer in older Afro-Caribbean men: Tobago Prostate Survey

Objective To test the hypothesis that bone mineral density (BMD), a possible surrogate of lifetime exposure to hormone/growth factor/vitamin D/calcium exposure, is higher in prostate cancer cases than controls. Methods Hip BMD was measured by dual X-ray absorptiometry in 222 Afro-Caribbean screening-detected prostate cancer cases and 1,503 screened non-cases, aged 45–79, in the population-based Tobago Prostate Survey. Because possible skeletal metastases may modulate BMD, men with prostate specific antigen >20 ng/ml or highly undifferentiated tumors (Gleason score ≥8) were excluded. Mean BMD, adjusted for age and body mass index, was compared in cases and non-cases by analysis of variance. Risk across age group-specific BMD quartiles was compared using logistic regression. Results Overall, adjusted mean hip BMD was higher in cases (1.157 g/cm²) than non-cases (1.134 g/cm²) (p = 0.02). In men aged 60–79, prostate cancer risk was two-fold higher (OR, 2.12; 95% CI: 1.21–3.71) in the highest BMD quartile compared to the lowest. There was no association in younger men (interaction, p = 0.055). Conclusions High bone density is associated with prostate cancer among older men, consistent with an etiological role for lifetime exposure to factors which modulate bone density. However, other etiologies may dominate prostate cancer risk among younger men. The study was supported, in part, by funding or in-kind services from the Division of Health and Social Services, Tobago House of Assembly, the University of Pittsburgh Cancer Institute, the Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, contract DAMD 17-99-109015, U.S. Department of Defense, and grants R01 CA84950, R25-CA57703, U.S. National Cancer Institute, R01-AR049747, U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases.     

Treatment failure after primary and salvage therapy for prostate cancer: likelihood, patterns of care, and outcomes

BACKGROUND: The authors report the likelihood of treatment failure and the outcomes after salvage therapy among men with prostate cancer who initially either received external-beam radiation therapy (EBRT) or underwent radical prostatectomy (RP). METHODS: Using a national disease registry, the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database, 5277 men with prostate cancer were identified who initially either underwent RP (4342 men) or received EBRT (935 men). Outcomes after disease recurrence and subsequent salvage therapy were assessed. RESULTS.: Recurrent disease developed in 1590 men (30%), including 1003 patients (23%) in the RP group and 587 patients (63%) in the EBRT group, at a mean of 34 months and 38 months, respectively (P= .003). Patients who had recurrent disease had greater rates of overall death (19% vs 3%; P< .01) and bone metastases (15% vs 1%; P< .01). Data after salvage therapy were available for 1050 patients (620 men in the RP group and 430 men in the EBRT group). Androgen-deprivation therapy (ADT) was the most common salvage treatment in both groups. Overall, 420 men in the RP group (68%) and 319 men in the EBRT group (74%) failed salvage therapy at mean of 43.6 months and 43.8 months, respectively (P= .95). These patients had a greater overall death rate than the 311 patients who did not fail salvage therapy (24.8% vs 6.9%, respectively; P< .001). No survival benefit in terms of prostate cancer-related death (P= .91) was identified with any particular combination of primary and salvage therapy. CONCLUSIONS: Disease recurrence developed in 30% of patients who were treated for prostate cancer, and ADT was the most common salvage therapy used. Patients who failed salvage therapy had worse overall survival, and no survival benefit was noted for any particular combination of primary and salvage therapy.     

Predictors of clinical metastasis in prostate cancer patients receiving androgen deprivation therapy

BACKGROUND:

Virtually all patients with prostate cancer who receive androgen deprivation therapy (ADT) will ultimately develop evidence of resistance to treatment. The prognosis for patients who develop metastatic castrate‐resistant disease is reported to be poor, with overall survival historically estimated to be 24 to 36 months. The goal of the current study was to identify predictors of clinical disease progression in patients with prostate cancer who were receiving ADT.

METHODS:

Of the 13,740 men with biopsy–proven prostate cancer who were enrolled in the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database from 1995 to 2007, 4003 men treated with ADT after diagnosis without evidence of metastases at treatment initiation were identified. The primary endpoint was the development of bone metastasis. Clinical and pathologic characteristics were compared between patients who developed metastasis and those who did not using chi‐square tests in a Cox proportional hazards regression model.

RESULTS:

The mean age of the men in the cohort was 70 years (range, 39‐94 years). One hundred ninety‐one men (4.8%) progressed to metastatic disease at a median of 18 months from the initiation of ADT (range, 1‐139 months). On multivariate analyses, risk category (hazards ratio [HR], 2.58; P < .0001), percent of biopsies positive >33% (HR, 3.36; P = .003), age ≤65 years at diagnosis (HR, 2.11; P = .001, and prostate–specific antigen velocity on ADT (HR, 1.04; P < .001) were found to be significantly associated with the development of metastatic disease after ADT.

CONCLUSIONS:

Younger men with high–risk disease appear to have worse prognosis than older men with similar disease. This, along with the other prognostic variables established in the current study, may help identify candidates for clinical trials evaluating secondary treatments for patients with castrate‐resistant disease. Cancer 2009. © 2009 American Cancer Society.     

Quality of life following localized prostate cancer treated initially with androgen deprivation therapy or no therapy

BACKGROUND: Many men diagnosed with clinically localized prostate cancer are initially treated conservatively, receiving neither surgery nor radiotherapy for the first year. Treatment patterns and quality-of-life outcomes have not been previously reported for a population-based sample of such men. METHODS: A population-based random sample of men (n = 661) from six geographic regions who had been newly diagnosed with clinically localized prostate cancer from 1994 through 1995 were followed for up to 1 year. Eligible subjects received neither surgery nor radiotherapy within 1 year of initial diagnosis. We assessed disease-specific and generic quality-of-life outcomes in men receiving androgen deprivation therapy (ADT) compared with men receiving no therapy. All statistical tests were two-sided. RESULTS: Two hundred and forty-five study patients received ADT and the remaining 416 patients received no therapy. Approximately two thirds of the patients (n = 159) receiving ADT had either baseline Gleason scores greater than six or serum prostate-specific antigen values above 20 ng/mL. Among men who were sexually potent before diagnosis (ADT = 88 patients; no therapy = 223 patients), 80% of those on ADT reported being impotent after 1 year compared with 30% of those receiving no treatment (P < .001). Patients receiving ADT reported more physical discomfort 1 year after diagnosis than did men who had received no therapy. However, patients receiving ADT, compared with those receiving no therapy, were more likely to be satisfied with their treatment decision (56% pleased versus 45.3%; P =.001). Patients on ADT also experienced a statistically significant decline in vitality, but not in physical function, after adjustment for the confounding factors (P =.05). CONCLUSION: ADT is a commonly used primary therapy for clinically localized prostate cancer. Therefore, men considering ADT as an initial treatment should be aware that sexual function and some aspects of physical well-being are likely to be affected in the first year following this treatment.     

Contribution of androgen deprivation therapy to elevated osteoclast activity in men with metastatic prostate cancer.

PURPOSE: Biochemical markers of both osteoblast and osteoclast activity are elevated in men with osteoblastic metastases from prostate cancer. Androgen deprivation therapy (ADT), the mainstay of therapy for advanced prostate cancer, increases markers of osteoblast and osteoclast activity, even in the absence of bone metastases. Little is known about the relative contributions of ADT and skeletal metastases to elevated bone turnover in men with prostate cancer. EXPERIMENTAL DESIGN: To evaluate the relative contributions of ADT and skeletal metastases to osteoblast and osteoclast activity, we performed a cross-sectional study in three groups of men with advanced prostate cancer: (a) hormone-na?ve men without bone metastases; (b) castrate men without bone metastases; and (c) castrate men with bone metastases. The primary study end points were serum levels of bone-specific alkaline phosphatase (BSAP), a marker of osteoblast activity, and N-telopeptide (NTX), a marker of osteoclast activity. RESULTS: Serum levels of both BSAP and NTX were significantly higher in groups of castrate men (groups 2 and 3) than in hormone-na?ve men (group 1; P < 0.01 for all comparisons). Among castrate men, serum BSAP was significantly higher in men with bone metastases than in men without bone metastases (P = 0.01). In contrast, serum levels of NTX were similar in groups 2 and 3 (P = 0.33). CONCLUSIONS: The unintended effects of ADT on the skeleton are sufficient to explain increased osteoclast activity in castrate men with bone metastases. These results may have important implications for the optimal timing and schedule of osteoclast-targeted therapy in men with advanced prostate cancer.     

Zoledronic acid to prevent bone loss in Chinese men receiving androgen deprivation therapy for prostate cancer

Aim: To explore the bone mineral density (BMD) preservation effect of zoledronic acid and its renal safety and tolerability in Chinese patients with prostate cancer on androgen deprivation therapy (ADT). Methods: Overall 26 prostate cancer patients with ADT were given zoledronic acid 4 mg by a 15‐min i.v. infusion every 3 months for up to 12 months. Assessment was made at baseline and at 3, 6, 9 and 12 months. Dual‐energy X‐ray absorptiometry was used to measure the BMD of the lumbar spine and the femoral neck at baseline and 12 months. Results: A total of 23 of 26 recruited patients completed the study. Seven patients had bone metastases. The overall mean increase in BMD (T‐score) of the lumbar spine and femoral head from baseline to follow up at 12 months was significant (−2.32 ± 0.98 to −2.03 ± 1.08, P = 0.02 and −1.77 ± 0.72 to −1.63 ± 0.76, P = 0.01, respectively). In subgroup analyses, significant BMD improvement was observed independent of the status of bone metastasis and the means of ADT. Zoledronic acid had no adverse effect on renal function. Adverse events related to zoledronic acid were minimal. Conclusion: Zoledronic acid administered every 3 months significantly increased BMD in prostate cancer patients receiving ADT. It had a satisfactory adverse event profile and imposed minimal risk on patients' renal function.     

Depression in men receiving androgen deprivation therapy for prostate cancer: a pilot study

PURPOSE: Prostate cancer is the most common malignancy in men and one of the leading causes of cancer death in men internationally. Treatment for prostate cancer frequently includes androgen deprivation therapy (ADT). Reports of depressive symptoms arising during ADT are emerging. This study examines the prevalence rates and risk factors associated with major depression in this population. METHOD: 45 men with prostate cancer receiving ADT at the MGH Cancer Center were surveyed for depression with the SCID for Axis I disorders for DSM-IV and the Beck Depression Inventory. RESULTS: Major depressive disorder was prevalent in 12.8% of the men with prostate cancer receiving ADT, eight times the national rate of depression in men, 32 times the rate in men over 65 years old. Major depression was not associated with worsening disease, medical response to ADT, receiving chemotherapy, or the type of ADT. Past history of depression was associated with current depression in this population (p<0.000). No first onset cases of depression occurred on ADT in this sample. CONCLUSION: This data suggests a significant rate of major depression in men with prostate cancer receiving ADT and that men with past histories of depression may be at particular risk for recurrence of their depression while undergoing this treatment.     

Depression,Anxiety, and Patterns of Mental Health Care Among Men With Prostate Cancer Receiving Androgen Deprivation Therapy

BackgroundAndrogen deprivation therapy (ADT) use is associated with an increased risk of developing depression and anxiety. Little is known about how the mental health of these men is treated.Materials and MethodsWe identified men with prostate cancer who received ADT between 2001 and 2015 using Optum’s de-identified Clinformatics Data Mart Database. We determined the incidence of depression or anxiety diagnoses, mental health treatments, and the specialty of providers initiating psychotropic medications, after the start of ADT. Outcomes were compared with those of men with prostate cancer not receiving ADT and men without prostate cancer.ResultsOf 37 388 men with prostate cancer treated with ADT, 3964 (10.6%) received a new diagnosis of depression or anxiety. Of those 3964 men, 1892 (47.7%) did not receive a documented treatment, 10 (0.3%) received psychotherapy, 1321 (33.3%) a selective serotonin reuptake inhibitor, and 744 (18.8%) a benzodiazepine. The median time from initiation of ADT to a depression or anxiety diagnosis was 9.3 months. Primary care physicians were the most common prescribers of psychotropic medications (72.2%). The proportion of men not receiving mental health treatments of interest (47.7%) was similar compared to men without prostate cancer (49.1%), but statistically significantly lower compared to men with prostate cancer not receiving ADT (52.7%).ConclusionsIn men with prostate cancer receiving ADT with a new diagnosis of depression or anxiety, nearly half are not receiving mental health care while one in five is introduced to a benzodiazepine. Further investigation toward improving the mental health care for men on ADT is needed.