Bone health in men receiving androgen deprivation therapy for prostate cancer

PURPOSE: Patients with recurrent or metastatic prostate cancer generally receive androgen deprivation therapy, which can result in significant loss of bone mineral density. We explored androgen deprivation therapy related bone loss in prostate cancer, current treatments and emerging therapies. MATERIALS AND METHODS: Literature published on the pathogenesis and management of androgen deprivation therapy related bone loss was compiled and interpreted. Recent drug therapy findings were reviewed, including treatment guidelines. RESULTS: Men with prostate cancer often present with bone loss and the initiation of androgen deprivation therapy can trigger further rapid decreases. This results in an increased fracture risk, and greater morbidity and mortality. Early detection of osteoporosis through androgen deprivation therapy screening and prompt initiation of therapy are critical to prevent continued decreases. Lifestyle changes such as diet, supplementation and exercise can slow the rate of bone loss. Pharmacological therapy with oral and intravenous bisphosphonates has been demonstrated to prevent or decrease the bone loss associated with androgen deprivation therapy. However, important differences exist among various bisphosphonates with respect to efficacy, compliance and toxicity. Only zoledronic acid has been shown to increase bone mineral density above baseline and provide long-term benefit by decreasing the incidence of fracture and other skeletal related events in men with bone metastases. CONCLUSIONS: Androgen deprivation therapy associated bone loss adversely affects bone health, patient quality of life and survival in men with prostate cancer. Increased awareness of this issue, identification of risk factors, lifestyle modification and initiation of bisphosphonate therapy can improve outcomes. Education of patients and physicians regarding the importance of screening, prevention and treatment is essential.     

Radiation therapy and androgen deprivation in the management of high risk prostate cancer

The combined use of radiation therapy (RT) and androgen deprivation for patients with localized high-risk prostate cancer is commonly accepted as the standard treatment among uro-oncologists. Preclinical studies have provided rationale for the use of this combination. Additionally, results of phase 3 studies using conventional doses of RT have supported the combined approach. Other phase 3 studies have also shown a benefit for using higher doses of RT; however, the role of androgen deprivation in this context is not clear. The optimal duration of the androgen deprivation, in both the neoadjuvant and adjuvant setting, is still under investigation. This article critically reviews the data on the use of RT combined with androgen deprivation for the treatment of high-risk prostate cancer with emphasis on the results of phase 3 trials.     

Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis

The objective of this study was to clarify the role of bisphosphonates in the treatment of osteoporosis in patients with prostate adenocarcinoma under androgen deprivation therapy (ADT). The Medline, EMBASE, Cancerlit and the American Society of Clinical Oncology abstract databases were searched for published randomized, placebo-controlled trials evaluating the usage of bisphosphonates in patients with prostate cancer (PC) under ADT. The outcomes assessed were fracture, osteoporosis, incidence of adverse events and changes in bone mineral density (BMD) during treatment. A total of 15 articles (2634 participants) were included in the meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing fractures (risk ratio (RR), 0.80; P = 0.005) and osteoporosis (RR, 0.39; P <0.00001). Zoledronic acid showed the best number needed to treat (NTT), compared with placebo, in relation to fractures and osteoporosis (NNT = 14.9 and NNT = 2.68, respectively). The between-group difference (bisphosphonates vs placebo) in the lumbar spine and femoral neck BMD were 5.18 ± 3.38% and 2.35 ± 1.16%, respectively. This benefit of bone loss prevention could be reached without major side effects (cardiovascular or gastrointestinal events). Bisphosphonates are effective in preventing bone loss in patients with PC who are under ADT.     

Clinical significance of risedronate for patients with prostate cancer receiving androgen deprivation therapy

PURPOSE: Androgen deprivation therapy (ADT) in patients with prostate cancer is associated with bone loss. We investigated the effectiveness of risedronate about a decreasing bone mineral density in patients with prostate cancer on ADT. MATERIAL AND METHOD: A prospective study was conducted in Kitasato University Hospital from April 2004 to October 2006. A total of 69 men with prostate cancer were assigned to receive either oral risedronate or none during ADT (hormone na?ve). The treatment group was 58 men and taking 2.5 mg risedronate per day. The control group was 11 men. At baseline, we assessed BMD (bone mineral density) by DEXA and urinary NTX, and measured for these changes every 6 months. RESULT: At baseline, each BMDs had no significant difference at the lumber and total hip. At the first 6-month stage, the change in BMD percentage between the 2 groups was statistically significantly different at lumber (p = 0.002) and total hip (p = 0.038). At the 12-month stage, the change in the BMD percentage between the 2 groups was statistically significantly different at the lumber (p = 0.038). And each difference made out that the risedronate group was preserving BMD. In urinary NTX, bone turn over was statistically significantly decreased with the risedronate group compared with the control group at the 12-month stage (p = 0.017). CONCLUSION: We assure the beginning of bone loss at an early date (6 months) with ADT. Daily oral risedronate in patients with receiving ADT reduces bone mineral loss and maintain BMD.     

Individual variations of serum testosterone in patients with prostate cancer receiving androgen deprivation therapy

OBJECTIVE

To analyse individual variations in serum testosterone level, the cumulative rate of ‘breakthrough’ increases over castrate levels, and to evaluate whether the increases can be predicted.

PATIENTS AND METHODS

Serum testosterone levels were determined every 6 months over 3 years in 73 consecutive patients with prostate cancer who were medically castrated, prospectively enrolled in a single tertiary academic centre. Patients recruited for this study were being treated with a 3‐monthly depot of luteinizing hormone‐releasing hormone agonist over 6–48 months. Serum testosterone was measured using a chemiluminescent assay with a lower sensitivity level of 15 ng/dL and interassay coefficient of variation of 25% at low testosterone concentrations.

RESULTS

Individual variations could not be explained by the interassay variation coefficient in 26% of the patients. The rate of breakthrough increases >50 ng/dL increased from 12.3% at the first determination to 24.7% at the third, then remaining stable. The rate of breakthrough increases of 20–50 ng/dL increased from 27.4% at the first determination to 31.5% at the second, and then remained stable. A first determination of <20 ng/dL provided an 11.4% probability for future increases of >50 ng/dL, with a 5.7% probability if two consecutive determinations were <20 ng/dL and a null probability when three consecutive determinations were <20 ng/dL.

CONCLUSIONS

Individual variations in serum testosterone level cannot be explained by the coefficient of variation of the assay in a quarter of patients who are medically castrated. Breakthrough increases over castrate levels increase over time and those of >50 ng/dL can be predicted from the previous levels.     

Increased risk of a herpes zoster attack in patients receiving androgen deprivation therapy for prostate cancer

This study aimed to examine the association of herpes zoster (HZ) with androgen deprivation therapy (ADT) use among patients with prostate cancer (PC), using a population‐based data set. The study sample for this study was retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We selected 877 patients with PC who had received ADT as the study group, while 849 patients with PC who had not received ADT served as the comparison group. Each study patient was individually tracked for a 3‐year period to discriminate those who subsequently received a diagnosis of HZ. Of the total 1,726 sampled patients, the incidence rate of HZ per 100 person‐years was 1.80 (95% CI: 1.41–2.25) during the 3‐year follow‐up period. In particular, incidence rates of HZ per 100 person‐years were 2.36 (95% CI: 1.75–3.13) and 1.24 (95% CI: 0.81–1.81), respectively, for patients with PC who had and those who had not received ADT. Furthermore, Cox proportional hazard regressions showed that the adjusted hazard ratio for an HZ attack during the 3‐year follow‐up period for patients with PC who had received ADT was 1.88 (95% CI: 1.13–3.11) than those who had not received ADT. We concluded that patients with PC who had received ADT had an increased risk of HZ.     

Neridronate prevents bone loss in patients receiving androgen deprivation therapy for prostate cancer.

Today, androgen deprivation therapy is a cornerstone of treatment for advanced prostate cancer, although it presents important complications such as osteoporosis. Neridronate, a relatively new bisphosphonate, is able to prevent bone loss in patients with prostate cancer during androgen ablation. INTRODUCTION: Androgen-deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer. This therapy has iatrogenic complications, such as osteoporosis. The aim of our study was to evaluate the efficacy of neridronate, a relatively new bisphosphonate, to prevent bone loss during androgen ablation. MATERIALS AND METHODS: Forty-eight osteoporotic patients with prostate cancer, treated with 3-month depot triptorelina, were enrolled and randomly assigned to two different treatment groups: group A (n = 24) was treated with a daily calcium and cholecalciferol supplement (500 mg of elemental calcium and 400 IU cholecalciferol), and group B (n = 24) received in addition to the same daily calcium and cholecalciferol supplement, 25 mg of neridronate given intramuscularly every month. All patients also received bicalutamide for 4 weeks. Lumbar and femoral BMD was evaluated by DXA at baseline and after 1 year of therapy; moreover, deoxypyridinoline (DPD) and bone alkaline phosphatase (BALP) were determined at the beginning, midway through, and at the end of the study. RESULTS: After 6 and 12 months, whereas patients treated only with calcium and cholecalciferol (group A) showed a marked bone loss, with increased levels of DPD and BALP compared with baseline values, patients treated also with neridronate (group B) had substantially unchanged levels of these markers. After 1 year of treatment, lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol (group A), whereas it did not change significantly at any skeletal site in patients treated also with neridronate (group B). No relevant side effects were recorded during our study. CONCLUSIONS: Neridronate is an effective treatment in preventing bone loss in the hip and lumbar spine in men receiving ADT for prostate cancer.     

Bone health in prostate cancer patients receiving androgen-deprivation therapy: the role of bisphosphonates

Androgen-deprivation therapy, a mainstay in the treatment of locally advanced and metastatic prostate cancer, is associated with significant bone loss and related complications, such as fracture. Bisphosphonates, osteoclast inhibitors, are effective in preventing skeletal-related events in patients with metastatic prostate cancer and also in preventing bone loss in patients with locally advanced disease. Understanding the management of bone health, including identifying patients at risk, the most appropriate therapy, and monitoring and managing side effects, is critical. This review provides the most recent bone health risk factor and bisphosphonate data available for prostate cancer patients.     

Androgen and prostate cancer: the role of primary androgen deprivation therapy in localized prostate cancer

BackgroundThe basic mechanisms and clinical efficacy of primary androgen deprivation therapy (PADT), especially combined androgen blockade (CAB) for localized or locally advanced prostate cancer (PCa) have been outlined. An important point relates to which patients are suitable candidates for PADT.MethodsA retrospective review of the efficacy of PADT in 628 patients with localized or locally advanced PCa treated with PADT at seven institutions in Japan was carried out.ResultsIt was found that more than 30% of low- or intermediate-risk localized PCa patients could have their disease controlled over the long-term by PADT alone. Short-term or intermittent PADT could not be recommended because of the possibility of character change in the cancer cells as a result of incomplete androgen ablation.ConclusionAlgorithms are proposed for the treatment of localized PCa not only in low- and intermediate-risk groups, but also in the high-risk group. Future research directions are indicated.     

Bone mineral density changes on androgen deprivation therapy for prostate cancer and response to antiresorptive therapy

Androgen deprivation therapy improves survival of patients with prostate cancer and leads to hypogonadal state. Gonadal hormones are essential for skeletal integrity and hypogonadism constitutes a major risk factor for osteoporosis. To examine the bone loss secondary to androgen deprivation therapy, we reviewed the bone mineral density (BMD) studies of 152 patients with prostate cancer with mean duration of androgen deprivation therapy of 58 months. Among them 55 subjects had follow-up BMD measurement at 12-15 months with 39 of them on antiresorptive therapy. Osteoporosis was noted at least at one site in 92 (60.5%), among which 74 (48.7%) had changes at hip with the more prominent changes at ward's triangle, 18 (11.8%) at other sites. Osteopenia was present in 37 (24%) and only 17 (11%) were normal. The duration of antiandrogen therapy did not correlate with the degree of bone loss. Significant in improvement in the BMD is noted at 12-15 month follow-up on antiresorptive therapy. We conclude that men treated with androgen deprivation therapy are at risk for bone loss and should have BMD measured at the time of initiation of androgen deprivation therapy and periodically.     

前列腺癌内分泌治疗所引起的骨质疏松

雄激素阻断治疗(Androgen-DeprivationTherapy.ADT)即内分泌治疗已成为前列腺癌、特别是进展期前列腺癌的常用治疗方法 .而抗雄治疗所引起的骨质疏松以及其他骨相关疾病也越来越受到重视.越来越多的人开始关注如何尽早发现、诊断由内分泌治疗所引起的骨质流失以及骨质疏松并能及时采取充分的预防和治疗措施从而改善患者的生活质茸.国内外的大量研究进一步明确了抗雄治疗与前列腺癌患者的骨质流失存在着密切的联系.通过DEXA检测骨盆骨密度被认为是诊断前列腺癌患者骨质疏松的首选方式,同时出于对患者生活质量的考虑,脊柱和股骨颈的骨密度测定也相当重要.对于接受ADT的前列腺癌患者骨质疏松的治疗,目前已经形成的共识是单纯的钙剂和维生索D治疗是远远不够的.通过诸多随机对照研究发现,二膦酸盐(氨羟二磷酸二钠和氨羟二磷酸二钠)和选择性雌激素受体调节剂(雷洛昔芬和托瑞米芬)可增加前列腺癌症患者的骨密度.在抗雄治疗的过程中,定期的骨密度检测.鼓励适量地运动以及根除不良的生活习惯对于保持骨骼健康也很莺要.     

Immunohistochemical changes in prostate cancer after androgen deprivation therapy

Androgen deprivation induces substantial changes in the phenotype of prostate cancer that are accompanied by alterations in protein expression. Immunohistochemical studies allow precise cellular localization of such expression, thereby providing an understanding of the biochemical alterations caused by therapy. Expression of proteins may be increased (e.g., multiple growth factors, heat shock protein), decreased (e.g., microvessel density, proliferation markers, certain integrins), or remain unchanged (e.g., prostate specific antigen, prostatic acid phosphatase, prostate-specific membrane antigen, and other secretory proteins). Variations in immunoreactivity may be of prognostic value in some patients. This report summarizes the existing literature regarding changes in tissue expression of proteins, as determined by immunohistochemistry, and the clinical implications of these changes.     

Use of androgen deprivation therapy in prostate cancer: indications and prevalence

Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer. This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.     

前列腺癌去雄激素治疗不良反应的预防和处理

目的观察去雄激素治疗前列腺癌的不良反应,并探讨其预防和治疗。方法回顾性分析1998年7月-2006年1月112例去雄激素治疗晚期前列腺癌的临床资料。结果112例患者中,97例完成了不良反应的调查。随访3-36月,去雄激素治疗后潮热、性功能障碍、病理性骨折发生率分别为46％、75％、4％;患者潮热、精神疲乏、四肢乏力、纳差症状明显加重(P<0．05);性功能明显减退(P<0．05)。12例潮热症状严重者使用抗抑郁药博乐欣(25mg,tid)1-2周症状减轻。7例有骨转移性疼痛或严重骨质疏松患者,应用唑来膦酸4mg静脉滴注,每45d一次,骨痛症状缓解。结论去雄激素对前列腺癌患者生活质量有一定影响。博乐欣可减轻患者潮热症状,唑来膦酸可预防和治疗去雄激素相关的骨质疏松并发症。