Preventing bone loss during androgen deprivation therapy for prostate cancer: early experience with neridronate

OBJECTIVE: Androgen-deprivation therapy (ADT) is the usual treatment for locally advanced or metastatic prostate cancer. Osteoporosis is a common complication of ADT. The aim of our study was to evaluate the efficacy of neridronate, a relatively new bisphosphonate to prevent bone loss during androgen ablation. METHODS: Sixty patients with prostate cancer and osteoporosis were enrolled and randomly assigned to 2 different treatment regimes: group A (30 patients) treated with maximum androgenic blockage (MAB), and group B (30 patients) treated with bicalutamide 150 mg. Each group was divided in 2 subgroups A1-A2 and B1-B2. All patients received calcium and cholecalciferol supplements (500 mg of elemental calcium and 400 IU cholecalciferol) daily. The A2 and B2 subgroups were also treated with neridronate (25 mg intramuscular monthly). Lumbar and femoral bone mineral density (BMD) was evaluated by dualenergy X-ray absorptiometry (DXA), both at baseline and after one year of treatment. Deoxypyridinoline (DPD) and bone-alkaline phosphatase (B-ALP) were determined at the beginning, midstudy and at the end. RESULTS: Patients treated only with calcium and cholecalciferol (A1, B1 subgroups) showed a marked bone loss after 6, and 12 months, with increased levels of DPD and BALP, compared to baseline values. Patients treated with neridronate (A2 et B2 subgroups) showed unchanged levels of these markers. After one year of treatment, lumbar and total hip BMD decreased significantly in patients treated only with calcium and cholecalciferol (A1 subgroup: -4.9% and -1.9% respectively). BMD did not change significantly at any site in patients treated also with neridronate (A2 subgroup: +1% and +0.8% respectively). Lumbar and total hip BMD did not change significantly (-1.5% and -1% respectively) in B1 subgroup. In B2 subgroup an important increase in lumbar spine and the total hip BMD was shown (+2.5% and 1.6% respectively). No relevant side effects were recorded during our study. CONCLUSION: In conclusion, neridronate is an effective and safe treatment in preventing bone loss in men receiving ADT for prostate cancer.     

Oral bisphosphonate prevents bone loss in androgen deprivation therapy for nonmetastatic prostate cancer

We studied the short-term efficacy of alendronate, an oral bisphosphonates, on bone mineral density (BMD) during androgen deprivation therapy (ADT) in 45 nonmetastatic prostate cancer patients at the beginning of ADT (treatment group). All received alendronate five mg daily from the initiation of ADT. Lumber BMD was evaluated by dual energy X-ray absorptiometry, at baseline and after six months of treatment. Historical data on 24 patients with prostate cancer who received ADT without bisphosphonate administration were studied as controls (control group). BMD decreased in 13.9 and 45.8% of the patients in the treatment and control groups, respectively. Mean BMD changes in the lumber spine were +1.6 +/- 3.0% in the treatment group and -1.1 +/- 2.7% in the control group (p = 0.006). No pathological fractures occurred during the study period. No severe adverse effects were observed, but three patients could not continue alendronate treatment because of adverse events. Despite the short-term of this evaluation, our results showed that oral alendronate is an effective and safe treatment for preventing bone loss and increasing BMD in patients receiving ADT for prostate cancer.     

Intravenous bisphosphonate therapy increases radial width in adults with osteogenesis imperfecta.

Neridronate therapy in adult patients with OI significantly increases the cross-sectional area of the proximal radius. This observation may provide an additional explanation for the antifracture efficacy of bisphosphonates. INTRODUCTION: Bisphosphonate therapy decreases by 70-90% the fracture risk in patients with osteogenesis imperfecta (OI). This decrease is somewhat greater than that expected from the BMD changes, supporting the hypothesis that bisphosphonate therapy is associated with structural changes, not detectable by BMD measurements. MATERIALS AND METHODS: To explore this hypothesis, pQCT measurements at the nondominant radius were obtained in a group of adult OI patients participating in a randomized clinical trial with neridronate. RESULTS: The total volumetric BMD of the ultradistal radius rose significantly in patients treated with neridronate and calcium + vitamin D (neridronate group) compared with patients treated with calcium + vitamin D alone (control group). No significant differences were observed in trabecular BMD and in volumetric cortical density in either group. In the neridronate group, the cross-sectional area rose significantly versus both baseline values and the control group. These latter changes were associated with approximately 20% increases in bending breaking resistance index (BBRI). CONCLUSION: Our observation, if extended to postmenopausal osteoporosis, may provide a new explanation for the fracture risk reduction observed in osteoporotic patients treated with bisphosphonates.     

Effects of androgen deprivation therapy and bisphosphonate treatment on bone in patients with metastatic castration‐resistant prostate cancer: Results from the University of Washington Rapid Autopsy Series

Qualitative and quantitative bone features were determined in nondecalcified and decalcified bone from 20 predetermined bone sites in each of 44 patients who died with castration‐resistant prostate cancer (CRPC), some of which received bisphosphonate treatment (BP) in addition to androgen‐deprivation therapy (ADT). Thirty‐nine of the 44 patients (89%) had evidence of bone metastases. By histomorphometric analysis, these bone metastases were associated with a range of bone responses from osteoblastic to osteolytic with a wide spectrum of bone responses often seen within an individual patient. Overall, the average bone volume/tissue volume (BV/TV) was 25.7%, confirming the characteristic association of an osteoblastic response to prostate cancer bone metastasis when compared with the normal age‐matched weighted mean BV/TV of 14.7%. The observed new bone formation was essentially woven bone, and this was a localized event. In comparing BV/TV at metastatic sites between patients who had received BP treatment and those who had not, there was a significant difference (28.6% versus 19.3%, respectively). At bone sites that were not invaded by tumor, the average BV/TV was 10.1%, indicating significant bone loss owing to ADT that was not improved (11%) in those patients who had received BPs. Surprisingly, there was no significant difference in the number of osteoclasts present at the metastatic sites between patients treated or not treated with BPs, but in bone sites where the patient had been treated with BPs, giant osteoclasts were observed. Overall, 873 paraffin‐embedded specimens and 661 methylmethacrylate‐embedded specimens were analyzed. Our results indicate that in CRPC patients, ADT induces serious bone loss even in patients treated with BP. Furthermore, in this cohort of patients, BP treatment increased BV and did not decrease the number of osteoclasts in prostate cancer bone metastases compared with bone metastases from patients who did not receive BP. © 2013 American Society for Bone and Mineral Research     

Skeletal morbidity in men with prostate cancer: quality-of-life considerations throughout the continuum of care

OBJECTIVE: With current treatments, men usually survive many years after being diagnosed with prostate cancer. However, without supportive care, the systemic effects of prostate cancer and therapies such as androgen deprivation therapy (ADT) can undermine skeletal integrity, resulting in skeletal complications that may erode quality of life (QOL). Prostate cancer patients are at risk for fractures from cancer treatment-induced bone loss. In addition, they are also at risk for pathologic fractures, severe bone pain, and other sequelae from bone metastases, which almost invariably occur during the progression of prostate cancer. This review investigates the incidence and pathophysiology of bone loss and skeletal morbidity in prostate cancer patients and reviews available treatment options for maintaining skeletal health throughout the continuum of care for these patients. METHODS: Studies were identified through MEDLINE searches, review of bibliographies of relevant articles, and review of abstracts from national meetings. RESULTS: Several supportive care options are available to prevent generalized and localized bone loss, including calcium and vitamin D supplements and bisphosphonates. Oral calcium and vitamin D supplementation alone, however, appears to be insufficient to prevent bone loss during ADT. Zoledronic acid administered every 3 months during ADT or every 3 to 4 weeks for patients with bone metastases can reverse bone loss and reduce skeletal morbidity, respectively, in patients with prostate cancer. CONCLUSIONS: Skeletal complications contribute to the erosion of QOL in prostate cancer patients. Palliative care can provide important benefits to these patients. Some agents, such as zoledronic acid, may provide skeletal health benefits throughout the course of prostate cancer progression. Further investigations of the QOL impact of these benefits are warranted.     

雄激素剥夺治疗前列腺癌引起的骨代谢变化

雄激素剥夺治疗(androgen deprivation therapy,ADT)是治疗转移性前列腺癌(PCa)的基石,显著延长了PCa患者生存期。然而在ADT治疗的PCa患者中,每年平均骨密度下降2%~10%,导致骨折发病率、相关发病率和死亡率增加,应该引起临床医师的注意。这种骨代谢状态,目前认为主要是雄激素、雌激素水平明显减低导致。临床工作者可通过监测骨转换指标、骨密度及FRAX算法筛选出需要提前干预的患者,并对该类患者提供生活方式的指导及干预,以达到减少骨质不良事件的发生。这些干预措施包括适当锻炼、减少吸烟喝酒、补充钙和维生素D、双膦酸盐、部分选择性雌激素受体调节剂(如托瑞米芬)和靶向RANK配体抑制剂等。     

Androgen Deprivation and Bone

Bone health in men with prostate cancer on androgen deprivation therapy (ADT) has gained increased attention in recent years. Therapies that are becoming available to prevent bone loss and associated complications are changing practice for this patient population. In addition to basic vitamin D and calcium supplementation, bisphosphonates may be an option to treat these patients, and denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, has been proven to be effective in preventing bone loss through a randomized clinical trial. This review examines the importance of bone health in patients on ADT, with an overview of available treatment modalities and guidelines for managing these patients.     

Intravenous intermittent neridronate in the treatment of postmenopausal osteoporosis

Bisphosphonates have been used with success in the treatment of osteoporosis, but oral therapy often lacks compliance. Here we report the results of clinical trial with aminobisphosphonate neridronate administered intravenously (i.v.). The study included 78 postmenopausal women with spine bone mineral density (BMD) at least -2.5 SD below peak. Patients were randomized to receive for 2 years either 50 mg i.v. neridronate bimonthly and 500 mg calcium plus 400 U vitamin D supplements daily (n=39) or calcium-vitamin D supplements alone (control group, n=39). Treatment was continued over 2 years with an additional 1 year follow-up of calcium-vitamin D supplements alone. Neridronate was well tolerated with the appearance of typical clinical signs of an acute phase reaction in only 3 of the patients after the first infusion. In the control group no significant changes in BMD or bone markers were observed. In the neridronate group BMD rose progressively at the spine rose up to 7.4% +/- 6.1% (SD) and at the femoral neck up to 5.8% +/- 8.2% (SD) at the end of the second year. In the succeeding follow-up these gains were maintained at both skeletal sites. Serum bone alkaline phosphatase (bone ALP) and serum type I collagen C-telopeptide (s-CTX) significantly decreased within 2 months. The bone ALP values reached a -35% plateau after 6 months, while s-CTX attained the lowest mean value (-47%) only by the end of the treatment with neridronate. Both bone markers returned almost to baseline values 1 year after treatment discontinuation. Treatment of postmenopausal osteoporosis with 50 mg i.v. neridronate bimonthly results in clinically relevant increases in BMD, among the largest so far observed with any other bisphosphonate.     

Understanding treatments for bone loss and bone metastases in patients with prostate cancer: a practical review and guide for the clinician

Prostate cancer patients are at risk for developing bone loss and bone metastases. Clinicians prescribing ADT should appreciate the potential effects of ADT on BMD as well as the morbidity and mortality that can result from osteoporotic fractures. Measures to address the evaluation of patients and when to treat patients with significant bone loss have been discussed. Bisphosphonates effectively prevent loss of BMD in prostate cancer patients. Treatment of prostate cancer patients with established bone metastases with zoledronic acid should be considered strongly based on the results of the Saad study and other studies of patients with bone metastases with other malignancies. Zoledronic acid is approved by the US FDA for use in men with metastatic hormone-refractory prostate cancer and in the European Union for any patient with bone metastases, including prostate cancer patients,because of the beneficial impact of zoledronic acid on skeletal-related events. There is no validated method to determine which patients might benefit most from bisphosphonate therapy in this setting. Many questions about the use of bisphosphonate therapy in men with prostate cancer must be addressed, both in terms of the use in bone loss and bone metastases. These questions include: What is the optimal timing of therapy? Which bisphosphonate is best? What is the best dose and dose schedule? Do bisphosphonates effectively decrease skeletal fracture rates in patients with osteoporosis? How long should patients receive therapy? Are bisphosphonate "holidays" warranted? What are the long-term skeletal and renal toxicities? Is there a role for sequencing bisphosphonate therapy either before or after chemotherapy? Is bisphosphonate therapy synergistic with certain chemotherapy or other bone-targeted therapies? Which patients are the most likely to benefit from bisphosphonate therapy? What are clinically significant endpoints of bisphosphonate trials in patients with metastatic disease? Does inhibiting bone turnover also inhibit formation of bone metastases? Preliminary work in these areas has been completed, but more questions than answers are available. Given the rising costs of health care, it is imperative that these questions be addressed to best use the health care dollar while offering high-risk patients the best available therapy. At present, no data suggest that bisphosphonates should be used routinely to prevent BMD loss in men with normal BMD or to prevent the development of bone metastases in men with biochemical relapse. Continuing trials may give us guidance in the future.     

Preserving bone health in patients with hormone‐sensitive prostate cancer: the role of bisphosphonates

Men with prostate cancer initiating androgen‐deprivation therapy (ADT) may have multiple factors that threaten their skeletal health, including increased fracture risk from bone loss during ADT and the propensity to develop bone metastases, which may lead to skeletal‐related events (SREs). Bisphosphonates have utility in oncology for patients with bone metastases to prevent bone loss during hormonal therapy and in the benign setting to treat osteoporosis. These agents have an emerging role in patients with hormone‐sensitive prostate cancer (HSPC). Etidronate, alendronate, pamidronate, and zoledronic acid have all shown efficacy in preventing ADT‐related bone loss. Alendronate and zoledronic acid have also been shown to increase bone mineral density vs baseline during ADT. Patients with bone metastases from HSPC who received 4 mg zoledronic acid every 3 or 4 weeks had a low incidence of skeletal complications, although controlled study data have not been reported. Bisphosphonate treatment in men with HSPC may be effective for the prevention of ADT‐related bone loss, underscoring the importance of treating early to avoid SREs and potentially delay disease progression to metastatic bone disease.     

Incidence and risk factors for low trauma fractures in men with prostate cancer

BACKGROUND: Men with prostate cancer on androgen deprivation therapy (ADT) are at increased risk of bone loss. The present study sought to determine the incidence of low trauma fracture in men with prostate cancer (PC), and to characterize the association between potential risk factors and fracture risk in these men. METHODS: In the prospective, population-based Dubbo Osteoporosis Epidemiology Study, 43 men aged 60+ years reported a history of prostate cancer; among whom, 22 men received ADT, and 21 men did not. Low-trauma fractures were ascertained between 1989 and 2004. Bone mineral density at the femoral neck (FNBMD), postural instability and lifestyle factors were obtained at baseline. RESULTS: Men with prostate cancer had significantly higher lumbar spine BMD than those without cancer (p=0.013). During the follow-up period, 15 men with prostate cancer had sustained a fracture, yielding the age-adjusted incidence of fracture among this group was 31.6 per 1000 person-years, which was greater than those without cancer (22.1 per 1000 person-years). The age-adjusted incidence of fracture was more pronounced among those with prostate cancer on ADT (40.2 per 1000 person-years). After adjusting for age, the increase in fracture risk among prostate cancer patients was associated with lower femoral neck BMD (hazard ratio [HR] per SD=1.8, 95% CI: 1.0-3.4) and increased rate of bone loss (HR 2.3, 1.2-4.6). CONCLUSIONS: Men with prostate cancer, particularly those treated with ADT, had an increased fracture risk. Although the average BMD in men with prostate cancer was higher than men without cancer, a low BMD prior to treatment or increased rate of bone loss after initiating ADT treatment was each a significant predictor of fracture in these.     

Intravenous neridronate in adults with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seems to be the most promising therapy, at least in children. We tested IV neridronate, an amino-bisphosphonate structurally similar to alendronate and pamidronate in adults with OI. Twenty-three men and 23 premenopausal women with OI were randomized to either iv neridronate (100 mg infused intravenously for 30 minutes every 3 months) or no treatment with a ratio of 2 to 1. Control patients were given the same bisphosphonate therapy at the end of the first year. Clinical evaluation included bone densitometry measurements using dual energy X-ray absorptiometry (DXA), fasting serum and urinary biochemistry every 6 months, and radiographs of the spine taken at baseline and after 12 and 24 months of follow-up. Spine and hip bone mineral density rose by 3.0 +/- 4.6% (SD) and by 4.3 +/- 3.9%, respectively, within the first 12 months of treatment, whereas small insignificant changes were observed in the control group. During the second year of follow-up, additional 3.91% and 1.49% increases were observed at the spine and hip, respectively. Markers of skeletal turnover significantly fell during neridronate treatment. Fracture incidence during neridronate treatment was significantly lower than before therapy and compared with controls. Neridronate iv infusions, administered quarterly, significantly increase bone mineral density and lowered the risk of clinical fracture in adults with OI. Bisphosphonate therapy seems to provide clinical benefits, not only to children with OI, but also to adult patients.     

Bone mineral density changes in patients with prostate cancer during the first 2 years of androgen suppression

PURPOSE: We characterized bone mineral density changes in patients with prostate cancer on androgen deprivation therapy during the first 2 years of uninterrupted therapy, and identified which location most reflects bone mass loss. MATERIALS AND METHODS: Using dual energy x-ray absorptiometry, bone mineral density was prospectively assessed in patients with nonmetastatic prostate cancer at the lumbar spine and femoral neck, Ward's triangle, trochanter and total hip. Measurements were performed at baseline and yearly thereafter in patients on ADT, and at baseline and 1 year in controls (age matched patients with prostate cancer, free of biochemical progression after radical prostatectomy). RESULTS: A total of 62 patients were included in the study, 31 in each group. Median age (70 and 69 years, respectively), mean Gleason score and mean baseline serum testosterone did not significantly differ. Patients receiving ADT experienced a significant bone mass loss at 12 months in all locations, ranging from 2.29% to 5.55% (p <0.001). In contrast, bone mineral density did not change significantly (0.64% to 1.68%) in patients not receiving ADT. In the 20 patients on ADT after 24 months, the second year decrease was not as severe, nor was it significant compared to first year values. The major bone mass loss occurred in Ward's triangle, with decreases of 5.55% at 12 months and 7.05% at 24 months. CONCLUSIONS: Bone mineral density decreases during the first 24 months of androgen suppression with the most relevant effect occurring in the first year. Ward's triangle is the axial skeletal site that reflects the major bone mass loss. Because the deleterious impact of long-term androgen suppression on bone mineral density is inversely related to fracture risk and indirectly related to survival in patients with prostate cancer, early diagnosis and prevention of bone mass loss are warranted in these patients.     

Androgen deprivation in men with prostate cancer is associated with an increased rate of bone loss

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.     

Risk factors for male osteoporosis

Hypogonadism from long-term androgen deprivation therapy (ADT), either by bilateral orchiectomy or administration of gonadotropin-releasing hormone (GnRH) agonists, causes significant and accelerated bone loss that may increase the risk of bone fractures in men with prostate cancer. Recent reports, as well as new data from our institution, have shown a high prevalence of pre-existing osteopenia and osteoporosis in men with prostate cancer before receiving ADT, and this is of great concern because of the risk of further bone loss during ADT. Data from these studies suggest the urgent need for clinical guidelines for screening, prevention, and treatment of these cases. This article reviews the prevalence and risk factors associated with osteoporosis in men and addresses risk factors in men with prostate cancer not receiving ADT. Considerations for the patient selection and timing of bone densitometry will also be discussed.     

New Tools for the Urologist in the Management of Patients with Bone Metastases

ObjectivesBone metastases are common among patients with hormone-refractory prostate cancer and advanced renal cell carcinoma. Moreover, androgen-deprivation therapy (ADT) in patients with early prostate cancer has been associated with bone loss. Current guidelines for monitoring and managing bone health in patients with prostate cancer are evolving to optimize patient screening and treatment.MethodsMedline keyword searches and reviews of presentations from recent international symposia were performed to identify new tools for screening for bone metastases. In addition, guidelines and consensus recommendations were reviewed to identify bone health issues and their management in patients with genitourinary cancers.ResultsMalignant bone disease contributes heavily to the burden of disease in patients with advanced prostate cancer. Furthermore, fractures are associated with decreased survival. The introduction of zoledronic acid has extended the skeletal health benefits of bisphosphonate therapy to the genitourinary cancer setting. Diagnosis of bone metastases while patients are still asymptomatic could allow the initiation of therapy before skeletal complications occur, thereby possibly delaying their onset. Recent analyses have identified risk factors for metastasis to bone, allowing urologists to better mobilize potentially limited resources for bone scans in their clinics. Moreover, algorithms for monitoring and treating bone loss in patients undergoing ADT may allow early detection and treatment of bone mineral density declines, thereby preserving patients’ functional independence throughout the continuum of care.ConclusionsThe introduction of zoledronic acid and updated monitoring and treatment algorithms may aid in the maintenance of bone health in patients with genitourinary cancers.     

Androgen-deprivation-therapy-induced fractures in men with nonmetastatic prostate cancer: what do we really know?

Androgen deprivation therapy (ADT) alone or in combination with radiation therapy or other drugs is increasingly used for the treatment of localized, high-risk, or biochemical relapse of prostate cancer (PC). Bone mineral density (BMD) loss is rapid during the first year of ADT; up to 4.6% of total hip, femoral neck, and lumbar spine BMD loss has been reported in PC patients without bone metastases (nonmetastatic PC). In prospective studies, concurrent administration of a bisphosphonate or selective estrogen receptor modulator stabilized or increased BMD. Results of retrospective studies of ADT-treated patients who did not receive antiresorptive therapy have demonstrated a 21-37% increase in fracture risk. Because of the documented bone loss and increased fracture risk, patients should receive adequate counseling, monitoring, and therapy aimed at preventing or treating ADT-induced bone loss. Future studies should address the long-term impact of antiresorptive therapy on actual fracture rate and the impact on quality of life and healthcare costs.     

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.     

Preventive effect of risedronate on bone loss in men receiving androgen-deprivation therapy for prostate cancer

AIM: Androgen-deprivation therapy for prostate cancer decreases bone mineral density and increases the risk of fracture. The effect of risedronate, a potent third-generation oral bisphosphonate, on bone loss during androgen deprivation therapy was investigated. METHODS: Sixty-one prostate cancer patients with a mean age (+/- SD) of 79 +/- 6 years who had received androgen deprivation therapy for 42 +/- 29 months were enrolled, and were treated with 2.5 mg of risedronate daily for six months. Bone mineral density was measured at the femoral neck, lumbar spine, and ultradistal radius by dual energy X-ray absorptiometry. The percent change of bone mineral density after treatment with risedronate was calculated as the primary efficacy variable. Urinary N-telopeptide of type I collagen was measured as a bone resorption marker. RESULTS: Bone mineral density remained stable in the femoral neck and radius during risedronate therapy. In contrast, the bone mineral density of the lumbar spine showed a significant increase from 1069 +/- 488 mg/cm(2)-1112 +/- 497 mg/cm(2) (P < 0.001), representing a gain of 4.9 +/- 8.9%. Urinary N-telopeptide of type I collagen decreased significantly (P < 0.001) after three months of risedronate treatment. CONCLUSIONS: Risedronate could prevent and reverse bone loss in men receiving androgen deprivation therapy for prostate cancer by inhibiting bone resorption.     

Immediate dual energy X-ray absorptiometry reveals a high incidence of osteoporosis in patients with advanced prostate cancer before hormonal manipulation

OBJECTIVE: To examine the incidence of osteoporosis in patients with advanced prostate cancer (using forearm densitometry) before commencing androgen deprivation therapy (ADT), as osteoporotic fractures are more frequent in patients with prostate cancer who have undergone either medical or surgical castration, because of rapid loss of bone mass. PATIENTS AND METHODS: In all, 174 patients (mean age 74.6 years, range 46-90) with advanced prostate cancer presented over 2 years. Their forearm bone densitometry values were compared with those from 106 age-matched controls (mean age 74.3 years, range 66-90). RESULTS: Of the 174 patients, 73 (42%) were osteoporotic (t score 相似文献