Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer patients are at significant risk for SREs, with up to 50% of androgen-insensitive patients experiencing an SRE at 24 months. The risk increases with the duration and type of cancer treatment. SREs decrease HRQOL, increase the cost of care, and are associated negatively with overall survival. Screening men at greatest risk (slender white men and men with hormone refractory disease or metastatic disease) with BMD measurements, and initiating empiric therapy (vitamin D3, calcium, parenteral estrogens, bisphosphates) may be warranted.
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PMID:The impact of osteoporosis in men treated for prostate cancer. 1512 10

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.
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PMID:Understanding treatments for bone loss and bone metastases in patients with prostate cancer: a practical review and guide for the clinician. 1512 12

Primary and secondary osteoporosis are prevalent in more than 2 million American men. One of the main causes of this is hypogonadism, in turn brought upon by early androgen deprivation therapy used in prostate cancer treatment. Androgen deprivation therapy produces a host of adverse effects on the skeleton, including an increase in bone turnover, a decrease in bone mineral density, and an increase in fracture risk. In addition, based on observations in preclinical models, these adverse effects on the skeletal integrity may promote the development of or progression of metastasis to bone. Loss of bone due to androgen deprivation therapy is an important clinical issue for many men with prostate cancer, but osteoporosis is not an inevitable consequence of androgen deprivation therapy. Because of interpatient variations in peak bone mass as well as differences in rates of treatment-related bone loss, not all men with prostate cancer require treatment for osteoporosis. All men on androgen deprivation therapy should receive calcium and multivitamin supplements and should be considered for bisphosphonate therapy; this is particularly so for men with either a low baseline BMD or observed high rates of bone loss during androgen deprivation therapy.
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PMID:The role of bisphosphonates in men with prostate cancer receiving androgen deprivation therapy. 1520 84

Cancer treatment-induced bone loss is an emerging problem for patients with breast and prostate cancer, who are often treated with cancer therapies earlier in the disease process. Bone loss associated with cancer therapy can also progress rapidly and may cause significant morbidity in these patients. Many patients with metastatic prostate or breast cancer develop bone metastases and subsequent skeletal-related events. Studies suggest that bisphosphonates can maintain bone health when introduced early in the continuum of cancer care. They have shown efficacy in the prevention of bone loss and the more potent i.v. bisphosphonate, zoledronic acid, has prevented bone loss in addition to increasing BMD in prostate cancer patients with cancer treatment-induced bone loss. Intravenous zoledronic acid or pamidronate can be considered the standard of care for the treatment of osteolytic bone metastases in breast cancer. Clinical trials addressing the treatment of bone metastases related to prostate cancer have shown zoledronic acid to be the only bisphosphonate to have a significant positive effect on skeletal-related events.
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PMID:New generation of bisphosphonates: broad clinical utility in breast and prostate cancer. 1520 85

Zoledronic acid (ZA) has been shown to inhibit prostate tumor growth in vitro and have beneficial effects in patients with advanced prostate cancer (CaP). The aim of this study was to determine whether ZA exhibits direct anti-tumor effects on CaP cells in vivo. To distinguish the effects of inhibition of osteolysis and direct anti-tumor activity of ZA in vivo, we compared the results of treatment with ZA and osteoprotegerin (Fc-OPG), which inhibits osteolysis, but without significant direct anti-tumor effects. In vitro Fc-OPG had no significant effects on C4-2 proliferation, whereas ZA decreased proliferation. However, both agents decreased tumor growth in bone. Moreover, both increased bone volume and prevented the overall decreases in BMD associated with growth of C4-2 cells in bone. Our study provides novel and significant observations that the in vivo effects of ZA are consistent with indirect effects mediated by osteoclasts.
Prostate Cancer Prostatic Dis 2005
PMID:Comparison of Fc-osteoprotegerin and zoledronic acid activities suggests that zoledronic acid inhibits prostate cancer in bone by indirect mechanisms. 1599 21

The majority of GU radiation oncologists in Canada attended a consensus meeting in November 2004. The topic of osteoporosis in men receiving androgen deprivation therapy (ADT) for prostate cancer was identified as a key theme. A chaired session with keynote speakers and review of the evidence took place followed by open debate. Participants were provided with background information. Osteoporosis was defined as a T-score < or = -2.5, but the importance of risk factors and clinical findings is noted. Dual DEXA is the current standard for assessment of bone density and relates well to fracture risk. The lifetime risk of fracture is 13% for men over the age of 50 years even without the influence of ADT. Lifestyle, dietary and supplementation advice are provided both to prevent and to manage osteoporosis. The role for prophylactic bisphosphonate therapy in men on ADT without osteoporosis has not been established. Follow-up DEXA scans are required to monitor density, risk and response to interventions. Fracture incidence and BMD should be considered in the trial design of studies involving prolonged ADT. Osteoporosis is a treatable condition and the oncologist should employ ADT with this knowledge. A follow-up e-mail survey was carried out regarding the consensus statement. Responses were received from 49 of the 69 attendees (71%), and overall there was an 89% agreement with the consensus statement. This is now adopted as national practice guidelines for radiation oncologists employed prolonged ADT in prostate cancer patients.
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PMID:GU radiation oncologists consensus on bone loss from androgen deprivation. 1651 50

More recently, osteoporosis in men has been recognized as an important public health problem. Bone loss begins in mid life and is associated with the decline of the sex steroids production. Although there is no equivalent of the menopause, gonadal function in men is affected in a slow progressive way leading to hypogonadism. Testosterone, the major androgen in men, exerts its effect on bone by local conversion to 5alpha-dihydrotestosterone or by aromatization to estrogens. Several studies have found that estrogen, rather than testosterone, levels are more closely correlated with BMD in elderly men. Selective estrogen receptor modulator (SERM) raloxifene binds to estrogen receptors and exhibit estrogenic effect in bone, but, contrary to estrogen, without feminizing effect. There are limited numbers of studies investigating the effects of SERMs in males. Animal studies demonstrated that SERMs inhibit bone turnover and prevent bone loss in orchidectomised adult male rats. Raloxifene has been shown to increase bone mineral density of the hip in men receiving androgen deprivation therapy for prostate cancer. Moreover, experimental data demonstrated dramatic increase in cell death in human prostate cancer cell lines after the treatment with raloxifene. All these observations suggest that SERMs may be useful for the prevention and treatment of osteoporosis not only in postmenopausal women but also in elderly men. However, our hypothesis should be tested in a proper designed clinical trial. Several important issues have to be addressed. Does the same drug dose that has been shown to be effective in postmenopausal women should be used in men, too? Does treatment with SERMs reduce the fracture risk in men and is it comparable to that observed in women? Does treatment with SERMs have any beneficial effect on cardiovascular system and prostate cancer? And finally, do men experience adverse events other than women treated with SERMs? Answering to these questions will have great impact in getting the decision of possible SERMs usage in the treatment of osteoporosis in elderly males.
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PMID:Selective estrogen receptor modulators: A possible new treatment of osteoporosis in males. 1679 Mar 22

Little is known about the magnitude, pattern, and determinants of bone loss with advancing age among men, particularly among those of African descent. We examined the rate of decline in hip BMD and identified factors associated with BMD loss among 1478 Afro-Caribbean men >or=40 yr of age. BMD was measured at baseline and after an average of 4.4 yr by DXA. The rate of decline in femoral neck BMD was 0.29 +/- 0.81%/yr in the total sample (p < 0.0001). However, a U-shaped relationship between advancing age and the rate of decline in BMD was observed. The rate of decline in BMD at the femoral neck was -0.38 +/- 0.77%/yr among men 40-44 yr of age, decelerated to -0.15 +/- 0.81%/yr among men 50-54 yr of age, and then accelerated to -0.52 +/- 0.90%/yr among those 75+ yr of age (all p < 0.003). Men who lost >or=5% of their body weight during follow-up had significantly greater BMD loss than those who remained weight stable or gained weight (p < 0.0001). The relationship between weight loss and BMD loss was more pronounced among men who were older and leaner at study entry (p < 0.03). We also observed a strong impact of advanced prostate cancer and its treatment with androgen deprivation on BMD loss. Men of African ancestry experience substantial BMD loss with advancing age that seems to be comparable to the rate of loss among white men in other studies. Additional studies are needed to better define the natural history and factors underlying bone loss with aging in men of African ancestry.
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PMID:Natural history and correlates of hip BMD loss with aging in men of African ancestry: the Tobago Bone Health Study. 1925 28

QCT provides a measure of volumetric BMD (vBMD) and distinguishes trabecular from cortical bone. Few studies have determined the factors related to vBMD in men, especially among men of African heritage. This study evaluated the relationship of anthropometric, medical, and behavioral factors and vBMD in a population-based cohort of men of African ancestry (n = 1901) >or=40 yr of age who had undergone screening for prostate cancer for the first time. Trabecular and cortical vBMD were measured at the radius and tibia by pQCT. Multiple linear regression analysis identified age, height, body weight, cigarette smoking, history of diabetes, fracture, and prostate cancer as the independent correlates of vBMD. However, associations with several variables differed between cortical and trabecular vBMD and between the radius and tibia. Longitudinal studies are needed to gain a better understanding of the mechanisms underlying these differential associations that may show new insight into the etiology of trabecular and cortical bone loss in men.
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PMID:Correlates of trabecular and cortical volumetric BMD in men of African ancestry. 1945 59

The bone loss and the fracture risk are enhanced in patients with hormonal deprivation for prostate cancer. The demineralisation can be quantified by BMD (Bone Mineral Density) and prevented by lifestyle and diet therapeutics or new therapeutic agents. These agents may have a preventive effect on metastasis occurrence, but it has to be confirmed. An intra-venous biphosphonate or a sub-cutaneous RANK-inhibitor administration prevent from bone metastasis-related events.
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PMID:[Bone prevention in prostate cancer]. 2139 31


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