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)

Twenty five hormone manipulated patients with prostate cancer and metastatic bone disease, treated at least 6/12 previously by hormone manipulation, were given intravenous infusions of Disodium Pamidronate (APD) over a 6 month period. Patients received 30 mg weekly for 4 weeks then twice monthly for 5 months. No other treatment was administered during study. Eleven of 17 patients with pain at the start of the study were pain free at the end. Fasting morning calcium excretion and serum osteocalcin fell significantly with Pamidronate (P less than 0.0001) and urine hydroxyproline was lowered in 13/20 evaluable patients at 6 months. Alkaline phosphatase fell in a proportion of patients and five of 17 patients with previously progressive bone scans stabilised (4) or regressed (1) on treatment. Rising acid phosphatase levels were also lowered in five patients. It is concluded that Pamidronate may be effective in palliating bone pain in some patients and has a stabilising influence on abnormally high bone turnover in metastatic prostate cancer. Further controlled studies of the compound are now warranted.
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PMID:Osteoclast inhibition by pamidronate in metastatic prostate cancer: a preliminary study. 200 84

The skeletal metabolic effects of androgen withdrawal have been studied in men with metastatic prostate cancer by using a combination of sequential biochemical measurement, quantitative and subjective bone histology and selective osteoclast inhibition with the bisphosphonate Pamidronate. Results showed dissociation in the levels of biochemical markers of bone formation (alkaline phosphatase and osteocalcin) following castration, whilst markers of bone breakdown (urinary hydroxyproline creatinine (OHP) and calcium excretion (CaE)) increased in the majority of patients. The osteolytic response was inhibited by the bisphosphonate Pamidronate (Aminohydroxypropylidene Bisphosphonate (APD)), thus confirming its osteoclastic origin. Histomorphometry of tumour free bone showed an acute drop in bone volume following surgery (p < 0.05). This effect was blocked by Pamidronate suggesting that osteoclastic activity surges immediately following castration, contributing to the acute bone loss. Histology of metastatic areas showed a marked diminution in bone volume due to decreased osteoblast activity and markedly increased osteoclast mediated osteolysis. In 56% of biopsies there were residual foci of active tumour within metastatic areas after orchidectomy. These disturbed metabolic bone activity in a typically localised manner.
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PMID:The effects of orchidectomy on skeletal metabolism in metastatic prostate cancer. 815 20

Osteoporosis is an important complication of androgen deprivation therapy (ADT). ADT by either orchiectomy or treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases fracture risk. Other factors, including diet and lifestyle, may contribute to bone loss in men with prostate cancer. Routine osteoporosis screening in men with prostate cancer is appropriate based on the high prevalence of osteoporosis. There is limited information about the best strategy to treat or prevent bone loss during ADT. Lifestyle modification, including smoking cessation, moderate alcohol consumption, and regular weight-bearing exercise should be encouraged. Supplemental calcium and vitamin D are also recommended. Additional treatment is warranted for men with osteoporosis, fractures, or high rates of bone loss during ADT. Pamidronate, an intravenous bisphosphonate, prevents bone loss during ADT. Other bisphosphonates are probably effective, although they have not been evaluated in this clinical setting. Alternative forms of hormonal therapy, including bicalutamide monotherapy, may cause less bone loss than ADT.
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PMID:Osteoporosis during androgen deprivation therapy for prostate cancer. 1223 Oct 56

Osteoporosis and other body composition changes are important complications of androgen deprivation therapy (ADT) for prostate cancer. Bilateral orchiectomy and gonadotropin-releasing hormone agonist treatment decrease bone mineral density and increase fracture risk. Other factors including diet and lifestyle may contribute tobone loss in men with prostate cancer. Estrogens play an important role in male bone metabolism. Androgen deprivation therapy with estrogens probably causes less bone loss than bilateral orchiectomy or gonadotropin-releasing hormone agonist treatment. Bicalutamide monotherapy increases serum estrogen levels and may also spare bone. Lifestyle modification including smoking cessation, moderation of alcohol use, and regular weight bearing exercise are recommended to decrease treatment-related bone loss. Supplemental calcium and vitamin D are also recommended. Pamidronate (Aredia), an intravenous bisphosphonate, prevents bone loss during ADT. Other bisphosphonates are probably effective but have not been studied in hypogonadal men. Androgen deprivation therapy increases fat mass and decreases muscle mass. These body composition changes may contribute to treatment-related decreases in physical capacity and quality of life.
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PMID:Osteoporosis and other adverse body composition changes during androgen deprivation therapy for prostate cancer. 1246 55

Osteoporosis is an important complication of androgen deprivation therapy for prostate cancer. Androgen deprivation therapy either by bilateral orchiectomies or treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density (BMD) and increases the risk of fracture. Dietary factors and lifestyle may contribute to bone loss. There are limited prospective data about treatment or prevention of osteoporosis in men with prostate cancer and many recommendations are based on studies of postmenopausal osteoporosis. Lifestyle modification including smoking cessation, moderation of alcohol consumption, and regular weight bearing exercise should be encouraged. Supplemental calcium and vitamin D are recommended. Additional treatment may be warranted for men with osteoporosis, fractures, or high rates of bone loss during androgen deprivation therapy. Recent studies have evaluated the efficacy of bisphosphonates to prevent bone loss during androgen deprivation therapy. Pamidronate (pamidronic acid), a second-generation bisphosphonate, prevents bone loss in the hip and spine during androgen deprivation therapy. Zoledronic acid, a more potent third-generation bisphosphonate, not only prevents bone loss but also increases BMD in the hip and spine. Alendronate (alendronic acid) is approved for the treatment of osteoporosis in men although its efficacy and that of other oral bisphosphonates has not been evaluated in men receiving androgen deprivation therapy. Additional prospective studies are needed to evaluate the long-term effects of bisphosphonates on fracture risk and disease-related outcomes.
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PMID:Bisphosphonates to prevent osteoporosis in men receiving androgen deprivation therapy for prostate cancer. 1257 98

Osteoporosis is an important and preventable adverse effect of androgen deprivation therapy for prostate cancer. Androgen deprivation therapy by either bilateral orchiectomies or administration of a gonadotropin-releasing hormone agonist decreases bone mineral density and increases fracture risk. Treatment-related osteoporosis can be prevented by intermittent administration of either intravenous pamidronate or zoledronic acid. Pamidronate (60 mg intravenously every 3 months) prevents bone loss during androgen deprivation therapy. Zoledronic acid (4 mg intravenously every 3 months) not only prevents bone loss but also increases bone mineral density. Alendronate and other oral bisphosphonates may be effective but have not been evaluated in men with castrate testosterone levels. Oestrogen replacement therapy and treatment with selective ooestrogen receptor modulators may prevent bone loss during androgen deprivation therapy. Bicalutamide (150 mg daily) monotherapy increases serum ooestrogen levels and maintains bone mineral density.
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PMID:Management of treatment-related osteoporosis in men with prostate cancer. 1278 15

Bisphosphonates offer a significant improvement in the quality of life for cancer patients; these potent inhibitors of bone resorption have been shown to markedly reduce the morbidity frequently resulting from bone metastases. Despite the success of bisphosphonates as therapeutic agents, however, toxicity in the form of osteonecrosis of the jaw (ONJ) is a rare complication whose incidence rate has climbed in recent years. ONJ is defined as an unexpected development of necrotic bone in the oral cavity, and is commonly associated with administration of the bisphosphonates Pamidronate and Zoledronate. Clinical features include local pain, soft-tissue swelling, and/or loose teeth; ONJ is also often correlated with previous dental procedures, such as tooth extractions, during biphosphonate therapy. Although additional risk factors-such as corticosteroids, chemotherapy, radiotherapy, trauma or infection-exhibit etiological associations with ONJ, the real pathobiology has not yet been fully elucidated. Here we report our findings on all 2005 OJN cases presented at our institution resulting from bone metastatic prostate cancer treated with zoledronic acid. The incidence of ONJ is nearly 3% (3 out of 104) in these patients.
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PMID:Osteonecrosis of the jaw as an adverse bisphosphonate event: three cases of bone metastatic prostate cancer patients treated with zoledronic acid. 1776 97

Many solid tumors metastasize to bone, leading to debilitating skeletal complications such as intractable bone pain and pathologic fractures. Patients who experience a skeletal-related event (SRE) are at higher risk for subsequent events. After an SRE such as a pathologic fracture, spinal cord compression, or the requirement for orthopedic surgery or palliative radiation therapy, a patient's quality of life and functional independence could decline substantially. Prevention or delay of skeletal complications provides clinical benefit to patients with bone metastases secondary to solid tumors. Treatment for the prevention of the first SRE might substantially improve patients' quality of life, functional independence, and pain throughout the course of their disease. Bisphosphonates have shown a palliative benefit in this setting. In particular, zoledronic acid is the only bisphosphonate that has provided benefits for patients with bone metastases secondary to a broad range of solid tumors. Among patients with metastatic breast or prostate cancer, zoledronic acid has demonstrated significant reductions in pain and skeletal morbidity compared with placebo. Zoledronic acid has also shown significant reductions in skeletal morbidity in patients with lung cancer or other solid tumors compared with placebo. Pamidronate, oral clodronate, and ibandronate compared with placebo have each shown significant benefits in reductions of pain and skeletal complications for patients with metastatic breast cancer. Further improvements in the management of skeletal health in patients with malignant bone disease could be achieved through ongoing bisphosphonate investigations to optimize dose, timing, and duration of treatment.
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PMID:Treatment of bone metastases and bone pain with bisphosphonates. 1863 73