Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bisphosphonates are a class of therapeutic agents originally designed to treat loss of bone density. It has been shown that the primary mechanism of action is inhibition of osteoclastic activity. Accumulating data show that these drugs are useful in diseases with propensities toward osseous metastases. In particular, they are effective in diseases in which there is clear upregulation of osteoclastic or osteolytic activity such as breast cancer and multiple myeloma. Despite the fact that osseous metastases in prostate cancer manifest as osteosclerosis rather than osteolysis, studies now show that bisphosphonates are useful in the management of this disease. In particular, they have demonstrated an impact on osteoporosis associated with hormonal therapy, bone pain from metastases, and skeleton-related events from prostatic adenocarcinoma. This review briefly summarizes the available clinical data on the utilization of bisphosphonates in the disease of prostate cancer.
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PMID:The emerging role of bisphosphonates in prostate cancer. 1470 97

Percutaneous vertebroplasty was first introduced in 1984 by Galibert et al. for the treatment of hemangiomas in the spine. The current indications for vertebroplasty also include compression fractures due to osteoporosis as well as osteolytic metastases and spinal myeloma lesions. With the numbers of percutaneous vertebroplasty performed by orthopedic and trauma surgeons, neurosurgeons, and radiologists steadily increasing, complications have also risen. Over the last 3 years an increasing number of cases with varying complications, their genesis, and their management have been reported in the literature. Complications include asymptomatic cement leakage, cardiovascular effects, embolism with lethal outcome as well as severe neurological deficits. This article presents a review of the complications reported in the literature, strategies for preventing possible complications as well as current concepts in therapy management. Several of our cases with cement leakages are presented.
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PMID:[Complications of vertebroplasty]. 1474 9

Androgen deprivation therapy (ADT) plays a central role in the management of prostate cancer. ADT is the mainstay of treatment for metastatic disease; the most common method is gonadal suppression via luteinizing hormone release hormone (LH) agonists, with or without antiandrogens. Antiandrogen monotherapy remains investigational, as is the appropriate role of 5alphareductase inhibition for prostate cancer. Intermittent ADT offers the promise of improved quality of life and reduced cost without a decrease found to date in oncologic efficacy. A growing menu of options exists for secondary androgen deprivation after disease progression on primary therapy: these include high-dose antiandrogens, estrogens, and adrenal androgen suppressants. ADT is being used with increasing frequency as primary monotherapy in patients with localized disease, but only small, nonrandomized studies of highly selected patients have been reported to date. Neoadjuvant ADT (NADT) has been demonstrated in prospective, multi-institutional trials to improve outcomes for patients with high-risk or locally advanced disease undergoing external-beam radiotherapy. Trials for patients with lower-risk, localized disease are still ongoing. Neoadjuvant therapy does not improve outcomes for patients with localized disease opting for radical prostatectomy (RP) and has not been well studied in association with brachytherapy. The side effects of ADT can be managed increasingly successfully; in particular, the introduction of zoledronate may reduce the impact of ADT-associated osteoporosis. Finally, contemporary practice pattern data suggest that use of ADT is increasing across patient risk groups, both in contexts where such therapy is well supported by current evidence and in others where it is not.
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PMID:The evolving role of androgen deprivation therapy in the management of prostate cancer. 1476 15

The skeleton is the most frequent site of metastatic disease in breast cancer and also the site of greatest morbidity. In addition, there is now recognition that accelerated bone loss associated with chemotherapy or hormonal therapy leads to an increased risk of osteoporosis in long-term breast cancer survivors. An improved range of treatment options is available and assessment of skeletal response both to the disease and to therapy is therefore of growing importance. Plain radiographs remain widely used to assess response, but are of limited sensitivity. The isotope bone scan is more sensitive, but lacks specificity. Computerised tomography, magnetic resonance imaging and positron emission tomography all have an increasing role. In treatment-induced osteoporosis, bone mineral density is now readily measured by DEXA scanning. Tumour markers such as CEA, CA 15-3, CA 549 and TPA may have a role in assessing response, but probably in combination rather than individually, using an appropriate quantitative model. Several trials have shown that bone markers, especially markers of bone resorption such as Ntx, Ctx, PYD and DPD, appear to have strong potential as rapid, convenient and inexpensive measures of response. There is also evidence that they may be used as predictive or prognostic indicators. Evidence is accumulating that the reduction of bone resorption markers into the normal range results in substantially reduced morbidity in metastatic breast cancer and that this should be a major target of therapy.
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PMID:Assessment of the effects of breast cancer on bone and the response to therapy. 1496 99

Percutaneous vertebroplasty is a minimally invasive procedure used to stabilise vertebral compression fractures caused by osteoporosis, haemangioma, myeloma, metastases and bone cysts. Acrylic bone cement is injected into the vertebral body to relieve pain and structurally reinforce the fracture. Interest in percutaneous vertebroplasty has grown as a result of technical procedural advances in radiology and the publication of an appraisal of, and guidelines for, the procedure by the National Institute for Clinical Excellence (2003). Nurses should be aware of the potential benefits of vertebroplasty and be involved in patient selection, and care of the patient before, during and after the procedure. Nurses should also be involved in audit analysis of the results of the procedure. More research into the effects of vertebroplasty is required and should involve nurses caring for this patient group.
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PMID:Percutaneous vertebroplasty. 1511 72

Post-fracture osteolysis of the pubic bone is rare. We report a case of a 70-year-old woman with osteoporosis and a history of radiation therapy 2 years earlier. At presentation, she was found to have a bilateral sacral fracture and fractures of both pubic rami on one side. The pain persisted, and follow-up radiographs showed osteolysis of the pubic rami suggestive of metastatic disease. The development of a bony callus within 8 months established the diagnosis of benign osteolysis. About 50 cases of osteolysis at fracture sites have been reported to date, of which about a dozen occurred after radiation therapy. All the patients were elderly women with post-menopausal osteoporosis. Radiation therapy probably further increases the risk in this setting. The possibility of osteolysis at fracture sites in patients with osteoporosis should be borne in mind to avoid unnecessary and burdensome investigations that are costly and cause undue anxiety to the patients. Rest is the only effective treatment.
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PMID:Post-fracture osteolysis of the pubic bone simulating a malignancy: report of a case. 1518 96

We report a 64-year-old woman who underwent mastectomy for stage II (T2N1M0) advanced breast cancer, in whom multiple spine metastases developed 18 months postoperatively. She received 6 cycles of CA (cyclophosphamide 500 mg/m2, ADM 50 mg/m2 3 wq) therapy and oral tamoxifen (20 mg/body) administration for adjuvant therapy. The multiple bone metastases of the spine were revealed by technetium bone scan. The level of serum tumor marker CA15-3 increased two times over the normal range 18 months after surgery. She also developed osteoporosis a few years later, so we selected high-dose toremifene administration (120 mg/body) as a second-line therapy. No adverse effects have occurred and bone metastases disappeared. Moreover, the tumor marker was also normalized 6 months after toremifene therapy started. It was shown that high-dose treatment of toremifene was useful for recurrent breast cancer with bone metastasis.
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PMID:[A case of breast cancer with multiple bone metastases demonstrating complete remission with high-dose toremifene therapy]. 1522 11

Bone architecture and mineralization are generally considered to be important components of bone quality, and determine bone strength in conjunction with bone mineral density. Although the features of bone quality have recently been studied under conditions in which bone density decreases, such as osteoporosis, little is known in osteosclerotic diseases. In this study, we compared the trabecular bone microarchitecture and degree of mineralization between osteoblastic bone metastasis and degenerative osteosclerosis using synchrotron radiation microcomputed tomography (SR-microCT). Small cubes of lumbar vertebrae were excised postmortem from the sites of osteoblastic metastasis, degenerative osteosclerosis, and comparative sites of normal subjects without skeletal lesions. The samples were imaged at high spatial resolution (voxel size = 6 microm) using the SR-microCT system developed at the synchrotron facility (SPring-8), Hyogo, Japan. The three-dimensional (3D) image data were then analyzed for the morphological parameters and the degree of mineralization of bone (DMB). Trabecular bone in metastatic lesions showed a highly connected and isotropic network pattern compared with the normal samples. Although the trabecular surface was markedly irregular in osteoblastic metastases, no significant difference was found in the mean trabecular thickness (Tb.Th) between osteoblastic metastases and normal tissue. The DMB of trabeculae in metastatic lesions had a broader range and lower mean than that of the normal tissue. In contrast, trabecular bone in degenerative osteosclerotic lesions showed a similar degree of anisotropy (DA) and connectivity to the normal tissue, whereas the trabecular thickness was greater in the degenerative osteosclerotic lesions. No significant difference in DBM between degenerative osteosclerosis and normal tissue was detected. These results characterize the difference in bone quality between osteoblastic bone metastasis and degenerative osteosclerosis. Further study on the relationship between bone quality and bone strength in these osteosclerotic lesions would improve our understanding of the pathogenesis of bone fragility.
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PMID:Analysis of three-dimensional microarchitecture and degree of mineralization in bone metastases from prostate cancer using synchrotron microcomputed tomography. 1526 94

Bone resorption by osteoclasts is coupled with bone formation by osteoblasts, and this balanced process continuously remodels and adapts the skeleton. The receptor activator of nuclear factor kappaB ligand (RANKL) has been identified as an essential cytokine for the formation and activation of osteoclasts. The effects of RANKL are physiologically counterbalanced by the decoy receptor osteoprotegerin (OPG). Estrogen deficiency, glucocorticoid exposure, T-cell activation (eg, rheumatoid arthritis), and skeletal malignancies (eg, myeloma, metastases) enhance the ratio of RANKL to OPG and, thus, promote osteoclastogenesis, accelerate bone resorption, and induce bone loss. Moreover, alterations of the OPG/RANKL/RANK system have been implicated in vascular diseases. RANKL blockade (using OPG or RANK fusion proteins or RANKL antibodies) has prevented bone loss caused by osteoporosis, chronic inflammatory disorders, and malignant tumors in animal models and may emerge as a therapy in humans based on studies in postmenopausal osteoporosis, myeloma bone disease, and osteolytic metastases. This review summarizes the clinical implications of the OPG/RANKL/RANK system for bone and vascular diseases.
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PMID:Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. 1528 Mar 47

At the present time, tamoxifen is the most widely used anti-estrogen for adjuvant therapy and metastatic disease in postmenopausal women with breast cancer, a population at high risk for osteoporosis. This prospective study was designed to evaluate the effect of adjuvant tamoxifen on bone mineral density and all biochemical markers concomitantly in women with early-stage breast cancer in one study. Using dual-energy X-ray absorptiometry, prior to and 12 mo after tamoxifen treatment, bone mineral density in lumbar spine and femoral neck was measured in 44 women with T1-T2N0M0 estrogen-receptor-positive breast cancer receiving adjuvant treatment with tamoxifen 20 mg/d. Biomarkers that can affect bone mineral metabolism were measured before and after 3 and 12 mo of tamoxifen treatment. Bone mineral density was minimally increased in lumbar spine and femoral neck after 12 mo treatment with tamoxifen (p = 0.79 and 0.55, respectively). No differences were found in serum levels of calcium, phosphate, creatinine, ALAT, albumin, LDH, calcitonin, or estradiol. A significant decrease in osteocalcin levels was found after 3 and 12 mo (p < or = 0.01). TSH and PTH levels were increased (p < or = 0.05) after 3 mo, returning to baseline after 12 mo. In conclusion, tamoxifen has an estrogen-like effect on bone metabolism in postmenopausal women and is associated with preservation of bone mineral density in lumbar spine and femoral neck. Changes in serum concentration of biochemical markers may reflect decreased bone turnover or bone remodeling and add to the understanding of tamoxifen's effect on bone mineral density.
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PMID:Effects of tamoxifen on bone mineral density and metabolism in postmenopausal women with early-stage breast cancer. 1529 83


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