Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151825 (bone pain)
 3,118 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastasis to bone marrow, though frequently occult, is an important clinical finding. Variables which correlate with carcinoma metastatic to bone marrow were studied retrospectively in 103 patients with malignancy whose bone marrow biopsies demonstrated metastatic disease. Sixty-six patients with metastatic cancer whose bone marrow biopsies were negative, served as controls. Since no single finding was diagnostic of marrow cancer, multiple variables were analyzed by stepwise discriminate analysis program. The four parameters which strongly correlated with marrow involvement were the leukoerythroblastic blood pattern, a serum lactic dehydrogenase over 500 IU/liter, a platelet count under 100,000/microliter and bone pain. Four parameters correlated less well and included a positive bone scan, hematocrit under 30%, uric acid over 10 mg/dl and blood urea nitrogen over 25 mg/dl. These data should help the clinician select those cancer patients with a high probability of marrow involvement.
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PMID:Variables predictive of bone marrow metastasis. 71 14

Twenty-two cases of multiple myeloma were seen in the Department of Internal Medicine, Tikur Anbessa (Black Lion) Hospital, a teaching and referral hospital in Addis Abeba, Ethiopia, from January 1983 to December 1990. The age range was 38 to 76 (mean +/- SD = 51.5 +/- 12.2) years; a third were in the fifth decade. The male:female ratio was 1.75:1. The common clinical findings were bone pain in 20 (91%), bone tenderness in 15 (68%), anaemia in 14 (64%) and spinal cord compression in 8 (36%). The erythrocyte sedimentation rate (ESR) was raised in 21. Serum protein was raised in 17 (77%) and hyperglobulinaemia was seen in 20 (91%). Serum uric acid, blood urea nitrogen (BUN) and calcium were elevated in 10, 8 and 5 patients respectively, Bence-Jones proteinuria and albuminuria were each found in 9 patients. All patients had radiological abnormalities; 9 had a combination of lytic lesions, osteoporosis and pathological fractures (41%). Ten patients presented in clinical stage III. Four patients are being followed after 3-84 (median 40.5) months; eight were lost to follow-up 1-8 (median 2.0) months after diagnosis. Ten patients have died after 1-55 (median 11) months. Multiple myeloma is not uncommon in Ethiopians. Except for a lower age at presentation, the clinical, haematological, biochemical, and radiological findings, and the response to therapy, are similar to those reported elsewhere.
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PMID:Multiple myeloma in Ethiopians: analysis of 22 cases. 139 16

Since 1972, 25 cases of multiple myeloma had been diagnosed. Of them, 22 (88%) were over 50 years old. Most of them had bone pain with anemia to different degrees. Marked elevation of ESR was found in 19 cases. Bence-Jones protein was detected in the urine in 15 cases resulting in elevation of blood urea nitrogen and creatinine. Twenty-two of 23 cases were found to have a high peak of abnormal globulin. Increased plasma cells with abnormal features in the bone marrow were observed in 17/21 cases. Multiple osteolytic lesions, compression fracture and osteoporosis on X-ray films were shown in the majority. Of these 25 cases, 10 had advanced myeloma. These 10 patients all died during admission and eight without any chemotherapy. In the other 15 cases treated with chemotherapy, marked response was seen in 1, partial response in 8 and no response in 6. The diagnosis of the disease is discussed in detail.
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PMID:[Clinical analysis of 25 cases of multiple myeloma]. 188 42

Bisphosphonates have been shown to increase bone mineral density in patients with established osteoporosis as well as those with osteopenia. The evidence conclusively shows a reduction in fracture rates in patients on the more potent nitrogen containing bisphosphonates. Indeed, significant vertebral fracture rate reduction has been demonstrated after only 1 year of therapy. Alendronate, a second-generation bisphosphonate, and risedronate, a third-generation bisphosphonate, are first line medications for the treatment of osteoporosis given their efficacy in preventing both vertebral and non-vertebral fractures. There is evidence that vertebral fractures may be prevented by intermittent cyclic therapy with etidronate. All three have been shown to increase bone mineral density in the spine, with alendronate and risedronate producing significant increases in hip bone density. Calcitonin has demonstrated the ability to reduce vertebral fracture rates with minimal changes in bone density. Calcitonin is also beneficial in reducing the bone pain associated with fractures.
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PMID:Role of bisphosphonates and calcitonin in the prevention and treatment of osteoporosis. 1148 41

Spinal cord compression (SCC) is a devastating complication of metastatic cancer. We investigated the potential beneficial effect of two palliative therapies--strontium-89 (Metastron) and the nitrogen-containing bisphosphonate olpadronate--on the incidence of SCC in hormone-refractory prostate cancer (HRPC) metastatic to the skeleton. We retrospectively studied 415 patients with histologically proven prostate cancer who underwent bone scintigraphy at the time of diagnosis and were followed up at the Leiden University Medical Center between 1990 and 1999. Medical or surgical castration was undertaken in 172 patients with evidence for skeletal metastases. Within 2 years, 147 of these patients (85%) developed HRPC associated with severe progressive bone pain. Palliative treatment was given to 131 patients in the form of local radiotherapy ( n=10), 89Sr ( n=46) or intravenous olpadronate ( n=66), with ( n=57) or without ( n=9) maintenance oral olpadronate. Nine patients received both 89Sr and olpadronate at various intervals. Sixteen patients who did not receive any of these treatments were used as historical controls. There was no significant difference in baseline characteristics between treatment modalities. The incidence of SCC was 17% in the whole group, and highest in controls receiving no palliation (50%). None of the patients treated with local radiotherapy, only 4% of patients receiving 89Sr and 21% of patients given olpadronate developed this complication. Our findings suggest a significant reduction in SCC in patients with symptomatic HRPC metastatic to the skeleton who receive palliative therapies. Local radiotherapy completely prevents the incidence of SCC, 89Sr leads to an important decrease in this complication and olpadronate induces a significant, albeit smaller decrease in the incidence of SCC. The use of these agents opens new avenues in the difficult management of patients with advanced prostate cancer who are most at risk of developing SCC.
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PMID:Strontium-89 (Metastron) and the bisphosphonate olpadronate reduce the incidence of spinal cord compression in patients with hormone-refractory prostate cancer metastatic to the skeleton. 1191 87

The skeleton is the most common site of metastatic disease in breast cancer and the most common site of first distant relapse. Bone metastases in breast cancer are the source of considerable morbidity, including severe pain, pathological fractures, need for radiotherapy or surgery, and hypercalcemia. Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption, and it is well known that breast cancer cells in bone can stimulate osteoclast formation and activity leading to the release of growth factors and cytokines, which will further stimulate cancer cell growth and their secretion of osteolytic factors. We are thus typically dealing with a vicious cycle, as the bone resorption-induced release of growth factors from the bone matrix will stimulate breast cancer cell growth (probably mainly by IGFs) and the production of the osteolytic factor PTHrP (probably mainly by TGF-beta but also by extracellular calcium). Clodronate, but not the aminobisphosphonates, can be metabolized to an ATP analog that is toxic for osteoclasts. Nitrogen-containing bisphosphonates, such as pamidronate, ibandronate, and zoledronate, interfere with the mevalonate pathway that is crucial to maintain cell membrane integrity. The net result, regardless of the mechanism, is osteoclast apoptosis, notably through the induction of caspase-3. Bisphosphonates are now the standard treatment for cancer hypercalcemia. Repeated bisphosphonate infusions also exert clinically relevant analgesic effects in at least one half of the patients with metastatic bone pain. Most importantly, prolonged administration of bisphosphonates (for at least 1 year) reduces the frequency of morbid skeletal events by 30-40% in breast cancer metastatic to bone and in up to 50% in patients with multiple myeloma. Newer bisphosphonates, such as ibandronate and zoledronate, will simplify the current therapeutic schemes and improve the cost-effectiveness ratio, and they have the potential to improve the therapeutic efficacy, at least in patients with aggressive osteolytic disease or in the adjuvant setting.
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PMID:Bisphosphonates in the treatment of metastatic breast cancer. 1201 36

Bone recurrence constitutes one third of initial sites of relapse and one half of distant sites of relapse at 10 years from diagnosis of breast cancer. Bone pain, fracture (including vertebral fracture resulting from increased bone resorption following chemotherapy-induced menopause), and hypercalcemia are components of skeletal morbidity. The pathophysiology of malignant osteopathy occurs because of the secretion of substances (such as parathyroid hormone-related peptide), by the malignant cell, which stimulate osteoclast function; this in turn feeds further growth, which causes a vicious cycle. Interruption of this cycle by bisphosphonates may inhibit the growth of malignant cells. Bisphosphonates are drugs that inhibit bone turnover by decreasing bone resorption. Side effects of bisphosphonates include upper gastrointestinal symptoms (in oral nitrogen-containing bisphosphonates) and diarrhea (in oral non-nitrogen-containing bisphosphonates) and an acute phase-like reaction with intravenous (I.V.) pamidronate. Bisphosphonates have different molecular mechanisms of action: Nitrogen-containing bisphosphonates (eg, pamidronate and alendronate) inhibit the mevalonate-signaling pathway while the non-nitrogen-containing drugs (eg, clodronate) incorporate into adenosine triphosphate analogues. There is in vitro evidence that these drugs also possess anticancer properties. In hypercalcemia patients, treatment with pamidronate and zoledronate produce prompt and efficient normocalcemia. Intravenous pamidronate and zoledronate, oral clodronate, and ibandronate reduce skeletal complications in patients with bone metastases; I.V. pamidronate and clodronate are useful for bone pain relief. Three adjuvant bisphosphonate trials are discussed herein: 2 small open-label studies giving conflicting results and a large placebo-controlled trial of oral clodronate. This latter trial shows a reduction in the incidence of skeletal metastases (while the patients are on therapy) and an improved survival at 5 years.
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PMID:Bisphosphonates: biological response modifiers in breast cancer. 1219 79

Bone metastases are a common feature of a variety of solid tumors and are associated with substantial skeletal morbidity, including severe bone pain and pathologic fractures. Treatment with bisphosphonates, primarily pamidronate, is the current standard of care for patients with breast cancer and multiple myeloma who have predominantly osteolytic lesions. However, until recently no bisphosphonate had demonstrated efficacy in patients with osteoblastic lesions, which are common during the progression of prostate cancer and other solid tumors. Zoledronic acid, a potent, new-generation, nitrogen-containing bisphosphonate, has demonstrated significant benefits for patients with bone metastases resulting from a broad range of primary tumors, including multiple myeloma and breast, lung, kidney, and prostate cancers, and other solid tumors. Benefits include a decreased incidence of pathologic fractures and longer time to the first skeletal complication. Zoledronic acid is the first and only bisphosphonate to be proved effective in patients with all types of bone lesions, from osteolytic to osteoblastic, and therefore represents an important therapeutic advancement in the treatment of bone metastases.
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PMID:Broad clinical activity of zoledronic acid in osteolytic to osteoblastic bone lesions in patients with a broad range of solid tumors. 1256 47

Advanced solid tumors are often aggressive and recurrent, and overall survival remains relatively poor despite contemporary therapeutic interventions. Bone metastases are common in these patients, and skeletal-related events, including bone pain, pathologic fractures, and potentially life-threatening hypercalcemia of malignancy, undermine the quality of patient survival. Bisphosphonates are widely used in the treatment of bone metastases associated with breast cancer and multiple myeloma, but have not been extensively investigated in the treatment of patients with solid tumors other than breast or prostate cancer. However, a new-generation nitrogen-containing bisphosphonate, zoledronic acid, has shown significant clinical benefits in indications in which other bisphosphonates have failed. In a phase III clinical trial in patients with bone metastases from solid tumors other than breast or prostate cancer, treatment with zoledronic acid (4 mg via 15-minute infusion) was well tolerated and significantly decreased the incidence of skeletal-related events and increased the time to first skeletal-related event compared with placebo-treated patients. This was the first demonstration of palliative efficacy for bisphosphonate therapy in patients with bone metastases from a wide variety of solid tumors.
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PMID:Efficacy and safety of zoledronic acid in the treatment of bone metastases associated with lung cancer and other solid tumors. 1258 92

Intravenous bisphosphonates are the preferred treatment to prevent skeletal complications for patients with breast cancer and bone metastases. Pamidronate, a single-nitrogen bisphosphonate, was the early standard of care for such patients based on 2 large, placebo-controlled trials involving 754 patients. Zoledronic acid, a new-generation bisphosphonate containing 2 nitrogens, was evaluated in 1130 patients with breast cancer in a large, randomized, comparative, phase III trial with pamidronate. At 25 months, zoledronic acid (4 mg) significantly reduced the overall risk of developing a skeletal-related event (SRE) by an additional 20% versus 90 mg pamidronate by multiple-event analysis. Furthermore, zoledronic acid was at least as effective as pamidronate in reducing the proportion of patients with > or = 1 SRE and in delaying the onset of SREs. Moreover, a retrospective subset analysis of 352 patients with > or = 1 osteolytic lesion proved zoledronic acid more effective than pamidronate in reducing the risk and delaying the onset of SREs. Intravenous ibandronate (6 mg via 1-2-hour infusion) was evaluated in a placebo-controlled, phase III trial of 466 patients and was significantly more effective than placebo in reducing the number of 12-week treatment periods in which an SRE occurred. The safety profiles among all intravenous bisphosphonates were similar; patients treated with intravenous bisphosphonates reported notably less bone pain but a higher incidence of mild to moderate transient infusion-related adverse events (eg, nausea, vomiting, myalgia, and anorexia) compared with placebo. In summary, intravenous bisphosphonates are effective for the treatment of bone metastases in patients with breast cancer and have similar safety profiles, but the shorter infusion time and greater efficacy of zoledronic acid in reducing overall skeletal morbidity provide advantages over other available agents.
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PMID:Efficacy and safety of intravenous bisphosphonates for patients with breast cancer metastatic to bone: a review of randomized, double-blind, phase III trials. 1600 90


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