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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The skeleton is a common site of breast carcinoma metastasis; 75% of patients with breast carcinoma demonstrate bone metastases at autopsy. The lytic destruction of bone in these patients is due to excessive osteoclastic activity. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Initial studies of breast carcinoma patients were performed with clodronate, a first-generation bisphosphonate. Studies with small cohorts suggested reduction of pain, analgesic requirement, and development of hypercalcemia. A larger randomized, double-blind, placebo-controlled trial of oral clodronate 1600 mg/day demonstrated a significant reduction of the combined rate of all morbid skeletal events (significant reduction of the incidence of vertebral fractures, rate of vertebral deformity, and hypercalcemic episodes). Trends were observed that favored clodronate for the treatment of nonvertebral fractures and radiotherapy for relief of bone pain. There was no survival difference between the clodronate and placebo groups (Paterson et al., J Clin Oncol 1993;11:59-65). Pamidronate is a second-generation aminobisphosphonate that is a much more potent inhibitor of osteoclastic activity. Phase II studies again suggested an improvement in many of the skeletal complications of breast carcinoma. Two large Phase III studies have recently been completed. Women with Stage IV breast carcinoma who were receiving cytotoxic chemotherapy (380 patients) or endocrine therapy (371 patients) and had at least 1 lytic bone lesion were given either pamidronate 90 mg as a 2-hour infusion monthly for 2 years or a placebo infusion. After the two studies were pooled, 367 patients treated with pamidronate and 384 patients given placebo were available for analysis. The median time to first complication (pathologic fracture, vertebral collapse, spinal cord compression, or treatment of bone with radiation or surgery) was 12.7 months for the pamidronate patients and 7.0 months for placebo patients (P = 0.001). The time to first fracture was 25.2 months for pamidronate patients and 12.8 months for placebo patients (P = 0.003). The proportion of patients with fracture was 40% for pamidronate vs. 52% for placebo (P = 0.002); the proportion with radiation administered to bone was 29% for pamidronate vs. 43% for placebo (P = 0.001); and the proportion with any skeletal event was 51% for pamidronate vs. 64% for placebo (P = 0.001). The skeletal morbidity rate (the number of complications per year) at 24 months was 2.4 for the pamidronate group and 3.7 for placebo (P = 0.001). Pain and analgesic use was decreased among the pamidronate patients. There was no difference in survival between the groups. Not all patients responded to the same dose of bisphosphonate. Recent data suggests that patients who have a normalization of their urinary excretion of N-telopeptide have a reduced risk of progression of disease in bone and fracture. In summary, the addition of pamidronate to standard chemotherapy or endocrine therapy produces a sustained reduction in skeletal complications in breast carcinoma patients with osteolytic bone metastases.
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PMID:Bisphosphonates and breast carcinoma. 936 34

Eighty-six patients with heavily pretreated progressive bone metastases (52 with breast carcinoma, 17 with prostate carcinoma, and 17 others) were included in 2 studies designed to assess the clinical and biochemical effects of a single 120 mg, 2-hour infusion of pamidronate. No other systemic anticancer treatment or radiotherapy were administered. Pamidronate had a significant beneficial effect, with a reduction in a symptom score measuring pain, World Health Organization performance status, and analgesic consumption and improvement in quality of life when compared with a placebo infusion. Symptomatic improvement corresponded with changes in the rate of bone resorption as indicated by the concentrations of pyridinoline crosslinks in the urine. In patients with the highest rates of bone resorption (N-terminal peptide-bound portion of the collagen crosslink or crosslaps excretion > or = twice that of normal) clinical response or normalization of the rate of bone resorption were rarely observed, with all clinical responses occuring in those patients with bone resorption rates of < twice that of normal. Intriguingly, symptomatic response also correlated with a modest (> 10%) fall in tumor marker levels, suggesting a possible effect of bisphosphonates on tumor activity.
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PMID:High dose pamidronate: clinical and biochemical effects in metastatic bone disease. 936 37

Pamidronate (APD) is a potent inhibitor of bone resorption that is useful in the management of patients with osteolytic bone metastases from breast cancer or multiple myeloma, tumour-induced hypercalcaemia or Paget's disease of bone. After intravenous administration, the drug is extensively taken up in bone, where it binds with hydroxyapatite crystals in the bone matrix. Matrix-bound pamidronate inhibits osteoclast activity by a variety of mechanisms, the most important of which appears to be prevention of the attachment of osteoclast precursor cells to bone. In patients with osteolytic bone metastases associated with either breast cancer or multiple myeloma, administration of pamidronate together with systemic antitumour therapy reduces and delays skeletal events, including pathological fracture, hypercalcaemia and the requirement for radiation treatment or surgery to bone. Pamidronate generally improves pain control. Quality-of-life and performance status scores in pamidronate recipients were generally as good as, or better than, those in patients who did not receive the drug. Overall survival does not appear to be affected by pamidronate therapy. Tumour-induced hypercalcaemia also responds well to pamidronate therapy: 70 to 100% of patients achieve normocalcaemia, generally 3 to 5 days after treatment. Response durations vary, but are commonly 3 weeks or longer, In comparative studies, pamidronate produced higher rates of normocalcaemia and longer normocalcaemic durations than other available osteoclast inhibitors, including intravenous etidronate, clodronate and plicamycin (mithramycin). In most patients with Paget's disease of bone, intravenous pamidronate reduces bone pain and produces biochemical response. Serum alkaline phosphatase levels generally fall 50 to 70% from baseline 3 to 4 months after pamidronate treatment. Biochemical response may be prolonged. Pamidronate is well tolerated by most patients. Transient febrile reactions, sometimes accompanied by myalgias and lymphopenia, occur commonly after the first infusion of pamidronate. Other reported adverse events include transient neutropenia, mild thrombophlebitis, asymptomatic hypocalcaemia and, rarely, ocular complications (uveitis and scleritis). Pamidronate should be considered for routine use together with systemic hormonal or cytotoxic therapy in patients with breast cancer or multiple myeloma and osteolytic metastases. At present, pamidronate is the drug of choice for first-line use in the management of patients with tumour-induced hypercalcaemia. It is an effective treatment for Paget's disease and is the treatment of choice where oral bisphosphonates are not an option.
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PMID:Pamidronate. A review of its use in the management of osteolytic bone metastases, tumour-induced hypercalcaemia and Paget's disease of bone. 950 93

A sample of 871.3 patients/year was conformed by 205 postmenopausal women, aged 64.8 +/- 18.2 years (mean +/- SD), followed up during 51 +/- 12 months. All have osteoporosis, diagnosis assessed through radiological findings of at least one atraumatic fracture or vertebral crush ("severe osteoporosis" according to the new WHO classification). Each woman received 100 mg/day oral pamidronate (enteric coated soft gelatin capsules), half an hour before breakfast. Additional calcium and vitamin D were supplemented as follows: Total daily calcium = 1 g provided by diet and/or calcium carbonate. Vitamin D equivalent to 400-1200 IU/day. All patients were recommended to improve their physical activity, at least by walking exercise. Clinical examination radiological, bone mineral density (BMD) and biochemical studies were periodically performed. But, fracture indicence was the end-point of the study. Same was related to the 1,673 fall episodes recorded in the sample. In addition, height loss, lumbar BMD, proximal femur BMD, are also reported. Data has been cross-sectional collected in March 1995. All patients improved the symptomatology, specifically pain. This, and the good tolerability of the treatments proved to be considerably favorable for their compliance. Within the observation period, only 12 patients decreased their height (5.85%; mean = 0.85 cm; range = 0.5-2.0 cm). Lumbar spine BMD increased in 90% of 48 women. Mean gain after 2 years was 5.3 +/- 1.0% (p < 0.001). Proximal femur increased in 78% of other 32 women. Mean gain 6.3 +/- 0.7% (p < 0.001) after 2 years. A total of 78 new fractures were recorded, 47 vertebral crush, 29 forearm fractures and 2 hip fractures. Its incidence related to the fall episodes was of 2.8; 1.7 and 0.12% respectively. When compared with a historical estimated data, from an untreated population (Cummings SR et al, 1994), both, the total number of new fractures and the new hip fractures were significantly lower (p < 0.01) in our treated population than the reference data. Pamidronate, in oral doses of 100 mg/day, adequately supplemented with calcium and vitamin D, proved to be effective and a well tolerated therapy. The low rate of height's loss, BMD significant increases in subgroups of patients and the low rate of new fractures, strongly support the use of the compound to treat severe osteoporotic women. To our knowledge, this is the first time, that the new fracture incidence is related to the fall frequency reported in a bisphosphonate treated sample.
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PMID:[New spine and non-spine fractures in 871 women/year treated with oral pamidronate plus calcium and vitamin D supplements]. 956 52

In order to study whether oral bisphosphonate therapy might prevent or reduce skeletal-related morbidity in patients with newly diagnosed multiple myeloma who required chemotherapy, 300 patients were included in a randomized multi-centre trial. Patients were given oral pamidronate at a dose of 300 mg daily, or placebo, in addition to conventional intermittent melphalan/prednisolone (and in some cases alpha-interferon) treatment. With a median treatment duration of about 550d, no statistically significant reduction in skeletal-related morbidity (defined as bone fracture, related surgery, vertebral collapse, or increase in number and/or size of bone lesions) could be demonstrated. Pamidronate treatment also did not have any influence on patient survival or on the frequency of hypercalcaemia. However, in patients treated with pamidronate there were fewer episodes of severe pain (P=0.02) and a decreased reduction of body height of 1.5 cm (P= 0.02). The overall negative result of the study is attributed to the very low absorption of orally administered bisphosphonates in general.
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PMID:Failure of oral pamidronate to reduce skeletal morbidity in multiple myeloma: a double-blind placebo-controlled trial. Danish-Swedish co-operative study group. 960 23

Metastatic bone disease is a frequent cause of morbidity in advanced cancer patients with a subsequent high incidence of skeletal complications (fractures, hypercalcemia, spinal cord compression) and severe pain. The osteolytic process is mainly characterized by an osteoclastic activity of bone resorption and inflammatory activity provoked by various cytokines and prostaglandins. Bisphosphonates represent a new class of drugs with inhibitory activity on bone resorption and on inflammatory processes which revealed themselves to be efficacious in a series of clinical conditions such as tumour-induced hypercalcemia, Paget's disease, osteoporosis and metastatic bone disease. The aim of this review of the literature is to show the analgesic efficacy of the different bisphosphonates in phase III studies carried out on patients with metastatic bone disease. Medline and Cancerlit database from January 1984 to February 1998 have been considered. From the analysis of the published studies it appears that bisphosphonates and, in particular, intravenous Disodium Pamidronate, are not only able to slow down the progression of the disease and to reduce the onset of skeletal complications but also have an analgesic effect and the possibility of improving the quality of life, above all in patients with osteolytic metastases due to breast cancer and multiple myeloma. Bisphosphonates represent a further valid therapy to add to an already consolidated list of therapies such as radio, chemo and endocrine therapy, analgesic drugs, orthopaedic and physiatric in the pain management of patients with bone metastases. These drugs meet with the patients' compliance, are well-tolerated as well as having a good cost/efficacy profile. It still remains to be seen if the newer and more potent bisphosphonates such as Ibandronate and Zoledronate can be administered differently from the intravenous route such as by mouth or by patch which are readily accepted by the patient and, moreover, if these more potent drugs are able to prevent or delay the onset and/or the progression of bone metastases.
Pain 1998 Dec
PMID:The role of bisphosphonates in the treatment of painful metastatic bone disease: a review of phase III trials. 987 May 69

The aim of this double-blind, randomized study was to compare the effects of two pamidronate dosages, given as repeated infusions in patients with advanced malignant osteolytic bone disease and bone pain. Seventy patients were randomly assigned to receive pamidronate 60 mg or 90 mg i.v. every 3 weeks for a maximum of six cycles. Pain parameters, analgesic consumption and performance status were assessed at baseline and throughout the study. Furthermore, total-body bone mineral density was measured using dual-energy X-ray absorptiometry at baseline, after three and after six infusions. Sixty percent (95% CI 41-77%) of the patients in the 60 mg group and 63% (95% CI 44-79%) of the patients in the 90-mg group had a sustained reduction of pain intensity and were classified as pain responders. Median duration of pain response was 15 versus 12 weeks in the 60-mg and 90-mg groups, respectively (P = 0.32). After two infusions, significant changes in pain intensity, pain frequency, general well-being and WHO pain score were observed (P<0.01). A trend toward improved performance status and reduced consumption of analgesics was also observed. Patients in the 90-mg group had more pronounced bone remineralization as measured by total-body bone mineral density. No significant difference was detectable between the two pamidronate treatments in any of the parameters evaluated. In conclusion, bone pain can be effectively reduced by repeated pamidronate infusions in patients with advanced osteolytic bone disease. Pamidronate 90 mg every 3 weeks results in higher bone remineralization, but this difference did not translate into a further increase of palliative effects.
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PMID:Pamidronate treatment in patients with malignant osteolytic bone disease and pain: a prospective randomized double-blind trial. 992 66

Multiple myeloma, a clonal B-cell malignancy, accounts for 10% of all hematologic cancers. In patients with multiple myeloma, median survival is approximately 30 to 36 months with conventional therapy, but high-dose chemotherapy resulted in better outcomes in a mature randomized trial. Pamidronate and other bisphosponates, used as supportive therapy, effectively reduce the incidence of skeletal events and decrease pain. They also have a role in disease control. Ongoing trials are now addressing such issues as further intensification with tandem transplantations, timing of transplantation, and decrease of malignant cell reinfusion by positive selection. Important laboratory observations have better defined the malignant clone and its interaction with the microenvironment. These observations will be important for the treatment of myeloma in the future.
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PMID:Recent advances in the treatment of multiple myeloma. 1040 Mar 69

McCune-Albright syndrome is a rare genetic disorder consisting of skin and bone dysplasia and peripheral endocrinopathies. Little data have been collected regarding bisphosphonate treatment of bone fibrous dysplasia in paediatric patients with this syndrome. The aim of our study was to investigate the therapeutic efficacy of pamidronate in these patients. Nine patients with moderate to severe forms of bone fibrous dysplasia were treated with pamidronate intravenously (0.5-1 mg/kg/daily for 2-3 d) at 0.5-1-y intervals. Patients were treated over a time period of 0.5-3.5 y. During treatment no spontaneous fracture occurred. Bone pain and gait abnormality due to pain disappeared after 2-3 therapeutic cycles. Cranial asymmetry and limb length discrepancy remained unchanged. Elevated serum alkaline phosphatase and urine hydroxyproline values were reduced by the treatment, demonstrating drug activity at the lesional level. The effectiveness of pamidronate was also seen at the non-lesional level through an increase in bone density. Radiographic and scintigraphic evidence of lesion healing was not attained. Pamidronate treatment can ameliorate the course of bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome.
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PMID:Pamidronate treatment of bone fibrous dysplasia in nine children with McCune-Albright syndrome. 1070 89

Case 1: A 43-year-old woman underwent mastectomy because of locally advanced breast cancer with multiple bone metastases. She was treated with CMF therapy but developed a compression fracture of a thoracic vertebra after 10 months and received pamidronate therapy. Pamidronate administration relived her back pain after 2 months and she was able to walk again after 3 months. However, she developed a resistance to the treatment, and then refused another treatment. She was found to have hypercalcemia 6 months later and received pamidronate again, but died 9 months after the treatment. Case 2: A 52-year-old woman underwent mastectomy because of breast cancer (T2) and was diagnosed as having multiple bone metastases 24 months after the operation. She could not turn over in bed due to progressing bone pain and received pamidronate therapy with CMF therapy at home 23 months after the diagnosis. After 2 months, pamidronate administration relieved her bone pain and she was free of pain after 4 months. After 5 months, X-rays revealed that lytic lesions showed sclerosis, and the pamidronate therapy was assessed as producing a PR. Pamidronate therapy improved her quality of life and activities of daily living, and she continues to receive it this time as an outpatient. Pamidronate therapy is promising as an effective treatment for bedridden patients with bone metastasis from breast cancer.
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PMID:[Two bedridden patients with bone metastases from breast cancer effectively treated with pamidronate therapy]. 1105 29


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