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)

Clodronate, one of the most investigated bisphosphonates, has been clinically utilised for over 10 years in malignancy. It is the most used, most effective and safest drug in the treatment of hypercalcaemia. It inhibits lytic bone destruction, prevents bone fractures and relieves bone pain. Supportive clodronate therapy may even reduce hypercalcaemia mortality and the morbidity caused by osteolysis. These results have stimulated studies on the patients' quality of life. New methods for the measurement of bone resorption, such as the degradation product of type I collagen (ICTP), may improve the possibility of monitoring the effect of clodronate. Comparative studies with different bisphosphonates in hypercalcaemia and long-term controlled trials using bisphosphonates as supportive therapy in osteolysis due to malignancy are reviewed.
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PMID:Clodronate and other bisphosphonates as supportive therapy in osteolysis due to malignancy. 754 30

Clodronate relieves bone pain in patients with skeletal metastases. Since the pain relieving mechanism of clodronate may be associated with the antiosteoclastic activity, we have investigated whether the drug has simultaneous actions on bone resorption and pain. Although osteosclerotic metastases are characteristic of prostate carcinoma, bone resorption is also accelerated. The resorbing process can be investigated using a specific immunoassay for ICTP (cross-linked carboxyterminal telopeptide region of type I collagen) which allows the measurement of the degradation of type I collagen in serum samples. We have also determined serum concentration of PICP (carboxyterminal propeptide of type I procollagen) which reflects the synthesis of type I collagen (osteoid). Patients who have relapsed after first-line hormonal therapy, were randomised to receive estramustine phosphate (E) with or without clodronate (C) (E + C, n = 50; E, n = 49). The dose of E was 560 mg and that of C 3.2 g for the first month, thereafter 1.6 g. We saw elevated ICTP and PICP levels in the majority of the patients. A transient decrease in ICTP values occurred simultaneously with pain relief. The changes were more accentuated in the E + C than in the E group but the difference was not significant. In each group serum phosphate concentration decreased markedly (P = 0.001) whereas the activity of alkaline phosphatase remained increased, both indicating a development of osteomalacia during E therapy. The short-term antiosteoclastic effect of C may be explained by the dose reduction, hyperosteoidosis and osteomalacia which inhibit the binding of C on the crystal surfaces and by the late phase of disease.
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PMID:Evaluation of the effect of oral clodronate on skeletal metastases with type 1 collagen metabolites. A controlled trial of the Finnish Prostate Cancer Group. 768 80

A panel of bone turn-over markers was assessed in 75 normocalcemic patients bearing bone metastases from breast cancer (BC), and in 25 advanced/metastatic BC patients without clinical appearance of bone involvement. 115 healthy women, stratified in three subgroups according to age served as controls. Bone formation was investigated by measuring serum carboxyterminal propeptide of type I procollagen (PICP), Bone Gla Protein (BGP, osteocalcin), bone isoenzyme of alkaline phosphatase (BALP); bone resorption by measuring serum carboxyterminal telopeptide of type I collagen (ICTP), fasting urinary hydroxyproline/creatinine (OHPro/Cr) and calcium/creatinine (Ca/Cr). In patients with bone metastases the percent of supranormal values (higher than mean plus 2 SD of the age-matched controls) ranged between 25% and 40% for indices of bone formation, about 73% for both ICTP and OHPro/Cr and about 30% for Ca/Cr. The median levels of all bone turn-over markers were higher in bone metastatic patients than in those without apparent skeletal involvement, but significance was attained only for OHPro/Cr, Ca/Cr and BALP. Supranormal levels of ICTP and OHPro/Cr were also found in about 65-70% of patients without apparent skeletal involvement. ICTP and Ca/Cr significantly correlated with bone pain score, BALP, ICTP, Ca/Cr significantly correlated with the number of tumour appearances in bone. In conclusion, the bone resorption indices, ICTP and OHPro/Cr, are much more frequently elevated than bone formation indices in BC patients with or without skeletal involvement. Their potential use in the early detection of bone metastases is hampered by the insufficient knowledge on specificity. Among the biochemical markers evaluated, Ca/Cr, ICTP and BALP, due to correlation with clinical aspects, appear the most interesting for follow-up studies.
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PMID:Biochemical picture of bone metabolism in breast cancer patients with bone metastases. 866 81

Fibrous dysplasia of bone (FD) is a rare disorder characterized by proliferation of fibrous tissue in bone marrow leading to osteolytic lesions. It causes bone pain and fractures. To date the only treatment is orthopedic. Histological and biochemical similarities between FD and Paget's bone disease related to increased osteoclastic resorption led us to propose treatment with the bisphosphonate pamidronate. The aim of the study was to assess the long-term effects of intravenous pamidronate in FD. In this open label phase III study, 20 patients with FD (11 males and 9 females; mean age 31 years) received courses of 180 mg of intravenous pamidronate every 6 months (60 mg/day during 3 days by infusion). The mean duration of follow-up was 39 months (range 18-64). Severity of bone pain, number of painful skeletal sites per patient, X-rays of all involved areas, serum alkaline phosphatase, fasting urinary hydroxyproline, and urinary type I collagen C-telopeptide were assessed every 6 months. The severity of bone pain and the number of painful sites appeared to be significantly reduced. All biochemical markers of bone remodeling were substantially lowered. We observed a radiographic response in nine patients with refilling of osteolytic lesions. A mineralization defect proven by bone biopsy was observed in one case. Four patients sustained bone stress lines, but no fracture occurred. We suggest that intravenous pamidronate alleviates bone pain, reduces the rate of bone turnover assessed by biochemical markers, and improves radiological lesions of FD. Few side effects were observed.
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PMID:Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. 933 37

The aim of this study was to evaluate the efficacy of low dose oral clodronate in palliation of pain arising from bone metastases (BM) and to determine the optimal oral clodronate dose which inhibits osteolysis caused by tumor. Fifty patients with bone pain caused by BM were included in this study. All were receiving antitumor chemotherapy or hormonal therapy. The patients were randomized into three groups according to the dose of clodronate. Groups A and B were given 800 mg/d and 1600 mg/d of oral clodronate respectively for 3 months. Group C was the control group. The effect of clodronate in pain palliation was evaluated with pain score, performance status, and changes in analgesic use. The effect on osteolysis was examined with urinary calcium, hydroxyproline (OHP) and serum cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) levels. Group A contained 16 patients, and groups B and C contained 17 patients each. After 3 months use of oral clodronate, significant decrease in the pain score of groups A and B was noted when compared to group C (P = 0.024 and P = 0.007, respectively). The analgesic use of 11 patients in group A (69%) and 8 patients in group B (47%) was decreased, but only the decrease in group A was statistically significant (P = 0.038). Pain score increased in 5 patients in group C (29%), and 3 patients in groups A (19%) and B (18%) each. Urinary calcium, OHP and serum ICTP levels increased in group C and decreased in groups A and B, but only the decrease of urinary calcium levels of group B was significant (P = 0.003). In conclusion, low dose (800 mg/d) oral clodronate seems to be as effective as standard dose (1600 mg/d) in palliation of bone pain secondary to BM.
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PMID:The effect of two different doses of oral clodronate on pain in patients with bone metastases. 1052 1

Bone involvement is a central feature of multiple myeloma (MM). We investigated whether serum markers of osteoblastic and osteoclastic activity correlate with the presence of bone disease and survival in 313 MM patients enrolled in a phase III trial (E9486). Five markers were measured, including osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP), bone alkaline phosphatase (BAP), carboxy-terminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). We analysed the relationship between serum levels of these markers and the presence of bone manifestations, and survival. Serum levels of ICTP and BAP correlated significantly with bone pain, lesions and fractures. Serum level of ICTP was also higher in stage II-III compared with stage I disease. The serum level of ICTP was significantly associated with shortened survival in the univariate analysis. The median survival times were 4.1 and 3.5 years for low and high ICTP respectively (P = 0.02). There was a strong relationship between ICTP and beta-2-micrgolobulin (B2M). ICTP stands out as a significant marker of bone disease. Incorporation of these markers into clinical trials assessing the use of bisphosphonates in MM is needed to determine whether they might serve as indicators of effectiveness of these agents.
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PMID:Prognostic value of serum markers of bone metabolism in untreated multiple myeloma patients. 1084 78

Prostate cancer is the most common malignancy in elderly men and is often associated with bone metastases. Although bone metastases are osteosclerotic, histological and biochemical studies clearly indicate an increase of both bone formation and bone resorption, providing the rational for using bisphosphonate as a palliative treatment in these patients. The recent development of specific and sensitive biochemical markers, reflecting the overall rate of bone formation and bone resorption, has improved the non-invasive assessment of bone turnover abnormalities in patients with prostate cancer. The immunoassays for bone-specific alkaline phosphatase and type I collagen propeptides are currently the most sensitive markers to assess bone, formation. The best indices of bone resorption are the immunoassay for the pyridinoline cross-links and the related peptides that can be measured in urine and more recently in serum. A better knowledge of the biochemistry, especially of the age-related post-translational modifications of type I collagen in the abnormal bone matrix, associated with bone metastases from prostate cancer may lead to markers of increased sensitivity. A recent example is the demonstration that the isomerization and racemization of the aspartic acid residue in C-telopeptides of type I collagen is impaired in patients with prostate cancer and bone metastases, a pattern than can be detected with specific conformational antibodies. The most sensitive markers of bone formation and bone resorption are markedly increased in patients with bone metastases compared with patients with cancer but without metastases, the levels correlating with the extent of the bone involvement. However, their sensitivity remains limited, suggesting that the currently available biochemical markers cannot be used as a surrogate for bone scintigraphy in the diagnosis of bone involvement. A few studies have suggested that the measurement of bone markers may be useful in the assessment of response to anti-endocrine therapy, although available data indicate a lower sensitivity than with prostates specific antigen. Additional longitudinal studies are required to assess the potential use of bone markers, especially to identify patients who relapse during the course of the treatment and, more specifically 3 those that result from the progression in bone metastases.Clearly, the established use of bone markers is for monitoring effects of bisphosphonate treatment. Several studies have shown a rapid decrease of bone resorption markers in patients with prostate cancer and bone metastases, the magnitude of the decrease correlating with the efficacy of the treatment in reducing bone pain. Thus, bone markers are likely to become a useful and objective tool to monitor bisphosphonate treatment and individual the therapy scheme.
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PMID:Markers of bone turnover in prostate cancer. 1141 70

The aims of the present study were to determine whether patients with painful bone metastases from primary cancer sites showed a higher level of a bone resorption marker than those with no evidence of skeletal-related events, and to clarify the efficacy of oral administration of etidronate for pain due to bone metastases and bone resorption. Thirty outpatients with cancer were recruited: 10 with pain due to bone metastasis from the primary cancer site; lung (4), prostate (3), and breast (3) (M group), and 20 with primary cancer of the stomach (11), colon (4), breast (3), lung (1), and bladder (1) with no such evidence of skeletal-related events (non-M group). None of the patients in the M group either needed morphine for pain relief or had hypercalcemia, although all of them had been taking nonsteroidal anti-inflammatory drugs (NSAIDs). During the study, they continued taking NSAIDs, as they had before the study. The level of urinary cross-linked N-telopeptides of type I collagen (NTx) at baseline was significantly higher in the M group than in the non-M group ( P < 0.01). Oral administration of etidronate (400 mg/day for 2 weeks) to patients in the M group significantly reduced bone pain 2 and 12 weeks after the start of treatment; however, the pain relief effect was diminished 12 weeks after the start of treatment, despite a significant decrease in urinary NTx level ( P < 0.05 by one-way analysis of variance [ANOVA] with repeated measurements). The present study provides evidence suggesting that patients with painful bone metastases from primary cancer sites may have a higher level of urinary NTx than those with no evidence of skeletal-related events, and that oral administration of etidronate at the dose we used may have the potential to transiently relieve their bone pain by decreasing abnormally raised bone resorption. Although the present study had a small sample size, and had no placebo controls, the results may be useful, especially as they raise additional questions that could stimulate further research in Japan.
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PMID:Transient relief of metastatic cancer bone pain by oral administration of etidronate. 1211 69

Osteogenesis Imperfecta (OI) is characterized by bone fragility. At least seven discrete types have been described ranging from mild disease to a lethal form. In a large number of cases, mutations in one of the two genes encoding type I collagen have been found. In forms recently described (types V, VI, VII), such mutations have been excluded. In two other forms, (Bruck, and osteoporosis - pseudoglioma syndromes) defects in other proteins have been characterized. In OI, bone fragility stems from: decreased bone mass, disturbed organization of bone tissue, and altered bone geometry (size and shape). Histologic studies have shown that increased bone turnover is the rule in OI bone. This justifies using bisphosphonates in order to reduce osteoclast mediated bone resorption. Initial results are encouraging. Cyclical intravenous pamidronate administration reduces bone pain and fracture incidence, and increases bone density and level of ambulation, with minimal side effects. Effects on bone include increase in size of vertebral bodies and thickening of cortical bone. These results allow for more efficacious corrective surgery using intramedullary rodding of the long bones and paravertegral instrumentation. Specific occupational and physiotherapy programs are integral parts of the treatment protocol. This multidisciplinary approach will prevail until strategies aiming at the correction of the basic defect(s) will have come to fruition.
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PMID:Modern approach to children with osteogenesis imperfecta. 1258 89

Bisphosphonates have proven to be effective in patients with fibrous dysplasia of the bone (FD) as shown by their effect on bone pain, markers of bone turnover, or radiological changes. The aim of this study was to evaluate the usefulness of measuring bone mineral density (BMD) of affected bones to assess the efficacy of bisphosphonate treatment. Seven patients (mean age 26 years) received courses of 180 mg intravenous infusion of pamidronate every 6 months (60 mg/day during 3 days). Clinical symptoms, serum alkaline phosphatase, and urinary C-terminal cross-linking telopeptide of type I collagen were assessed every 3 months. BMD of total skeleton and X-rays of FD areas (FDa) were performed at baseline and at 12 months. BMD of FDa was compared with the contralateral side (CL) using the region of interest program on the total skeleton scan. BMD of total skeleton was normal at baseline. Average BMD of FDa was -11.4% compared with CL, a significantly greater difference than that observed between the left and right sides in healthy controls, -0.7% (P < 0.02). At 12 months bone pain diminished in all patients. Bone turnover markers decreased. Mean total skeleton BMD increased 3.3% (P < 0.02). Subregions of the total skeleton scan presenting FD lesions augmented: arms +9.6% (P < 0.02), legs +4.2%, and pelvis +3.5% (P < 0.05). The increase in mean BMD of FDa was +6.8% compared with +2.6% in CL. No changes were observed on the X-ray. These results indicate that simultaneous determination of markers of bone turnover and BMD of FDa is useful in short-term follow-up to determine the efficacy of intravenous pamidronate.
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PMID:Effect of intravenous pamidronate on bone markers and local bone mineral density in fibrous dysplasia. 1455 62


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