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Bone Pain (bone + pain)
Selected AbstractsDouble-Blind Placebo-Controlled Trial of Adjuvant Pamidronate with Palliative Radiotherapy and Intravenous Doxorubicin for Canine Appendicular Osteosarcoma Bone PainJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2009T.M. Fan Background: Canine osteosarcoma (OSA) causes focal malignant osteolysis leading to severe pain. Despite the documented efficacy of radiotherapy or IV aminobisphosphonates for managing cancer bone pain, their potential combined therapeutic value has not been reported in OSA-bearing dogs. Hypothesis: Pamidronate combined with standardized palliative therapy will improve pain control and bone biologic effects in OSA-bearing dogs. Animals: Fifty dogs with appendicular OSA treated with standardized palliative therapy and either pamidronate or sterile saline. Methods: Randomized, prospective, double-blinded, placebo-controlled study. Treatment responses for dogs receiving standardized palliative therapy with (n = 26) or without (n = 24) adjuvant pamidronate were serially evaluated for changes in subjective pain scores, urine N-telopeptide (NTx) excretion, primary tumor relative bone mineral density (rBMD), and computerized pressure platform gait analysis. Results: Median duration of subjective pain relief for dogs treated with adjuvant pamidronate or placebo was 76 and 75 days, respectively (P= .39). Forty percent (20/50; pamidronate [11/26] and placebo [9/24]) of dogs experienced durable analgesia, defined by pain alleviation ,112 days. For patients achieving durable pain control, dogs treated with pamidronate achieved greater reductions in NTx excretion and larger increases in rBMD compared with placebo controls. Changes in peak vertical force assessed by computerized pressure platform gait analysis correlated with pain alleviation in OSA-bearing dogs. Conclusions and Clinical Importance: Combining pamidronate with standardized palliative therapy is safe, but does not clearly improve pain alleviation. However, in dogs achieving durable pain control, adjuvant pamidronate appears to decrease focal bone resorption in the local tumor microenvironment. [source] Single-Agent Pamidronate for Palliative Therapy of Canine Appendicular Osteosarcoma Bone PainJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2007Timothy M. Fan DVM Background:Canine appendicular osteosarcoma (OSA) causes focal bone destruction, leading to chronic pain and reduced quality-of-life scores. Drugs that inhibit pathologic osteolysis might provide additional treatment options for managing cancer-induced bone pain. Aminobisphosphonates induce osteoclast apoptosis, thereby reducing pain associated with malignant osteolysis in human patients with cancer. Hypothesis:Treatment of dogs with pamidronate administered intravenously will alleviate bone pain and reduce pathologic bone turnover associated with appendicular OSA in dogs. Animals:Forty-three dogs with naturally occurring appendicular OSA administered pamidronate intravenously. Methods:Prospective study. Therapeutic responses in dogs treated with pamidronate administered intravenously and nonsteroidal anti-inflammatory drugs (NSAID) were evaluated by using a numerical cumulative pain index score (CPIS), and by quantifying urine N-telopeptide (NTx) excretion and relative primary tumor bone mineral density (rBMD) assessed with dual energy x-ray absorptiometry. In addition, variables, including pamidronate dose, skeletal mass, baseline and change for CPIS, urine NTx and rBMD during treatment, and baseline tumor volume and radiographic pattern were compared between dogs clinically responsive and nonresponsive to pamidronate therapy. Results:Twelve of 43 dogs (28%) had pain alleviation for > 4 months, lasting a median of 231 days. Changes in CPIS and rBMD during treatment were statistically different between responders and nonresponders (P= .046 and .03, respectively). Conclusions and Clinical Importance: Substantiated by reductions in CPIS and increases in rBMD, single-agent pamidronate administered intravenously with NSAID therapy relieves pain and diminishes pathologic bone turnover associated with appendicular OSA in a subset of dogs. [source] Pamidronate treatment of bone fibrous dysplasia in nine children with McCune-Albright syndromeACTA PAEDIATRICA, Issue 2 2000R Lala 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. [source] The effect of enzyme replacement therapy on bone crisis and bone pain in patients with type 1 Gaucher diseaseCLINICAL GENETICS, Issue 3 2007J Charrow The effect of enzyme replacement therapy (ERT) on bone crisis and bone pain was investigated in patients with Gaucher disease (GD) type 1 followed over 4 years. Data from the International Collaborative Gaucher Group Gaucher Registry were used. Only patients with bone crisis and/or bone pain data for 1 year prior to ERT, and for each of 3 years after the start of ERT, were included. Bone crises were reported in 17% of patients during the year before starting ERT. The frequencies of bone crises decreased to 5%, <1% and 3% for 1, 2, and 3 years after initiation of treatment, respectively (p < 0.0001). Bone pain followed a similar pattern of response. Bone pain was reported in 49% of patients the year before treatment and decreased to 30% in the first year, 29% in the second year, and 30% in the third year of ERT (p < 0.0001). ERT is associated with a reduction in bone crisis and bone pain in patients with GD type 1 . This study shows that significant improvements in symptoms of skeletal disease are achievable clinical outcomes and treatment goals in GD type 1. [source] Clinical findings, diagnosis, prevalence and predisposing factors for lameness localised to the middle carpal joint in young Standardbred racehorsesEQUINE VETERINARY JOURNAL, Issue 2 2006C. M. Steel Summary Reasons for performing study: Lameness related to the middle carpal joint (MCJ) occurs in up to 30% of young Standardbred horses in race training and the incidence increase with radiographic severity of third carpal bone (C3) sclerosis on DPr-DDIO (skyline) view of the carpus. Factors predisposing horses to carpal injury have not been well investigated. Objectives: To determine the importance of MCJ lameness as a cause of wastage in young Standardbred racehorses, stage of training at which it occurs and predisposing factors, and to describe clinical findings and diagnosis. Methods: Standardbred horses (n = 114) entering their first year of race training were examined at approximately 3-month intervals over 12,18 months. For 87 of the horses, a training diary was available and these horses were trained at 3 different stables, each using a different exercise regime. At each examination, forelimb conformation, MCJ effusion, MCJ lameness and radiographic findings were graded, and training history and reasons for lost training days recorded. Nuclear scintigraphy and exploratory arthroscopy were performed on a limited selection of horses. Results for horses that developed MCJ lameness during the study period were compared statistically with results for horses that did not. Results: Carpal lameness occurred in 28% of horses and was present in 56% with forelimb lameness. In most cases lameness was mild, bilateral and with little or no MCJ effusion and was attributed to subchondral bone pain associated with radiographic evidence of C3 sclerosis. Carpal lameness was the most common reason for >1 month's rest during the study period. It occurred at any stage of training but, in most cases, some speed training had begun. Of the variables studied, poor forelimb conformation and more intense speed training were predisposing factors. Conclusions and potential relevance: The information gained should assist in making recommendations regarding training young Standardbreds to reduce the incidence of MCJ lameness. However, further investigations to determine the optimal training regime are warranted. [source] Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shuntEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Elena Mishchenko Abstract Clinical care of patients with polycythemia vera, essential thrombocythemia and myelofibrosis (MF) requires not only a broad understanding of general treatment principles but also familiarity with the management of hydroxyurea-refractory disease complications. The latter include progressive splenomegaly, symptomatic portal hypertension (e.g. ascites, variceal bleeding), pulmonary hypertension, bone pain, intractable pruritus, constitutional symptoms (e.g. fatigue, night sweats) and cachexia (i.e. loss of lean body mass, general ill health, poor appetite). Some of these symptoms are directly or indirectly related to extramedullary hematopoiesis (EMH) and others to proinflammatory cytokine excess. Results from recent clinical trials of JAK inhibitors suggest remarkable activity in MF-associated constitutional symptoms, cachexia, pruritus and hydroxyurea-refractory splenomegaly. Involved-field radiotherapy is best utilized in the setting of EMH-associated symptoms, including ascites, bone (extremity) pain and pulmonary hypertension. Splenectomy is indicated in the presence of drug-refractory splenomegaly and frequent red cell transfusion requirement. Transjugular intrahepatic portosystemic shunt is used to alleviate symptoms of portal hypertension. [source] Hypnosis shows an advantage over counselling in an RCT of patients with advanced cancer and bone painFOCUS ON ALTERNATIVE AND COMPLEMENTARY THERAPIES AN EVIDENCE-BASED APPROACH, Issue 3 2005Article first published online: 14 JUN 2010 [source] Identification of prospective factors promoting osteotropism in breast cancer: a potential role for CITED2INTERNATIONAL JOURNAL OF CANCER, Issue 4 2010Wen Min Lau Abstract Breast cancer metastases develop in the bone more frequently than any other site and are a common cause of morbidity in the form of bone pain, pathological fractures, nerve compression and life-threatening hypercalcemia. Despite ongoing research efforts, the molecular and cellular mechanisms that regulate breast cancer cell homing to and colonization of the bone as well as resultant pathological bone alteration remain poorly understood. To identify key mediators promoting breast cancer metastasis to bone, we utilized an immunocompetent, syngeneic murine model of breast cancer metastasis employing the mammary tumor cell line NT2.5. Following intracardiac injection of NT2.5 cells in neu-N mice, metastases developed in the bone, liver and lung, closely mimicking the anatomical distribution of metastases in patients with breast cancer. Using an in vivo selection process, we established NT2.5 sublines demonstrating an enhanced ability to colonize the bone and liver. Genome-wide cDNA microarray analysis comparing gene expression between parental NT2.5 cells and established sublines revealed both known and novel mediators of bone metastasis and osteolysis, including the transcriptional co-activator CITED2. In further studies, we found that expression of CITED2 was elevated in human primary breast tumors and bone metastasis compared to normal mammary epithelium and was highest in breast cancer cell lines that cause osteolytic bone metastasis in animal models. In addition, reducing CITED2 expression in NT2.5 cells inhibited the establishment of bone metastasis and osteolysis in vivo, suggesting a potential role for CITED2 in promoting breast cancer bone metastasis. [source] Spontaneous splenic haematoma in a multiple myeloma patient receiving pegfilgrastim supportINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2006E. HATZIMICHAEL Summary Growth factors are a significant advance in the supportive care of patients with cancer with a wide range of indications. Frequent side effects of G-CSF include bone pain, headache, fatigue and nausea. We report a case of subcapsular splenic haematoma following pegfilgrastim administration in a 65-year old patient with multiple myeloma. Proposed mechanisms accounting for splenic enlargement include extramedullary haemopoiesis, intrasplenic infiltration by mature and immature myeloid cells and intrasplenic stem cell homing and proliferation. The risk of spontaneous splenic rupture is difficult to quantify. Physicians should be aware of this life-threatening condition and early diagnosis can be difficult since anemia and splenomegaly are common findings in haematologic patients. [source] Leukaemic infiltration of the mandible in a young girlINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 2 2007RACHAEL E. BENSON Background., This report presents a case of leukaemic infiltration of the mandible in a 10-year-old female of Sudanese extraction. Case report., The patient was in remission from acute lymphoblastic leukaemia when she presented with pain localized to the alveolar ridge overlying the unerupted lower right second permanent molar. Two days later, she developed right inferior alveolar nerve paraesthesia. Radiographic imaging demonstrated cortical line absence around the developing lower right second and third permanent molars, and distal displacement of the lower right third molar. In addition, the cortical outline of the right inferior dental canal lacked clarity. Biopsy confirmed leukaemia recurrence demonstrating the Philadelphia chromosome. Tailored chemotherapy was commenced, and a bone marrow transplant was carried out 12 weeks later. At 6-month dental review, the patient remained exceptionally well with no bone pain and normal sensation in the right lower lip. Conclusion., The importance of regular and long-term dental examination of patients with leukaemia is discussed. [source] The Schnitzler syndrome: Chronic urticaria and monoclonal gammopathy , an autoinflammatory syndrome?JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 8 2008Elisabeth Eiling Summary Schnitzler syndrome describes the simultaneous occurrence of monoclonal gammopathy and chronic urticaria with at least two additional minor symptoms (arthralgia, bone pain, fever of uncertain origin, hepato- or splenomegaly, lymphadenopathy, increased erythrocyte sedimentation rate, leukocytosis/thrombocytosis or increased bone density). Schnitzler syndrome is not wellknown and very likely under-recognized. Comprehensive diagnostic examinations are necessary to rule out other diseases, especially those of hematologic origin. Close interdisciplinary collaboration is mandatory. The etiology of Schnitzler syndrome is unclear, but the rapid response to the interleukin-1 receptor inhibitor anakinra underlines the pivotal role which the proinflammatory cytokine interleukin-1 may play in the pathophysiology of this potentially autoinflammatory disorder. [source] Bisphosphonate-Induced Osteopetrosis: Novel Bone Modeling Defects, Metaphyseal Osteopenia, and Osteosclerosis Fractures After Drug Exposure Ceases,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2008Michael P Whyte Abstract In 2003, we reported on a 12-yr-old boy who had developed osteopetrosis (OPT) while receiving pamidronate (PMD) for idiopathic bone pain and enigmatic elevation in circulating bone alkaline phosphatase. Now 17 yr of age, he was re-evaluated 6.5 yr after PMD exposure stopped. Our patient described less bone pain but further limb fractures. His growth plates were fused, yet hyperphosphatasemia persisted. Radiographs documented interval fractures of a metacarpal, an osteosclerotic distal radius, and a dense diaphyseal segment of an ulna where a "chalkstick" break remained incompletely healed after 2 yr. There was new L4 spondylolysis, and previous L5 spondylolysis had caused spondylolisthesis. Modeling disturbances of OPT persisted, but partial recovery was shown by metaphyseal surfaces with a unique concave shape. Metaphyseal osteosclerosis had remodeled imperfectly to become focal areas of dense, diaphyseal bone. Newer metaphyseal bone was unexpectedly osteopenic, especially in his distal femurs where cortices were thin and a paucity of trabeculae was documented by CT. Femoral necks had become short and wide with an abnormal contour. A "bone-within-bone" configuration was now present throughout his skeleton. In vertebrae, endplates were thin, and trabecular osteopenia was present central and peripheral to the bands of osteosclerosis. BMD Z-scores assessed by DXA had decreased into the normal range in his spine, hip, and whole body. Iliac crest biopsy showed active bone formation, with much less accumulated primary spongiosa than during the PMD infusions. Osteoclasts that had been dysmorphic, round cells without polarization and off of bone surfaces were now unremarkable in number, location, and appearance. In conclusion, bisphosphonate toxicity during childhood can impair skeletal modeling and remodeling with structural changes that evolve and carry into adult life. [source] Bilateral Femoral Head Osteonecrosis After Septic Shock and Multiorgan Failure,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2004Mark J Bolland Abstract A case of bilateral femoral head osteonecrosis after septic shock is presented. We suggest that the osteonecrosis was caused by ischemic insults to the proximal femora. The association between septic shock and osteonecrosis has not been previously reported. Introduction: Osteonecrosis is an uncommon disorder characterized by the in situ death of bone. A diverse range of conditions has been associated with osteonecrosis. We present a case of bilateral femoral head osteonecrosis that occurred after an episode of septic shock. Materials and Methods: A 66-year-old woman presented with a left-sided renal stone and a urinary tract infection. Her condition rapidly progressed to a life-threatening illness with septic shock complicated by multiorgan failure, which necessitated prolonged intensive care and inotropic support. She made a full recovery but 3 months later developed bilateral osteonecrosis of the femoral heads requiring bilateral total hip joint replacement. Results and Conclusions: We propose that the osteonecrosis was caused by ischemic insults to the femoral heads as a result of the widespread systemic ischemia that occurred during her initial illness. To our knowledge, septic shock has not been previously described as a cause of osteonecrosis. Clinicians should be aware of this association, particularly in patients presenting with bone pain after episodes of sepsis. [source] Harvesting peripheral blood progenitor cells from healthy donors: retrospective comparison of filgrastim and lenograstimJOURNAL OF CLINICAL APHERESIS, Issue 3 2005Massimo Martino Abstract Mobilization of CD34+ into peripheral blood is attained by either glycosylated (lenograstim) or non-glycosylated recombinant G-CSF (filgrastim). 101 donors, 57 males, median age 42 years (range 16,63) entered this retrospective study. Group I (55 cases) received filgrastim and group II lenograstim subcutaneously for 5,6 days. The peak number of CD34+ cells/,l blood observed on day 4 and 5 was not significantly different in the two groups. No differences were shown in terms of both circulating CFU-GM at the time of harvesting and CD34+ target of collection. The most frequent side effects were bone pain (18.2% grade I; 36.4% grade II, 7.3% grade III), headache (18.2%), nausea (9.1%), fever (5.5%) and a mild splenomegaly (>2cm) (5.5%) in filgrastim group, and bone pain (37.0% grade I, 26.1% grade II, 2.2% grade III), headache (17.4%), nausea (15.2%), fever (4.4%) and a mild splenomegaly (4.3%) in lenograstim group, respectively. CD34+ collection was associated with thrombocytopenia, which was not significantly different between the two groups. No donor in either group developed long-term adverse effects. We conclude that both G-CSFs are comparable in terms of CD34+ cell collection, safety and tolerability. J. Clin. Apheresis © 2005 Wiley-Liss, Inc. [source] Double-Blind Placebo-Controlled Trial of Adjuvant Pamidronate with Palliative Radiotherapy and Intravenous Doxorubicin for Canine Appendicular Osteosarcoma Bone PainJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2009T.M. Fan Background: Canine osteosarcoma (OSA) causes focal malignant osteolysis leading to severe pain. Despite the documented efficacy of radiotherapy or IV aminobisphosphonates for managing cancer bone pain, their potential combined therapeutic value has not been reported in OSA-bearing dogs. Hypothesis: Pamidronate combined with standardized palliative therapy will improve pain control and bone biologic effects in OSA-bearing dogs. Animals: Fifty dogs with appendicular OSA treated with standardized palliative therapy and either pamidronate or sterile saline. Methods: Randomized, prospective, double-blinded, placebo-controlled study. Treatment responses for dogs receiving standardized palliative therapy with (n = 26) or without (n = 24) adjuvant pamidronate were serially evaluated for changes in subjective pain scores, urine N-telopeptide (NTx) excretion, primary tumor relative bone mineral density (rBMD), and computerized pressure platform gait analysis. Results: Median duration of subjective pain relief for dogs treated with adjuvant pamidronate or placebo was 76 and 75 days, respectively (P= .39). Forty percent (20/50; pamidronate [11/26] and placebo [9/24]) of dogs experienced durable analgesia, defined by pain alleviation ,112 days. For patients achieving durable pain control, dogs treated with pamidronate achieved greater reductions in NTx excretion and larger increases in rBMD compared with placebo controls. Changes in peak vertical force assessed by computerized pressure platform gait analysis correlated with pain alleviation in OSA-bearing dogs. Conclusions and Clinical Importance: Combining pamidronate with standardized palliative therapy is safe, but does not clearly improve pain alleviation. However, in dogs achieving durable pain control, adjuvant pamidronate appears to decrease focal bone resorption in the local tumor microenvironment. [source] Single-Agent Pamidronate for Palliative Therapy of Canine Appendicular Osteosarcoma Bone PainJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2007Timothy M. Fan DVM Background:Canine appendicular osteosarcoma (OSA) causes focal bone destruction, leading to chronic pain and reduced quality-of-life scores. Drugs that inhibit pathologic osteolysis might provide additional treatment options for managing cancer-induced bone pain. Aminobisphosphonates induce osteoclast apoptosis, thereby reducing pain associated with malignant osteolysis in human patients with cancer. Hypothesis:Treatment of dogs with pamidronate administered intravenously will alleviate bone pain and reduce pathologic bone turnover associated with appendicular OSA in dogs. Animals:Forty-three dogs with naturally occurring appendicular OSA administered pamidronate intravenously. Methods:Prospective study. Therapeutic responses in dogs treated with pamidronate administered intravenously and nonsteroidal anti-inflammatory drugs (NSAID) were evaluated by using a numerical cumulative pain index score (CPIS), and by quantifying urine N-telopeptide (NTx) excretion and relative primary tumor bone mineral density (rBMD) assessed with dual energy x-ray absorptiometry. In addition, variables, including pamidronate dose, skeletal mass, baseline and change for CPIS, urine NTx and rBMD during treatment, and baseline tumor volume and radiographic pattern were compared between dogs clinically responsive and nonresponsive to pamidronate therapy. Results:Twelve of 43 dogs (28%) had pain alleviation for > 4 months, lasting a median of 231 days. Changes in CPIS and rBMD during treatment were statistically different between responders and nonresponders (P= .046 and .03, respectively). Conclusions and Clinical Importance: Substantiated by reductions in CPIS and increases in rBMD, single-agent pamidronate administered intravenously with NSAID therapy relieves pain and diminishes pathologic bone turnover associated with appendicular OSA in a subset of dogs. [source] Pro-Opiomelanocortin Expression in a Metastatic Breast Carcinoma with Ectopic ACTH SecretionTHE BREAST JOURNAL, Issue 4 2004Marie-Françoise Pelte MD Abstract: Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation., [source] Periostitis Secondary to Prolonged Voriconazole Therapy in Lung Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009T. F. Wang We report five cases of possible drug-induced periostitis associated with long-term use of voriconazole therapy after lung transplantation (LT). The diagnosis of periostitis was made by the documentation of bone pain, elevation of serum alkaline phosphatase and characteristic findings on radionuclide bone imaging in the absence of any identifiable rheumatologic disease. This periostitis appears similar to hypertrophic osteoarthopathy (HOA) but does not meet all criteria for HOA. In all patients, the symptoms resolved rapidly after discontinuation of voriconazole therapy. Awareness of this potential syndrome, which manifests as bone pain, elevated serum alkaline phosphatase and a bone scan suggestive of periostitis, is necessary in LT recipients on long-term voriconazole. [source] The dental implications of bisphosphonates and bone diseaseAUSTRALIAN DENTAL JOURNAL, Issue 2005A. Cheng Abstract In 2002/2003 a number of patients presented to the South Australian Oral and Maxillofacial Surgery Unit with unusual non-healing extraction wounds of the jaws. All were middle-aged to elderly, medically compromised and on bisphosphonates for bone pathology. Review of the literature showed similar cases being reported in the North American oral and maxillofacial surgery literature. This paper reviews the role of bisphosphonates in the management of bone disease. There were 2.3 million prescriptions for bisphosphonates in Australia in 2003. This group of drugs is very useful in controlling bone pain and preventing pathologic fractures. However, in a small number of patients on bisphosphonates, intractable, painful, non-healing exposed bone occurs following dental extractions or denture irritation. Affected patients are usually, but not always, over 55 years, medically compromised and on the potent nitrogen containing bisphosphonates, pamidronate (Aredia/Pamisol), alendronate (Fosamax) and zolendronate (Zometa) for non-osteoporotic bone disease. Currently, there is no simple, effective treatment and the painful exposed bone may persist for years. The main complications are marked weight loss from difficulty in eating and severe jaw and neck infections. Possible preventive and therapeutic strategies are presented although at this time there is no evidence of their effectiveness. Dentists must ask about bisphosphonate usage for bone disease when recording medical histories and take appropriate actions to avoid the development of this debilitating condition in their patients. [source] A randomized study of docetaxel and dexamethasone with low- or high-dose estramustine for patients with advanced hormone-refractory prostate cancerBJU INTERNATIONAL, Issue 3 2006THOMAS NELIUS OBJECTIVE To test the combination of docetaxel with two different doses of estramustine in patients with hormone-refractory prostate cancer (HRPC), to improve response rates and to lower side-effects, as docetaxel-based chemotherapy is an increasing option for men with advanced HRPC, and alone or combined with estramustine, docetaxel improves median survival. PATIENTS AND METHODS In all, 72 patients with metastatic HRPC were randomly assigned to receive docetaxel (70 mg/m2 intravenously, on day 2 every 21 days) and estramustine (3 × 280 mg/day oral starting 1 day before docetaxel, for 5 consecutive days) for arm A, or estramustine (3 × 140 mg/day oral starting 1 day before docetaxel, for 3 consecutive days) for arm B. Premedication with oral dexamethasone at a total daily dose of 16 mg, in divided doses twice a day was administered in arm A on day 1,5 and in arm B on day 1,3. Initially, six cycles were administered. Chemotherapy was restarted after a significant increase in prostate-specific antigen (PSA) level. Patients were monitored for any measurable PSA response and toxicity. RESULTS Between the arms there was no statistically significant difference in time to progression and overall survival. However, treatment B had less treatment-related toxicity than A. Independent prognostic variables were baseline factors like PSA level, haemoglobin level, Eastern Cooperative Oncology Group performance status, and bone pain at presentation. CONCLUSIONS In this randomized phase II study the combination of docetaxel and estramustine had substantial activity in HRPC, with a significant incidence of severe toxicity, both haematological and not. Nevertheless, treatment-related toxicity was predictable and manageable. There was no better effect with a higher dose of estramustine with docetaxel than for a lower dose. There was a slight tendency to higher toxicity for high-dose estramustine but this was not statistically significant. The present results support the assertion that estramustine is not necessary in docetaxel-based treatment regimens. [source] Long-term outcome of antiandrogen monotherapy in advanced prostate carcinoma: 12-year results of a phase II studyBJU INTERNATIONAL, Issue 6 2003V. Serretta OBJECTIVE To present the long-term outcome of patients with locally advanced or metastatic prostate carcinoma treated by first-line antiandrogen monotherapy. PATIENTS AND METHODS From 1983 to 1990, 41 patients with advanced prostate carcinoma were treated with flutamide monotherapy until progression or the appearance of toxicity. Twenty-five patients (61%) had T3-T4N0M0 and 16 (39%) T2,4N0,3M1 prostate carcinoma. Consensus criteria were adopted to evaluate the response. Plasma testosterone and sexual function were recorded for the first 3 years. RESULTS Flutamide was administered for up to 147 months; seven patients (17%) interrupted the treatment because of toxicity. There was an objective response in 17 (41%) patients; 20 (49%) had stable disease while four (10%) progressed. There were objective responses, lasting up to 150 months, in 82% of those with M0 and in 18% with M1 disease (P = 0.05). The median time to progression in patients with an objective response and stable disease was 45 and 16 months, respectively (P < 0.001). Thirty-one patients (76%) died from prostate cancer and 10 (24%) from unrelated diseases. The median survival was 67 and 36 months in patients with an objective response and stable disease, respectively (P < 0.001). There was an improvement in performance status in 85% and reduction in bone pain in 83% of the patients; sexual activity was maintained in 63%. CONCLUSION Monotherapy with flutamide is well tolerated. Objective responses are more frequent in patients with locally advanced disease. Patients with an objective response within 6 months have a prolonged progression-free and overall survival. [source] A phase 1 trial of 2 dose schedules of ABT-510, an antiangiogenic, thrombospondin-1-mimetic peptide, in patients with advanced cancer,CANCER, Issue 12 2008Michael S. Gordon MD Abstract BACKGROUND. ABT-510 is a substituted nonapeptide that mimics the antiangiogenic activity of the endogenous protein thrombospondin-1 (TSP-1). The current study was designed to establish the safety of ABT-510 in the treatment of patients with advanced malignancies on a once-daily (QD) and twice-daily dosing schedule. METHODS. Patients were randomly assigned to 1 of 6 dosing regimens: 20 mg, 50mg, or 100 mg QD or 10 mg, 25 mg, or 50 mg twice daily. ABT-510 was administered by subcutaneous bolus injection in cycles of 28 days. Tumor response and disease progression were monitored at 8-week intervals by computed tomography scan or magnetic resonance imaging. RESULTS. Thirty-six patients were randomly assigned in equal numbers to the 6 study regimens, with an additional 13 patients randomized to the 10-mg-twice-daily and 50-mg-twice-daily ABT-510 regimens. The expected pharmacokinetic target was achieved at all dose levels tested. The majority of adverse events were grade 1 or 2 (according to National Cancer Institute Common Toxicity Criteria [version 2]) and were not found to be dose related. The most frequently reported adverse events that were possibly related to ABT-510 included injection site reactions, asthenia, headache, and nausea. Grade 3 events considered to possibly be related included nausea, dyspnea, bone pain, constipation, vomiting, asthenia, and chills and tremors. One partial response was observed in a patient with carcinosarcoma who received 20 mg QD. The 6-month progression-free survival rate was 6%. Approximately 42% of patients (21 of 50 patients) had stable disease for ,3 months. CONCLUSIONS. ABT-510 can be administered at doses of 20 mg/day to 100 mg/day without significant toxicity. In the current study, minimal antitumor activity was observed, which was similar to observations in other single-agent antiangiogenic trials. Cancer 2008. © 2008 American Cancer Society. [source] Kaposi sarcoma of the musculoskeletal systemCANCER, Issue 6 2007A review of 66 patients Abstract Kaposi sarcoma (KS) of bone and skeletal muscle is unusual. In this report, the authors review 66 published patients with KS who had involvement of the musculoskeletal system reported from 1925 to 2006. In only 3 patients was acquired immunodeficiency syndrome (AIDS)-related KS identified within skeletal muscle. Osseous KS lesions were more frequent and occurred with African, classic, and AIDS-related KS and occurred rarely in transplantation-associated KS. Patients seldom were asymptomatic. They usually had bone pain with limited mobility or infrequently developed serious sequelae like spinal cord compression. Locally aggressive African and classic KS lesions typically involved the peripheral skeleton; whereas, in patients with AIDS, the axial (vertebrae, ribs, sternum, and pelvis) and/or maxillofacial bones more commonly were involved. Almost all patients had concomitant nonosseous KS lesions. Joint involvement was exceptional, and pathologic fractures were not observed. Computed tomography scans and magnetic resonance images were better at detecting osseous KS lesions, which frequently went undetected on plain x-ray films or bone scans. Pathologic diagnosis was important to exclude similar lesions like bacillary angiomatosis. Treatment options, including surgery and, in more recent patients, radiation and/or chemotherapy, had limited success. Cancer 2007 © 2007 American Cancer Society. [source] Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acidCANCER, Issue 1 2005Chiara Pilatrino M.D. Abstract BACKGROUND The authors investigated the efficacy and safety of the histone deacetylase inhibitors valproic acid (VPA) and all-trans retinoic acid (ATRA) as differentiation agents in a cohort of older, poor-risk patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). METHODS Twenty older patients with recurrent or refractory AML or MDS were treated in a Phase II protocol with sequential VPA and ATRA therapy. VPA was started at a dose of 10 mg/kg per day and then escalated to achieve the serum concentration of 45,100 ,g/mL. ATRA was added at 45 mg/square meters (sm) per day when VPA reached the target serum concentration. Only patients treated continuously for , 2 months were considered evaluable. RESULTS Hematologic improvement, according to World Health Organization criteria, was observed in 6 of 20 patients enrolled in the protocol but in 6 of 11 considered evaluable. In five patients, a major platelet response was observed, achieving platelet transfusion independence. Three of these five patients also exhibited a minor erythroid response. A sixth patient showed both a minor erythroid response and a platelet response. The median duration of response was 189 days (range, 63,550 days). No significant reduction in the blast count was observed. Grade 3 neurocortical toxicity was observed in four patients. Severe bone pain was experienced by 4 patients (2 Grade 4 and 2 Grade 3) and was associated with an increase in the peripheral blast cell count. Treatment with ATRA did not modify the response observed with VPA alone. CONCLUSIONS Differentiation therapy with VPA was of clinical benefit in approximately 30% of elderly patients with AML and MDS of the refractory anemia with excess of blast type with unfavorable prognostic features. A striking platelet transfusion independence lasting several months may be obtained in some patients, reducing the burden of palliative care and improving the quality of life. Cancer 2005;. © 2005 American Cancer Society. [source] Zoledronic acid delays the onset of skeletal-related events and progression of skeletal disease in patients with advanced renal cell carcinomaCANCER, Issue 5 2003Allan Lipton M.D. Abstract BACKGROUND The objective of this study was to assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to renal cell carcinoma (RCC). METHODS A retrospective subset analysis of patients with RCC enrolled in a multicenter, randomized, placebo-controlled study of zoledronic acid was performed. Patients were randomized to receive zoledronic acid (4 or 8 mg as a 15-minute infusion) or placebo with concomitant antineoplastic therapy every 3 weeks for 9 months. The primary efficacy analysis was the proportion of patients with one or more skeletal-related events (SREs), which were defined as pathologic fracture, spinal cord compression, radiation therapy, or surgery to bone. Secondary analyses included time to first SRE, skeletal morbidity rate (events per year), disease progression, and multiple event analysis. RESULTS In this subset of 74 patients with RCC, zoledronic acid (4 mg) was found to significantly reduce the proportion of patients with an SRE (37% vs. 74% for placebo; P = 0.015). Similarly, zoledronic acid significantly reduced the mean skeletal morbidity rate (2.68 vs. 3.38 for placebo; P = 0.014) and extended the time to the first event (median not reached vs. 72 days for placebo; P = 0.006). A multiple event analysis demonstrated that the risk of developing an SRE was reduced by 61% compared with placebo (hazard ratio of 0.394; P = 0.008). The median time to progression of bone lesions was significantly longer for patients who were treated with zoledronic acid (P = 0.014 vs. placebo). Zoledronic acid appeared to be well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and emesis. CONCLUSIONS Zoledronic acid (4 mg as a 15-minute infusion) demonstrated significant clinical benefit in patients with bone metastases from RCC, suggesting that further investigation of zoledronic acid in this patient population is warranted. Cancer 2003;98:962,9. © 2003 American Cancer Society. DOI 10.1002/cncr.11571 [source] Effectiveness and cost of bisphosphonate therapy in tumor bone diseaseCANCER, Issue S3 2003Jean-Jacques Body M.D., Ph.D. Abstract BACKGROUND Tumor-induced osteolysis due to breast carcinoma and myeloma is responsible for a considerable morbidity that severely impairs patients'quality of life. Osteoclast-mediated bone resorption is reported to be increased markedly in patients with tumor bone disease and can be inhibited by bisphosphonate therapy. METHODS The incidence of skeletal complications and the effectiveness of bisphosphonate therapy in patients with breast carcinoma metastatic to bone or in those with myeloma were derived from large-scale, long-term, placebo-controlled trials with clodronate or pamidronate. To the authors' knowledge, there are few studies published to date evaluating the cost-effectiveness of bisphosphonate therapy, and the majority that do exist often are based on models and are applicable only to a particular health care system. RESULTS From the placebo groups of the above-mentioned trials, one can estimate that approximately 25,40% of the patients with breast carcinoma metastatic to bone will require radiotherapy for bone pain and approximately 17,50% will sustain incident vertebral fractures yearly. The incidence of complications is reported to be lower in myeloma patients. The prolonged administration of bisphosphonates reportedly can reduce the frequency of skeletal-related events by approximately 25,50%. Maximal efficacy appears to have been achieved with the current therapeutic schemes based on monthly intravenous infusions. Beneficial effects appear to be obtained more readily using the intravenous route rather than the oral route. The costs of bisphosphonate therapy appear to be higher than the cost savings from the prevention of skeletal-related events. The costs per quality of life-adjusted year have been estimated to be > $100,000, but more research is needed. Limited data suggest that zoledronic acid will not reduce treatment costs but the short infusion time will lead to substantial time savings for patients and for outpatient oncology facilities. CONCLUSIONS As is the case for many agents used in oncology, bisphosphonates remain a relatively expensive therapy. More studies are needed to evaluate their cost-effectiveness ratio correctly. A ceiling effect has been reached with current therapeutic schemes and tailoring therapy to the individual patient needs to be evaluated correctly to increase therapeutic effectiveness and improve quality of life further without increasing treatment costs. Cancer 2003;97(3 Suppl):859,65. © 2003 American Cancer Society. DOI 10.1002/cncr.11139 [source] The effect of enzyme replacement therapy on bone crisis and bone pain in patients with type 1 Gaucher diseaseCLINICAL GENETICS, Issue 3 2007J Charrow The effect of enzyme replacement therapy (ERT) on bone crisis and bone pain was investigated in patients with Gaucher disease (GD) type 1 followed over 4 years. Data from the International Collaborative Gaucher Group Gaucher Registry were used. Only patients with bone crisis and/or bone pain data for 1 year prior to ERT, and for each of 3 years after the start of ERT, were included. Bone crises were reported in 17% of patients during the year before starting ERT. The frequencies of bone crises decreased to 5%, <1% and 3% for 1, 2, and 3 years after initiation of treatment, respectively (p < 0.0001). Bone pain followed a similar pattern of response. Bone pain was reported in 49% of patients the year before treatment and decreased to 30% in the first year, 29% in the second year, and 30% in the third year of ERT (p < 0.0001). ERT is associated with a reduction in bone crisis and bone pain in patients with GD type 1 . This study shows that significant improvements in symptoms of skeletal disease are achievable clinical outcomes and treatment goals in GD type 1. [source] Hypercalcaemia of malignancy: an undiagnosed and undertreated diseaseJOURNAL OF INTERNAL MEDICINE, Issue 1 2001O. Lamy Lamy O, Jenzer-Closuit A, Burckhardt P (University Hospital, Lausanne, Switzerland). Hypercalcaemia of malignancy: an undiagnosed and undertreated disease. J Intern Med 2001; 250: 73,79. Background.,Hypercalcaemia of malignancy, a relatively frequent phenomenon, seems to be insufficiently recognized and treated. Its symptoms are not specific, but they affect the quality of life. Methods.,A prospective study to analyse the influence of symptoms caused by hypercalcaemia on the decision of the admitting physician, the motivation for treatment, and the effect of the treatment on the given symptoms in hospitalized patients with oncologic disease in progression, where confounding causes of similar symptoms such as cerebral metastasis, radiotherapy, treatment with opioids, etc., were excluded. Results.,A total of 71 patients, mean age 65 + 11 years, fulfilled the strict inclusion criteria. About 42% were hospitalized because of symptoms caused by hypercalcaemia, but none of the medical reports mentioned hypercalcaemia as reason for hospitalization. Specific antihypercalcaemic therapy was given to only 37% of patients, and only 25% got an adequate rehydratation. Antihypercalcaemic treatment was guided by the severity of hypercalcaemia (>3.00 mmol L,1), not by the symptoms. Polyuria-polydipsia, nausea-vomiting and constipation were correlated with hypercalcaemia. These symptoms, as well as confusion-stupor and bone pains improved significantly when calcaemia was normalized. Patients with calcaemia normalized returned home most frequently (P < 0.03). Conclusions.,Malignant hypercalcaemia remains mostly undiagnosed in medical praxis. Specific treatment occurs in too small fractions of the patients. As the normalization of calcaemia significantly improves the symptoms because of hypercalcaemia and the quality of life, rapid rehydration and specific calcium lowering treatments should be part of palliative measures in all patients with malignant hypercalcaemia. [source] |