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1.
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.  相似文献   

2.
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 ( r BMD), 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 r BMD 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.  相似文献   

3.
Introduction: Dogs with appendicular osteosarcoma (OSA) excrete higher concentrations of urine cross‐linked N‐telopeptide of type I collagen (NTx) than normal dogs. NTx is a specific biochemical marker of osteoclastic activity. Pamidronate is a bone‐modulating agent that exerts potent inhibitory effects on osteoclasts. The use of pamidronate is currently being evaluated for the management of osteolytic bone pain in dogs with appendicular osteosarcoma. Despite pamidronate's increasing usage in veterinary oncology, optimal dosing has yet to be determined. Commonly utilized dosages range from 1–2 mg/kg, given intravenously (IV) as a 2‐hour constant rate infusion every 28 days. The purpose of this prospective study was to compare the biological activity of two pamidronate doses (1 mg/kg vs. 2 mg/kg) in the suppression of urine NTx excretion in normal dogs and dogs with appendicular osteosarcoma. Methods: Seventeen OSA dogs receiving single‐agent pamidronate as palliative therapy were evaluated. Group 1A (n = 10) received a dose of 1 mg/kg and group 2A (n = 7) received a dose of 2 mg/kg IV. Urine NTx level were measured at day 0 and 28 using a commercial ELISA (Ostex International). Urine NTx level were also measured in 6 normal dogs: Group 1B (n = 3) received a dose of 1 mg/kg and group 2B (n = 3) received a dose of 2 mg/kg. In normal dogs, urine NTx levels were recorded weekly for six consecutive weeks. Results: In dogs with osteosarcoma, greater reductions in urine NTx excretion from baseline values were demonstrated at 2 mg/kg versus 1 mg/kg (57% and 23%, respectively). Likewise, in normal dogs, urine NTx excretion was suppressed to a greater extent with a dosage of 2 mg/kg versus 1 mg/kg (69% and 23%, respectively). Conclusion: Pamidronate possesses biologic activity in both normal dogs and in dogs with osteosarcoma, as assessed by reductions in urine NTx excretion. Based upon reductions in urine NTx excretion, a dosage of 2 mg/kg appears more effective than 1 mg/kg.  相似文献   

4.
Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti‐tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post‐operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease‐free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment.  相似文献   

5.
Objective: To report outcome in dogs after internal fixation of a sarcoma‐related pathologic fracture of the appendicular skeleton. Study Design: Multi‐institutional case series. Animals: Dogs (n=16). Methods: Medical records of participating VSSO members were reviewed for dogs with pathologic fracture associated with a confirmed bone sarcoma of the appendicular skeleton repaired by external or internal fixation. Dogs were included if they had a histological diagnosis of osteosarcoma or sarcoma and excluded if they had radiation before fracture. Data collected were analyzed for signalment, fracture location, staging performed, method of fracture fixation, histopathology, adjunctive treatment and outcome. Results: Signalment and fracture location of 16 dogs that met the inclusion criteria was similar to dogs with appendicular OSA without fracture. One of 14 dogs had pulmonary metastasis and 3 of 5 dogs had bone metastasis. Bone plate or interlocking nail were used for repair in 12 dogs. Limb use immediately after surgery in 13 dogs was good (4), weight‐bearing but lame (7) and non‐weight bearing (2). Adjunctive therapy was administered in 5 dogs (chemotherapy, 3; radiation, 4; pamidronate, 3). Survival time ranged from 18 to 897 days; median survival was 166 days. Conclusions: Repair of pathologic fracture can result in palliation and prolonged survival.  相似文献   

6.
The purpose of this study was to evaluate the clinical safety of pamidronate when administered at a mean dosage of 1.0 mg/kg IV q28d in 33 tumor-bearing dogs. Biochemical tests of renal function were evaluated before each successive pamidronate treatment. Of 33 dogs treated with pamidronate, 1 dog had clinically relevant increases in serum creatinine and blood urea nitrogen concentrations. The biologic activity of IV pamidronate was assessed prospectively in 10 dogs with appendicular osteosarcoma and was assessed on reductions in urine N-telopeptide excretion (P = .042) and enhanced bone mineral density of the primary tumor measured with dual-energy x-ray absorptiometry (P = .024). Additionally, in these 10 dogs, pamidronate's therapeutic activity was supported by subjective improvement in pain control in 4 of the 10 dogs treated. IV pamidronate appears clinically safe in tumor-bearing dogs and may possess modest biologic activity for managing neoplastic complications associated with pathologic bone resorption.  相似文献   

7.
Canine appendicular osteosarcoma (OSA) is a commonly diagnosed cancer that is capable of inducing pathologic bone remodeling. Investigating surrogate indices of bone metabolism may contribute to the diagnostic and therapeutic management of bone malignancies in companion animals. This study evaluated the excretion of N-terminal telopeptide (NTx), a marker of bone resorption that is detected in urine. Sixty-three dogs with appendicular OSA were compared with 29 age-matched healthy dogs. Dogs with appendicular OSA had significantly higher baseline urine NTx excretion than healthy controls (P < .0001). In 17 dogs with OSA treated with either amputation or standardized palliative therapies, significant reductions in urine NTx excretion were observed, suggesting that excessive bone resorption in dogs with OSA may be linked with focal skeletal osteolysis or its consequences. To identify any relationship between indicators of pathologic bone turnover, baseline urine NTx excretion was correlated with serum bone alkaline phosphatase (bALP) or radiographic tumor lengths at diagnosis. No significant correlations were identified between baseline urine NTx excretion and either bALP or tumor length. The findings from this study suggest that high urinary NTx excretion may support the diagnosis of focal skeletal osteolysis in dogs, and reductions in urine NTx excretion after treatment may reflect elimination or minimization of pathologic bone resorption.  相似文献   

8.
Background: Appendicular osteosarcoma (OSA), the most common bone tumor in dogs, is typically treated by amputation and adjuvant chemotherapy. Despite numerous efforts, the median survival time (MST) for dogs receiving a platinum compound, doxorubicin, or a combination of these remains at 8–12 months. Evidence from studies in mice suggests that gemcitabine has activity against OSA in vivo. Our preliminary work demonstrated that the addition of low‐dosage (10 mM) gemcitabine to carboplatin resulted in synergistic inhibition of OSA cell viability in vitro. Objective: The purpose of the following study was to determine whether the addition of low‐dosage (2 mg/kg) gemcitabine to carboplatin chemotherapy in dogs with OSA after amputation would improve MST over carboplatin monotherapy. Animals: Fifty dogs with histologically confirmed appendicular OSA. Methods: Dogs were treated prospectively with amputation and up to 4 dosages of carboplatin and gemcitabine in combination every 3 weeks. Results: The chemotherapeutic regimen was well tolerated with only 5 episodes of grade 3 or 4 hematologic toxicity. The median disease‐free interval (DFI) was 203 days and the MST was 279 for all dogs in this study. The 1‐ and 2‐year survival rates were 29.5 and 11.3%, respectively. Dogs with proximal humeral OSA had a shorter median DFI (P= .04) compared with dogs with OSA in other locations. Conclusions and Clinical Importance: These results are comparable to those reported for carboplatin monotherapy indicating that the addition of gemcitabine to carboplatin in dogs with appendicular OSA does not appear to improve outcome.  相似文献   

9.
BACKGROUND: Malignant osteolysis is a process whereby cancer cells in concert with osteoclasts erode bone matrix. Aminobisphosphonates (NBPs) such as zoledronate induce osteoclast apoptosis and thereby decrease malignant skeletal destruction, severity of bone pain, and frequency of pathologic fracture. HYPOTHESIS: IV-administered zoledronate will reduce homeostatic bone turnover in healthy dogs and pathologic bone resorption in dogs diagnosed with primary and secondary bone tumors. ANIMALS: Six healthy dogs and 20 dogs with naturally occurring primary or metastatic bone tumors were administered zoledronate IV. METHODS: Prospective study: In all dogs, healthy (n = 6) and with malignant osteolysis (n = 20), the bone biologic effects of zoledronate were evaluated by quantifying changes in serum C-telopeptide (CTx) or urine N-telopeptide (NTx) concentrations or both. In dogs with osteosarcoma (OSA) (n = 10), serial changes in tumor relative bone mineral density (rBMD) assessed by dual-energy x-ray absorptiometry were used to characterize zoledronate's antiresorptive effects within the immediate tumor microenvironment. Additionally, the biochemical tolerability of zoledronate was assessed in 9 dogs receiving multiple (> or =2) consecutive treatments. RESULTS: All dogs had significant reductions in serum CTx or urine NTx concentrations or both after zoledronate administration. In a subset of dogs with appendicular OSA, reduced urine NTx concentrations and increased primary tumor rBMD coincided with improved limb usage as reported by pet owners in dogs treated with zoledronate and concurrent oral analgesics. Multiple zoledronate infusions were not associated with biochemical evidence of toxicosis. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with skeletal neoplasms, IV-administered zoledronate exerts bone biologic effects, appears safe, and can provide pain relief.  相似文献   

10.
Background: Identification of biomarkers that predict outcomes in dogs with osteosarcoma (OSA) would be valuable to veterinarians and owners. Leukocyte numbers in peripheral blood are associated with outcomes in some types of cancer in humans. Hypothesis/Objectives: We hypothesized that increased numbers of monocytes would be associated with reduced disease‐free interval (DFI) in dogs with OSA. Animals: Medical data from 69 dogs with appendicular OSA treated with amputation and chemotherapy were selected for study. Methods: Retrospective study. Statistical associations were assessed by univariate and multivariate analysis. Information about DFI and leukogram values, tumor location, and serum alkaline phosphatase was abstracted from the medical record. Results: Higher numbers of circulating monocytes (>0.4 × 103 cells/μL) and lymphocytes (>1.0 × 103 cells/μL) before treatment were found to be significantly (P < .05) associated with shorter DFI in dogs with OSA. Other parameters associated with poor outcomes were increased alkaline phosphatase, primary tumor location, and age. Conclusion and Clinical Importance: These results indicated that pretreatment evaluation of monocyte and lymphocyte counts provided prognostic information for dogs with appendicular OSA. Notably, most animals in this study had monocyte counts within the normal reference range, indicating that variations within the reference range of leukocyte values might also have prognostic significance.  相似文献   

11.
Osteosarcoma (OSA) is the most common primary bone tumor diagnosed in dogs. Our understanding of the risk factors and genetic changes in canine OSA patients is growing, but specific, innovative therapeutic strategies are slow in coming. Appendicular skeletal osteosarcoma, the most frequent form of this disease, is typically seen in large to giant breeds, with males being overrepresented in most reports. Axial skeletal OSA is less common than appendicular OSA, but the biologic behavior of the disease is equally aggressive in all skeletal sites except for the mandible. Though the current standard of care for dogs with osteosarcoma remains surgical resection of the affected site, followed by chemotherapy with either a platinum- (cisplatin or carboplatin) or doxorubicin-based protocol, novel therapies are being actively investigated.  相似文献   

12.
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13.
The objective was to determine signalment-related differences in bone mineral content (BMC) and bone mineral density (BMD) in dogs. Unilateral appendicular bones were harvested from 62 canine cadavers. Mid-diaphyseal regions of interest (ROIs) were scanned using a Hologic DXA device Braincon, Vienna, Austria). BMC and BMD were calculated within this region. Middle-aged dogs (3-10 years) revealed the highest BMC and BMD levels. Mean BMC and BMD were higher in males compared to females. Furthermore, body-weight of the male dogs was significantly higher compared to the females (P < 0.0001). Body weight and bone length were significantly associated with BMC and BMD (P < or = 0.023) in all bones but the radius. These data suggest that BMC and BMD appear to be highest in male large-breed dogs with a body weight greater than 30 kg. These results may help determine risk factors in fracture development and healing.  相似文献   

14.
Osteosarcoma (OSA) is the most common primary bone tumour in dogs. The appendicular locations are most frequently involved and large to giant breed dogs are commonly affected, with a median age of 7–8 years. OSA is a locally invasive neoplasm with a high rate of metastasis, mostly to the lungs. Due to similarities in biology and treatment of OSA in dogs and humans, canine OSA represents a valid and important tumour model. Differences between canine and human OSAs include the age of occurrence (OSA is most commonly an adolescent disease in humans), localisation (the stifle is the most common site of localisation in humans) and limited use of neoadjuvant chemotherapy in canine OSA.  相似文献   

15.
Appendicular osteosarcoma (OSA) is a highly metastatic tumour in dogs. The aim of the study was to compare thoracic radiographs with thoracic computed tomography (CT) in the staging of canine appendicular OSA. In all, 39 canine patients histologically diagnosed with OSA were reviewed in the retrospective study. All dogs underwent radiographic examination as well as CT examination of the thoracic cavity. Pulmonary nodules were detected radiographically in two cases (5%), whereas the CT imaging showed that pulmonary nodules were evident in 11 cases (28%, P = 0.024). There was an improved detection of small pulmonary nodules in the lung parenchyma with CT (P = 0.021). The number of nodules in CT examination had a significant negative influence on survival time (P = 0.005). However, whether nodules were present in CT or not did not influence overall survival (P = 0.368). CT examination was superior to thoracic radiography in the screening and detection of pulmonary nodules in dogs with OSA.  相似文献   

16.
The purpose of this study was to assess the usefulness of serial bone scintigraphy in the detection of skeletal and extraskeletal metastases in dogs with appendicular osteosarcoma. Twenty-six dogs with primary, appendicular osteosarcoma were entered into a limb-sparing protocol. Bone scintigraphy was performed upon presentation, after neoadjuvant therapy but prior to surgery and at selective intervals after limb-sparing surgery to evaluate for the presence of metastasis. Thoracic radiographs, and radiographs of other sites, were also made at the time of each bone scan. All dogs had a complete necropsy. No dog had bone or lung metastases detected prior to treatment. The bone scans, medical records, and radiographs of each dog were reviewed retrospectively. All but one dog developed metastatic disease. Bone metastatic sites were confirmed at necropsy in 12 of the 26 dogs. Seven of these 12 dogs had bone metastatic sites which were not producing clinical signs, i.e. an occult metastasis. In five of the seven dogs, the occult site was the first metastatic site detected. Extraskeletal metastases were identified scintigraphically in six of the 26 dogs, but these were clinically apparent prior to bone scintigraphy in each dog. Suspected malignant scintigraphic lesions were proven benign in six dogs. In five dogs with malignant bone lesions at necropsy the last bone scan prior to euthanasia was normal. The time interval between scintigraphy and necropsy was variable in these five dogs. All dogs without bone metastases at necropsy had normal bone scans. This study validates the usefulness of bone scintigraphy for detection of occult bone metastasis and improved ability for tumor staging in dogs with appendicular osteosarcoma.  相似文献   

17.
Background: We demonstrated previously that canine osteosarcoma (OSA) cell lines and samples from clinical patients are predominantly telomerase positive. In contrast, the majority of OSA samples from human patients appear to be telomerase negative, maintaining telomere length by an alternative lengthening of telomeres (ALT) mechanism. The purpose of the current study was to examine the telomerase status of a large number of OSA samples from dogs and determine if telomerase status can serve as a prognostic factor. Hypothesis: The majority of clinical canine OSA appendicular lesions will be telomerase positive, and telomerase positivity will negatively impact disease outcome. Animals: Sixty‐seven dogs with appendicular OSA presenting to the Colorado State University Animal Cancer Center for treatment. Methods: The Telomeric Repeat Amplification Protocol was performed on tissue samples from primary canine appendicular OSA to determine the presence of telomerase activity. Telomere restriction fragment (TRF) analysis was utilized to determine telomere length and detect ALT. Outcome data were obtained in a retrospective manner and correlated with telomerase status. Results: Seventy‐three percent of canine OSA samples were telomerase positive. Telomerase status did not have an impact on disease‐free interval or survival time. Nine of 10 telomerase‐negative samples examined were consistent with an ALT phenotype, based on TRF analysis. Conclusions and Clinical Importance: These results are consistent with the hypothesis that the majority of canine OSA are telomerase positive, suggesting that telomerase may be a valuable target for canine OSA therapy. Additionally, telomerase status does not appear to be a prognostic factor in canine OSA.  相似文献   

18.
Fifteen dogs with appendicular osteosarcoma (presumptive diagnosis, n = 6 dogs; biopsy confirmed, n = 9 dogs) were treated with palliative radiotherapy. Treatment entailed a total of three 10 Gy fractions of 60Co radiation delivered over a three week period on days 0, 7 and 21, for a total dose of 30 Gy. Twelve dogs experienced improvement in limb function 7–22 days after the start of treatment. Long term followup was available for nine of the twelve responders. The duration of response was 17–288 days (n = 9 dogs; median = 130 days; mean = 116 days). Response duration did not appear to be related to initial tumor size. Palliative radiotherapy can result in improved limb function in dogs with appendicular osteosarcoma.  相似文献   

19.
Medical-records of 22 large-breed dogs (>15 kg) with osteosarcoma (OSA) of the axial skeleton were reviewed to determine prevalence of metastasis and survival associated with this neoplasm. All dogs were treated with more than 1 mode of therapy including palliative radiation (n = 12), definitive radiation (n = 8), surgery (n = 7), chemotherapy (n = 12), or some combination of these therapies. Metastasis was documented in 10 of 22 dogs (46%), and the median survival for all dogs was 137 days. Primary cause of death was local tumor recurrence (54%). Breed (retriever versus purebred versus mixed-breed survival was 100, 182, and 264 days, respectively) and radiation therapy protocol (survival in dogs treated with palliative radiation therapy versus those treated with definitive radiation therapy was 79 and 265 days, respectively) were significantly related to survival (P < .05). Prevalence of metastasis and median survival for large-breed dogs with axial skeleton OSA seems to be similar to that reported for large-breed dogs with appendicular skeleton OSA. Definitive radiation therapy may have a role in the treatment of axial skeleton osteosarcoma.  相似文献   

20.
OBJECTIVE: To compare bone mineral measurements obtained by use of dual-energy x-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), and chemical-physical analyses and determine effects of age and femur size on values obtained for the various techniques. SAMPLE POPULATION: Femurs obtained from 15 juvenile and 15 adult large-breed dogs. PROCEDURE: n each femur, 7 regions of interest were examined by use of DEXA to measure the bone mineral content (BMC) and bone mineral density (BMD), and 5 were examined by use of pQCT to measure BMD. Among these, 1 region was examined by both noninvasive methods and an invasive method. Volume of the femur was determined by water displacement. Volumetric bone density (VBD) was calculated. Calcium (Ca), phosphorus (P), total Ca, and total P contents were determined. RESULTS: DEXA- and pQCT-derived results revealed that all values increased with age in juvenile dogs. In adults, VBD and pQCT-derived BMD decreased significantly and DEXA-derived BMD increased with increasing femur length.The pQCT-derived BMD correlated well with VBD and Ca content, whereas DEXA-derived BMC was strongly correlated with Ca content. In juveniles, values correlated regardless of the technique used, whereas in adult dogs, DEXA-derived BMD did not correlate with pQCT-derived BMD, Ca concentration, or VBD unless data were adjusted on the basis of femur length. CONCLUSIONS AND CLINICAL RELEVANCE: DEXA-derived BMD adjusted for femur length yields approximately the same percentage variability in VBD as for pQCT-derived BMD. However, pQCT-derived BMD is still more sensitive for determining variability BMD in Ca concentration, compared with DEXA-derived BMD adjusted for femur length.  相似文献   

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