Evaluation of intravenous pamidronate administration in 33 cancer-bearing dogs with primary or secondary bone involvement

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.     

Single-agent pamidronate for palliative therapy of canine appendicular osteosarcoma bone pain

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.     

Double-Blind Placebo-Controlled Trial of Adjuvant Pamidronate with Palliative Radiotherapy and Intravenous Doxorubicin for Canine Appendicular Osteosarcoma Bone Pain

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.     

Adverse effects on growth performance and bone development in nursery pigs fed diets marginally deficient in phosphorus with increasing calcium to available phosphorus ratios

The objective of this experiment was to evaluate the growth performance and bone mineral content (BMC) of nursery pigs in response to increasing total calcium (Ca) to available phosphorus (aP) ratios in diets containing phytase (250 FTU/kg; Natuphos E, BASF, Florham Park, NJ). A total of 480 nursery pigs (body weight (BW) = 5.7 ± 0.6 kg) with 10 pigs per pen and 7 pens per treatment (6 pens fed 2.75:1 diet) were allotted to seven treatments consisting of increasing ratios of calcium to available phosphorus (Ca:aP): 1.25, 1.50, 1.75, 2.00, 2.25, 2.50, and 2.75. From day −7 to 0, pigs were fed a common diet. They were then fed the treatment diets during two experimental phases from day 1 to 14 and 15 to 28, respectively. Available P was formulated to 0.33% and 0.27% (approximately 90% of requirement) in dietary phases 1 and 2, respectively. BW, average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F) were determined. BMC of the femur was measured on day 28 on one pig per pen using dual x-ray absorptiometry. Data were analyzed as a linear mixed model using PROC MIXED (SAS, 9.3). Orthogonal polynomial contrasts were used to determine the linear and quadratic effects of increasing the Ca:aP. Over the 28-d experimental period, increasing Ca:aP resulted in a linear decrease in ADG (353, 338, 328, 304, 317, 291, and 280 g/d; P < 0.01), ADFI (539, 528, 528, 500, 533, 512, and 489 g/d; P < 0.05), and G:F (0.68, 0.66, 0.64, 0.62, 0.61, 0.59, and 0.58; P < 0.01). Increasing Ca:aP also resulted in decreased BW on days 14 and 28 (P < 0.01). The BMC of the femur decreased with increasing Ca:aP (6.2, 6.3, 5.7, 5.9, 5.5, 5.6, and 5.3 g; P < 0.05). Regression analysis explained the impact of Ca:aP as follows on ADG (ADG [g/d] = 339 − 36x; r² = 0.81), G:F (G:F = 0.61 – 0.03x; r² = 0.72), and BMC (BMC [g] = 6.4 – 0.27x; r² = 0.43), where x is the Ca:aP. In conclusion, all outcomes indicated that any level of calcium above the minimum used in this experiment impaired growth performance and skeletal development. Further research using even lower levels of dietary Ca is warranted.     

Intercalary bone grafts for joint and limb preservation in 17 dogs with high-grade malignant tumors of the diaphysis

OBJECTIVE: To evaluate postoperative complications, limb function, and tumor control after intercalary resection and reconstruction for preservation of limb and joint function in dogs with high-grade malignant tumors of diaphyseal bone. STUDY DESIGN: Retrospective study. ANIMALS: Seventeen client-owned dogs. METHODS: The bone tumor database and medical records were reviewed (1986-2002) for dogs with diaphyseal tumors treated with intercalary resection and reconstruction with either an allograft or irradiated autograft. Clinical presentation, diagnostic findings, surgical management, and outcome were determined from medical records and telephone interviews with veterinarians and owners. Statistical analyses included chi2 to test associations between intra- and postoperative variables with complications, and Kaplan-Meier survival analysis for disease-free interval, metastasis-free interval (MFI), and median survival time. RESULTS: Intercalary limb-sparing surgery was performed in 17 dogs with diaphyseal tumors: osteosarcoma (OSA) (15), histiocytic sarcoma (1), and solitary metastasis from a pulmonary adenocarcinoma (1). One dog was excluded from further analysis when the spared limb was amputated 4 days postoperatively because of incomplete tumor resection. In 16 dogs, limb function was good to excellent. Complications occurred in 5 dogs (31.3%) and included superficial infection in 2 dogs (12.5%) and implant failure in 4 dogs (25%). All implant failures occurred in the ulna and there was a significant association between implant failure and non-cemented allografts (P=.042). Non-union of 1 or both osteotomies was diagnosed in 10 dogs (83.3%) and, despite lack of clinical signs in all cases, was significantly associated with the use of intracavitary locally released cisplatin (P=.046) and cemented intercalary grafts (P=.046). Local tumor recurrence was diagnosed in 1 dog (6.3%) and metastatic disease in 12 dogs (75.0%), including 10 dogs with OSA. The median MFI was 137 days. The local disease-free and overall limb-salvage rate was 94% and 100%, respectively. Overall median survival time was 393 days and the median survival time for dogs with OSA was 449 days. CONCLUSION: Intercalary limb-sparing surgery results in better postoperative limb function with fewer and less severe complications than historical reports of dogs treated with non-intercalary limb-sparing surgery. CLINICAL RELEVANCE: In dogs with diaphyseal tumors, intercalary limb-sparing surgery preserves normal joint function and results in good to excellent limb use with few complications and good local tumor control.     

SPA活体测定蛋鸡胫骨骨矿含量方法及其重复性、准确度的探讨

单光子吸收法 (SPA)是活体测定人或动物骨矿含量的非侵入性方法之一。用SPA活体测定蛋鸡胫骨骨矿含量 ,探讨其测定方法的可行性、重复性及准确度。结果表明 ,以胫跖关节内侧隆起作为定位标志 ,并以距此标志 3cm处作为胫骨骨矿含量的测试部位较为理想 ,其重复性 (CV)为 7 90 % ,准确度为 2 633% (r=0 992 6,P <0 0 1 )。本试验所建立的方法 ,为研究禽类骨骼代谢疾病 (如笼养蛋鸡骨质疏松症 )奠定了基础。     

The analgesic and sedative effects of GV20 pharmacopuncture with low-dose hydromorphone in healthy dogs undergoing ovariohysterectomy

This study evaluates the analgesic efficacy of low-dose hydromorphone administered via pharmacopuncture at Governing Vessel 20 (GV20) for postoperative pain management following canine ovariohysterectomy. Fifty clinically healthy female dogs undergoing ovariohysterectomy were allocated to receive hydromorphone [0.1 mg/kg body weight (BW)] intramuscularly (IM, n = 25) or hydromorphone (0.01 mg/kg BW) pharmacopuncture at GV20 (GV, n = 25) following extubation. This was a prospective, blinded, randomized clinical trial. Pain and sedation scores were evaluated using the Glasgow Composite Measure Pain Scale Short Form (CMPS-SF) at 1, 2, 3, 4, and 12 hours following study treatment. Time of treatment failure (CMPS-SF ≥ 6/24) was recorded and analyzed using Kaplan-Meier survival analysis. Patient demographics and duration of surgery and anesthesia were analyzed using the appropriate unpaired Student’s t-test. The Glasgow CMPS-SF and sedation score were analyzed using a repeated measures 2-way analysis of variance (ANOVA) followed by Bonferroni post-test where appropriate. Significance was set a P < 0.05. There were no significant differences in patient demographics, anesthesia and surgery duration, and study treatment failure. The Glasgow CMPS-SF scores were significantly higher for IM compared with GV [2 (0 to 8) versus 1 (0 to 6), respectively; P = 0.044] at 4 hours. Sedation scores were significantly higher for IM compared with GV at 2 [2 (1 to 3) and 1 (1 to 3), respectively; P = 0.0004] and 4 [1 (1 to 3) and 1 (1 to 2), respectively; P = 0.03] hours. Pharmacopuncture with low-dose hydromorphone provided adequate postoperative analgesia in dogs undergoing ovariohysterectomy with reduced sedative effects. Pharmacopuncture is a good alternative in dogs when reduced dosing of opioids is recommended.     

Correlation between cytologic and histopathologic diagnoses of bone lesions in dogs: a study of the diagnostic accuracy of bone cytology

Background: The diagnostic value of cytology compared with histopathology varies by tissue, but there is little information regarding this comparison involving canine bone. Objectives: The objective of this retrospective study was to compare primary pathologic processes for cytology and histopathology of canine bone lesions. We adopted a proposed standardized format for reporting studies of diagnostic accuracy. Methods: A computer search of canine medical records at the University of Minnesota Veterinary Medical Center from September 2002 through October 2006 identified 52 bone cytology samples that had incisional (IncB) and/or excisional (ExcB) biopsy performed. The primary pathologic process was determined by evaluation of original reports. Cytologic vs IncB and cytologic vs ExcB were compared pairwise for agreement. Agreement was compared for neoplastic and non-neoplastic processes using the combined IncB/ExcB data, which included all ExcB (n=21) and IncB when that was the only biopsy available (n=31). Combined data were used to determine the effect of cytology cellularity on the diagnostic correlation. Results: The correlation in primary process between cytology and IncB was 71%, and for ExcB was 71%. For lesions with a cytologic diagnosis of neoplasia compared with the combined IncB/ExcB data set, cytology and histopathology agreed in 92% of cases, which was significantly greater (P<.0001, chi(2)) than the 27% for non-neoplastic processes. Cytology cellularity significantly affected rates of correlation (P=.026), with high, moderate, and poor cellularity samples having concordant primary processes in 88%, 77%, and 47% of cases, respectively. Conclusions: Cytologic diagnosis of neoplasia for samples collected from canine bone correlates better with histopathology than cytologic diagnosis of non-neoplastic proliferative processes or inflammation. Cytologic diagnoses from highly cellular samples are more likely to correlate with histopathology than those from less cellular samples.     

The immunophenotype of peripheral blood lymphocytes in clinically healthy dogs and dogs with lymphoma in remission

Lymphoma is a common cancer of dogs that frequently is treated with chemotherapy or radiation therapy. Response to therapy is variable and currently available diagnostic tests do not reliably predict response to therapy. Treatment for lymphoma often results in lymphopenia, but it is unknown whether the changes in circulating lymphocytes result from generalized or specific reduction of lymphocytes. In this study, blood lymphocytes from 12 clinically healthy dogs, 10 dogs in remission because of treatment for B-cell lymphoma, and 8 dogs in remission from T-cell lymphoma were analyzed by flow cytometry by using a panel of 20 antibodies reactive with canine leukocyte antigens. Results identified similar lymphocyte parameters in treated dogs regardless of the type of lymphoma. Treated dogs had >50% reduction in blood lymphocyte concentration, and an absolute decrease in most subsets of lymphocytes. Both groups of treated dogs had relative increases in the proportion of CD3+, T-cell receptor (TCR)αβ+, and CD90+ lymphocytes, and a decreased proportion of CD45RA+ cells. In addition, dogs with T-cell lymphoma in remission had a significant increase in the proportion of CD49d+ lymphocytes. These findings were interpreted as representing likely suppression of lymphocyte regeneration by chemotherapy, with a relative increase in the proportion of memory over naïve lymphocytes. Lack of correlation with the T- or B-cell origin of the initial lymphoma suggested that, by using flow cytometric methods, residual circulating neoplastic cells could not be detected. However, the changes in the lymphocyte profile of dogs treated with chemotherapy may have relevance to their immunocompetence.     

The pharmacokinetics and analgesic effects of extended‐release buprenorphine administered subcutaneously in healthy dogs

Buprenorphine is a partial μ agonist opioid used for analgesia in dogs. An extended‐release formulation (ER‐buprenorphine) has been shown to provide effective analgesia for 72 hr in rats and mice. Six healthy mongrel dogs were enrolled in a randomized, blinded crossover design to describe and compare the pharmacokinetics and pharmacodynamics of ER‐buprenorphine administered subcutaneous at 0.2 mg/kg (ER‐B) and commercially available buprenorphine for injection intravenously at 0.02 mg/kg (IV‐B). After drug administration, serial blood samples were collected to measure plasma buprenorphine concentrations using liquid chromatography/mass spectrometry detection. Heart rate, respiratory rate, body temperature, sedation score, and thermal threshold latency were recorded throughout the study. Median (range) terminal half‐life, time to maximum concentration, and maximum plasma concentration of ER‐buprenorphine were 12.74 hr (10.43–18.84 hr), 8 hr (4–36 hr), and 5.00 ng/ml (4.29–10.98 ng/ml), respectively. Mild bradycardia, hypothermia, and inappetence were noted in both groups. Thermal threshold latency was significantly prolonged compared to baseline up to 12 hr and up to 72 hr in IV‐B and ER‐B, respectively. These results showed that ER‐buprenorphine administered at a dose of 0.2 mg/kg resulted in prolonged and sustained plasma concentrations and antinociceptive effects up to 72 hr after drug administration.     

Comparison of bone healing,as assessed by computed tomography,following tibial tuberosity advancement in dogs with and without autogenous cancellous bone grafts

Abstract

AIMS: To objectively compare measures of bone healing, using computed tomography (CT) in dogs following bilateral tibial tuberosity advancement (TTA), between tibiae treated with and without autogenous cancellous bone grafts.

METHODS: Ten dogs with bilateral cranial cruciate ligament disease requiring surgical stabilisation were prospectively recruited to undergo single-session bilateral TTA, with only one, randomly assigned, tibia receiving bone graft in the osteotomy deficit. Bone healing at the osteotomy site was assessed using CT performed 38–70 days post-operatively. CT images were evaluated using both objective measurements of osseous bridging and subjective evaluation by six radiologists. Repeated measures ANOVA was used to compare the objective outcomes between the grafted and non-grafted tibiae.

RESULTS: The mean percentage of the osteotomy deficit bridged at the lateral cortex was greater in grafted (77.6, SD 35.2%) compared to non-grafted (63.0, SD 36.5%) tibiae (p=0.001), but did not differ at the medial cortex (p=0.1). The mean minimum callus width was greater in grafted (7.2, SD 3.3 mm) compared to non-grafted (3.6, SD 2.9 mm) tibiae (p<0.001). There was no difference in mean attenuation (measured in Hounsfield units) of the callus between grafted and non-grafted tibiae (p=0.5). The grafted tibia was deemed to have superior bone healing in 50/60 subjective assessments made by radiologists.

CONCLUSIONS: Superior osseous bridging was detected by CT analysis following TTA using autogenous cancellous bone grafts compared with no graft. This was shown by greater bridging percentage at the lateral cortex and formation of a broader callus. Qualitative assessments made by six radiologists also supported the conclusion that bone healing was improved by use of autogenous cancellous bone graft. CT was a useful method for assessing evidence of bone healing following TTA.

CLINICAL RELEVANCE: These findings justify the application of autogenous cancellous bone graft to augment healing following TTA in dogs.     

Hemodynamic and electrocardiographic effects of graded doses of amiodarone in healthy dogs anesthetized with morphine/alpha chloralose

This research was designed to study acute hemodynamic and electrocardiographic effects of amiodarone and to determine an IV dose of amiodarone that minimally affects left ventricular function and does not increase the tendency for ventricular arrhythmia.     

Clinicopathological findings and results of bone marrow aspiration in dogs with cutaneous mast cell tumours: 157 cases (1999–2002)*

Bone marrow aspiration for routine staging of canine cutaneous mast cell tumour is not consistently performed, and the overall incidence of bone marrow infiltration and predictive value of the complete blood count (CBC) is unknown. This study evaluated a series of 157 dogs presented for cutaneous mast cell tumours in which a CBC and bone marrow aspiration were performed. The incidence of bone marrow infiltration at initial staging was low at 2.8%, and 4.5% overall. Factors significantly associated with bone marrow infiltration included increased age, leucocytosis, anaemia, neutrophilia, monocytosis, eosinophilia, thrombocytopenia, being purebred and staging at the time of recurrent or progressive disease. Our study suggests that a bone marrow sample is not indicated for routine staging but maybe indicated for those dogs with mast cell tumours having either an abnormal haemogram (neutrophilia, monocytosis, eosinophilia, basophilia, anaemia and thrombocytopenia) or presenting for tumour regrowth, progression or new occurrence.     

Neurohormonal and circulatory effects of short-term treatment with enalapril and quinapril in dogs with asymptomatic mitral regurgitation

The aim of the study was to compare the effect of 2 angiotensin-converting enzyme (ACE) inhibitors on neurohormonal and circulatory variables in Cavalier King Charles Spaniels (CKCSs) with asymptomatic mitral regurgitation (MR). Ten CKCSs with mild to severe untreated MR were treated with 2 ACE inhibitors, quinapril and enalapril (each at 0.5 mg/kg PO q24h for 7 days), in a double-blind, crossover study with a washout period of 7 days between treatments. Blood samples were drawn and echocardiography was performed on days 0, 7, 14, and 21. Both treatments reduced ACE activity (P < .001) and increased renin activity (P < .001) and atrial natriuretic peptide concentration (P < .005). The ACE inhibitors had no effect on the concentrations of nitrate and nitrite (NOx) or asymmetric dimethylarginine (ADMA). On day 0, a lower NOx concentration (P = .02) was found in samples taken in the clinic as compared to samples taken in the homes of the dogs. Quinapril caused a significant reduction in more variables that reflect the severity of MR (eg, jet size and left ventricular end diastolic diameter) than did enalapril. However, in terms of specific variables, no significant difference was identified between the effects of the 2 treatments on MR. These results suggest that ACE inhibitors do not affect NOx and ADMA concentrations in asymptomatic dogs, but exercise, stress, or some combination may influence NOx concentrations in these dogs.     

Sedative and analgesic effects of two subanaesthetic doses of ketamine in combination with methadone and a low dose of dexmedetomidine in healthy dogs

ObjectiveTo evaluate the sedative, analgesic and recovery characteristics of two subanaesthetic ketamine doses in combination with dexmedetomidine and methadone for intramuscular sedation in healthy Beagles.Study designRandomized, blinded, crossover, experimental study.AnimalsSix healthy adult Beagles.MethodsDogs were randomly given three treatments: dexmedetomidine (3 μg kg^–1) and methadone (0.3 mg kg^–1) combined with ketamine at 1 and 2 mg kg^–1 (K1 and K2, respectively) or saline (K0), intramuscularly. Sedation score, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35, and 45 minutes posttreatment. Pulse rate (PR), respiratory rate, oxygen haemoglobin saturation and noninvasive blood pressure were also recorded at baseline and every 5 minutes until 45 minutes posttreatment. Onset and duration of recumbency, response to venous catheterization and recovery quality were also assessed. Sedation and physiological variables were compared between treatments and within treatments compared to baseline (analysis of variance). Nonparametric data were analysed with the Friedman and Cochran’s Q tests; p < 0.050.ResultsIncreased sedation was found at 15 (K0 and K1), 25 (all treatments) and 35 (K1) minutes compared with baseline. Sedation score, onset (3–12 minutes) and duration of recumbency (29–51 minutes) were similar between treatments. Recovery quality was considered acceptable in all cases. Response to tail clamping was inconsistent within treatments with no differences between them. None of the dogs responded to venous catheterization. There were no differences between treatments in physiological variables, except for PR which was higher in K2 than in K0. Oxygen supplementation was required in five and three dogs administered saline and ketamine, respectively.Conclusions and clinical relevanceThe addition of 1 or 2 mg kg^–1 of ketamine to methadone and dexmedetomidine combination did not enhance sedation or antinociception in healthy dogs. Recovery quality was unaffected.