A prospective, multi-centre, Veterinary Radiation Therapy Oncology Group study reveals potential efficacy of toceranib phosphate (Palladia) as a primary or adjuvant agent in the treatment of canine nasal carcinoma.

Radiation is the standard of care for dogs with nasal tumours. The addition of another therapy that could improve outcome without increasing toxicity is attractive. Medical therapy that could offer better outcome than maximally tolerated dose chemotherapy when radiation therapy (RT) is not possible or is declined is also attractive. This article reports the findings from a prospective, multi-centre, non-randomized, Veterinary Radiation Therapy Oncology Group clinical trial designed to evaluate whether toceranib phosphate (toceranib) has primary activity and if the addition of toceranib to RT could positively impact outcome. Owner's discretion determined enrolment in toceranib alone or toceranib + RT arm. Historical controls for radiation alone were selected from patients treated with identical RT and imaging protocols. Responses were evaluated with pre-treatment and week-16 CT scans. RT total dose of 42 Gy was completed in 10 fractions. Sixty-three dogs enrolled from 10 study sites. Overall response rates (CR + PR) were significantly improved in the toceranib + RT (79.4%) and RT alone (68.9%) arms over toceranib alone (22%) (p = .011). Clinical benefit rates (CR + PR + SD) were significantly improved in the toceranib + RT arm over the RT alone arm at 97.3% and 79.2% respectively (p = .036). Treatment with toceranib alone, toceranib + RT and RT alone resulted in median survival times of 298, 615 and 368 days respectively, but were not statistically significantly different (p = .0502). Adverse events associated with toceranib administration did not potentiate the RT side effect profile. Toceranib appears to have primary activity against nasal carcinoma.

Outcome of external beam radiotherapy for treatment of noncutaneous tumors of the head in horses: 32 cases (1999-2015).

BACKGROUND: The long-term outcomes of external beam radiotherapy for treatment of noncutaneous tumors of the head in horses is unknown. OBJECTIVE: To report the long-term outcomes for treatment of noncutaneous tumors of the head of horses, and report short and long-term clinical adverse effects. ANIMALS: Thirty-two horses treated in 2 referral hospitals. METHODS: In this retrospective study, medical records of horses receiving radiation therapy for noncutaneous tumors between 1999 and 2015 were reviewed. Signalment, tumor type, treatment protocol, tumor control duration, and survival were recorded. Kaplan-Meier survival curves were generated for overall survival (OS), by tumor type and location, and compared using Log-rank tests, and treatment protocol adherence. RESULTS: Follow-up ranged from 2 to 145 months (median 14 months). Of 32 horses, 16 (50%) were alive at the time of reporting, with complete tumor response occurring in 12 (38%). Horses with tumors of the maxilla/nasal cavity had significantly shorter median OS compared to horses with tumors in other locations (21 months vs 145 months) (P = .06). Adverse effects resulting from the tumor or the therapy occurred in 20/32 (63%). The occurrence of major adverse effects and delays in treatment protocol were not significantly associated with median survival estimates. CONCLUSIONS AND CLINICAL IMPORTANCE: External beam radiotherapy can be used to treat a variety of noncutaneous tumors of the head of horses. Adverse effects related to radiotherapy or the tumor are common.

Effect of heartworm disease and heartworm-associated respiratory disease (HARD) on the right ventricle of cats.

BACKGROUND: Dirofilaria immitis infection occurs in dogs and cats, both of which species are clinically affected by mature adult infections. Cats are uniquely affected by immature-adult infections with an inflammatory pulmonary disease called Heartworm-Associated Respiratory Disease (HARD). D. immitis infection causes pulmonary parenchymal and vascular pathology in the dog and cat. Dogs develop pulmonary hypertension and cor pulmonale, whereas the development of pulmonary hypertension is rare in the cat. D. immitis infection in the dog causes alteration of the right ventricular (RV) extracellular matrix, including a decrease in myocardial collagen. In this study, the RV myocardial changes of cats infected with adult and immature-adult D. immitis were assessed. METHODS: The cardiopulmonary systems of six groups of SPF cats (n = 9-10 per group) were examined 8 or 18 months after infection with L3 D. immitis. Two groups were untreated and allowed to develop adult HW; two groups were treated with ivermectin starting 3 months post infection, thus allowing HARD but no mature adult heartworms; and two groups were treated with selamectin beginning 1 month post infection, preventing development of L5 or adult heartworms. A group of specific pathogen free (SPF) normal cats was utilized as a negative control (n = 12). Lung pathologic lesions were objectively assessed, and both RV and left ventricular (LV) weights were obtained to calculate an RV/LV ratio. Intramural RV myocardial collagen content was quantitatively assessed. RESULTS: RV/LV weight ratios were not different between groups. Negative control cats had significantly greater RV collagen content than all other affected groups (P = 0.032). Analysis of the RV/LV ratios and collagen content revealed no significant relationship (r = 0.03, P = 0.723, respectively). Collagen content had a modest, but significant, negative correlation, however, with both pulmonary vascular pathology (r = -0.25, P = 0.032) as well as the total pulmonary parenchymal and vascular pathology (r = -0.26, P = 0.025). CONCLUSIONS: Cats infected with mature and immature D. immitis did not develop RV hypertrophy but did demonstrate loss of RV myocardial collagen content. The collagen loss was present at 8 and 18 months after infection in all infected cats. This loss of RV myocardial collagen was correlated with the severity of pulmonary parenchymal and vascular pathology.

Heartworm-associated respiratory disease (HARD) induced by immature adult Dirofilaria immitis in cats.

BACKGROUND: A controlled, blind research study was conducted to define the initial inflammatory response and lung damage associated with the death of immature adult Dirofilaria immitis in cats as compared with cats developing adult heartworm infections and cats on preventive medication. METHODS: Three groups of cats were utilized, 10 per group. All cats were infected with 100 third-stage (L3) larvae by subcutaneous injection. Group A cats were treated topically with selamectin (Revolution®; Zoetis) per label directions at 28 days post infection (PI) and once monthly for 8 months. Group B cats were treated orally with ivermectin (Ivomec®; Merial) at 150 µg/kg at 70 days PI, then every 2 weeks for 5 months. Group C cats were untreated PI. At baseline (Day 0) and on Days 70, 110, 168, and 240 PI, peripheral blood, serum, bronchial lavage, and thoracic radiographic images were collected on all cats. Upon completion of the study (Day 245), cats were euthanized and necropsies were conducted. RESULTS: Results were analyzed statistically between groups by ANOVA and by paired sample T testing for changes within the group over time. The selamectin-treated cats (Group A) did not develop radiographically evident changes throughout the study and were free of adult heartworms or worm fragments at necropsy. The heartworm life cycle was abbreviated with oral doses of ivermectin (Group B), shown by the absence of adult heartworms or worm fragments at necropsy. The early stage of immature adult worm in Group B cats, however, did induce severe pulmonary airway, interstitial, and arterial lung lesions, revealing that the abbreviated infection is a significant cause of respiratory pathology in cats. Cats in Groups B and C could not be differentiated based on radiographic changes, serologic antibody titers, complete blood count, or bronchoalveolar lavage cytology at any time point throughout the study. Eighty percent of cats in Group A and 100% of cats in Groups B and C became heartworm antibody positive at some time point post infection. CONCLUSIONS: The clinical implications of this study are that cats that become infected with immature adult heartworms may not develop fully mature heartworms and are only transiently heartworm antibody positive, but do develop Heartworm-Associated Respiratory Disease (HARD).

The progression of heartworm associated respiratory disease (HARD) in SPF cats 18 months after Dirofilaria immitis infection.

BACKGROUND: Heartworm-associated respiratory disease (HARD) in cats is induced by the arrival and death of immature adult Dirofilaria immitis in the pulmonary system and is indistinguishable from mature adult heartworm infection. METHODS: A controlled, blind research study investigated the long-term (18 months post infection, PI) consequences of the inflammatory response associated with the death of immature adult heartworms in cats. Three groups of cats, 10 per group, were infected with 100 third-stage (L3) larvae by subcutaneous injection. Group A cats were treated with selamectin (Revolution®; Zoetis) per label directions at 28 days PI and once monthly for 17 months. Group B cats were treated orally with ivermectin (Ivomec®; Merial) at 150 µg/kg) at 70 days PI, then every 2 weeks for 15 months. Group C cats were untreated PI. At baseline (Day 0) and on Days 70, 110, 168, 240, 309, 380, and 505 PI, peripheral blood, serum, bronchial lavage, and thoracic radiographic images were collected. RESULTS: The selamectin-treated cats (Group A) and ivermectin-treated cats (Group B) were free of heartworms or heartworm fragments at necropsy. All cats became heartworm antibody positive at some time point in the study except for one cat in Group A. Only cats in Group C (all with adult heartworms) were heartworm antigen positive. The heartworm antibody titer for Group B was highest on Days 110 to 168 and then decreased over time and 50% were serologically antibody negative on Day 240. Eosinophilic bronchoalveolar lavage (BAL) cytology and peripheral eosinophilia were most pronounced on Day 110 in all cats. Randomly distributed myofibrocytes in the lungs of some Group A cats suggest that precardiac larval stages were affecting the lungs. Radiographs in Group B cats demonstrated partial resolution of the initial HARD reaction but chronic myofibrocyte proliferation was histologically evident 18 months after infection. CONCLUSION: HARD was induced by immature adult worm infection with progressive improvement starting 6 to 8 months after infection but histologic lesions were evident in some cats 18 months after infection. The serologic antibody assay was negative in 50% of cats at 8 months and 100% of cats at 18 months post infection. Abnormal radiographic lung patterns continued in a subset of Group B cats for months after heartworm antibody serology and BAL cytology returned to normal.

Multimodal non-surgical treatment of a feline tracheal adenocarcinoma.

CASE SUMMARY: A 10-year-old, castrated male domestic shorthair cat presented with a 2-3 month history of weight loss, lethargy and coughing. Thoracic radiographs revealed a soft tissue opacity overlying the dorsal trachea from the first rib to second rib and the ventral aspect of the trachea extending from the second rib to approximately the fourth rib. CT confirmed a mass involving the dorsal, right lateral and ventral aspects of the trachea narrowing the lumen and extending from vertebra C7 through T4. Bronchoscopy revealed a partially circumferential irregular and multilobulated tracheal mass, which was biopsied. The histopathological diagnosis was tracheal adenocarcinoma. The cat was treated with a definitive course of external beam radiation therapy (RT; 3 Gy × 18), cytotoxic chemotherapy, a tyrosine kinase inhibitor and palliative RT. The cat remained asymptomatic for 2 months and the mass remained stable radiographically for 11 months after RT. RELEVANCE AND NOVEL INFORMATION: With multimodal treatment the cat had a survival time of 755 days. Initial treatment included definitive RT, carboplatin and piroxicam, followed by toceranib phosphate and palliative RT when the mass recurred. This case report describes the first documented use of non-surgical treatment and long-term outcome of tracheal adenocarcinoma in a cat. This case report is an indication that prolonged survival can be achieved with multimodal therapy.

OUTCOME OF DOGS WITH INTRANASAL LYMPHOMA TREATED WITH VARIOUS RADIATION AND CHEMOTHERAPY PROTOCOLS: 24 CASES.

Tumors of the nasal cavity comprise approximately 1% of all neoplasms in dogs. Canine intranasal lymphoma is rare and reports evaluating the outcome of treatment are lacking. The goal of this observational, descriptive, multi-institutional study was to evaluate the overall median survival times (MSTs) in a group of dogs with intranasal lymphoma that were treated with irradiation and/or chemotherapy. Dogs meeting these inclusion criteria were retrospectively recruited from medical archives at multiple institutions. Eighteen cases of intermediate to high grade intranasal lymphoma and six cases of low-grade intranasal lymphoma were identified. The date of diagnosis, method of diagnosis, treatment received (radiation and/or chemotherapy protocols), and date of death were recorded. Kaplan-Meier survival analysis was performed on the intermediate to high grade group to calculate overall MST. Log-rank tests were performed to compare effects of treatment with radiation therapy ± chemotherapy and chemotherapy alone. Kaplan-Meier survival analysis was performed separately on the low-grade group. The overall MST was 375 days for the intermediate to high grade group. Cases treated with radiation ± chemotherapy had an MST of 455 days (n = 12) and those treated with chemotherapy alone (n = 6) had an MST of 157 days in the intermediate to high grade group. The MST was 823 days for the low-grade group. Results support the use of radiation therapy for treatment of canine intranasal lymphoma, however a randomized, controlled, clinical trial would be needed for more definitive recommendations. The role of adjunctive chemotherapy also may require further investigation.

Survival times for canine intranasal sarcomas treated with radiation therapy: 86 cases (1996-2011).

Sarcomas comprise approximately one-third of canine intranasal tumors, however few veterinary studies have described survival times of dogs with histologic subtypes of sarcomas separately from other intranasal tumors. One objective of this study was to describe median survival times for dogs treated with radiation therapy for intranasal sarcomas. A second objective was to compare survival times for dogs treated with three radiation therapy protocols: daily-fractionated radiation therapy; Monday, Wednesday, and Friday fractionated radiation therapy; and palliative radiation therapy. Medical records were retrospectively reviewed for dogs that had been treated with radiation therapy for confirmed intranasal sarcoma. A total of 86 dogs met inclusion criteria. Overall median survival time for included dogs was 444 days. Median survival time for dogs with chondrosarcoma (n = 42) was 463 days, fibrosarcoma (n = 12) 379 days, osteosarcoma (n = 6) 624 days, and undifferentiated sarcoma (n = 22) 344 days. Dogs treated with daily-fractionated radiation therapy protocols; Monday, Wednesday and Friday fractionated radiation therapy protocols; and palliative radiation therapy protocols had median survival times of 641, 347, and 305 days, respectively. A significant difference in survival time was found for dogs receiving curative intent radiation therapy vs. palliative radiation therapy (P = 0.032). A significant difference in survival time was also found for dogs receiving daily-fractionated radiation therapy vs. Monday, Wednesday and Friday fractionated radiation therapy (P = 0.0134). Findings from this study support the use of curative intent radiation therapy for dogs with intranasal sarcoma. Future prospective, randomized trials are needed for confirmation of treatment benefits.

Barbershops as venues to assess and intervene in HIV/STI risk among young, heterosexual African American men.

African Americans, particularly men, are disproportionately affected by the HIV epidemic. Inconsistent condom use and concurrent sexual partnerships are risk factors; there is limited investigation on how these factors influence HIV risk engagement in young, heterosexual, African American men. To identify contextual risk factors that place young men (18-24 years) at risk for HIV infection, one focus group was conducted with 13 men, and questionnaires were administered to 48 men. Participants were 18 to 24 years old and were recruited from local barbershops. The majority engaged in noncondom use (83%) and had multiple sexual partners (64%). Qualitative themes revealed noncondom use "when in the moment" and enhanced condom use with casual partners. This study provided an understanding of participants' attitudes, intentions, and behaviors as they related to HIV risk and revealed the need for culturally relevant, theory-based HIV prevention programs to reduce HIV transmission among this population.

Rifaximin diminishes neutropenia following potentially lethal whole-body radiation.

Terrorist attacks involving radiological or nuclear weapons are a substantial geopolitical concern, given that large populations could be exposed to potentially lethal doses of radiation. Because of this, evaluating potential countermeasures against radiation-induced mortality is critical. Gut microflora are the most common source of systemic infection following exposure to lethal doses of whole-body radiation, suggesting that prophylactic antibiotic therapy may reduce mortality after radiation exposure. The chemical stability, easy administration and favorable tolerability profile of the non-systemic antibiotic, rifaximin, make it an ideal potential candidate for use as a countermeasure. This study evaluated the use of rifaximin as a countermeasure against low-to-intermediate-dose whole-body radiation in rodents. Female Wistar rats (8 weeks old) were irradiated with 550 cGy to the whole body and were evaluated for 30 d. Animals received methylcellulose, neomycin (179 mg/kg/d) or variably dosed rifaximin (150-2000 mg/kg/d) one hour after irradiation and daily throughout the study period. Clinical assessments (e.g. body weight) were made daily. On postirradiation day 30, blood samples were collected and a complete blood cell count was performed. Animals receiving high doses of rifaximin (i.e. 1000 or 2000 mg/kg/d) had a greater increase in weight from the day of irradiation to postirradiation day 30 compared with animals that received placebo or neomycin. For animals with an increase in average body weight from irradiation day within 80-110% of the group average, methylcellulose rendered an absolute neutrophil count (ANC) of 211, neomycin rendered an ANC of 334, rifaximin 300 mg/kg/d rendered an ANC of 582 and rifaximin 1000 mg/kg/d rendered an ANC of 854 (P = 0.05 for group comparison). Exposure to rifaximin after near-lethal whole-body radiation resulted in diminished levels of neutropenia.

Magnetic resonance imaging of radiation-induced thymic atrophy as a model for pathologic changes in acute feline immunodeficiency virus infection.

The development of a protocol to reproducibly induce thymic atrophy, as occurs in feline immunodeficiency virus (FIV) infection and other immunosuppressive diseases, and to consistently estimate thymic volume, provides a valuable tool in the search of innovative and novel therapeutic strategies. Magnetic resonance imaging (MRI) using the short tau inversion recovery (STIR) technique, with fat suppression properties, was determined to provide an optimized means of locating, defining, and quantitatively estimating thymus volume in young cats. Thymic atrophy was induced in four, 8-10-week-old kittens with a single, directed 500 cGy dose of 6 MV X-rays from a clinical linear accelerator, and sequential MR images of the cranial mediastinum were collected at 2, 7, 14, and 21 days post irradiation (PI). Irradiation induced a severe reduction in thymic volume, which was decreased, on average, to 47% that of normal, by 7 days PI. Histopathology confirmed marked, diffuse thymic atrophy, characterized by reduced thymic volume, decreased overall cellularity, increased apoptosis, histiocytosis, and reduced distinction of the corticomedullary junction, comparable to that seen in acute FIV infection. Beginning on day 7 PI, thymic volumes rebounded slightly and continued to increase over the following 14 days, regaining 3-35% of original volume. These findings demonstrate the feasibility and advantages of using this non-invasive, in vivo imaging technique to measure and evaluate changes in thymic volume in physiologic and experimental situations. All experimental protocols in this study were approved by the Institutional Animal Care and Use Committee (IACUC) at Auburn University.

Evaluation of clinical status, renal function, and hematopoietic variables after unilateral nephrectomy in canine kidney donors.

OBJECTIVE: To determine clinical status and renal and hematopoietic function after kidney donation and identify risks associated with kidney donation in dogs. DESIGN: Prospective study. ANIMALS: 14 dogs that underwent unilateral nephrectomy for kidney donation. PROCEDURES: Records were reviewed retrospectively to collect data regarding prenephrectomy clinicopathologic variables. Dogs were reexamined prospectively at various times after nephrectomy, and pre- and postnephrectomy CBC, serum biochemical analyses, urinalysis, and urine protein-to-urine creatinine ratio were compared. Six dogs had postnephrectomy renal volume determined ultrasonographically, and 4 of those dogs also underwent scintigraphic determination of glomerular filtration rate and renal biopsy. RESULTS: All dogs were clinically normal at the time of reevaluation. There were no significant differences between prenephrectomy and postnephrectomy values for BUN concentration or urine specific gravity. Mean postnephrectomy serum creatinine concentration was significantly greater than prenephrectomy concentration. Mean serum phosphorus concentration was significantly decreased after nephrectomy, and mean Hct, corpuscular volume, and corpuscular hemoglobin concentration were significantly increased after nephrectomy. Postnephrectomy renal volume was greatest in dogs < 12 months old at the time of surgery. Mean postnephrectomy glomerular filtration rate was 2.82 +/- 1.12 mL/kg/ min (1.28 +/- 0.51 mL/lb/min). Renal biopsy specimens obtained during and after nephrectomy were histologically normal. CONCLUSIONS AND CLINICAL RELEVANCE: Renal and hematopoietic variables were within reference ranges in dogs examined up to 2.5 years after unilateral nephrectomy. Compensatory renal hypertrophy was greatest in dogs < 1 year of age at donation. Donor age, along with histocompatability, may be an important factor in selecting dogs for kidney donation.

Hematopoietic chimerism induces renal and skin allograft tolerance in DLA-identical dogs.

OBJECTIVE: Hematopoietic chimerism, a state where donor and recipient bone marrow cells coexist, is associated with donor-specific tolerance. Nonmyeloablative bone marrow transplantation (BMT) has been shown to induce stable mixed hematopoietic chimerism in dog leukocyte antigen (DLA)-matched dogs. The potential for inducing renal and skin allograft tolerance with nonmyeloablative BMT was investigated in DLA-identical and DLA-haploidentical dogs in this study. MATERIALS AND METHODS: Renal allografts were performed in 8 DLA-identical and 4 DLA-haploidentical dogs with nonmyeloablative conditioning (200 cGy TBI) and transient immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF) with (n = 8) and without (n = 4) simultaneous BMT. Skin allografts were performed in 2 DLA-identical and 4 DLA-haploidentical dogs after stopping CSP and MMF. Two DLA-identical control dogs received renal allografts without TBI, BMT, or immunosuppression with CSP and MMF. Molecular chimerism was determined with a PCR-based DNA microsatellite assay. Serum creatinine (Cr) concentration, urine specific gravity, and sequential renal biopsies were monitored to assess renal allograft function. RESULTS: Donor-type blood cells were first detected 4 weeks posttransplantation in both the myeloid and lymphoid lineages. Donor chimerism was present for at least 76 weeks in the DLA-identical dogs. Mixed chimerism was not observed in the DLA-haploidentical dogs or DLA-identical dogs that did not undergo BMT. The renal allografts were acutely rejected within 14 days in the 2 DLA-identical control dogs. There was long-term (> 5 yrs) renal allograft survival as evidenced by a normal (< 2.0 mg/dL) serum Cr concentration in both the DLA-identical and DLA-haploidentical dogs that underwent 200 cGy TBI and transient immunosuppression with CSP and MMF either with or without simultaneous BMT. Renal allograft inflammation was severe in the control dogs, mild to moderate in the DLA-haploidentical dogs, and minimal in the DLA-identical dogs. Donor-specific skin grafts were accepted in the DLA-identical dogs but rejected in the DLA-haploidentical dogs. Nonmyeloablative conditioning (200 cGy TBI) and transient immunosuppression with CSP and MMF induce renal and skin allograft tolerance in DLA-identical and permit long-term renal allograft survival in DLA-haploidentical dogs. These findings suggest it may possible to obtain long-term allograft survival in DLA-identical and -haploidentical dogs without the need for chronic immunosuppressive therapy.

Renal allograft histopathology in dog leukocyte antigen mismatched dogs after renal transplantation.

OBJECTIVE: To evaluate allograft histopathology in dog leukocyte antigen (DLA)-mismatched dogs undergoing renal transplantation, with transient immunosuppression. STUDY DESIGN: Prospective study. ANIMALS: Ten healthy adult mongrel dogs. METHODS: Reciprocal renal transplantation and bilateral nephrectomy were performed. Immune conditioning consisted of nonmyeloablative (200 cGy), total body irradiation (TBI), bone marrow transplantation (BMT; 7 dogs), cyclosporine (CSA; 15 mg/kg every 12 hours), mycophenolate mofetil (MMF; 10 mg/kg every 12 hours) and intermittent prednisone (1 mg/kg every 12-24 hours). Biopsies were collected at transplantation, during full immunosuppression (44-90 days), and once medications were reduced or discontinued (228-580 days). Biopsies were evaluated for interstitial, tubular, vascular, and glomerular lesions. Blood urea nitrogen, creatinine, serum CSA concentrations, and clinical score were determined at each biopsy. RESULTS: Seven dogs survived >200 days (mean, 380 days). Transient CSA toxicity was suspected in 6 dogs. Lymphocytic, plasmacytic interstitial inflammation, and tubulitis progressed when immunosuppressive medications were decreased. All 7 dogs had histologic lesions consistent with some degree of allograft rejection at study end. CONCLUSION: Nonmyeloablative TBI, BMT, and short-term immunosuppression with CSA, MMF, and prednisone allowed renal allograft function and dog survival for >200 days. It appears unlikely that total drug withdrawal will be possible in unrelated DLA-mismatched dogs using this protocol. CLINICAL RELEVANCE: Transient immunosuppression with MMF, CSA, and prednisone along with BMT and nonmyeloablative TBI may make kidney transplantation a clinical reality for treatment of kidney failure in dogs. Initiating both MMF and CSA at lower dosages may potentially eliminate early renal allograft injury.

Influence of dietary calcium and phosphorus content in a fixed ratio on growth and development in Great Danes.

OBJECTIVE: To study the musculoskeletal development of Great Dane puppies fed various dietary concentrations of calcium (Ca) and phosphorus (P) in fixed ratio by use of dual energy x-ray absorptiometry (DEXA), determination of serum insulin-like growth factor 1 and parathyroid hormone concentrations, radiography, and blood chemistry analysis results. ANIMALS: 32 purebred Great Dane puppies from 4 litters. PROCEDURE: At weaning, puppies were assigned randomly to 1 of 3 diets. Blood was collected for biochemical analyses and hormone assays, and radiography and DEXA were performed through 18 months of age. Changes in body weight, bone mineral content, fat tissue weight, lean mass, result of serum biochemical analyses, hormonal concentrations, and radius lengths were analyzed through 18 months of age. RESULTS: Bone mineral content of puppies correlated positively with Ca and P content of the diets fed. Significant differences between groups in bone mineral content, lean mass, and body fat were apparent early. The disparity among groups increased until 6 months of age and then declined until body composition was no longer different at 12 months of age. Accretion rates for skeletal mineral content, fat, and lean tissue differed from each other and by diet group. CONCLUSIONS AND CLINICAL RELEVANCE: Ca and P concentrations in the diet of young Great Dane puppies are rapidly reflected in the bone mineral content of the puppies until 5 to 6 months of age, after which hormonal regulation adjusts absorption and excretion of these minerals. Appropriate Ca and P concentrations in diets are important in young puppies < 6 months of age.