Spurious hyperbicarbonatemia and a negative anion gap in a cat and a dog with severe rhabdomyolysis.

A 3-year-old male neutered domestic shorthair cat and a 2-year-old male neutered Labrador-mix dog were separately presented to the Veterinary Medical Center for evaluation after sustaining significant muscle trauma due to a dog attack and seizure activity, respectively. In both cases, biochemical analysis was consistent with rhabdomyolysis. Additionally, a markedly increased measured serum bicarbonate concentration and negative calculated anion gap were observed. As these biochemical abnormalities were not expected and deemed incompatible with life, an interference with the analyzer measurement of bicarbonate involving marked increases in pyruvate and lactate dehydrogenase (LDH) following myocyte injury was suspected. Venous blood gas analysis calculated bicarbonate concentration and anion gap were within reference interval, while measured LDH activity was markedly increased. These findings supported an analyzer-generated interference. This is the first published report of a previously described chemistry analyzer interference of markedly increased LDH activity with serum bicarbonate concentration measurement in dogs and cats. Awareness of this interference is important, particularly in the emergency setting, as it may influence case management.

An atypical presentation of anticoagulant rodenticide toxicosis in a dog.

A 5-month-old intact female Australian shepherd dog was referred to our clinic for neurologic signs including ataxia, a head tilt, and altered mentation following consumption of an unidentified rodenticide several days prior to developing clinical signs. A provisional diagnosis of bromethalin toxicosis had been made, given the neurologic signs seen and the general increased use of bromethalin-containing rodenticide products. However, on physical examination, the dog was noted to have scleral hemorrhage and bleeding at the venipuncture sites, which was inconsistent with bromethalin toxicosis. Coagulation testing was supportive of anticoagulant rodenticide toxicosis and the rodenticide was later identified as the first-generation anticoagulant rodenticide diphacinone. The neurologic signs seen were attributed to a coagulopathy causing multifocal hemorrhage into the central nervous system. Neurologic signs rapidly resolved following treatment with a frozen plasma transfusion and vitamin K1. This atypical presentation of an anticoagulant rodenticide toxicosis highlights the need for accurate product identification, if available, and thorough patient examination and laboratory testing. An atypical presentation of anticoagulant rodenticide toxicosis should be considered when neurologic signs are present with clinical bleeding, especially if the type of rodenticide is unknown, or even if it was not thought to have an anticoagulant as the active ingredient. Key clinical message: Given the change in commercially available rodenticide products, this case highlights the need for accurate product identification in cases of suspected toxicosis, and the variable clinical signs that can be seen following anticoagulant rodenticide toxicosis.

Présentation atypique d'une toxicose aux rodenticides anticoagulants chez un chien. Une chienne berger australien intacte âgée de 5 mois a été référée à notre clinique pour des signes neurologiques, notamment de l'ataxie, une inclinaison de la tête et une altération de l'état mental à la suite de la consommation d'un rodenticide non identifié plusieurs jours avant l'apparition des signes cliniques. Un diagnostic provisoire de toxicose à la brométhaline avait été posé, compte tenu des signes neurologiques observés et d'une utilisation historique accrue de produits rodenticides contenant de la brométhaline. Cependant, lors de l'examen physique, il a été constaté que le chien présentait une hémorragie sclérale et des saignements au niveau des sites de ponction veineuse, ce qui n'était pas cohérent avec une toxicose à la brométhaline. Les tests de coagulation ont confirmé la toxicose au rodenticide anticoagulant et le rodenticide a ensuite été identifié comme étant le rodenticide anticoagulant de première génération diphacinone. Les signes neurologiques observés ont été attribués à une coagulopathie provoquant une hémorragie multifocale du système nerveux central. Les signes neurologiques ont rapidement disparu après un traitement par transfusion de plasma congelé et de vitamine K1. Cette présentation atypique d'une toxicose aux rodenticides anticoagulants met en évidence la nécessité d'une identification précise du produit, si disponible, ainsi que d'un examen approfondi du patient et de tests de laboratoire. Une présentation atypique de toxicose des rodenticides anticoagulants doit être envisagée lorsque des signes neurologiques sont présents avec saignement clinique, en particulier si le type de rodenticide est inconnu, ou même si l'on ne pense pas qu'un anticoagulant soit l'ingrédient actif.Message clinique clé :Compte tenu de l'évolution des produits rodenticides disponibles dans le commerce, ce cas met en évidence la nécessité d'une identification précise du produit en cas de suspicion de toxicose et les signes cliniques variables qui peuvent être observés à la suite d'une toxicose au rodenticide anticoagulant.(Traduit par Dr Serge Messier).

Retrospective evaluation of the clinical course and outcome of zinc toxicosis due to metallic foreign bodies in dogs (2005-2021): 55 cases.

OBJECTIVE: To describe the overall clinical course of zinc toxicosis in dogs including source, time to source control, incidence of hemolytic anemia, acute liver injury (ALI), acute kidney injury (AKI), and pancreatitis. DESIGN: Retrospective case series from 2005 to 2021. SETTING: Six university veterinary teaching hospitals. ANIMALS: Fifty-five client-owned dogs with known zinc toxicosis due to metallic foreign body (MFB) ingestion. MEASUREMENTS AND MAIN RESULTS: The most common source of zinc was US pennies minted after 1982 (67.3%). Forty-five of 55 (81.8%) dogs survived and 10 of 55 (18.2%) died or were euthanized. Median length of hospitalization for survivors and nonsurvivors was 3 days. The most common clinical sequelae of zinc toxicosis were anemia (87%), ALI (82%), coagulopathy (71%), thrombocytopenia (30.5%), AKI (26.9%), and acute pancreatitis (5.5%). Most dogs (67.3%) required blood products and 83% of dogs achieved a stable HCT or PCV in a median of 24 hours after MFB removal. The median duration of illness prior to presentation was 48 hours for both survivors and nonsurvivors and there was no impact of time to presentation on the incidence of ALI, AKI, or pancreatitis. CONCLUSIONS: Zinc toxicosis secondary to MFB ingestion should be considered a differential diagnosis for dogs with gastrointestinal signs, hemolytic anemia, ALI, hemostatic abnormalities, AKI, and pancreatitis. AKI may be a more common sequela of zinc toxicosis than previously suspected. Acute pancreatitis is a rare but potentially serious sequela to zinc toxicosis.

Successful Resuscitation of Neonatal Kittens Delivered by a Perimortem Cesarean Section Following Maternal Cardiopulmonary Arrest.

A 9 yr old, unknown weight, intact female domestic shorthair presented for evaluation of dystocia with dyspnea. En route to the hospital for treatment, the owners noted the queen stopped breathing. On presentation, cardiopulmonary arrest was confirmed. The exact cause was unknown but suspected to be secondary to acute fulminant congestive heart failure or acute respiratory distress syndrome due to a large volume of serosanguineous fluid within the mouth and nose. Cardiopulmonary resuscitation (CPR) was immediately started. After 2 min of CPR without return of spontaneous circulation, the owners consented to perimortem Cesarean section. Two kittens were removed via emergency hysterotomy within 3-4 min. Both kittens were successfully resuscitated. CPR efforts were continued on the queen for 2 min after delivery of the kittens, at which time the owners elected to stop further resuscitative efforts. Both kittens were discharged from the hospital and were alive at last follow-up, 2 yr and 4 mo after birth. There are no previous reports regarding the use of a perimortem Cesarean section to deliver neonates in small animal medicine. Therefore, this report represents a novel treatment approach that can be considered in the case of maternal arrest during dystocia.

Retrospective evaluation of fluid production at the time of thoracostomy tube removal following elective and emergency surgery in dogs (2010-2017): 185 cases.

OBJECTIVE: To report the rate of fluid production at the time of removal of thoracostomy tubes placed intraoperatively and to determine the association of this rate with specific patient factors, surgical factors, or clinical diagnosis. The secondary objective was to determine whether identification of pleural effusion within 2 weeks of thoracostomy tube removal was associated with the same variables. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: One hundred eighty-five client-owned dogs with thoracostomy tubes placed intraoperatively between January 2010 and March 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thoracostomy tubes were removed at a median fluid production of 0.09 mL/kg/h (range, 0-7.0 m L/kg/h). Median fluid production at the time of thoracostomy tube removal was significantly higher in dogs with preoperative pleural effusion compared to dogs without preoperative pleural effusion (0.21 vs 0.05 mL/kg/h; P = 0.0001) and in dogs that had a median sternotomy compared to dogs that had a lateral thoracotomy (0.14 vs 0.09 mL/kg/h; P = 0.04). Of the 169 dogs available for follow-up, 12 (7.1%) had pleural effusion within 2 weeks of removal of the thoracostomy tube. Detection of pleural effusion during the follow-up period was significantly associated with the presence of preoperative pleural effusion (P = 0.0019) and the diagnosis (P = 0.01). A greater proportion of dogs with a lung lobe torsion (4/9, 44.4%) and idiopathic chylothorax (2/7, 28.5%) had pleural effusion within 2 weeks compared to other diagnoses. Reintervention was performed in 4.7% of dogs. CONCLUSIONS: Thoracostomy tubes were removed at pleural fluid production rates that frequently exceeded current veterinary guidelines. However, the fluid production rate at the time of thoracostomy tube removal was not associated with the detection of pleural effusion within 2 weeks of thoracostomy tube removal, and the overall need for reintervention following thoracostomy tube removal was low (4.7%).

Successful Management of Urinary Bladder Clot with Intravesical Tissue Plasminogen Activator Infusion in a Cat.

A 5 yr old male neutered domestic shorthair with intermittent signs of urinary tract obstruction was suspected of having a blood clot in the urinary bladder secondary to trauma. The cat was hospitalized and received standard supportive therapy for urinary tract obstruction with urinary catheterization, with the addition of intravesical saline flushes in an attempt to promote bladder clot lysis. The cat was subsequently discharged after voluntary urination was observed. The cat was represented 28 hr after discharge because of clinical signs consistent with urinary tract obstruction. The cat was hospitalized and intravesical tissue plasminogen activator (tPA) infusions (0.5 mg of tPA in 10 mL of saline with 2 hr dwell time q 8 hr) were administered to break down the bladder clot (2.78 × 4.46 cm). Thirty-two hours after starting tPA, the clot was no longer visible on ultrasound. The cat was discharged with no recurrent symptoms in the subsequent 11 mo. This is the first report of tPA being used for dissolution of bladder clot in a cat. There were no observed complications, suggesting that intravesical instillation of tPA may be a safe and efficacious therapy in cats, similar to the previously reported successes in dogs and humans.

Use of a platelet-rich plasma-collagen scaffold as a bioenhanced repair treatment for management of partial cruciate ligament rupture in dogs.

Dogs are commonly affected with cruciate ligament rupture (CR) and associated osteoarthritis (OA), and frequently develop a second contralateral CR. Platelet rich plasma (PRP) is a component of whole blood that contains numerous growth factors, which in combination with a collagen scaffold may act to promote bioenhanced primary repair of ligament. This study tested the hypothesis that treatment of partial stable CR stifles with an intra-articular collagen scaffold and PRP would decrease the disease progression, synovitis and risk of complete CR over a 12-month study period. We conducted a prospective cohort study of 29 client-owned dogs with an unstable stifle due to complete CR and stable contralateral stifle with partial CR. All dogs were treated with tibial plateau leveling osteotomy (TPLO) on the unstable stifle and a single intra-articular application of PRP-collagen in the stable partial CR stifle. Dogs were evaluated at the time of diagnosis, and at 10-weeks and 12-months after treatment. We evaluated correlation between both development of complete CR and time to complete CR with diagnostic tests including bilateral stifle radiographs, 3.0 Tesla magnetic resonance (MR) imaging, and bilateral stifle arthroscopy. Additionally, histologic evaluation of synovial biopsies, C-reactive protein (CRP) concentrations in serum and synovial fluid, and synovial total nucleated cell count, were determined. Results indicated that a single application of PRP-collagen in partial CR stifles of client owned dogs is not an effective disease-modifying therapy for the prevention of progression to complete CR. Radiographic effusion, arthroscopic evaluation of cranial cruciate ligament (CrCL) damage, and MR assessment of ligament fiber tearing in partial CR stifles correlated with progression to complete CR over the 12-month follow-up period. We determined that the best predictive model for development of complete CR in PRP-collagen treated partial CR stifles included variables from multiple diagnostic modalities.

Radiographic and magnetic resonance imaging predicts severity of cruciate ligament fiber damage and synovitis in dogs with cranial cruciate ligament rupture.

Cruciate ligament rupture (CR) and associated osteoarthritis (OA) is a common condition in dogs. Dogs frequently develop a second contralateral CR. This study tested the hypothesis that the degree of stifle synovitis and cranial cruciate ligament (CrCL) matrix damage in dogs with CR is correlated with non-invasive diagnostic tests, including magnetic resonance (MR) imaging. We conducted a prospective cohort study of 29 client-owned dogs with an unstable stifle due to complete CR and stable contralateral stifle with partial CR. We evaluated correlation of stifle synovitis and CrCL fiber damage with diagnostic tests including bilateral stifle radiographs, 3.0 Tesla MR imaging, and bilateral stifle arthroscopy. Histologic grading and immunohistochemical staining for CD3+ T lymphocytes, TRAP+ activated macrophages and Factor VIII+ blood vessels in bilateral stifle synovial biopsies were also performed. Serum and synovial fluid concentrations of C-reactive protein (CRP) and carboxy-terminal telopeptide of type I collagen (ICTP), and synovial total nucleated cell count were determined. Synovitis was increased in complete CR stifles relative to partial CR stifles (P<0.0001), although total nucleated cell count in synovial fluid was increased in partial CR stifles (P<0.01). In partial CR stifles, we found that 3D Fast Spin Echo Cube CrCL signal intensity was correlated with histologic synovitis (SR = 0.50, P<0.01) and that radiographic OA was correlated with CrCL fiber damage assessed arthroscopically (SR = 0.61, P<0.001). Taken together, results of this study show that clinical diagnostic tests predict severity of stifle synovitis and cruciate ligament matrix damage in stable partial CR stifles. These data support use of client-owned dogs with unilateral complete CR and contralateral partial CR as a clinical trial model for investigation of disease-modifying therapy for partial CR.

Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture.

Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response associated with cranial cruciate ligament matrix degeneration or damage.

3D FSE Cube and VIPR-aTR 3.0 Tesla magnetic resonance imaging predicts canine cranial cruciate ligament structural properties.

Estimation of cranial cruciate ligament (CrCL) structural properties in client-owned dogs with incipient cruciate rupture would be advantageous. The objective of this study was to determine whether magnetic resonance imaging (MRI) measurement of normal CrCL volume in an ex-vivo canine model predicts structural properties. Stifles from eight dogs underwent 3.0 Tesla 3D MRI. CrCL volume and normalized median grayscale values were determined using 3D Fast Spin Echo (FSE) Cube and Vastly under-sampled Isotropic PRojection (VIPR)-alternative repetition time (aTR) sequences. Stifles were then mechanically tested. After joint laxity testing, CrCL structural properties were determined, including displacement at yield, yield load, load to failure, and stiffness. Yield load and load to failure (R(2)=0.56, P <0.01) were correlated with CrCL volume determined by VIPR-aTR. Yield load was also correlated with CrCL volume determined by 3D FSE Cube (R(2)=0.32, P <0.05). Structural properties were not related to median grayscale values. Joint laxity and CrCL stiffness were not related to MRI parameters, but displacement at yield load was related to CrCL volume for both sequences during testing (R(2)>0.57, P <0.005). In conclusion, 3D MRI offers a predictive method for estimating canine CrCL structural properties. 3D MRI may be useful for monitoring CrCL properties in clinical trials.

Role of calcitonin gene-related peptide in functional adaptation of the skeleton.

Peptidergic sensory nerve fibers innervating bone and periosteum are rich in calcitonin gene-related peptide (CGRP), an osteoanabolic neurotransmitter. There are two CGRP isoforms, CGRPα and CGRPß. Sensory fibers are a potential means by which the nervous system may detect and respond to loading events within the skeleton. However, the functional role of the nervous system in the response of bone to mechanical loading is unclear. We used the ulna end-loading model to induce an adaptive modeling response in CGRPα and CGRPß knockout mouse lines and their respective wildtype controls. For each knockout mouse line, groups of mice were treated with cyclic loading or sham-loading of the right ulna. A third group of mice received brachial plexus anesthesia (BPA) of the loaded limb before mechanical loading. Fluorochrome labels were administered at the time of loading and 7 days later. Ten days after loading, bone responses were quantified morphometrically. We hypothesized that CGRP signaling is required for normal mechanosensing and associated load-induced bone formation. We found that mechanically-induced activation of periosteal mineralizing surface in mice and associated blocking with BPA were eliminated by knockout of CGRPα signaling. This effect was not evident in CGRPß knockout mice. We also found that mineral apposition responses to mechanical loading and associated BPA blocking were retained with CGRPα deletion. We conclude that activation of periosteal mineralizing surfaces in response to mechanical loading of bone is CGRPα-dependent in vivo. This suggests that release of CGRP from sensory peptidergic fibers in periosteum and bone has a functional role in load-induced bone formation.

Functional adaptation in female rats: the role of estrogen signaling.

BACKGROUND: Sex steroids have direct effects on the skeleton. Estrogen acts on the skeleton via the classical genomic estrogen receptors alpha and beta (ERα and ERß), a membrane ER, and the non-genomic G-protein coupled estrogen receptor (GPER). GPER is distributed throughout the nervous system, but little is known about its effects on bone. In male rats, adaptation to loading is neuronally regulated, but this has not been studied in females. METHODOLOGY/PRINCIPAL FINDINGS: We used the rat ulna end-loading model to induce an adaptive modeling response in ovariectomized (OVX) female Sprague-Dawley rats. Rats were treated with a placebo, estrogen (17ß-estradiol), or G-1, a GPER-specific agonist. Fourteen days after OVX, rats underwent unilateral cyclic loading of the right ulna; half of the rats in each group had brachial plexus anesthesia (BPA) of the loaded limb before loading. Ten days after loading, serum estrogen concentrations, dorsal root ganglion (DRG) gene expression of ERα, ERß, GPER, CGRPα, TRPV1, TRPV4 and TRPA1, and load-induced skeletal responses were quantified. We hypothesized that estrogen and G-1 treatment would influence skeletal responses to cyclic loading through a neuronal mechanism. We found that estrogen suppresses periosteal bone formation in female rats. This physiological effect is not GPER-mediated. We also found that absolute mechanosensitivity in female rats was decreased, when compared with male rats. Blocking of adaptive bone formation by BPA in Placebo OVX females was reduced. CONCLUSIONS: Estrogen acts to decrease periosteal bone formation in female rats in vivo. This effect is not GPER-mediated. Gender differences in absolute bone mechanosensitivity exist in young Sprague-Dawley rats with reduced mechanosensitivity in females, although underlying bone formation rate associated with growth likely influences this observation. In contrast to female and male rats, central neuronal signals had a diminished effect on adaptive bone formation in estrogen-deficient female rats.

Are bacterial load and synovitis related in dogs with inflammatory stifle arthritis?

It has been proposed that small quantities of microbial material within synovial joints may act as a trigger for development of synovitis. We have previously identified an association between intra-articular bacteria and development of inflammatory stifle arthritis and cranial cruciate ligament rupture (CCLR) in dogs, and now wished to quantify bacterial load and markers of synovitis in dogs with and without stifle arthritis and CCLR. Joint tissues were collected from dogs with CCLR (n=51) and healthy dogs with normal stifles (n=9). Arthritis was assessed radiographically in CCLR dogs. Bacterial load was assessed using qPCR and broad-ranging 16S rRNA primers. qRT-PCR was used to estimate expression of the T lymphocyte antigen receptor (TCR Vß), CD3ɛ, tartrate-resistant acid phosphatase (TRAP), IL-4, IL-17, and TNF-α genes. Severity of synovitis was assessed histologically. Bacterial load was increased in arthritic stifles, when compared with healthy stifles. Histologic synovitis in arthritic stifles was mononuclear and was significantly correlated with bacterial load (1 of 2 primer sets) (S(R)=0.49, p<0.001). In arthritic stifles, expression of TRAP in synovium was increased relative to healthy stifles. Expression of pro-inflammatory genes was not correlated with bacterial load, histologic inflammation, or radiographic arthritis. Translocation of bacterial material to the canine stifle is related to the presence of joint inflammation. The lack of a strong positive correlation suggests that bacterial load is unlikely to be a primary pro-inflammatory factor. However, dysregulation of immune responses within synovial tissues may be dependent upon an environmental microbial trigger.

Comparison of fixation methods for treatment of long bone fractures in llamas and alpacas.

OBJECTIVE: To determine outcome after repair of long bone fractures in llamas and alpacas. STUDY DESIGN: Case series. ANIMALS: Llamas (n=11) and alpacas (8). METHODS: Medical records (1998-2008) of camelids with long bone fractures were reviewed for history, repair method, and complications. Outcome was also assessed by owner telephone questionnaire. RESULTS: Mean age at repair was 39 months. There were 8 males and 11 females. Fracture distribution was tibia (n=6), metatarsus (5), metacarpus (4), radius and ulna (2), humerus (1), and femur (1), with 13 closed and 6 open fractures. Fracture repair was by internal fixation (n=11), external fixation with a transfixation pin cast (5), external coaptation (2), and cross-pinning (1). In 1 llama, the limb was amputated to revise a failed external fixation repair. Seventeen animals (89%) were discharged, and 2 were euthanatized. Outcome was available for 13 animals: 9 were used for breeding and 4 as pets. Fewer major complications occurred with internal fixation than with external fixation with a transfixation pin cast (P<.005); however, there were no significant differences in minor complications between groups. CONCLUSIONS: Internal fixation with bone plates was associated with fewer major complications than external fixation with a transfixation pin cast.

Systemic effects of ulna loading in male rats during functional adaptation.

Functional skeletal adaptation is thought to be a local phenomenon controlled by osteoctyes. However, the nervous system also may have regulatory effects on adaptation. The aim of this study was to determine the effects of loading of a single bone on adaptation of other appendicular long bones and whether these responses were neuronally regulated. Young male Sprague-Dawley rats were used. The right ulna was loaded to induce a modeling response. In other rats, a second regimen was used to induce bone fatigue with a mixed modeling/remodeling response; a proportion of rats from each group received brachial plexus anesthesia to induce temporary neuronal blocking during bone loading. Sham groups were included. Left and right long bones (ulna, humerus, tibia, and femur) from each rat were examined histologically 10 days after loading. In fatigue- and sham-loaded animals, blood plasma concentrations of TNF-α, RANKL, OPG, and TRAP5b were determined. We found that loading the right ulna induced an increase in bone formation in distant long bones that were not loaded and that this effect was neuronally regulated. Distant effects were most evident in the rats that received loading without bone fatigue. In the fatigue-loaded animals, neuronal blocking induced a significant decrease in plasma TRAP5b at 10 days. Histologically, bone resorption was increased in both loaded and contralateral ulnas in fatigue-loaded rats and was not significantly blocked by brachial plexus anesthesia. In young, growing male rats we conclude that ulna loading induced increased bone formation in multiple bones. Systemic adaptation effects were, at least in part, neuronally regulated.