Pathological calcification in canine tendon-derived cells is modulated by extracellular ATP.

Tendon calcification is a commonly associated with degenerative tendinopathy of the Achilles tendons in dogs. It is characterised by the formation of calcific deposits and is refractory to treatment, often re-forming after surgical removal. Little is known about its pathogenesis and therefore the aims of this study were to develop an in vitro model of canine tendon calcification and use this model to investigate mechanisms driving calcification. Cells from the canine Achilles tendon were cultured with different calcifying media to establish which conditions were best able to induce specific, cell-mediated calcification. Once optimum calcification conditions had been established, the effect of ATP treatment on calcification was assessed. Results revealed that 2 mM di-sodium phosphate combined with 2 mM calcium chloride provided the optimum calcifying conditions, increasing calcium deposition and expression of osteogenic-related genes similar to those observed in tendon calcification in vivo. ATP treatment inhibited calcification in a dose-dependent manner, reducing calcium deposition and increasing cell viability, while osteogenic-related genes were no longer upregulated. In conclusion, the in vitro model of canine tendon calcification developed in this study provides the ability to study mechanisms driving tendon calcification, demonstrating that ATP plays a role in modulating tendon calcification that should be explored further in future studies.

A mismatch of planning and achieved tibial plateau angle in cranial closing wedge surgery: An in silico and clinical evaluation of 100 cases.

OBJECTIVE: (1) To determine whether Oxley's modified cranial closing wedge osteotomy (CCWO) results in a tibial plateau angle (TPA) of 5° in silico, (2) compare in silico to clinical postoperative TPA and (3) determine the impact of ostectomy distalization in silico. STUDY DESIGN: Cross-sectional retrospective radiographic in silico study. SAMPLE POPULATION: A total of 100 stifle radiographs; 90 dogs (small ≤25 kg = 84; large >25 kg = 16). METHODS: Tibial plateau angles were measured preoperatively (TPAPre ), after in silico planning (TPAPlan ), and postoperatively (TPAPost ). Virtual ostectomies were evaluated for plate fit. Postoperative ostectomy position was measured. Virtual ostectomies were performed 5/7.5/10/15 mm from the patellar tendon insertion in 10 dogs from each preoperative TPA category (≤20°/21-25°/ 26-30°/31-35°/>35°). Comparisons for TPAPre , TPAPost , and TPAPlan were made between small and large dogs, and the outcome to the target 5° between TPA categories and ostectomy positions. RESULTS: Mean ± SD TPAPre was 28.6 ± 6.2° and higher in small than large dogs. Mean TPAPlan was 7.6 ± 2.7°. Plate fit was appropriate in all. In silico, TPAs were greater than 5° except for cases with TPAPre > 35°. Median TPAPost was 5.5° (-4-21) and was higher in small (7°) than large (4.5°) dogs. Postoperative ostectomy position was more distal than Oxley's guidelines. When distalized >7.5 mm in silico, the magnitude of under-correction increased. CONCLUSIONS: Oxley's modified CCWO did not result in TPA of 5° in most cases. Ostectomy distalization exacerbated under-correction. CLINICAL IMPACT: Current guidelines should be modified to achieve 5° TPA postoperatively.

Evaluation of subchondral bone cysts in canine elbows with radiographic osteoarthritis secondary to elbow dysplasia.

OBJECTIVE: To investigate whether subchondral bone cysts (SBCs) were present in dogs with radiographic elbow osteoarthritis (OA) and to investigate their relationship with radiographic OA severity. STUDY DESIGN: Retrospective cross-sectional study. SAMPLE POPULATION: Thirty-eight Labrador retrievers (total of 76 elbows). METHODS: Elbow computed tomography (CT) images of 18 young (≤2 years old) and 20 old (>2 years old) Labrador retrievers, which presented for elbow-associated lameness, were reviewed. Radiographic elbow OA was graded into four groups based on the largest osteophyte size on CT. The presence, number, and maximum diameter of SBCs were determined. RESULTS: Subchondral bone cysts were only identified in elbows with osteophytic new bone formation. The number and size of SBCs were associated with radiographic OA severity (p < .001 and p = .041 respectively). Specifically, the rate at which SBCs were present increased for both moderate and severe OA in comparison with the mild OA (moderate OA RR = 2.46, 95% CI 2.08-2.92, p < .001; severe OA RR = 5.60, 95% CI 4.79-6.55, p < .001). For dogs with severe OA, there was an increased likelihood that their SBCs were larger than SBCs from dogs with mild OA (OR = 1.056, 95% CI 1.012-1.101, p = .012). No SBCs were observed in elbows without radiographic evidence of OA. CONCLUSION: Subchondral bone cysts were identified as a feature of radiographic elbow osteoarthritis in Labrador retrievers, and their number and size were indicative of the presence and severity of radiographic elbow OA. CLINICAL SIGNIFICANCE: Subchondral bone cysts are a potential imaging biomarker for quantitative assessment for canine OA.

Comparison of three radiographic assessment methods for detecting slipped capital femoral epiphyses in cats: Klein's line, modified Klein's line and the S-sign.

OBJECTIVES: The aim of the present study was to investigate whether diagnostic assessment methods used on radiographs in humans with slipped capital femoral epiphysis (SCFE) can be used in cats. METHODS: The ventrodorsal (VD) extended-leg and VD frog-leg pelvic radiographs of 20 cats with SCFE without fully displaced femoral capital epiphyses (FCE), eight cats with fully displaced FCE and five control cats with normal pelvic anatomy were assessed by five observers on two separate occasions 3 months apart. The Klein's line and modified Klein's line were assessed on each VD extended-leg radiograph, and the S-sign was assessed on each VD extended-leg and VD frog-leg radiograph. RESULTS: Excluding cases of fully displaced FCE, the S-sign on the VD frog-leg radiographs more accurately diagnosed SCFE than the S-sign on the VD extended-leg radiographs and the Klein's line (92.4% vs 88.8% vs 60.6%, respectively), and had the greatest sensitivity (93.9% vs 79.2% vs 30.6%, respectively). The S-sign on the VD extended-leg radiographs had greater specificity than the Klein's line and S-sign on the VD frog-leg radiographs (99.2% vs 97.9% vs 90.9%, respectively). The modified Klein's line detected SCFE in 40.2% of cases that were negative for the Klein's line. CONCLUSIONS AND RELEVANCE: The S-sign in both VD extended-leg and VD frog-leg views successfully detected SCFE in cats and can be used to increase early diagnosis and treatment in cats with SCFE that have only subtle radiographic changes.

Defining the safe corridor for transcondylar screw placement in the feline humeral condyle.

OBJECTIVES: The aim of this study was to develop guidelines for the optimal location of drill entry and exit points for insertion of a transcondylar screw across the feline humeral condyle. METHODS: Multiplanar reconstruction of feline elbow CT scans performed between 2016 and 2021 at one referral institution were reviewed. The optimum medial and lateral epicondylar entry and exit points for transcondylar screw placement were determined. These values were normalised to the humeral condylar diameter (HCD) for each elbow to determine the transcondylar screw placement guidelines. These guidelines were applied to each elbow and tolerance angles were determined in the transverse and frontal plane CT images to determine the safe corridor for screw placement. RESULTS: Twenty elbows from 12 cats were evaluated in this study. The guidelines for transcondylar screw placement were as follows: the medial entry/exit point was 0.38 × HCD cranial and 0.16 × HCD distal to the medial epicondyle, and the lateral entry/exit point was 0.3 × HCD cranial and 0.16 × HCD distal to the lateral epicondyle. Tolerance angles were statistically significantly (P <0.05) larger in both frontal (34.5% larger) and transverse (21.1% larger) planes when drilled from a lateral to medial direction compared with drilling from a medial to lateral direction. CONCLUSIONS AND RELEVANCE: The guidelines determined from this study may aid clinicians in the placement of humeral transcondylar screws in cats. Where possible, drilling from a lateral to medial direction is recommended owing to the higher tolerance angles reducing the likelihood of articular surface damage. Further studies are warranted to determine whether these guidelines are clinically useful and result in the safe insertion of a transcondylar screw in the clinical setting.

Assessment of normal radial joint orientation angles in nonchondrodystrophic small-breed dogs.

OBJECTIVE: To establish reference intervals for radial joint orientation angles in the frontal and sagittal planes in small-breed dogs and to compare them to those previously reported for medium- and large-breed dogs. ANIMALS: Antebrachii of 30 skeletally mature, nonchondrodystrophic small-breed dogs were evaluated radiographically. PROCEDURES: Orthogonal radiographs were retrospectively assessed to determine the anatomic medial proximal radial angle, anatomic lateral distal radial angle, anatomic cranial proximal radial angle (aCrPRA), and anatomic caudal distal radial angle (aCdDRA). The frontal plane angle, θ angle, and procurvatum were also calculated. The radial joint orientation angles determined were compared to those previously reported for medium- and large-breed dogs via a 1-sample t test. RESULTS: Mean and SD values for anatomic medial proximal radial angle, anatomic lateral distal radial angle, aCrPRA, and aCdDRA were 80.86 ± 2.86°, 85.60 ± 1.74°, 87.99 ± 2.79°, and 83.08 ± 3.14°, respectively. The mean and SDs for frontal plane angle, θ angle, and procurvatum were 4.75 ± 2.46°, 11.88 ± 1.76°, and 16.79 ± 4.13°, respectively. aCrPRA and aCdDRA were significantly different when compared to previously reported radial joint angles for medium- and large-breed dogs. CLINICAL RELEVANCE: Reference intervals for small-breed dog radial joint orientation angles were reported. Significant differences were identified for some joint orientation angles when compared to medium- and large-breed dogs. This small-breed reference interval reported can be utilized in planning of radial angular limb deformity corrective surgery, particularly when dogs are bilaterally affected.

Feline Femoral Fracture Fixation: What are the options?

PRACTICAL RELEVANCE: The femur is the most commonly fractured bone in cats. Femoral fractures usually result from high-velocity trauma such as a road traffic accident or fall from a height and, as such, are associated with a wide variety of concurrent injuries. The initial focus of treatment should always be on assessment and stabilisation of the major body systems. Once any concurrent injuries have been addressed, all femoral fractures need surgical stabilisation, with the notable exception of greenstick fractures in very young cats, which can heal with cage rest alone. A number of different surgical options are available depending on the fracture type, location, equipment, surgeon experience and owner finances. CLINICAL CHALLENGES: Femoral fractures can vary hugely in complexity and the small size of feline bones can limit the choice of implants. Furthermore, cats can present unique challenges in the postoperative period due to their active nature and the limited means to control their exercise level. AUDIENCE: This review is aimed at general and feline-specific practitioners who have some experience of feline orthopaedics, as well as those simply wishing to expand their knowledge. AIMS: The aim of this review is to help clinicians assess, plan and manage feline femoral fractures. It provides an overview of diagnostic imaging and a discussion of a range of suitable surgical options, including the principles of different types of fixation. It also highlights cat-specific issues, approaches and implants pertinent to the management of these cases. EVIDENCE BASE: A number of original articles and textbook chapters covering many aspects of femoral fractures in cats and dogs have been published. Where possible, this review draws on information from key feline research and, where necessary, extrapolates from relevant canine literature. The authors also offer practical guidance based on their own clinical experience.

CT characterisation and classification of feline temporomandibular joint trauma: a case series of 79 cats.

OBJECTIVES: The aim of this study was to characterise and describe patterns of temporomandibular joint (TMJ) injuries occurring in cats using CT. METHODS: A cross-sectional study was carried out in adherence with the STROBE guidelines. Among the medical and CT records of 79 cats, 158 TMJs were reviewed in a collaborative study between six institutions. RESULTS: TMJ injuries were most commonly unilateral, representing 70.9% of cases. The mandibular condyle was fractured in 88 cases (55.7%) of the 158 TMJs observed. Of those, 84.0% were intra-articular condyle fractures, with the medial half of the mandibular condyle over-represented. Luxations occurred in 32.9% of cases, which was 19.0% of all evaluated TMJs. Rostrodorsal luxations were most common representing 87.0% of all luxations. Temporal bone fractures were observed in 30.4% of all cases, which was 18.4% of TMJs. The majority of fractures were of an unknown cause. When the cause was determined, road traffic accident (RTA) was the most frequent, followed by animal interaction, other external forces (sharp or blunt force) and high-rise trauma. Bilateral injuries were 13.1 times more likely to occur in high-rise trauma (P = 0.01) and temporal bone fracture was significantly associated with RTAs (P = 0.016). No other significant associations were observed between cause of injury and the resulting TMJ injury pattern. CONCLUSIONS AND RELEVANCE: Various TMJ injury patterns can occur in cats as a result of trauma. Intra-articular fractures of the medial half of the mandibular condyle occur most commonly. Although unilateral injuries are more frequent, high-rise trauma tends to present with bilateral lesions. Further studies with a larger sample size should be performed to better understand TMJ patterns of injury and how they relate to possible causes.

Traumatic physeal fractures in cats: a review of 36 cases (2010-2020).

OBJECTIVES: The aim of this study was to describe the demography, aetiology, location and classification of physeal fractures in cats, and to describe their management and outcomes. METHODS: Clinical records and radiographs of cats referred for management of physeal fractures were retrospectively reviewed. Fractures of the proximal femoral physis were excluded. Descriptive statistics were used to describe signalment, cause of injury, presence of concurrent injuries, fracture description, treatment modality, complications, follow-up, physeal closure, implant removal and outcome. RESULTS: Thirty-four cats with 36 fractures were included, of which 17 affected the distal femur, 11 the distal tibia and fibula, five the distal radius and ulna, two the proximal tibia and one the distal humerus. Salter-Harris classification was type I in 14, type II in 16, type III in two and type IV in four fractures. Thirty-four fractures were treated with primary fixation, and the most common method was crossed Kirschner wires (24/34 fractures). Complications were observed in 14 fractures, of which 12 were minor. At radiographic follow-up, physeal closure was reported in 23 fractures, of which 15 were considered premature. Implant removal was performed in three fractures. Outcome was good in 28, fair in four and poor in two fractures. CONCLUSIONS AND RELEVANCE: Fracture of the distal femoral physis was the most common physeal fracture seen. Cats presenting with physeal fractures may be skeletally immature or mature with delayed physeal closure. The rate of physeal closure after fracture repair was relatively high but without apparent impact. The frequency of implant removal was very low, indicating that despite having a physeal fracture repair, most cats did not require a second procedure to remove implants. Overall, internal fixation provided a good outcome in most fractures.

The role of intermittent PTH administration in conjunction with allogenic stem cell treatment to stimulate fracture healing.

AIMS: A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. METHODS: A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 106 cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 µg/kg) or low (25 µg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis. RESULTS: Combination therapy treatment led to increased callus formation compared to controls. In the high-dose combination group there was significantly greater mineralized tissue volume and trabecular parameters compared to controls (p = 0.039). This translated to significantly improved stiffness (and ultimate load to failure (p = 0.049). The high-dose combination therapy group had the most significant improvement in mean modified Radiographic Union Score for Tibia fractures (RUST) compared to controls (13.8 (SD 1.3) vs 5.8 (SD 0.5)). All groups demonstrated significant increases in the radiological scores - RUST and Allen score - histologically compared to controls. CONCLUSION: We demonstrate the beneficial effect of localized MSC injections on fracture healing combined with low- or high-dose teriparatide, with efficacy dependent on PTH dose. Cite this article: Bone Joint Res 2021;10(10):659-667.

CD146 Delineates an Interfascicular Cell Sub-Population in Tendon That Is Recruited during Injury through Its Ligand Laminin-α4.

The interfascicular matrix (IFM) binds tendon fascicles and contains a population of morphologically distinct cells. However, the role of IFM-localised cell populations in tendon repair remains to be determined. The basement membrane protein laminin-α4 also localises to the IFM. Laminin-α4 is a ligand for several cell surface receptors, including CD146, a marker of pericyte and progenitor cells. We used a needle injury model in the rat Achilles tendon to test the hypothesis that the IFM is a niche for CD146+ cells that are mobilised in response to tendon damage. We also aimed to establish how expression patterns of circulating non-coding RNAs alter with tendon injury and identify potential RNA-based markers of tendon disease. The results demonstrate the formation of a focal lesion at the injury site, which increased in size and cellularity for up to 21 days post injury. In healthy tendon, CD146+ cells localised to the IFM, compared with injury, where CD146+ cells migrated towards the lesion at days 4 and 7, and populated the lesion 21 days post injury. This was accompanied by increased laminin-α4, suggesting that laminin-α4 facilitates CD146+ cell recruitment at injury sites. We also identified a panel of circulating microRNAs that are dysregulated with tendon injury. We propose that the IFM cell niche mediates the intrinsic response to injury, whereby an injury stimulus induces CD146+ cell migration. Further work is required to fully characterise CD146+ subpopulations within the IFM and establish their precise roles during tendon healing.

Management and Long-Term Outcome of Acetabular Fractures in Dogs: A Retrospective Study of 49 Dogs.

OBJECTIVE: The aim of this study was to categorize the presentation, management, complications and long-term outcome of canine acetabular fractures, and to determine the factors affecting outcome. MATERIALS AND METHODS: Case records and imaging for dogs with acetabular fractures were reviewed with long-term follow-up via canine brief pain inventory (CBPI) and owner questionnaires. RESULTS: The majority of fractures were in the mid-third (36/52) and caudal-third (13/52) with few in the cranial-third of the acetabulum (3/52). Concurrent injuries were diagnosed in 47/49 dogs; 10/34 dogs had neurological deficits on presentation. Forty-seven fractures received treatment: 25/47 had direct surgical repair (DSR), 10/47 had salvage surgery (SS) and 12/47 had conservative management (CM). Fracture location significantly affected treatment group (p = 0.001). New neurological deficits were documented after DSR in 5/24 dogs and SS in 2/10 dogs. Short-term complications occurred after DSR in 10/18 dogs (five minor, five major) and CM in 1/8 dogs (major). Long-term complications occurred after DSR in 2/15 dogs (major) and CM in 2/7 dogs (catastrophic). Conservative management dogs had worse average owner-reported CBPI scores than DSR or SS dogs. CLINICAL SIGNIFICANCE: Acetabular fractures predominate in the mid and caudal acetabulum, with high levels of concurrent injuries. Fracture location significantly influenced the treatment approach taken. Postoperative neurological deficits are common following SS and DSR.

Traumatic joint luxations in cats: Reduce, repair, replace, remove.

PRACTICAL RELEVANCE: Traumatic joint luxations are usually associated with significant trauma and there may be concomitant systemic injury. Joints are unstable as a result of injury to one or more supporting structures and the clinician should aim to determine which structures are damaged with physical examination, diagnostic imaging and careful assessment under sedation/anaesthesia. The aim is to reduce the joint back to its anatomical position, and then to maintain this through repair of damaged structures. However, where this is not possible, replacement or removal (arthrodesis/excision arthroplasty) of the joint remain viable options. CLINICAL CHALLENGES: Owing to the small size of feline joints and the severity of damage often seen, surgical management of these cases can be challenging. The first priority is to ensure the patient is systemically well before embarking on any specific surgical treatment of a luxated joint. Cats also present challenges in the postoperative period and a lack of patient and owner compliance can be detrimental to postoperative outcomes. AIMS: This article aims to help the reader diagnose joint luxations and to assist decision-making with an overview of the management and treatment options available. EVIDENCE BASE: There are a number of original articles and textbook chapters in the literature covering aspects of different joint luxations, particularly for the more common luxations. This article draws on information from key feline research and, where necessary, extrapolates from relevant canine research. The authors also offer practical guidance based on their own clinical experience.

Epidemiology and clinical management of elbow joint disease in dogs under primary veterinary care in the UK.

BACKGROUND: Conditions affecting the elbow joint are a common cause of lameness in dogs. Primary-care veterinary clinical data are now recognised as a valuable research resource. Using data from the VetCompass Programme, this study aimed to report the frequency and risk factors for elbow joint disease in dogs under primary veterinary care in the UK and describe clinical management. RESULTS: From 455,069 dogs under veterinary care, the one-year period prevalence for elbow joint disease diagnosis was 0.56% (95% CI: 0.53-0.60). Of 616 incident cases, the most common specific variants of elbow joint disease were osteoarthritis (n = 468, 75.97%), elbow dysplasia (190, 30.84%) and traumatic (41, 6.66%). The most common signs described by the owners were lameness (n = 466, 75.65%), difficulty exercising (123, 19.97%) and pain (86, 13.96%). The most common findings recorded on veterinary examination were pain (n = 283, 45.94%), lameness (278, 45.13%) and reduced range of movement (243, 39.45%). Common medications used included non-steroidal anti-inflammatory drugs (n = 544, 88.31%), tramadol (121, 19.64%) and disease modifying agents (118, 19.16%). Of 109 deaths involving euthanasia with information available from the 616 incident cases, elbow joint disease contributed to the decision to euthanase in 45 (41.28%) dogs.Five breeds showed increased odds of elbow joint disease compared with crossbred dogs: Rottweiler (OR: 6.16, 95% CI 3.89-9.75), Labrador Retriever (OR: 5.94, 95% CI 4.65-7.60), German Shepherd Dog (OR: 4.13, 95% CI 2.88-5.93), Golden Retriever (OR: 3.11, 95% CI 1.93-5.00) and English Springer Spaniel (OR: 2.00, 95% CI 1.26-3.18). Additional risk factors included having an adult bodyweight that was equal or higher than their breed/sex mean, advancing age, being male, being neutered, being insured and larger bodyweight. CONCLUSIONS: Elbow joint disease is a relatively common diagnosis in dogs and has a high welfare impact as evidenced by the high proportion of cases recorded with pain, lameness and analgesic therapy. There are strong breed predispositions, in particular for large breed dogs. These findings present a clear case for improved breeding programmes to reduce the burden of elbow joint disease.

Impact of breed on canine humeral condylar fracture configuration, surgical management, and outcome.

OBJECTIVE: To report the prevalence, configuration, risk factors, fixation methods and outcomes after repair of humeral condylar fractures (HCF) in dogs. STUDY DESIGN: Retrospective nested cohort study. SAMPLE POPULATION: One hundred twelve dogs. METHODS: Medical records of dogs referred between January 2010 and August 2018 were searched for HCF. Demographics, fracture configuration, repair, and complications were obtained from medical records. Radiographs were assessed for fracture reduction, implant positioning, and bone healing. Short-term radiographic and clinical outcomes, and long-term owner-assessed outcome was determined. Associations between these variables were statistically analyzed. RESULTS: Dogs with HCF represented 112 of 43 325 (0.26%, 95% CI 0.22-0.31) referrals. French bulldogs and spaniel breeds were predisposed to HCF (P < .02). French bulldogs were 6.58 times (95% CI 1.62-26.7) more likely than other breeds to have a medial HCF (P = .008). Epicondylar plate fixation was associated with reduced complications compared with lag screws and Kirschner wires (P = .009). Lameness was scored as 1 of 5 (median) in the 85 dogs with initial follow-up (median 6 weeks) after HCF repair. Outcome was considered excellent in 26 of 31 dogs with long-term follow-up (median 36 months). CONCLUSION: French bulldogs and spaniels were predisposed to HCF, and medial HCF were more common in French bulldogs. Epicondylar plate fixation was associated with reduced complications. CLINICAL SIGNIFICANCE: French bulldogs are predisposed to HCF, including medial HCF. Epicondylar plate fixation is recommended over other epicondylar fixation methods to reduce complications.

The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats.

OBJECTIVES: Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1). METHODS: Cells were isolated from the adipose and bone marrow of juvenile, adult, and previously OVX Wistar rats, and were characterized with flow cytometry, proliferation assays, osteogenic and adipogenic differentiation, and migration to SDF-1. Experiments were repeated with and without intermittent hPTH 1-34. RESULTS: Juvenile and adult MSCs demonstrated significantly increased osteogenic and adipogenic differentiation and superior migration towards SDF-1 compared with OVX groups; this was the case for AdMSCs and bMSCs equally. Parathyroid hormone (PTH) increased parameters of osteogenic differentiation and migration to SDF-1. This was significant for all cell types, although it had the most significant effect on cells derived from OVX animals. bMSCs from all groups showed increased mineralization and migration to SDF-1 compared with AdMSCs. CONCLUSION: Juvenile MSCs showed significantly greater migration to SDF-1 and significantly greater osteogenic and adipogenic differentiation compared with cells from osteopenic rats; this was true for bMSCs and AdMSCs. The addition of PTH increased these characteristics, with the most significant effect on cells derived from OVX animals, further illustrating possible clinical application of both PTH and MSCs in bone regenerative therapies.Cite this article:L. Osagie-Clouard, A. Sanghani-Kerai, M. Coathup, R. Meeson, T. Briggs, G. Blunn. The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats. Bone Joint Res 2019;8:397-404. DOI: 10.1302/2046-3758.88.BJR-2019-0018.R1.

Feline head trauma: a CT analysis of skull fractures and their management in 75 cats.

OBJECTIVES: The aim of this study was to describe and evaluate the configurations and management of feline skull fractures and concurrent injuries following head trauma. METHODS: Medical records and CT images were reviewed for cats with skull fractures confirmed by CT that were managed conservatively or with surgery. Details of signalment, presentation, skull fracture configuration, management, re-examination, and complications or mortality were recorded and analysed. RESULTS: Seventy-five cats (53 males, 22 females) with a mean age of 4.8 ± 3 years met the inclusion criteria. Eighty-nine percent of cats had fractures in multiple bones of the skull, with the mandible, upper jaw (maxilla, incisive and nasal bones) and craniofacial regions most commonly affected. Temporomandibular joint injury occurred in 56% of cats. Road traffic accidents (RTAs) were the most common cause of skull fractures, occurring in 89% of cats, and caused fractures of multiple regions of the skull. RTAs were also associated with high levels of concurrent injuries, particularly ophthalmic, neurological and thoracic injuries. A more limited distribution of injuries was seen in non-RTA cats. Equal numbers of cats were managed conservatively or surgically (47%). Mortality rate was 8% and complications were reported in 22% of cats. Increasing age at presentation and presence of internal upper jaw fractures were risk factors for development of complications. No risk factors were identified for mortality. CONCLUSIONS AND RELEVANCE: RTAs were the most common cause of feline skull fractures and resulted in fractures in multiple regions of the skull and concurrent injuries occurred frequently. Problems with dental occlusion were uncommon post-treatment. An increased risk of implant loosening and malocclusion was seen with palatine and pterygoid bone fractures and hard palate injuries. This study provides useful additional information regarding feline skull fractures, concurrent injuries and management techniques following head trauma.

VEGF with AMD3100 endogenously mobilizes mesenchymal stem cells and improves fracture healing.

A significant number of fractures develop non-union. Mesenchymal stem cell (MSC) therapy may be beneficial, however, this requires cell acquisition, culture and delivery. Endogenous mobilization of stem cells offers a non-invasive alternative. The hypothesis was administration of VEGF and the CXCR4 antagonist AMD3100 would increase the circulating pool of available MSCs and improve fracture healing. Ex-breeder female wistar rats received VEGF followed by AMD3100, or sham PBS. Blood prepared for culture and colonies were counted. P3 cells were analyzed by flow cytometry, bi-differentiation. The effect of mobilization on fracture healing was evaluated with 1.5 mm femoral osteotomy stabilized with an external fixator in 12-14 week old female Wistars. The mobilized group had significantly greater number of cfus/ml compared to controls, p = 0.029. The isolated cells expressed 1.8% CD34, 35% CD45, 61% CD29, 78% CD90, and differentiated into osteoblasts but not into adipocytes. The fracture gap in animals treated with VEGF and AMD3100 showed increased bone volume; 5.22 ± 1.7 µm3 and trabecular thickness 0.05 ± 0.01 µm compared with control animals (4.3 ± 3.1 µm3 , 0.04 ± 0.01 µm, respectively). Radiographic scores quantifying fracture healing (RUST) showed that the animals in the mobilization group had a higher healing score compared to controls (9.6 vs. 7.7). Histologically, mobilization resulted in significantly lower group variability in bone formation (p = 0.032) and greater amounts of bone and less fibrous tissue than the control group. Clinical significance: This pre-clinical study demonstrates a beneficial effect of endogenous MSC mobilization on fracture healing, which may have translation potential to prevent or treat clinical fractures at risk of delayed or non-union fractures. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:1294-1302, 2019.

Postoperative complications associated with external skeletal fixators in cats.

OBJECTIVES: The objective of this study was to quantify complications associated with external skeletal fixators (ESFs) in cats and to identify potential risk factors. METHODS: A retrospective review of medical records and radiographs following ESF placement was performed. RESULTS: Case records of 140 cats were reviewed; fixator-associated complications (FACs) occurred in 19% of cats. The region of ESF placement was significantly associated with complication development. Complications developed most frequently in the femur (50%), tarsus (35%) and radius/ulna (33%). Superficial pin tract infection (SPTI) and implant failure accounted for 45% and 41% of all FACs, respectively. SPTI occurred more frequently in the femur, humerus and tibia, with implant failure more frequent in the tarsus. No association between breed, age, sex, weight, fracture type (open vs closed), ESF classification, number of pins per bone segment, degree of fracture load sharing, and the incidence or type of FAC was identified. No association between region of placement, breed, age, sex, weight, fracture type (open vs closed), ESF classification, number of pins per bone segment, fracture load sharing and the time to complication development was identified. CONCLUSIONS AND RELEVANCE: Complication development is not uncommon in cats following ESF placement. The higher complication rate in the femur, tarsus and radius/ulna should be considered when reviewing options for fracture management. However, cats appear to have a lower rate of pin tract infections than dogs.

Combined physeal fractures of the distal radius and ulna: complications associated with K-wire fixation and long-term prognosis in six cats.

Objectives The objective was to describe the complications and long-term outcome associated with Kirschner (K)-wire fixation of combined distal radial and ulnar physeal fractures in six cats. Methods Medical records (2002-2014) of six referral institutions were searched for cats with combined distal radial and ulnar physeal fractures. Cases with complete clinical files, radiographs and surgical records were retrospectively reviewed. Long-term outcome was assessed via telephone interviews using an owner questionnaire. Results Complete files were available for 6/9 identified cases (cases 1-6). All fractures were classified as Salter-Harris type I or II. Five cases underwent open reduction and internal fixation via cross-pinning of the distal radius and intramedullary pinning of the ulna (cases 1-3); fixation of the distal radial and ulnar physes with one K-wire each (case 4); and K-wire fixation of the radial physis in combination with two transulnoradial K-wires (case 5). One case underwent closed reduction and percutaneous cross-pinning of the distal radius under fluoroscopic guidance (case 6). The complications encountered were: reduced radiocarpal range of motion (ROM) (cases 1, 3, 4, 5); implant loosening/migration (cases 1, 2, 5); and radioulnar synostosis (case 4). None of the cats developed angular limb deformity. Long-term outcome (12 months to 7 years after surgery) was graded as 'excellent' by the owners in all cases. Conclusions and relevance Prognosis is favourable for feline combined distal radial and ulnar physeal fractures following K-wire fixation in cats over 7 months of age. Implant removal after bony union is recommended to minimise reduction in ROM and to prevent implant loosening/migration.