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.

Risk Factors Associated with Plantar Necrosis following Tarsal Arthrodesis in Dogs.

OBJECTIVES: The aim of this study was to define landmarks of the intermetatarsal channel of the dorsal pedal artery and to assess whether damage to the dorsal pedal artery during metatarsal screw placement in dogs undergoing pan- and partial-tarsal arthrodesis (PanTA/ParTA) could be a mechanism in the development of plantar necrosis. STUDY DESIGN: This study was divided in to two parts: (1) ex-vivo anatomical study: 19 canine cadavers, (2) retrospective clinical study: 39 dogs. Cadaveric dissection documented the mean intermetatarsal channel position. Metatarsal screw position was evaluated on postoperative radiographs of dogs after PanTA or ParTA. Screw position, arthrodesis type and surgical approach were assessed for their impact on complications, including plantar necrosis. RESULTS: The mean proximal and distal extent of the intermetatarsal channel lies between 4.3% ± 1.9 and 22.8% ± 2.9 the length of metatarsal III (MTIII) respectively. The intermetatarsal channel lies within the most proximal 25% of MTIII in 95% of cases. At least one screw risked damaging the mean intermetatarsal channel position in 92% of dogs; 8% of these dogs went on to develop plantar necrosis. The mean screw position did not differ between ParTA cases with or without plantar necrosis (p > 0.05). CONCLUSION: Violation of the intermetatarsal channel is possible during metatarsal screw placement. Care should be taken when placing screws in the proximal 25% of the metatarsals, specifically avoiding exiting dorsally between MTII and MTIII and across the distal region of the intermetatarsal channel, where the perforating metatarsal artery passes interosseously, as damage may contribute to the aetiology of plantar necrosis.

Multiligament stifle injury, a multicenter retrospective study in 26 dogs.

OBJECTIVES: To describe multiligament stifle injury in dogs and report complications and long-term outcomes. METHODS: Medical records of dogs surgically treated for multiligament stifle injury were reviewed from six veterinary hospitals. Long-term follow-up was collected from referring veterinarians. RESULTS: Twenty-six client-owned dogs and 26 stifles were included. Road traffic accidents and limb entrapment were the most common causes of injury. Cranial cruciate and lateral collateral ligament rupture was the most common combination of injury (10 cases). The caudal cruciate ligament was damaged in 12/23 cases but was surgically addressed in only 2 cases. Cranial cruciate ligament rupture was present in all cases and was managed using TPLO (6 cases), extracapsular suture (15 cases) and TTA (2 cases). Postoperative immobilisation with a transarticular external skeletal fixator was used in 4/26 cases. Intraoperative complications were reported in 2/23 cases, short-term complications in 17/25 cases, of which eight were major, and long-term complications in 7/18, of which two were major. Patella luxation was seen in one case and is a previously unreported complication. The overall outcome was excellent in 9/24 cases, good in 5/24 cases, fair in 7/24 cases and poor in 3/24 cases. Follow-up time ranged from 1.5 months to 9 years with the median (IQR) of 9.5 (4.0 to 28.5) months. CONCLUSIONS: Multiligament stifle injury in dogs is associated with a high rate of major complications. The overall outcome was good to excellent in just over half of the dogs.

A new method for segmentation and analysis of bone callus in rodent fracture models using micro-CT.

Fracture burden has created a need to better understand bone repair processes under different pathophysiological states. Evaluation of structural and material properties of the mineralized callus, which is integral to restoring biomechanical stability is, therefore, vital. Microcomputed tomography (micro-CT) can facilitate noninvasive imaging of fracture repair, however, current methods for callus segmentation are only semiautomated, restricted to defined regions, time/labor intensive, and prone to user variation. Herein, we share a new automatic method for segmenting callus in micro-CT tomograms that will allow for objective, quantitative analysis of the bone fracture microarchitecture. Fractured and nonfractured mouse femurs were scanned and processed by both manual and automated segmentation of fracture callus from cortical bone after which microarchitectural parameters were analyzed. All segmentation and analysis steps were performed using CTAn (Bruker) with automatic segmentation performed using the software's image-processing plugins. Results showed automatic segmentation reliably and consistently segmented callus from cortical bone, demonstrating good agreement with manual methods with low bias: tissue volume (TV): -0.320 mm3 , bone volume (BV): 0.0358 mm3 , and bone volume/tissue volume (BV/TV): -3.52%, and was faster and eliminated user-bias and variation. Method scalability and translatability across rodent models were verified in scans of fractured rat femora showing good agreement with manual methods with low bias: TV: -3.654 mm3 , BV: 0.830 mm3 , and BV/TV: 7.81%. Together, these data validate a new automated method for segmentation of callus and cortical bone in micro-CT tomograms that we share as a fast, reliable, and less user-dependent tool for application to study bone callus in fracture, and potentially elsewhere.

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.

Demography, management and outcomes of canine physeal fractures (103 cases).

BACKGROUND: This study is a retrospective review of the demography, management, complications and outcomes of canine physeal fractures. METHODS: Clinical records were reviewed for dogs with appendicular physeal fractures, and descriptive statistical analysis was applied to the data set. RESULTS: One hundred and three fractures were included, of which 68 had follow-up. Fractures of the distal humerus were the most common (n = 57), followed by proximal tibial fractures (n = 16). Outcome was fair for most fractures at all locations, aside from the distal humerus, where most outcomes were good. At radiographic follow-up, most physes were closed at all locations aside from the distal tibia. Implant removal to allow ongoing physeal growth was performed in only 3/18 (17%) fractures, in 15/18 (83%) implant removal related to complications. LIMITATIONS: Only short-term follow-up data were present, and hence it is not possible to give a longer term indication of return to function. CONCLUSIONS: The management and demography of canine physeal fractures have evolved considerably from previous publications. Routine implant removal to allow ongoing growth was not regularly performed at all locations in this cohort.

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.

Moving Beyond the Limits of Detection: The Past, the Present, and the Future of Diagnostic Imaging in Canine Osteoarthritis.

Osteoarthritis (OA) is the most common orthopedic condition in dogs, characterized as the chronic, painful end-point of a synovial joint with limited therapeutic options other than palliative pain control or surgical salvage. Since the 1970s, radiography has been the standard-of-care for the imaging diagnosis of OA, despite its known limitations. As newer technologies have been developed, the limits of detection have lowered, allowing for the identification of earlier stages of OA. Identification of OA at a stage where it is potentially reversible still remains elusive, however, yet there is hope that newer technologies may be able to close this gap. In this article, we review the changes in the imaging of canine OA over the past 50 years and give a speculative view on future innovations which may provide for earlier identification, with the ultimate goal of repositioning the limit of detection to cross the threshold of this potentially reversible disease.

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.

Computed Tomographic Features of Non-Lame French Bulldog Elbows.

OBJECTIVE: French Bulldogs are predisposed to humeral condylar fractures. Computed tomography (CT) in English Springer Spaniel elbows has allowed identification of humeral intracondylar fissures (HIF), which can cause lameness and predispose to condylar fractures. This study aimed to evaluate CT characteristics of non-lame French Bulldog elbows, to determine the presence of underlying elbow disease. STUDY DESIGN: Retrospective evaluation of CT images from elbows of non-lame French Bulldogs from scans obtained for soft tissue or neurological evaluation was performed. Images were evaluated for the presence of HIF and other elbow abnormalities: condylar and supracondylar remodelling, humeral condylar sclerosis, elbow incongruency, medial coronoid process disease and elbow osteoarthritis. Descriptive statistics were performed. RESULTS: Computed tomographic scans from 37 dogs (74 elbows) were reviewed. No HIF were identified, although 28/74 elbows had an intracondylar sclerotic band. Medial coronoid process disease was noted in 16/74 elbows, and small osteophytes were present in 21/74 elbows, suggesting a degree of subclinical elbow disease. Widening of the caudolateral aspect of the radial incisure was identified (37/74) as a breed normal. Elbow incongruency was otherwise rare. CONCLUSION: Non-lame French Bulldogs showed a low prevalence of occult elbow disease but a proportion had radial incisure widening. Although humeral intracondylar sclerosis was present in over a third of dogs, no HIF were identified and therefore no clear cause for their increased risk of humeral condylar fracture was identified.

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.

An examination of two different approaches for the study of femoral neck fracture: Towards a more relevant rodent model.

Femoral neck fractures are a massive personal and health programme burden. Methods to study femoral neck strength, across its combined trabecular and cortical components are therefore essential. Rodent ovariectomy-induced osteoporosis models are commonly coupled with ex vivo 3-/4-point bending methods to measure changes in femoral cortical diaphysis. The loading direction used to assess these properties are often non-physiologic and, moreover, these ovariectomy models are linked to marked weight gain that can influence the biomechanical properties. Herein, we explore whether more physiological axial ex vivo loading protocols applied to femoral neck samples of ovariectomised (OVX) rodents provide anatomically-relevant models for the assessment of strength. We examine the use of mouse and rat femurs, loaded in constrained and unconstrained configuration, respectively, and explore whether weight-correction increases their utility. Accordingly, the mid-shaft of the proximal half of femurs from OVX and sham-operated (Sham) mice was methacrylate-anchored and the head loaded parallel to the diaphysis (constrained). Alternatively, femurs from OVX and Sham rats were isolated intact and axially-loaded through hip and knee joint articular surfaces (unconstrained). Yield displacement, stiffness, maximum load and resilience were measured and fracture pattern classified; effects of body weight-correction via a linear regression method or simple division were assessed. Our data reveal significant deficiencies in biomechanical properties in OVX mouse femurs loaded in constrained configuration, only after weight-correction by linear regression. In addition, evaluation of rat femur biomechanics in unconstrained loading demonstrated greater variation and that weight-correction by simple division improved scope to reveal significant OVX impact. We conclude that greater femoral neck fracture susceptibility can indeed be measured in OVX rodents as long as multiple biomechanical parameters are reported, care is taken in choosing the method for assessing load-bearing strength and weight-correction applied. These studies advance the establishment of more relevant rodent models for the study of femoral neck fracture.

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.