Anterior vertebral body tethering (AVBT) is a growth modulating procedure used to manage idiopathic scoliosis by applying a flexible tether to the convex surface of the spine in skeletally immature patients. The purpose of this study is to determine the preliminary clinical outcomes for an adolescent patient cohort. 18 patients with scoliosis were selected using a narrow selection criteria to undergo AVBT. Of this cohort, 11 had reached a minimum follow up of 2 years, 4 had reached 18 months, and 3 had reached 6 months. These patients all demonstrated a primary thoracic deformity that was too severe for bracing, were skeletally immature, and were analysed in this preliminary study of coronal plane deformity correction. Using open-source image analysis software (ImageJ, NIH) PA radiographs taken pre-operatively and at regular follow-up visits post-operatively were used to measure the coronal plane deformity of the major and compensatory curves. Pre-operatively, the mean age was 12.0 years (S.D. 10.7 – 13.3), mean Sanders score 2.6 (S.D. 1.8-3.4), all Risser 0 and pre-menarchal, with mean main thoracic Cobb angle of 52° (S.D. 44.2-59.8°). Post-operatively the mean angle decreased to 26.4° (S.D. 18.4-32°) at 1 week, 30.4° (S.D. 21.3-39.6°) at 2 months, 25.7° (S.D. 18.7-32.8°) at 6 months, 27.9° (S.D. 16.2-39.6°) at 12 months, and 36.8° (S.D. 22.6– 51.0°) at 18 months and 38.2° (S.D. 27.6-48.7°) at 2 years. The change in curve at 2 years post-operative was statistically significant (P=0.004). There were 4 tether breakages identified that did not require return to theatre as yet, one patient underwent a posterior spinal instrumented fusion due to curve progression. AVBT is a promising new growth modulation technique for skeletally immature patients with progressive idiopathic scoliosis. This study has demonstrated a reduction in scoliosis severity

To evaluate the functional outcome of open humerus diaphyseal fractures treated with the Three-stitch technique of antegrade humerus nailing. This is a retrospective study conducted at the Department of Orthopaedics in D. Y. Patil University, School of Medicine, Navi Mumbai, India. The study included 25 patients who were operated on from January 2019 to April 2021 and follow-ups done till May 2022. Inclusion criteria were adult patients with open humerus diaphyseal fractures (Gustilo-Anderson Classification). All patients with closed fractures, skeletally immature patients, and patients with associated head injury were excluded from the study. All patients were operated on with a minimally invasive Three-stitch technique for antegrade humerus nailing. All patients were evaluated based on DASH score. Out of the 25 patients included in the study, all patients showed complete union. The mean age of the patients was 40.4 years (range 23–66 years). The average period for consolidation of fracture was 10.56 weeks (range 8–14 weeks). The DASH score ranged from 0 to 15.8 with an average score of 2.96. Five patients reported complications with three patients of post-operative infection and delayed wound healing and two patients with screw loosening. All complications were resolved with proper wound care and the complete union was noted. None of the patients had an iatrogenic neurovascular injury. Three-stitch antegrade nailing technique is a novel method to treat diaphyseal humerus fractures and provides excellent results. It has various advantages such as minimal invasiveness, minimal injury to the rotator cuff, fewer infection rates, minimal iatrogenic injuries, and good functional outcomes. Therefore, this treatment modality can be effectively used for open humerus diaphyseal fractures

Introduction. Epiphysiodesis, defined as the process of closing the growth plate (physis), have been used for several years as a treatment option of cases where the predicted leg-length discrepancy (LLD) falls between 2 to 5 cm. The aim of this study was to systematically review the existing literature on the effectiveness of three different epiphysiodesis techniques with implant usage for the treatment of leg-length discrepancy in the pediatric population. The secondary aim was to address the reported complications of staples, tension-band plates (TBP) and percutaneous epiphysiodesis screws (PETS). Method. This systematic review was performed according to PRISMA guidelines. We searched MEDLINE (PubMed), Embase, Cochrane Library, Web of Science and Scopus for studies on skeletally immature patients with LLD treated with epiphysiodesis with an implant. The extracted outcome categories were effectiveness of epiphysiodesis (LLD measurements pre/post-operatively, successful/unsuccessful) and complications that were graded on severity. Result. Forty-four studies (2184 patients) were included, from whom 578 underwent TBP, 455 PETS and 1048 staples. From pooled analysis of the studies reporting success rate, 64% (150/234) successful TBP surgeries (10 studies), 78% (222/284) successful PETS (9 studies) and 52% (212/407) successful Blount staples (8 studies). Severe complications rate was 7% for PETS, 17% for TBP and 16% for Blount staples. TBP had 43 cases of angular deformity (10%), Blount staples 184 (17%) while PETS only 18 cases (4%). Conclusion. Our results highlighted that PETS seems to be the most successful type of epiphysiodesis surgery with an implant, with higher success rate and lower severe complications than TBP or Blount staples

Abstract. Objective. A higher prevalence of cam morphology has been reported in the athletic population but the development of the cam morphology is not fully understood. The purpose of this systematic review is to establish the timing of development of the cam morphology in athletes, the proximal femoral morphologies associated with its development, and other associated factors. Methods. Embase, MEDLINE and the Cochrane Library were searched for articles related to development of the cam morphology, and PRISMA guidelines were followed. Data was pooled using random effects meta-analysis. Study quality was assessed using the Downs and Black criteria and evidence quality using the GRADE framework. Results. This search identified 16 articles involving 2,028 participants. In males, alpha angle was higher in athletes with closed physes than open physes (SMD 0.71; 95% CI 0.23, 1.19). Prevalence of cam morphology was associated with age during adolescence when measured per hip (β 0.055; 95% CI 0.020, 0.091) and per individual (β 0.049; 95% CI 0.034, 0.064). Lateral extension of the epiphysis was associated with an increased alpha angle (r 0.68; 95% CI 0.63, 0.73). A dose-response relationship was frequently reported between sporting frequency and cam morphology. There was a paucity of data regarding the development of cam morphology in females. Conclusions. Very low and low quality evidence suggests that in the majority of adolescent male athletes’ osseous cam morphology developed during skeletal immaturity, and that prevalence increases with age. Very low quality evidence suggests that osseous cam morphology development was related to lateral extension of the proximal femoral epiphysis

Abstract. Objectives. The purpose of this trial is to investigate the safety and efficacy of immediate weight-bearing (IWB) and range of motion exercise regimes following ORIF of unstable ankle fractures with a particular focus on functional outcomes and complication rates. Methods. A pragmatic randomised controlled multicentre trial, comparing IWB in a walking boot and ROM within 24 hours versus NWB and immobilisation in a cast for six weeks, following ORIF of all types of unstable adult ankle fractures. The exclusion criteria are skeletal immaturity and tibial plafond fractures. The primary outcome measure is the functional Olerud-Molander Ankle Score (OMAS). Secondary outcomes include wound infection, displacement of osteosynthesis, the full arc of ankle motion, RAND-36 Item Short Form Survey (SF-36) scoring, time to return to work and postoperative hospital length of stay. Results. We recruited 160 patients with an unstable ankle fracture. Participants’ ages ranged from 15 to 94 years (M = 45.5, SD = 17.2), with 54% identified as female. The mean time from injury to surgical fixation was 1.3 days (0 to 17 days). Patients in the IWB group had a 9.5-point higher mean OMAS at six weeks postoperatively (95% CI 1.48, 17.52) P = 0.021 with a similar result at three months. The complications rate was similar in both groups. The rate of surgical site infection was 4.3%. One patient had DVT, and another patient had a PE, both were randomised to NWB. Length of hospital stay was 1 ± 1.5 (0, 12) for the IWB group vs 1.5 ± 2.5 (0, 19) for the NWB group. Conclusion. In this large multicentre RCT, we investigated WB following ORIF of all ankle fracture patterns in the usual care condition using standard fixation methods. Our result suggests that IWB following ankle fracture fixation is safe and resulted in a better functional outcome

The use of retrograde femoral intramedullary nails in children for deformity correction is controversial. It is unknown if the injury to the central part of the growth plate results in premature bony union, leading to limb deformities or discrepancies. The aim of this study was to assess physeal healing and bone growth after insertion of a retrograde femoral nail thorough the centre of the physis in a skeletally immature experimental porcine model. Eleven immature pigs were included in the study. One leg was randomised for operation with a retrograde femoral nail (diameter 10.7 mm), whilst the non-operated contralateral remained as control. All nails were inserted centrally in coronal and sagittal plane under fluoroscopic guidance, and the nails spanned the physis. The nails were removed at 8 weeks. Both femora in all animals underwent MRI at baseline (pre-operatively), 8 weeks (after nail removal) and 16 weeks (before euthanasia). Femoral bone length was measured at 5 sites (anterior, posterior, central, lateral and medial) using 3d T1-weighted MRI. Growth was calculated after 8 weeks (growth with nail) and 16 weeks (growth without nail). Physeal cross-sectional area and percentage violated by the nail was determined on MRI. Operated side was compared to non-operated. Corresponding 95% confidence intervals were calculated. No differences in axial growth were observed between operated and non-operated sides. Mean growth difference was 0,61 mm [−0,78;2,01] whilst the nail was inserted into the bone and 0,72 mm [−1,04;1,65] after nail removal. No signs of angular bone deformities were found when comparing operated side to non-operated side. No premature bony healing at the physis occurred. Histology confirmed fibrous healing. Mean physeal violation was 5.72% [5.51; 5.93] by the femoral nail. The insertion of a retrograde femoral nail through the centre of an open physis might be a safe procedure with no subsequent growth arrest. However, experiments assessing the long term physeal healing and growth are needed

Introduction and Objective. Ankle fractures are common and affect young adults as well as the elderly. An unstable ankle fracture treatment typically involves surgical fixation, immobilisation, and modified weight-bearing for six weeks. Non-weight bearing (NWB) cast immobilisation periods were used to protect the soft tissue envelope and osteosynthesis. This can have implications on patient function and may reduce independence, mobility and return to work. Newer trends in earlier mobilisation compete with traditional NWB doctrine, and weak consensus exists as to the best postoperative strategy. The purpose of this trial is to investigate the safety and efficacy of immediate weight-bearing (IWB) and range of motion (ROM) exercise regimes following ORIF of unstable ankle fractures with a particular focus on functional outcomes and complication rates. Materials and Methods. A pragmatic randomised controlled multicentre trial, comparing IWB in a walking boot and ROM within 24 hours versus non-weight-bearing (NWB) and immobilisation in a cast for six weeks, following ORIF of all types of unstable adult ankle fractures (lateral malleolar, bimalleolar, trimalleolar with or without syndesmotic injury). The exclusion criteria are skeletal immaturity and tibial plafond fractures. The primary outcome measure is the functional Olerud-Molander Ankle Score (OMAS). Secondary outcomes include wound infection (deep and superficial), displacement of osteosynthesis, the full arc of ankle motion (plantar flexion and dorsal flection), RAND-36 Item Short Form Survey (SF-36) scoring, time to return to work and postoperative hospital length of stay. Results. We recruited 160 patients with an unstable ankle fracture. Participants’ ages ranged from 15 to 94 years (M = 45.5, SD = 17.2), with 54% identified as female. The mean time from injury to surgical fixation was 1.3 days (0 to 17 days). Patients in the immediate weight-bearing group had a 9.5-point higher mean OMAS at six weeks postoperatively (95% CI 1.48, 17.52) P = 0.021. The complications rate was similar in both groups. The rate of surgical site infection was 4.3%. One patient had DVT, and another patient had a pulmonary embolism; both were randomised to NWB. Length of hospital stay (LOS) was 1 ± 1.5 (0, 12) for the IWB group vs 1.5 ± 2.5 (0, 19) for the NWB group. Conclusions. There is a paucity of quality evidence supporting the postoperative management regimes used most commonly in clinical practice. To our knowledge, immediate weight-bearing (IWB) following ORIF of all types of unstable ankle fractures has not been investigated in a controlled prospective manner in recent decades. In this large multicentre, randomised controlled trial, we investigated immediate weight-bearing following ORIF of all ankle fracture patterns in the usual care condition using standard fixation methods. Our result suggests that IWB following ankle fracture fixation is safe and resulted in a better functional outcome. Once anatomical reduction and stable internal fixation is achieved, we recommend IWB in all types of ankle fractures in a compliant patient

Joint surface restoration of deep osteochondral defects represents a significant unmet clinical need. Moreover, untreated lesions lead to a high rate of osteoarthritis. The current strategies to repair deep osteochondral defects such as osteochondral grafting or sandwich strategies combining bone autografts with ACI/MACI fail to generate long-lasting osteochondral interfaces. Herein, we investigated the capacity of juvenile Osteochondral Grafts (OCGs) to repair osteochondral defects in skeletally mature animals. With this regenerative model in view, we set up a new biological, bilayered, and scaffold-free Tissue Engineered (TE) construct for the repair of the osteochondral unit of the knee. Skeletally immature (5 weeks old) and mature (11 weeks old) Lewis rats were used. Cylindrical OCGs were excised from the intercondylar groove of the knee of skeletally immature rats and transplanted into osteochondral defects created in skeletally mature rats. To create bilayered TE constructs, micromasses of human periosteum-derived progenitor cells (hPDCs) and human articular chondrocytes (hACs) were produced in vitro using chemically defined medium formulations. These constructs were subsequently implanted orthotopically in vivo in nude rats. At 4 and 16 weeks after surgery, the knees were collected and processed for subsequent 3D imaging analysis and histological evaluation. Micro-computed tomography (µCT), H&E and Safranin O staining were used to evaluate the degree of tissue repair. Our results showed that the osteochondral unit of the knee in 5 weeks old rats exhibit an immature phenotype, displaying active subchondral bone formation through endochondral ossification, the absence of a tidemark, and articular chondrocytes oriented parallel to the articular surface. When transplanted into skeletally mature animals, the immature OCGs resumed their maturation process, i.e., formed new subchondral bone, partially established the tidemark, and maintained their Safranin O-positive hyaline cartilage at 16 weeks after transplantation. The bilayered TE constructs (hPDCs + hACs) could partially recapitulate the cascade of events as seen with the immature OCGs, i.e., the regeneration of the subchondral bone and the formation of the typical joint surface architecture, ranging from non-mineralized hyaline cartilage in the superficial layers to a progressively mineralized matrix at the interface with a new subchondral bone plate. Cell-based TE constructs displaying a hierarchically organized structure comprising of different tissue forming units seem an attractive new strategy to treat osteochondral defects of the knee

INTRODUCTION. Endochondral ossification in the growth plate is directly responsible for skeletal growth and its de novo bone-generating activity. Growth plates are vulnerable to disturbances that may lead to abnormal skeletal development. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used analgesics but have been reported to impair endochondral ossification-driven fracture healing. Despite the general awareness that NSAIDs affect endochondral ossification, the consequences of NSAIDs on skeletal development are unknown. We hypothesise that the NSAID celecoxib leads to impaired growth plate development and consequently impairs skeletal development. METHODS. Healthy skeletally immature (5 weeks old) C57BL/6 mice were treated for ten weeks with celecoxib (daily oral administration 10 mg/kg) or placebo (water) (institutional approval 2013–094) (n=12 per group). At 15 weeks postnatally, total growth plate thickness, the thickness of specific growth plate zones, (immuno)histological analysis of extracellular matrix composition in the growth plate, cell number and cell size, longitudinal bone growth and bone micro-architecture by micro-CT were analysed. Inhibition of COX-2 activity was confirmed by determining PGE2 levels in plasma using an ELISA. RESULTS. No significant difference in total growth plate thickness or thickness of the resting zone, proliferative or hypertrophic zone was found between groups. Staining of growth plate extracellular matrix components revealed, however, a significantly higher proteoglycan content and less collagen type II staining in the proliferative zone. In the hypertrophic zone of the growth plates of celecoxib treated mice collagen type X was hardly detectable as compared to placebo mice. In addition, a significantly decreased cell number was observed in the hypertrophic zone of the growth plate and cells were significantly smaller in the celecoxib group. Micro-CT analysis of the subchondral bone region directly beneath the growth plate showed significantly higher bone density, bone volume density and trabecular thickness following celecoxib treatment. Despite the detected differences in extracellular matrix composition of the growth plate, no difference was found in the length of the tibia in celecoxib treated mice. DISCUSSION. In summary, there are no measurable differences found in murine skeletal formation as a result of treatment with celecoxib in this study. However, there are notable phenotypic features found in the maturation of the growth plate (hypertrophic zone and subchondral bone) as a result from the celecoxib treatment, of which the potential consequences we do not yet understand. SIGNIFICANCE. When follow-up actions from the use of celecoxib on the growing individual are found this may warrant re-evaluation for the use of celecoxib in these individuals

Anterior cruciate ligament (acl) reconstruction is one of the most commonly performed procedures in orthopedics for acl injury. While literature suggest short-term good-to-excellent functional results, a significant number of long-term studies report unexplained early oa development, regardless type of reconstruction. The present study reports the feasibility analysis and development of a clinical protocol, integrating different methodologies, able to determine which acl reconstruction technique could have the best chance to prevent oa. It gives also clinicians an effective tool to minimize the incidence of early oa. A prospective clinical trial was defined to evaluate clinical outcome, biochemical changes in cartilage, biomechanical parameters and possible development of oa. The most common reconstruction techniques were selected for this study, including hamstring single-bundle, single-bundle with extraarticular tenodesis and anatomical double-bundle. Power analysis was performed in terms of changes at cartilage level measurable by mri with t2 mapping. A sample size of 42 patients with isolated traumatic acl injury were therefore identified, considering a possible 10% to follow-up. Subjects presenting skeletal immaturity, degenerative tear of acl, other potential risk factors of oa and previous knee surgery were excluded. Included patients were randomized and underwent one of the 3 specified reconstruction techniques. The patients were evaluated pre-operatively, intra-operatively and post-operatively at 4 and 18 months of follow-up. Clinical evaluation were performed at each time using subjective scores (koos) and generic health status (sf-12). The activity level were documented (marx) as well as objective function (ikdc). Preliminary results allow to verify kinematic patterns during active tasks, including level walking, stair descending and squatting using dynamic roentgen sterephotogrammetric analysis (rsa) methodology before and after the injured ligament reconstruction. Intra-operative kinematics was also available by using a dedicated navigation system, thus to verify knee laxity at the time of surgery. Additionally, non-invasive assessment was possible both before the reconstruction and during the whole follow-up period by using inertial sensors. Integrating 3d models with kinematic data, estimation of contact areas of stress patterns on cartilage was also possible. The presented integrate protocol allowed to acquired different types of information concerning clinical assessment, biochemical changes in cartilage and biomechanical parameters to identify which acl reconstruction could present the most chondroprotective behavior. Preliminary data showed all the potential of the proposed workflow. The study is on-going and final results will be shortly provided

We aimed to highlight the relationship between age and the architectural properties of trabecular bone, to outline the patterns in which the variations in these properties take place, and to investigate the influence of the architecture on the mechanical properties of trabecular bone in growing animals. We studied 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. They were serially sectioned and their architectural properties were determined. Similar cubes were obtained from the identical anatomical position of the contralateral tibia and their compressive mechanical properties measured. The values obtained from the skeletally immature and mature individuals were compared. Multiple regression analyses were performed between the architectural and the mechanical properties. The bone volume fraction, the mean trabecular volume, the architectural and the mechanical anisotropy, the elastic modulus, the bone strength, the energy absorption to failure, and the elastic energy correlated positively with increasing age whereas the connectivity density, the bone surface density, the ultimate strain, the absorption of viscoelastic energy and the relative loss of energy correlated inversely. The values of all variables were significantly different in the skeletally mature and immature groups. We determined the patterns in which the variations took place. The bone volume fraction of the trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the mean trabecular volume and the bone surface density, it explained 81% of the variations in the compressive elastic modulus of specimens obtained from the contralateral tibiae

Our aim was to determine the relationship between age and the mechanical and physical properties of trabecular bone, to describe the patterns in which the variations in these properties take place, and to investigate the influence of the physical properties on the mechanical characteristics of trabecular bone during growth. We used 30 lambs in three age groups and 20 sheep in two age groups. Cubes of subchondral bone were cut from the proximal tibia according to a standardised protocol. We performed non-destructive compression tests of the specimens in three orthogonal directions and compression tests to failure in the axial direction. The physical properties of the specimens were also determined. The data were correlated with age and compared in skeletally immature and mature animals. Multiple regression analyses were performed between the mechanical and the physical properties. Age correlated positively with elastic modulus, bone strength, energy absorption to failure, elastic energy, mechanical anisotropy ratio, tissue density, apparent density, apparent ash density, and bone mineral content, and inversely with ultimate strain, viscoelastic energy absorption, relative energy loss, the collagen content of bone and the percentage porosity. The values of all variables were significantly different in the skeletally mature and immature groups. The apparent density of trabecular bone tissue was found to be the major predictor of its compressive mechanical properties. Together with the content of bone muscle and bone collagen, the apparent density could explain 84% of the variation in the elastic modulus, whereas only a small portion of the variation in ultimate strain could be explained by the variation in apparent density

Summary Statement. Extended expansion of cells derived from equine articular cartilage reveal maintenance of chondrogenic potency and no evidence of senescence up to 100 population doublings. The data suggests the reclassification of these cells from progenitor cells to stem cells. Introduction. One sign of ‘in vitro aging’ is the diminishing capacity for cell division. In contrast to embryonic stem cells that show no loss of proliferative potency, the maximal population doublings (PD) for mesenchymal stem cells (MSCs) in vitro is reported to be between 30 and 40 replications 1,2,3. We have isolated a population of chondroprogenitor cells from articular cartilage of several species, including equine4. These cells have demonstrated functional equivalence in their differentiation capacity when compared with MSCs but have the advantage of retaining the highly desirable stable (permanent) chondrocyte phenotype. In this study, we examined the age-related capacity of these cells for extended division and retention of potency. Methods. Chondroprogenitors were isolated from equine articular cartilage by adhesion onto fibronectin5. Cells were isolated from both skeletally immature (1 year-old) and mature animals (8 year-old). Clonal and polyclonal cell lines (at least 5 of each for each age) were cultured in the presence of 10% FCS, 1ng/ml TGFb-1 & 2.5 ng/ml FGF-2. Cells were seeded at low density and passaged weekly. Results. Chondroprogenitors from both animals reached over 40 (mean) PD in 50 days with growth remaining linear. Little difference in growth rates was observed between clonal and polyclonal cell lines. For the mature animal, 96% of cells were BrDU positive at 22 PD whilst none of cells were (senescence associated) β-gal positive. At 44 PD, 88% of cells were BrDU positive and just 15% of cells were β-gal positive. Three clonal and three polyclonal cell lines from the mature animal were cultured beyond the 50-day time point. At 120 days, cells reached up to 90 PD with the same pattern of linear growth observed. When tested at 70 PD, 79% of these cells were still BrDU positive (range 55–97%) and just 11% of cells were β-gal positive (range 2–22%). Furthermore, little difference in cell morphology was observed throughout this extended expansion. At 70 PD, we found that both clonal and polyclonal cell lines in monolayer culture were still expressing the chondrogenic transcription factor; Sox-9. Expression of genes for aggrecan and collagen type II was also detected in cells that were chondrogenically induced for 72 hours. Discussion & Conclusions. We have demonstrated for the first time the extended expansion of cells derived from articular cartilage that retain chondrogenic potency. These equine cells have since been cultured to over 100 PD without evidence of senescence. One hundred PD is equivalent to 1 × 1030 cells originating from a single cell. We have previously reported that the human equivalents of these cells surpass MSCs in doubling capacity but senesce at approximately 60 PD6. The properties of these equine chondroprogenitor cells make them ideal candidates for allogeneic cell therapy for articular cartilage repair. In addition, the data suggest the reclassification of these cells from progenitor cells to stem cells

Objectives

The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models.