Aim. The aim of the study was to define the peculiarities of bone remodeling and identify specific parameters to development to heterotopic ossification. Materials and methods. Markers of bone formation (Osteocalcin, serum type 1 procollagen (N-terminal) (tP1NP)) and bone resorption (serum collagen type 1 cross-linked C-telopeptide (β-CTx)) were determined by the electrochemiluminiscence immunoassay “ECLIA” for Elecsys user cobas immunoassay analyser. In the study were included 23 patients with spinal cord injury – first group (average age 26.8 ± 3.9, duration of spinal cord injury from 3 to 12 months) and 23 healthy people's appropriate age and gender (average age 30.6 ± 6.0, years). In the first group included 11 patients with spinal cord injury with the presence of heterotopic ossification – subgroup I and 12 patients with spinal cord injury without heterotopic ossification – subgroup II. Results. The results of examination showed that patients of first group had significantly higher bone markers than control group: P1NP (256.7±48.2 ng/ml vs 49.3±5.1 ng/ml, p<0.001), serum β-CTx (1.47±0.23 ng/ml vs 0.45±0.04 ng/ml, p<0.0001), osteocalcin (52.2±9.8 ng/ml vs 24.9±2.08 ng/ml, p<0.001). There were obtained that levels of bone remodeling markers in patients with HO were significantly higher in comparison with patients without HO: P1NP (404.9±84.9 ng/ml vs 133.2±15.7 ng/ml, p<0.001), serum β-CTx (1.75±0.23 ng/ml vs 0.28±0.14 ng/ml, p<0.0001), osteocalcin (87.1±18.9 ng/ml vs 29.4±3.7 ng/ml, p<0.001). Conclusion. The bone formation and bone resorption markers in patient of first group were significantly higher than in healthy individuals of appropriate age. The rate of bone turnover markers in patient with HO was considerably higher than in patient without HO and the process of formation dominated over the resorption in patient with HO

Introduction and Objective. Heterotopic ossification is the formation of extraskeletal mineralized tissue commonly associated with either trauma or surgery. While several mouse models have been developed to better characterize the pathologic progression of HO, no model currently exists to study HO of the hip, the most common location of acquired HO in patients. Owing to the unique biological mechanisms underpinning the formation of HO in different tissues, we sought to develop a model to study the post-surgical HO of the hip. Materials and Methods. Wild-type mice C57BL/6J mice were used to study the procedure outcomes, while Pdgfra-CreERT2;mT/mG and Scx-GFP reporter animals were used for the lineage tracing experiments (total n=16 animals, male, 12 weeks old). An anterolateral approach to the hip was performed. Briefly, a 2 cm incision was made centered on the great trochanter and directed proximal to the iliac crest and distally over the lateral shaft of the femur. The joint was then reached following the intermuscular plane between the rectus femoris and gluteus medius muscles. After the joint was exposed, the articular cartilage was removed using a micropower drill with a 1.2 mm reamer. The medius gluteus and superficial fascia were then re-approximated with Vicryl 5-0 suture (Ethicon Inc, Somerville, NJ) and skin was then closed with Ethilon 5-0 suture (Ethicon Inc). Live high resolution XR imaging was performed every 2 wks to assess the skeletal tissues (Faxitron Bioptics, Tucson, AZ). The images were then scored using the Brooker classification. Ex-vivo microCT was conducted using a Skyscan 1275 scanner (Bruker-MicroCT, Kontich, Belgium). 3D reconstruction and analysis was performed using Dragonfly (ORS Inc., Montreal, Canada). For the histological analysis of specimens, Hematoxylin and Eosin (H&E), modified Goldner's Trichrome (GMT) stainings were performed. Reporter activity was assessed using fluorescent imaging. Results. Substantial periarticular heterotopic bone was seen in all cases. A periosteal reaction and an initial formation of calcified tissue within the soft tissue was apparent starting from 4 wks after surgery. By XR, progressive bone formation was observed within the periosteum and intermuscular planes during the subsequent 8 weeks. Stage 1 HO was observed in 12.5% of cases, stage 2 in 62.5% of cases, and stage 3 HO in 25% of cases. 3D microCT reconstructions of the treated hip joints demonstrated significant de novo heterotopic bone in several location which phenocopy human disease. Heterotopic bone was observed in an intracapsular location, periosteal location involving the iliac bone and proximal femur, and intermuscular locations. Histological analyses further confirmed these findings. To assess the cells which gave rise to HO in this model, an inducible PDGFRα and constitutive Scx-GFP reporter mice were used. A dramatic increase in mGFP reporter activity was noted PDGFRα within the HO injury site, including in areas of new cartilage and bone formation. Scx-associated reporter activity increased in the soft tissue and periosteal periacetabular areas of injured hips. Conclusions. HO has a diverse set of pathologies, of which joint associated HO after elective surgery is the most common. Here, we present the first mouse model of hip dislocation and acetabular reaming that mimics elements of human periarticular HO. The diverse locations of HO after acetabular reaming (intracapsular, intermuscular and periosteal) suggests the activation of different and specific HO program after surgery. Such a field effect would be consistent with local trauma and inflammation, which is a well-studied contributor to HO genesis. Not surprisingly, joint-associated HO significantly derives from PDGFRα-expressing cells, which has been shown to similarly give rise to intramuscular and intratendinous HO

Abstract. Objectives. The term heterotopic ossification (HO) describes lamellar bone formation within soft tissues following injury. A genome-wide scan of patients after hip arthroplasty has identified that variation within the lncRNA CASC20 is associated with HO susceptibility. Previous findings in our lab have demonstrated upregulation of CASC20 during BMP2-induced osteodifferentiation of adipose-derived stem cells (hMAD) alongside osteodifferentiation markers, RUNX2 and OSX. We hypothesize that CASC20 is a novel regulator of bone formation and aim to investigate CASC20 function in bone formation. Methods. 1) We used miRanda prediction algorithm and the ENCORI database to respectively predict which miRNAs CASC20 interacts with and to select for experimentally validated miRNAs. 2) We characterized the expression and functional role of CASC20-interacting miRNAs by respectively analyzing publicly available datasets (GSE107279 and pubmed.ncbi.nlm.nih.gov/26175215/) and by using Gene Ontology (GO) analysis. 3) We overexpressed CASC20 in hMAD using a lentiviral system and tested the effect of CASC20 overexpression in osteodifferentiation and expression of putative CASC20-interacting miRNAs. Results. 1) We identified 64 experimentally validated miRNAs that are predicted to interact with CASC20. 2) GO analysis revealed that the most frequently targeted molecular functions included SMADs, MAPKK and other kinase activities known to play a central role in osteo and chondrogenesis. We found 10 miRNAs including hsa-miR-485-3p that demonstrated down-regulation in both osteo- and chondrogenesis. 3) We found that CASC20-overexpression augmented the osteodifferentiation of hMAD measured in mineralization using Alizarin Red S. CASC20 overexpression increased the expression of osteogenic marker ALP and decreased the expression of hsa-miR-485-3p. Conclusion. Here we show how CASC20 may regulate bone formation by acting as a competitive endogenous RNA (ceRNA). We are currently using CASC20 overexpression model in osteo- and chondrogenesis, and testing CASC20-miRNA interaction to establish the underlying mechanism for the observed associations

We have developed an animal model to examine the formation of heterotopic ossification using standardised muscular damage and implantation of a beta-tricalcium phosphate block into a hip capsulotomy wound in Wistar rats. The aim was to investigate how cells originating from drilled femoral canals and damaged muscles influence the formation of heterotopic bone. The femoral canal was either drilled or left untouched and a tricalcium phosphate block, immersed either in saline or a rhBMP-2 solution, was implanted. These implants were removed at three and 21 days after the operation and examined histologically, histomorphometrically and immunohistochemically. Bone formation was seen in all implants in rhBMP-2-immersed, whereas in those immersed in saline the process was minimal, irrespective of drilling of the femoral canals. Bone mineralisation was somewhat greater in the absence of drilling with a mean mineralised volume to mean total volume of 18.2% (. sd. 4.5) versus 12.7% (. sd. 2.9, p < 0.019), respectively. Our findings suggest that osteoinductive signalling is an early event in the formation of ectopic bone. If applicable to man the results indicate that careful tissue handling is more important than the prevention of the dissemination of bone cells in order to avoid heterotopic ossification

Heterotopic ossification (HO) is lamellar bone formation that occurs within tissues that do not normally have properties of ossification. The pathoaetiology of HO is poorly understood. We conducted a genome wide association study to better understand the genetic architecture of HO. 891 patients of European descent (410 HO cases) following THA for primary osteoarthritis were recruited from the UK. HO was assessed from plain AP radiographs of the pelvis. Genomic DNA was extracted, genotyped using the Illumina 610 beadchip and referenced using the 1000 Genome Project panel. HO susceptibility case-control analysis and an evaluation of disease severity in those with HO was undertaken using SNPTESTv2.3.0 on>10 million variants. We tested variants most strongly associated with HO in an independent UK THA replication cohort comprising 209 cases and 211 controls. The datasets were meta-analysed using PLINK. In the discovery cohort 70 signals with an index variant at p<9×10–5 were suggestively associated with HO susceptibility. The strongest signal lay just downstream of the gene ARHGAP18 (rs59084763, effect allele frequency (EAF) 0.19, OR1.87 [1.48–2.38], p=2.48×10–8), the second strongest signal lay within the long non-coding (LNC) RNA gene CASC20 (rs11699612, EAF 0.25, OR1.73 [1.1.40–2.16, p=9.3×10–8). In the discovery cohort 73 signals with an index variant at p<9×10–5 were associated with HO severity. At replication, 12 of the leading 14 susceptibility signals showed a concordant direction of allelic effect and 5 replicated at nominal significance. Following meta-analysis, the lead replicating susceptibility signal was the CASC20 variant rs11699612 (p=2.71×10–11). We identify consistent replicating association of variation within the LNC RNA CASC20 with HO susceptibility after THA. Although the function of CASC20 is currently unknown, possible mechanisms include transcriptional, post-transcriptional and epigenetic regulation of downstream target genes. The work presented here provides new avenues for the development of novel predictive and therapeutic approaches towards HO

Abstract. Objectives. Operative management of distal humerus fractures is challenging. In the past, plates were manually contoured intraoperatively, however this was associated with high rates of fixation failure, nonunion and metalwork removal. Anatomically pre-contoured distal humerus locking plates have since been developed. Owing to the rarity of distal humeral fractures, literature regarding outcomes of anatomically pre-contoured locking plates is lacking and patient numbers are often small. The purpose of this study is to investigate the outcomes of these patients. Methods. We retrospectively identified patients with distal humeral fractures treated at our institution from 2009–2018. Inclusion criteria were patients with a distal humeral fracture, who underwent two-column plate fixation with anatomically pre-contoured locking plates. Clinical records and radiographs were reviewed to elicit outcome measures, including range of motion, complications and reoperation rate. Results. We identified 50 patients with mean age of 55 years (range 17–96 years). Mean length of follow up was 5.2 years. AO fracture classification Type A occurred most frequently (46%), followed by Type B (22%) and Type C (32%). Low energy mechanisms of injury predominated in 72% of patients. Mean time from injury to fixation was seven days. Mean range of motion at the elbow was 13–123o postoperatively. The overall reoperation rate was 22%, the majority of which required subsequent removal of prominent metalwork (18%). The incidence of nonunion, heterotopic ossification, deep infection and neuropathy requiring decompression was 2% each. Fixation failure occurred in only one patient however the fracture went on to heal. Conclusions. Previously reported reoperation rates with manually contoured plates were as high as 44%, which is twice our reported rate. Modern locking plates are no longer subject to implant failure (previously 27% reported metalwork failure rate). Likewise, heterotopic ossification and non-union have also reduced, highlighting that modern plates have significantly improved overall patient outcomes. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Heterotopic ossification (HO) is defined as aberrant bone formation in extraskeletal locations. In this process, local stromal cells of mesenchymal origin abnormally differentiate, resulting in pathologic cartilage and bone matrix deposition. However, the specific cell type and mechanisms beyond this process are not well understood, in part due to the heterogeneity of progenitor cells involved. Here, a combination of single cell RNA sequencing (scRNA-Seq) and lineage tracing, defined the extent to which synovial / tendon sheath progenitor cells contribute to HO. For this purpose, a Tppp3 (tubulin polymerization-promoting protein family member 3) inducible reporter model was used, in combination with either Scx (Scleraxis) or Pdgfra (Platelet derived growth factor receptor alpha) reporter animals. Both arthroplasty-induced and tendon injury-mouse experimental HO models were utilized. ScRNA-Seq of tendon-induced traumatic HO suggested that Tppp3 is a progenitor cell marker for either osteochondral or tendon or cells. After HO induction, Tppp3 reporter+ cell population expanded in number and contributed to cartilage and bone formation in tendon and joint-associated HO. Using double reporter animals, we found that both Pdgfra+Tppp3+ and Pdgfra+Tppp3- progenitor cells produced HO-associated cartilage. Finally, the examination of human samples showed a significant population of TPPP3+ cells overlapping with osteogenic markers in areas of HO. Overall, these results provide novel observations that peritenon and synovial progenitor cells undergo abnormal osteochondral differentiation and contribute to heterotopic bone formation after trauma

Patients with Paget's Disease of Bone (PDB) more frequently require total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, controversy remains regarding their outcome. This project aims to evaluate the current literature regarding outcomes following THA and TKA in PDB patients. MEDLINE, EMBASE and Cochrane databases were searched on February 15th, 2022. Inclusion criteria comprised studies evaluating outcomes following THA/TKA in PDB patients. Quality of included studies was assessed using the Newcastle-Ottawa Scale. 19 articles (published between 1976–2022) were included, comprising 58,695 patients (48,766 controls and 10,018 PDB patients), from 209 potentially relevant titles. No study was of high quality. PDB patient pooled mortality was 32.5% at mean 7.8(0.1-20) years following THA and 31.0% at mean 8.5(2-20) years following TKA. PDB patient revision rate was 4.4% at mean 7.2(0-20) years following THA and 2.2% at mean 7.4(2-20) years following TKA. Renal complications, respiratory complications, heterotopic ossification, and surgical site infection were the most common medical and surgical complications. The largest systematic review, to date, evaluating outcomes following THA and TKA in PDB patients. All functional outcome scores improved. PDB patient revision rate was comparable to UK National Joint Registry. However, there is a significant need for prospective matched case-control studies to robustly compare outcomes in PDB patients with unaffected counterparts

Introduction and Objective. Interest for direct anterior approach (DAA) in hip hemiarthroplasty (HHA) has greatly increased in recent years, however which is the best surgical approach in hip replacement treating femoral neck fractures (FNFs) is already unclear. The aim of this study is to perform a radiographic and perioperative complications analysis by comparing the direct anterior approach (DAA) with the direct lateral approach (DLA) in patients treated with hemiarthroplasty for FNFs. Materials and Methods. Patients with FNFs surgically treated between 2016–2020 with HHA were enrolled. The radiographical outcomes of DAA and DLA are compared. Several peri-operative and post-operative variables were evaluated: mean surgery time, complications as periprosthetic fractures or episodes of dislocation, the average of post-operative diaphyseal filling of the stem (Canal Fill Index, CFI), the extent of heterotopic ossification (HO) (simplified Broker classification) and metadiaphiseal bone loss (Paprosky classification) within one year from surgery. Results. 86 patients underwent HHA by DAA and 80 patients by DLA. The two groups are qualitatively comparable. No statistically significate differences were showed in all variables analyzed (p>0.05). The average of surgical time of DAA were 61 minutes compared to 67 of DLA. No differences were showed in the post-operative CFI (DAA 0.71 ± 6.1; DLA 0.76 ± 13.5), the extent of the HO (DAA 79.07% low; DLA 75% low) and metadiaphiseal bone loss (DAA Grade I 91.86%; DLA Grade I 93.75%). Regarding perioperative complications, we have discovered only one periprosthetic fracture each group. Although there was no statistically significant difference, we highlighted a higher number of dislocations in the group of DLA (2 episodes vs no one). Conclusions. In this study we have shown that the DAA is an adequate surgical choice comparing with the classical DLA for FNFs treated with HHA. The analysis of our radiographic parameters and perioperative complications have not shown a significant difference between the two surgical approach. This study is limited by a purely radiographic analysis without addition of clinical parameters

Systemic factors are believed to be pivotal for the development of heterotopic ossification in severely-injured patients. In this study, cell cultures of putative target cells (human fibroblastic cells, osteoblastic cells (MG-63), and bone-marrow stromal cells (hBM)) were incubated with serum from ten consecutive polytraumatised patients taken from post-traumatic day 1 to day 21 and with serum from 12 healthy control subjects. The serum from the polytraumatised patients significantly stimulated the proliferation of fibroblasts, MG-63 and of hBM cells. The activity of alkaline phosphatase in MG-63 and hBM cells was significantly decreased when exposed to the serum of the severely-injured patient. After three weeks in 3D cell cultures, matrix production and osteogenic gene expression of hBM cells were equal in the patient and control groups. However, the serum from the polytraumatised patients significantly decreased apoptosis of hBM cells compared with the control serum (4.3% vs 19.1%, p = 0.031). Increased proliferation of osteoblastic cells and reduced apoptosis of osteoprogenitors may be responsible for increased osteogenesis in severely-injured patients

Keywords. Complete Abductor Detachament, Direct Lateral Approach, Abductor Insuffenciency, Hip Arthroplasty. Backgroung. Approach of Total hip replacement (THR) is a very important part of the surgery, the approach dictates the postoperative complications. Lateral approach is one of the most commonly used approaches. The initial lateral approach relied on bony (trochanteric) osteotomy which was later modified to tendon detachment, there are many versions of the lateral approach but the main goal is to detach the hip abductors mechanism to gain access to the underlying joint. One of the modifications is to completely detach the abductors tendon, this offers superior exposure compared to the traditional partial detachment (Hardinge) approach. Objectives. We aimed to perform the first study comparing the complications rate following complete detachment of hip abductors to the documented complications rate of the traditional approach. Study Design & Methods. Retrospective study to evaluate the rate of approach specific complications following complete abductor detachment approach, we included s all patients who had THR using this approach 8–18 months ago. The study group comprised of 44 patients of different age groups and genders. Patients were reviewed to assess gait abnormality, abductor weakness with Trendlenberg test, lateral trochanteric pain (LTP) and heterotopic ossification (H.O). Results. Out of the 44 patients in our study group 20 patients had abductor weakness with positive Trendelnberg test (45.5%) while the reported percentage of abductor weakness following the traditional approach is 4–20%.7 patients (15%) were dissatisfied with the postoperative gait. LTP was reported in 5 patients (11%) compared to 4.9% associated with standard lateral approach. In our series 9 (20.4%) patients had H.O which is within the acceptable range (up to 25%). Conclusions. Complete abductor detachment approach offers better exposure and quicker alternative to the traditional lateral approach of the hip (Hardinge) but on the other hand it has relatively higher complication rate

Background. Acetabular fractures occur as a result of high-velocity trauma and are often associated with other life threatening injuries. Approximately one-third of these fractures are associated with dislocation of the femoral head but there are only few studies documenting the long term outcomes of this group of acetabular fracture. Methods. This was undertaken at the Royal Infirmary of Edinburgh which provides the definitive orthopaedic treatment for all major trauma including all acetabular fractures for the South East of Scotland. We retrospectively reviewed patients who sustained an acetabular fracture associated with a posterior hip dislocation from a prospectively gathered trauma database between 1990 to 2010. Patient characteristics, complications and the requirement for further surgery were recorded. Patient outcomes were measured using the Oxford Hip score and Short Form SF-12 health survey. Results. A total of 99 patients were treated over a 24 year period. The mean age was 41.3 years. The majority were male (75%). Road traffic accidents were the most common mechanism of injury (47%). The most common Letournal & Judet classification was a posterior wall fracture. Complications such as Sciatic Nerve Palsy was 12.1%, DVT 3%, Infection 5%, Heterotopic ossification 6.1%, Avascular necrosis at 11.1% and 19.2% went on to have a total hip replacement. The mean Oxford Score for Native hip was 34.7 and 31.8 for those who converted to hip replacement. SF12 Physical score was was 40.3 and 39 for the native hips and converted hips respectively. And the SF12 Mental score was 45.5 and 44.9 for the native hips and converted hips respectively. Conclusions. This is the first study to present the long term outcomes following an acetabular fracture dislocation. Our study suggests there is considerable disability in this group of patients and the requirement for subsequent THR has inferior patient reported outcomes. Level of Evidence. Cohort study, Level 2B

Heterotopic ossi?cation is the abnormal formation of bone in soft tissues and is a frequent complication of hip replacement surgery. Heterotopic ossi?cations are described to develop via endochondral ossification and standard treatment is administration of indomethacin. It is currently unknown how indomethacin influences heterotopic ossi?cation on a molecular level, therefore we aimed to determine whether indomethacin might influence heterotopic ossi?cation via impairing the chondrogenic phase of endochondral ossification. ATDC5, human bone marrow stem cells (hBMSCs) and rabbit periosteal agarose cultures were employed as progenitor cell models; SW1353, human articular chondrocytes and differentiated ATDC5 cells were used as matured chondrocyte cell models. All cells were cultured in the presence of (increasing) concentrations of indomethacin. The action of indomethacin was confirmed by decreased PGE2 levels in all experiments, and was determined by specific PGE2 ELISA. Gene- and protein expression analyses were employed to determine chondrogenic outcome. Progenitor cell models differentiating in the chondrogenic lineage (ATDC5, primary human bone marrow stem cells and ex vivo periosteal agarose cultures) were treated with increasing concentrations of indomethacin and a dose-dependent decrease in gene- and protein expression of chondrogenic and hypertrophic markers as well as decreased glycosaminoglycan content was observed. Even when hypertrophic differentiation was provoked the addition of indomethacin resulted in decreased hypertrophic marker expression. Interestingly, when mature chondrocytes were treated with indomethacin, a clear increase in collagen type 2 expression was observed. Similarly, when ATDC5 cells and bone marrow stem cells were pre-differentiated to obtain a chondrocyte phenotype and indomethacin was added from this time point onwards, low concentrations of indomethacin also resulted in increased chondrogenic differentiation. Indomethacin induces differential effects on in vitro endochondral ossification, depending on the chondrocyte's differentiation stage, with complete inhibition of chondrogenic differentiation as the most pronounced action. This observation may provide a rationale behind the elusive mode of action of indomethacin in the treatment of heterotopic ossifications

Summary Statement. This experimental study showed that platelet rich fibrin matrix can improve muscle regeneration and long-term vascularization without local adverse effects. Introduction. Even though muscle injuries are very common, few scientific data on their effective treatment exist. Growth Factors (GFs) may have a role in accelerating muscle repair processes and a currently available strategy for their delivery into the lesion site is the use of autologous platelet-rich plasma (PRP). The present study is focused on the use of Platelet Rich Fibrin Matrix (PRFM), as a source of GFs. Materials and Methods. Bilateral muscular lesions were created on the longissimus dorsi muscle of Wistar rats. One side of the lesion was filled with a PRFM while the contralateral was left untreated (controls). Animals were sacrificed at 5, 10, 40 and 60 days from surgery. Histological, immunohistochemical and histomorphometric analyses were performed to evaluate muscle regeneration, neovascularization, fibrosis and inflammation. The presence of metaplasic zones, calcifications and heterotopic ossification were also assessed. Results. PRFM treated muscles exhibited an improved muscular regeneration, an increase in neovascularization, and a slight reduction of fibrosis compared with controls. No differences were detected for inflammation. Metaplasia, ossification and heterotopic calcification were not detected. Conclusions. This preliminary morphological experimental study shows that PRFM use can improve muscle regeneration and long-term vascularization. Since autologous blood products are safe, PRFM may be a useful and handily product in clinical treatment of muscle injuries

Adequate range of knee motion is critical for successful total knee arthroplasty. While aggressive physical therapy is an important component, manipulation may be a necessary supplement. There seems to be a lack of consensus with variable practices existing in managing stiff postoperative knees following arthroplasty. Hence we did a postal questionnaire survey to determine the current practice and trend among knee surgeons throughout the United Kingdom. A postal questionnaire was sent out to 100 knee surgeons registered with British Association of Knee Surgeons ensuring that the whole of United Kingdom was well represented. The questions among others included whether the surgeon used Manipulation Under Anaesthaesia (MUA) as an option for stiff postoperative knees; timing of MUA; use of Continuous Passive Motion (CPM) post-manipulation. We received 82 responses. 46.3% of the respondents performed MUA routinely, 42.6% sometimes, and 10.9% never. Majority (71.2%) performed MUA within 3 months of the index procedure. 67.5% routinely used CPM post-manipulation while 7.3% of the respondents applied splints or serial cast post MUA. 41.5% of the surgeons routinely used Patient Controlled Analgaesia +/− Regional blocks. Majority (54.8%) never performed open/arthroscopic debridement of fibrous tissue for adhesiolysis. Knee manipulation requires an additional anaesthetic and may result in complications such as: supracondylar femur fractures, wound dehiscence, patellar tendon avulsions, haemarthrosis, and heterotopic ossification. Moreover studies have shown that manipulation while being an important therapeutic adjunct does not increase the ultimate flexion that can be achieved which is determined by more dominant factors such as preoperative flexion and diagnosis. Manipulation should be reserved for the patient who has difficult and painful flexion in the early postoperative period

Summary. Indomethacin has differential effects on chondrogencic outcome depending on differentiation stage. Introduction. Heterotopic ossification (HO) is the abnormal formation of bone in soft tissues and is a frequent complication of hip replacement surgery. The standard treatment to prevent HO is administration of the NSAID indomethacin. HOs are described to develop via endochondral ossification. As it is currently unknown how indomethacin prevents HO, we aimed to define whether indomethacin might influence HO via impairing the chondrogenic phase of endochondral ossification. Materials. ATDC5, human bone marrow stem cells (hBMSCs) and rabbit periosteal agarose cultures were employed as progenitor cell models; SW1353, human articular chondrocytes and differentiated ATDC5 cells were used as matured chondrocyte cell models. All cells were cultured in the presence of (increasing) concentrations of indomethacin. The action of indomethacin was confirmed by decreased PGE. 2. levels in all experiments, and was determined by specific PGE. 2. ELISA. Gene- and protein expression analyses were employed to determine chondrogenic outcome. Results. A dose-dependent decrease in expression of Col2a1, Col10a1 and GAG content was observed when progenitor ATDC5 cells differentiating in the chondrogenic lineage were treated with increasing concentrations of indomethacin. These results were confirmed on primary hBMSCs and ex vivo periosteal agarose cultures. Even when hypertrophic differentiation of ATDC5 cells was provoked by BMP-2 (30ng/ml) the addition of indomethacin resulted in decreased hypertrophic marker expression. Interestingly, when adult chondrocytes (SW1353 and primary human articular chondrocytes) were treated with indomethacin, a clear increase in Col2a1 expression was observed. Similarly, when ATDC5 cells were differentiated for 10 days to obtain a chondrocyte phenotype and indomethacin was added from this time point onwards, low concentrations of indomethacin also resulted in increased Col2a1 expression. Conclusions. Indomethacin (dose-dependently) prevents chondrogenic and hypertrophic differentiation from progenitor cells. In addition we found thatindomethacin (in low concentrations) is able to increase the chondrogenic phenotype of maturated chondrocytes. Together, these data indicate that indomethacin has differentiation stage-dependent effects on chondrogenic differentiation and part of the HO-preventing action of indomethacin might be contributed to inhibition of chondrogenic differentiation

Objectives. Fracture non-union poses a significant challenge to treating orthopaedic surgeons. These patients often require multiple surgical procedures. The incidence of complications after Autologous Bone Graft (ABG) harvesting has been reported up to 44%. These complications include persistent severe donor site pain, infection, heterotopic ossification and antalgic gait. We retrospectively compared the use of BMP-7 alone in long bone fracture Non-union, with patients in whom BMP-7 was used in combination with the Autologous Bone Graft (ABG). Material and Methods. The databases of our dedicated Limb Reconstruction Unit were searched for patient with three common long bone fractures Non-unions (Tibia, Femur and Humerus). The patients who had intra-operative use of Bone Morphogenetic Protein (BMP-7) alone and in combination with ABG were evaluated. 53 Patients had combined use of ABG and BMP-7, and 65 patients had BMP-7 alone. Results. In the ABG and BMP-7 group, the union rate for femoral (n=18) Non-unions was 83%, for humeral (n=16) Non-unions 81%, and for tibia (n=19) Non-unions it was 47%. In the BMP-7 alone group, 83% of the femoral (n=12) Non-unions, 87% of the humeral (n=16) and 56% of the tibial (n=37) Non-unions healed. The common risk factors for Non-union were comparable in both the groups and included location and nature (open vs closed) of fracture, infection, smoking and NSAIDs use. The average time to union in ABG+BMP-7 group was 8.1 months (range 3-30 months) and in BMP-7 alone group it was 7.2 months (range 3-24 months). Conclusion. Autologous Bone Grafting has a pivotal role in limb reconstruction surgery but its indication should be carefully evaluated in view of considerable morbidity associated with graft donor site. Our study did not show any significant difference in the union rates of common long bone fracture Non-unions treated with BMP-7 alone or with a combination of Autologous Bone Graft and BMP-7

Introduction. The purpose of this study was to evaluate the functional and radiographical results in patients younger than 30 years who underwent cementless third generation ceramic-on-ceramic total hip arthroplasty for osteonecrosis of the femoral head. Methods. Forty one patients (55 hips) who underwent total hip arthroplasty with third generation ceramic-on-ceramic bearings for osteonecrosis of the femoral head with a minimum 4-year follow-up were included in this study. There were 26 men and 15 women who had a mean age of 26 years (range, 16 to 29 years). The average duration of follow-up was 6 years (range, 4 to 7 years). All surgeries were done by a single hip surgeon and third generation ceramic-on-ceramic articulations were used. Securefit (Stryker) acetabular components were used in 46 hips and Duraloc (Depuy) in 9 hips. Accolade (Stryker) femoral stems were used in 33 hips, cone prosthesis (Zimmer) in 18 hips and CLS (Zimmer) in 4 hips. Functional results were measured by Harris hip (HHS) and WOMAC scores. Radiographic evaluation was assessed for loosening and osteolysis according to Gruen and Delee and Charnley criteria. Results. The average HHS improved from 53 points (range, 24 to 59 points) pre-operatively to 95 points (range, 88 to 100 points) at last follow-up. WOMAC scores improved from 72 points (range, 50 to 98 points) to 25 points (range, 21 to 37 points). Thirty nine patients (51 hips) continued their normal occupation. There was no aseptic loosening, osteolysis, and no prosthesis had been revised. There was one patient who complained of continuous squeaking and two patients with Brooker grade I heterotopic ossification. There were no other major complications such as ceramic fracture. Conclusion. Total hip arthroplasty with third generation ceramic-on-ceramic bearings for osteonecrosis of the femoral head especially in active and young patients resulted in satisfactory clinical and radiological results at minimum 4 year follow-up. If long-term follow-up shows excellent results, then the age limit for total hip arthroplasty might be lowered

Long term, secondary implant fixation of Total Disc Replacements (TDR) can be enhanced by hydroxyapatite or similar osseo-conductive coatings. These coatings are routinely applied to metal substrates. The objective of this in vivo study was to investigate the early stability and subsequent bone response adjacent to an all polymer TDR implant over a period of six months in an animal model. Six skeletally mature male baboons (Papio annubis) were followed for a period of 6 months. Using a transperitoneal exposure, a custom-sized Cadisc L device was implanted into the disc space one level above the lumbo-sacral junction in all subjects. Radiographs of the lumbar spine were acquired prior to surgery, and post-operatively at intervals up to 6 months to assess implant stability. Flourochrome markers (which contain molecules that bind to mineralization fronts) were injected at specified intervals in order to investigate bone remodeling with time. Animals were humanely euthanized six months after index surgery. Test and control specimens were retrieved, fixed and subjected to histological processing to assess the bone-implant-bone interface. Fluorescence microscopy and confocal scanning laser microscopy were utilized with BioQuant image analysis to determine the bone mineral apposition rates and gross morphology. Radiographic evaluation revealed no loss of disc height at the operative level or adjacent levels. No evidence of subsidence or significant migration of the implant up to 6 months. Heterotopic ossification was observed to varying degrees at the operated level. Histology revealed the implant primary fixation features embedded within the adjacent vertebral endplates. Flourochrome distribution revealed active bone remodeling occurring adjacent to the polymeric end-plate with no evidence of adverse biological responses. Mineral apposition rates of between 0.7 and 1.7 microns / day are in keeping with literature values for hydroxyapatite coated implants in cancellous sites of various species. Radiographic assessment demonstrates that the Cadisc L implant remains stable in vivo with no evidence of subsidence or significant migration. Histological analysis suggests the primary fixation features are engaged, and in close apposition with the adjacent vertebral bone. Flourochrome markers provide evidence of a positive bone remodelling response in the presence of the implant

Colchicine is often used in the treatment of diseases such as familial Mediterranean fever (FMF) and gout. We have previously reported that patients with FMF who had colchicine on a daily basis and who had a total hip arthroplasty showed no heterotopic ossification after surgery. The mechanism by which colchicine causes this clinical phenomenon has never been elucidated. We therefore evaluated the effect of various concentrations of colchicine on cell proliferation and mineralisation in tissue culture, using rat and human cells with and without osteogenic potential. Cell proliferation was assessed by direct cell counts and uptake of (. 3. H)thymidine, and mineralisation by measuring the amount of staining by Alizarin Red. Our findings indicate that concentrations of colchicine of up to 3 ng/ml did not affect cell proliferation but inhibition was observed at 10 to 30 ng/ml. Mineralisation decreased to almost 50%, which was the maximum inhibition observed, at concentrations of colchicine of 2.5 ng/ml. These results indicate that colchicine at low concentrations, of up to 3 ng/ml, has the capacity to inhibit selectively bone-like cell mineralisation in culture, without affecting cell proliferation. Further clinical and laboratory studies are necessary to evaluate the effects of colchicine on biological processes involving the proliferation of osteoblasts and tissue mineralisation in vivo, such as the healing of fractures, the formation of heterotopic bone and neoplastic bone growth