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

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

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

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

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

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

Restoration of anatomy is paramount in total hip arthroplasty (THA) to optimise function and stability. Leg-length discrepancy of ≥10mm is poorly tolerated and can be the subject of litigation. We routinely use a multimodal protocol to optimise soft tissue balancing which involves pre-operative templating, leg-length measurement supine and in the lateral position after positioning, and the use of an intra-operative leg-length measurement device to ensure optimisation of leg-length. We have analysed the results of our protocol in restoring leg-length in primary THA. Radiological leg-length was measured in a consecutive series of 50 patients who had THA for unilateral arthritis by an independent observer pre- and post-operatively using validated methods utilising radiological software. The measurements pre- and post-operative were compared. Patients with bilateral hip arthritis and poor imaging were excluded. Leg-length was successfully restored to within 5.0mm of the target leg-length in 84.0% of patients (mean +0.7mm (95% CI +0.2 to +1.1)). The other 14.0% of patients were restored to within 5.1–8.0mm (mean +2.2mm (95% CI −2.7 to +7.1)) and 2.0% of patients were restored to within 8.1–10.0mm. Leg length was accurately restored across the subset of patients within a narrow range of either side of the mean target leg length. Intra-operative measurement of leg length can be difficult but is vital in ensuring appropriate restoration of leg-length. We recommend a similar multimodal protocol to ensure restoration of leg-length within narrow limits to maximise function and patient satisfaction.

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

Introduction and Objective

Lower limb fractures are amongst the most common surgically managed orthopaedic injuries, with open reduction and internal fixation (ORIF) as the conventional method of treatment of the fibula. In recent years, dedicated intramedullary implants have emerged for fibula fixation in tandem with the move towards minimally invasive surgery in high-risk patients. This is the largest multicentre review to date with the aim of establishing the clinical outcomes following intramedullary nail (IMN) fixation of the fibula and to identify the absolute indication for fibula IMN fixation.

In therapeutic bone repairs, autologous bone grafts, conventional or vascularized allografts, and biocompatible artificial bone substitutes all have their shortcomings. Tissue engineering may be an alternative for cranial bone repair. Titanium (Ti) and its alloys are widely used in many clinical devices because of perfect biocompatibility, highly corrosion resistance and ideal physical properties. An important progress in treating bone defects has been the introduction of bone morphogenetic proteins (BMPs), specifically BMP-2. The proteins induce osteogenic cell differentiation in vitro, as well as bone defect healing in vivo. In this study, we fabricated the titanium plate with dioxide creating by microarc oxidation (MAO) and then electronic deposition of Ca.P that can carrier recombinant human bone morphogenetic protein-2 (rhBMP-2) to enhance osteogenesis in vitro and bone formation in vivo. The rhBMP-2 was controlled released from MAO-Ca.P-rhBMP2 implant was maintain within 35days longer than Ti without MAO modification group and without CaP electronic deposition group. In addition, the in vitro results revealed that the bioactivity of rhBMP-2 released from MAO-Ca.P-rhBMP2 implant with an ideal therapeutic dose was well maintained. In vivo, the critical-sized defect (20-mm diameter) of New Zealand White rabbits was used to experiment. We concluded that sustained controlled-release of rhBMP-2 above a therapeutic dose could induce osseointegration between the implant and surrounding bone the rate of bone formation into the implant and produce neovascularization. Our study combined the concept of osteoconductive and osteoinductive to do the bone tissue regeneration.

Fracture healing is an issue that has not yet been fully elucidated. It is generally accepted in the literature that head trauma accelerates fracture healing and causes higher volume callus tissue. Recent studies have examined the relationship between head trauma and fracture healing more molecularly. Based on this research; the aim of this study is to show the effect of head trauma on fracture healing radiologically and histologically and to investigate the relationship between serum β-Catenin level and fracture healing with the experiment we performed on rats.

A total of 36 Wistar Albino female rats with a mean age of 24 weeks were included in the study with the permission of Mersin University Animal Experiments Local Ethics Committee. Six rats in the first group were not traumatized and their blood samples were collected on the day of the experiment started, end of the third week and end of the sixth week. In the second group, only head trauma was performed and blood samples were collected at the end of the third and sixth weeks. In the third group, only open femoral fracture model was applied, blood samples were collected at the third and sixth weeks and AP and Lateral radiographs of the fractured femurs were taken. After sacrification, femurs were dissected from the surrounding soft tissues and subjected to histological examination. In the fourth group, both head trauma and open femur fracture model were applied, blood samples were collected at the end of third and sixth weeks and AP and Lateral radiographs of the fractured femurs were taken. After sacrification, femurs were dissected from the surrounding soft tissues and subjected to histological examination. The expression level of β-Catenin was measured by PCR from all blood samples. Direct radiographs of the third and fourth groups at 3 and 6 weeks were evaluated by two orthopedists according to Rust and Lane & Sandhu scoring system. The histomorphometric examination was performed by evaluating the Huo scoring and the ratio of fracture callus components (cartilage callus, bone callus, fibrous callus) to areas.

According to PCR analysis, the change of expression of β-Catenin by weeks was not statistically significant in the first and second groups. However, a statistically significant decrease was observed in the 0–6 week interval in the third and fourth groups (p = 0.002, p <0.0001, respectively). In the radiological examination, the union scores of the rats with head trauma + femoral fracture were higher than the isolated femoral fractures at 3 weeks and 6 weeks. In histomorphometric examination, no statistically significant difference was found between head trauma + femur fracture group and isolated femur fracture group. In addition, there was no correlation between the groups in the correlation studies between radiological findings, histomorphmetric findings and PCR findings.

Considering that each molecule involved in fracture healing processes has a time interval and concentration; We concluded that the expression levels of β-catenin can be repeated in smaller time periods including the early stages of fracture healing.

To date there has been no material for endoprosthetics providing excellent resistance to abrasion and corrosion combined with great tensile strength, fracture toughness, and bending strength, as well as adequate biocompatibility. Carbon-fiber-reinforced silicon carbide (C/SiC, C/C-SiC or C/SiSiC) is as a ceramic compound a potentially novel biomaterial offering higher ductility and durability than comparable oxide ceramics.

Aim of this investigation was to test the suitability of C/SiC ceramics as a new material for bearing couples in endoprosthetics. One essential quality that any new material must possess is biocompatibility. For this project the in-vitro biocompatibility was investigated by using cuboid like scaffolds made of CMC. To determine whether the material is suited as a lubricant partner in endoprosthetics, we measured its abrasion coefficient and wear tolerance against various antibodies. The C/SiC samples tested were produced via the Liquid Silicon Infiltration (LSI) of pyrolized porous fiber preforms made by warm-flow pressing free-flowing granulates on a hydraulic downstroking press with a heated die of the type HPS-S, 1000 kN. After preparation of the composites, the tribological characteristics are determined. Flexural strength was determined at room temperature according to DIN685-3 with an universal testing machine Z100 and the Young”s -modulus was carried out via resonant frequency-damping analysis RFDA. The samples”surface as well as cell adhesion and cell morphology were assessed via ESEM. The human osteoblast-like cell line MG-63 and human ostoeblast were used for cel culture ecperiments (WST, Live/dead, Cytotoxicity, cell morphology). Based on the raw data the mean value and the standard deviation were calculated. The Mann-Whitney-U-Test was used to evaluate the differences between experiment and control samples. The flexural strength at room temperature is approx. 180 MPa, while the elongation at break is about 0.13%. The Young”s modulus is detected between 120 and 150 GPa. The density lies between 2.5 and 3.0 g/cm³. We noted a friction coefficient µ between 0.31. The cell lines exhibited no morphological alterations, and adhered well to the C/SiC samples. Vitality was not impaired by contact with the ceramic composite. Cell growth was observed evenly distributed over a 21-day period. In the future, investigators aiming to apply this composite in endoprosthetics will have to focus on its efficacy in conjunction with sudden, strong demands, and long-term performance in bodily fluids within joint simulators, etc. In conclusion: C/SiC can definitely be considered a new material with genuine potential for use in endoprosthetics.

Composites of chondrocytes and polymerised fibrin were supplemented with insulin-like growth factor-I (IGF-I) during the arthroscopic repair of full-thickness cartilage defects in a model of extensive loss of cartilage in horses. Repairs facilitated with IGF-I and chondrocyte-fibrin composites, or control defects treated with chondrocyte-fibrin composites alone, were compared before death by the clinical appearance and repeated analysis of synovial fluid, and at termination eight months after surgery by tissue morphology, collagen typing, and biochemical assays. The structure of cartilage was evaluated histologically by Toluidine Blue reaction and collagen type-I and type-II in situ hybridisation and immunohistochemistry. Repair tissue was biochemically evaluated by DNA assay, proteoglycan quantitation and characterisation, assessment of collagen by reverse-phase high-performance liquid chromatography, and collagen typing using cyanogen bromide digestion and peptide separation by polyacrylamide gel electrophoresis.

The results at eight months showed that the addition of IGF-I to chondrocyte grafts enhanced chondrogenesis in cartilage defects, including incorporation into surrounding cartilage. Gross filling of defects was improved, and the tissue contained a higher proportion of cells producing type-II collagen. Measurements of collagen type II showed improved levels in IGF-I-treated defects, supporting in situ hybridisation and immunohistochemical assessments of the defects. IGF-I improves the repair capabilities of chondrocyte-fibrin grafts in large full-thickness repair models.

Background context

Fusion is a fundamental procedure in spine surgery. Although autogenous grafts have ideal bone graft characteristics, their use may remain limited due to various morbidities. Even though ceramic based synthetic bone grafts are used commonly at present, in order to enhance their efficacy, their combined use with other materials has been investigated. The use of carbon nanotubes (CNTs) together with synthetic bone grafts such as hydroxyapatite (HA) has contributed to positive developments in bone tissue engineering.

One of the most controversial issues in total knee replacement is whether or not to resurface the patella. In order to determine the effects of different designs of femoral component on the conformity of the patellofemoral joint, five different knee prostheses were investigated. These were Low Contact Stress, the Miller-Galante II, the NexGen, the Porous-Coated Anatomic, and the Total Condylar prostheses. Three-dimensional models of the prostheses and a native patella were developed and assessed by computer. The conformity of the curvature of the five different prosthetic femoral components to their corresponding patellar implants and to the native patella at different angles of flexion was assessed by measuring the angles of intersection of tangential lines.

The Total Condylar prosthesis had the lowest conformity with the native patella (mean 8.58°; 0.14° to 29.9°) and with its own patellar component (mean 11.36°; 0.55° to 39.19°). In the other four prostheses, the conformity was better (mean 2.25°; 0.02° to 10.52°) when articulated with the corresponding patellar component. The Porous-Coated Anatomic femoral component showed better conformity (mean 6.51°; 0.07° to 9.89°) than the Miller-Galante II prosthesis (mean 11.20°; 5.80° to 16.72°) when tested with the native patella. Although the Nexgen prosthesis had less conformity with the native patella at a low angle of flexion, this improved at mid (mean 3.57°; 1.40° to 4.56°) or high angles of flexion (mean 4.54°; 0.91° to 9.39°), respectively. The Low Contact Stress femoral component had the best conformity with the native patella (mean 2.39°; 0.04° to 4.56°). There was no significant difference (p > 0.208) between the conformity when tested with the native patella or its own patellar component at any angle of flexion.

The geometry of the anterior flange of a femoral component affects the conformity of the patellofemoral joint when articulating with the native patella. A more anatomical design of femoral component is preferable if the surgeon decides not to resurface the patella at the time of operation.

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.

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.

We investigated the effect of locally administered bisphosphonate on distraction osteogenesis in a rabbit model and evaluated its systemic effect. An osteotomy on the right tibia followed by distraction for four weeks was performed on 47 immature rabbits. They were divided into seven equal groups, with each group receiving a different treatment regime. Saline and three types of dosage of alendronate (low, 0.75 μg/kg; mid, 7.5 μg/kg and high 75 μg/kg) were given by systemic injection in four groups, and saline and two dosages (low and mild) were delivered by local injection to the distraction gap in the remaining three groups. The injections were performed five times weekly during the period of distraction.

After nine weeks the animals were killed and image analysis and mechanical testing were performed on the distracted right tibiae and the left tibiae which served as a control group. The local low-dose alendronate group showed a mean increase in bone mineral density of 124.3 mg/cm³ over the local saline group (analysis of variance, p < 0.05) without any adverse effect on the left control tibiae.

The findings indicate that the administration of local low-dose alendronate could be an effective pharmacological means of improving bone formation in distraction osteogenesis.