The efficacy of β-tricalcium phosphate (β-TCP) loaded with bone morphogenetic protein-2 (BMP-2)-gene-modified bone-marrow mesenchymal stem cells (BMSCs) was evaluated for the repair of experimentally-induced osteonecrosis of the femoral head in goats. Bilateral early-stage osteonecrosis was induced in adult goats three weeks after ligation of the lateral and medial circumflex arteries and delivery of liquid nitrogen into the femoral head. After core decompression, porous β-TCP loaded with BMP-2 gene- or β-galactosidase (gal)-gene-transduced BMSCs was implanted into the left and right femoral heads, respectively. At 16 weeks after implantation, there was collapse of the femoral head in the untreated group but not in the BMP-2 or β-gal groups. The femoral heads in the BMP-2 group had a normal density and surface, while those in the β-gal group presented with a low density and an irregular surface. Histologically, new bone and fibrous tissue were formed in the macropores of the β-TCP. Sixteen weeks after implantation, lamellar bone had formed in the BMP-2 group, but there were some empty cavities and residual fibrous tissue in the β-gal group. The new bone volume in the BMP-2 group was significantly higher than that in the β-gal group. The maximum compressive strength and Young’s modulus of the repaired tissue in the BMP-2 group were similar to those of normal bone and significantly higher than those in the β-gal group. Our findings indicate that porous β-TCP loaded with BMP-2-gene-transduced BMSCs are capable of repairing early-stage, experimentally-induced osteonecrosis of the femoral head and of restoring its mechanical function

In about 50% of cases, osteonecrosis of the femoral head is known to occupy more than one site. There is controversy as to whether a single focus may increase in size. We have reviewed 606 consecutive femoral heads which had been surgically removed for osteonecrosis. Extension of osteonecrosis was observed in only two (0.3%) and was confirmed histopathologically by the enlargement of the necrotic segment beyond the repair zone formed for the primary necrosis into the adjacent, previously uninvolved bone. In both cases, the necrotic regions were wedge-shaped and occupied over 80% of the femoral head. It appears that an increase in size is extremely rare and that osteonecrosis is due to a single event. Our findings may be of value in assessing the use of joint-salvage procedures for osteonecrosis of the femoral head

Using in situ hybridisation and the terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end-labelling (TUNEL) reaction in rats with osteonecrosis of the femoral head we have studied the effect of ischaemia on the gene expression of the stress proteins oxygen-regulated protein 150 (ORP150) and haemoxygenase 1 (HO1) and the death mechanism of the cells involved in osteonecrosis. Both ORP150 and HO1 have been reported to have important roles in the successful adaptation to oxygen deprivation. ORP150 and HO1 mRNA expression was induced by ischaemia in osteoblasts and osteocytes. In proliferative chondrocytes, these signals were detected constitutively. During the development of ischaemic osteonecrosis, the mechanism of cell death was apoptosis as indicated by DNA fragmentation and the presence of apoptotic bodies in osteocytes, chondrocytes and bone-marrow cells. After the initial ischaemic event, expression of ORP150 and HO1 mRNA, the TUNEL-positive reaction and empty lacunae were found sequentially. These findings were exclusive and may be considered to be markers for each stage in the development of osteonecrosis

The use of a composite osteochondral device for simulating partial hemiarthroplasty was examined. The device was composed of a polyvinyl alcohol hydrogel and a titanium fibre mesh, acting as artificial cartilage and as porous artificial bone, respectively. The titanium fibre mesh was designed to act as an interface material, allowing firm attachment to both the polyvinyl alcohol gel (through injection moulding) and the femoral joint surface (through bony ingrowth). We implanted 22 of these devices into canine femoral heads. Histological findings from the acetabular cartilage and synovial membrane, as well as the attachment of the prosthesis to bone, were examined up until one year after operation. No marked pathological changes were found and firm attachment of the device to the underlying bone was confirmed. The main potential application for this device is for partial surface replacement of the femoral head after osteonecrosis. Other applications could include articular resurfacing and the replacement of intervertebral discs

Osteonecrosis of the femoral head usually affects young individuals and is responsible for up to 12% of total hip arthroplasties. The underlying pathophysiology of the death of the bone cells remains uncertain. We have investigated nitric oxide mediated apoptosis as a potential mechanism and found that steroid- and alcohol-induced osteonecrosis is accompanied by widespread apoptosis of osteoblasts and osteocytes. Certain drugs or their metabolites may have a direct cytotoxic effect on cancellous bone of the femoral head leading to apoptosis rather than purely necrosis

Intracapsular neck of femur fractures may be treated with fixation or arthroplasty, depending on fracture characteristics and patient factors. Two common methods of fixation are the sliding hip screw, with or without a de-rotation screw, and cannulated screws. Each has its merits, and to date there is controversy around which method is superior, with either method thought to risk avascular necrosis of the femoral head (AVN) rates in the region of 10–20%.

Fixation with cannulated screws may be performed in various ways, with current paucity of evidence to show an optimum technique. There are a multitude of factors which are likely to affect patient outcomes: technique, screw configuration, fracture characteristics and patient factors. We present a retrospective case series analysis of 65 patients who underwent cannulated screw fixation of a hip fracture.

Electronic operative records were searched from July 2014 until July 2019 for all patients with a neck of femur fracture fixed with cannulated screws: 68 were found. Three patients were excluded on the basis of them having a pathological fracture secondary to malignancy, cases were followed up for 2 years post-operatively. Electronic patient records and X-rays were reviewed for all included patients. All X-rays were examined by each team member twice, with a time interval of two weeks to improve inter-observer reliability.

65 patients were included with 2:1 female to male ratio and average age of 72 years. 36 patients sustained displaced fractures and 29 undisplaced. Ten patients sustained a high-energy injury, none of which developed AVN. Average time to surgery was 40 hours and 57 patients mobilised on day one post-operatively. All cases used either 7 or 7.3mm partially threaded screws in the following configurations: 2 in triangle apex superior, 39 triangle apex inferior, 22 rhomboid and 2 other, with 9 cases using washers. All reductions were performed closed.

Five (8%) of our patients were lost to follow-up as they moved out of area, 48 (74%) had no surgical complications, seven (11%) had mild complications, three (5%) moderate and two (3%) developed AVN. Both of these sustained displaced fractures with low mechanism of injury, were female, ASA 2 and both ex-smokers. One received three screws in apex inferior configuration and one rhomboid, neither fixed with washers.

Our AVN rate following intracapsular hip fracture fixation with cannulated screws is much lower than widely accepted. This study is under-powered to comment on factors which may contribute to the development of AVN. However, we can confidently say that our practice has led to low rates of AVN. This may be due to our method of fixation; we use three screws in an apex inferior triangle or four screws in a rhomboid, our consultant-led operations, closed reduction of all fractures, or our operative technique. We pass a short thread cannulated screw across the least comminuted aspect of the fracture first in order to achieve compression, followed by two or three more screws (depending on individual anatomy) to form a stable construct. Our series shows that fixation of intracapsular hip fractures with cannulated screws as we have outlined remains an excellent option. Patients retain their native hip, have a low rate of AVN, and avoid the risks of open reduction.

Thermal osteonecrosis is a side effect when used Kirschner (K) wires and drills in orthopaedic surgeries. This osteonecrosis may endanger the fixation. Orthopaedic surgeons sometimes have to use unsharpened K-wires in emergent surgery. The thermal effect of used and unsharpened K wire is ambiguous to the bone. This experimental study aims to assess the thermal osteonecrosis while drilling bone with three different types of K-wires especially a previously used unsharpened wire and its thermographic measurements correlation. Two different speeds of rotation were chosen to investigate the effect of speed on thermal necrosis to the bone. A total of 16 New Zealand white rabbits weighing a mean of 2.90 kg (2.70 – 3.30 kg) were used. All rabbits were operated under general anaesthesia in a sterile operating room. Firstly, 4 cm longitudinal lateral approach was used to the right femur and then the femur was drilled with 1.0 mm trochar tip, spade tip and previously used unsharpened K-wires and 1.0 mm drill bit at 1450 rpm speed. Left femur was drilled with same three type K-wires and drill bit at 330 rpm speed. One cm distance was left among four penetrations on the femur. The thermal changes were recorded by Flir® E6 Thermal Camera from 50 cm distance and 30-degree angle. Thermographic measurements saved for every drilling process and recorded for the highest temperature (°C) during the drilling. All subjects were sacrificed post-operatively on the eighth day and specimens were prepared for the histological examination. The results of osteonecrosis assessment score and thermographic correlation were evaluated statistically. Histological specimens were evaluated by the scoring of osteonecrosis, osteoblastic activity, haemorrhage, microfracture and inflammation. Results were graded semi-quantitatively as none, moderate or severe for osteonecrosis, haemorrhage and inflammation. The microfracture and osteoblastic activity were evaluated as present or absent. There was no meaningful correlation between osteonecrosis and the drilling speed (p=0.108). There was less microfracture zone which was drilled with trochar tip K-wires at 1450 rpm speed (p=0.017). And the drilling temperature of trochar tip K-wires was higher than the others(p=0.001). Despite this evaluation, osteonecrosis zone of spade and unsharpened tip K-wires were more than trochar tip K-wires (p=0.039). The drill bit at 330 rpm caused the least osteonecrosis and haemorrhage and respectfully the lowest drilling temperature (p=0,001). The osteoblastic activity shows no difference between the groups. (p=0,122; 0,636;0.289). On the contrary to the literature, our experiment showed that there is no meaningful correlation between osteonecrosis score and temperature produced by drilling. The histological assessment showed the osteonecrosis during short drilling time but, not clarify the relation with drilling temperature. Eventually, the osteonecrosis showed a positive correlation with drilling time independently of drilling temperature at 330 rpm. (p=0,042) These results show that we need more studies to understand about osteonecrosis and its relationship with drilling heat temperature. Trochar tip K-wires creates higher drilling temperature but less osteonecrosis than a spade and unsharpened cut tip K-wires. Using unsharpened tip K-wire causes more osteonecrosis. Previously used and, unsharpened K-wires should be discarded

Despite considerable legacy issues, Girdlestone's Resection Arthroplasty (GRA) remains a valuable tool in the armoury of the arthroplasty surgeon. When reserved for massive lysis in the context of extensive medical comorbidities which preclude staged or significant surgical interventions, and / or the presence of pelvic discontinuity, GRA as a salvage procedure can have satisfactory outcomes. These outcomes include infection control, pain control and post-op function. We describe a case series of 13 cases of GRA and comment of the indications, peri, and post-operative outcomes. We reviewed all cases of GRA performed in our unit during an 8 year period, reviewing the demographics, indications, and information pertaining to previous surgeries, and post op outcome for each. Satisfaction was based on a binary summation (happy/unhappy) of the patients’ sentiments at the post-operative outpatient consultations. 13 cases were reviewed. They had a mean age of 75. The most common indication was PJI, with 10 cases having this indication. The other three cases were performed for avascular necrosis, pelvic osteonecrosis secondary to radiation therapy and end stage arthritis on a background of profound learning disability in a non-ambulatory patient. The average number of previous operations was 5 (1-10). All 13 patients were still alive post girdlestone. 7 (54%) were satisfied, 6 were not. 3 patients were diabetic. 5 patients developed a sinus tract following surgery. With sufficient pre-op patient education, early intensive physiotherapy, and timely orthotic input, we feel this procedure remains an important and underrated and even compassionate option in the context of massive lysis and / or the presence of pelvic discontinuity / refractory PJI. GRA should be considered not a marker of failure but as a definitive procedure that gives predictability to patients and surgeon in challenging situations

The pathophysiological basis of alterations in trabecular bone of patients with osteonecrosis of the femoral head (ONFH) remains unclear. ONFH has classically been considered a vascular disease with secondary changes in the subchondral bone. However, there is increasing evidence suggesting that ONFH could be a bone disease, since alterations in the functionality of bone tissue distant from the necrotic lesion have been observed. We comparatively studied the transcriptomic profile of trabecular bone obtained from the intertrochanteric region of patients with ONFH without an obvious aetiological factor, and patients with osteoarthritis (OA) undergoing total hip replacement in our Institution. To explore the biological processes that could be affected by ONFH, we compared the transcriptomic profile of trabecular bone from the intertrochanteric region and the femoral head of patients affected by this condition. Differential gene expression was studied using an Affymetrix microarray platform. Transcriptome analysis showed a differential signature in trabecular bone from the intertrochanteric region between patients with ONFH and those with OA. The gene ontology analyses of the genes overexpressed in bone tissue of patients with ONFH revealed a range of enriched biological processes related to cell adhesion and migration and angiogenesis. In contrast, most downregulated transcripts were involved in cell division. Trabecular bone in the intertrochanteric region and in the femoral head also exhibited a differential expression profile. Among the genes differentially expressed, we highlighted those related with cytokine production and immune response. This study identified a set of differently expressed genes in trabecular bone of patients with idiopathic ONFH, which might underlie the pathophysiology of this condition. Acknowledgements: This work was supported by grants PI18/00643 and PI22/00939 from ISCIII-FEDER, Ministerio de Ciencia, Innovación y Universidades (MICINN)-AES

Mesenchymal stem cells (MSC) have potent immunomodulatory and regenerative effects via soluble factors. One approach to improve stem cell-based therapies is encapsulation of MSC in hydrogels based on natural proteins such as collagen and fibrin, which play critical roles in bone healing. In this work, we comparatively studied the influence of collagen and fibrin hydrogels of varying stiffness on the paracrine interactions established by MSC with macrophages and osteoblasts. Type I collagen and fibrin hydrogels in a similar stiffness range loaded with MSC from donants were prepared by modifying the protein concentration. Viability and morphology of MSC in hydrogels as well as cell migration rate from the matrices were determined. Paracrine actions of MSC in hydrogels were evaluated in co-cultures with human macrophages from healthy blood donors or with osteoblasts from bone explants of patients with osteonecrosis of the femoral head. Lower matrix stiffness resulted in higher MSC viability and migration. Cell migration rate from collagen hydrogels was higher than from fibrin matrices. The secretion of the immunomodulatory factors interleukin-6 (IL-6) and prostaglandin E. 2. (PGE. 2. ) by MSC in both collagen and fibrin hydrogels increased with increasing matrix stiffness. Tumor necrosis factor-α (TNF-α) secretion by macrophages cultured on collagen hydrogels was lower than on fibrin matrices. Interestingly, higher collagen matrix stiffness resulted in lower secreted TNF-α while the trend was opposite on fibrin hydrogels. In all cases, TNF-α levels were lower when macrophages were cultured on hydrogels containing MSC than on empty gels, an effect partially mediated by PGE. 2. Finally, mineralization capacity of osteoblasts co-cultured with MSC in hydrogels increased with increasing matrix stiffness, although this effect was more notably for collagen hydrogels. Paracrine interactions established by MSC in hydrogels with macrophages and osteoblasts are regulated by matrix composition and stiffness

Total hip arthroplasty (THA) outcome in patients with osteonecrosis of the femoral head ONFH) are excellent, however, there is controversy when compared with those in patients with osteoarthritis (OA). Reduced mineralization capacity of osteoblasts of the proximal femur in patients with ONFH could affect implant fixation. We asked if THA fixation in patients with ONFH is worse than in those with OA. We carried out a prospective comparative case (OA)-control (ONFH) study of patients undergoing THA at our hospital between 2017 and 2019. The minimum follow-up was 2 years. Inclusion criteria were patients with uncemented THA, younger than 70 years old, a Dorr femoral type C and idiopathic ONFH. We compared the clinical (Merlé D'Aubigné-Postel score) and radiological results related with implant positioning and fixation. Engh criteria and subsidence were assessed at the immediate postoperative, 12 weeks, 6 months, 12 months and yearly. Osteoblastic activity was determined by mineralization assay on primary cultures of osteoblasts isolated from trabecular bone samples collected from the intertrochanteric area obtained during surgery. Group 1 (ONFH) included 18 patients and group 2 (OA), 22. Average age was 55.9 years old in group 1 and 61.3 in group 2. (p=0.08). There were no differences related with sex, Dorr femoral type or femoral filling. The mean clinical outcome score was 17.1 in group 1 and 16.5 in group 2 (p=0.03). There were no cases of dislocation, infection, or revision surgery in this series. There were 5 cases (28%) of femoral stem subsidence greater than 3mm within 6 first months in group 1 and 1 case (4.5%) in group 2 (p=0.05). Although there were no significant differences related to clinical results, bone fixation was slower, and a greater subsidence was observed in patients with ONFH. Greater femoral stem subsidence was associated with a lower capacity for mineral nodule formation in cultured osteoblasts. The surgical technique could influence THA outcome in patients with reduced mineralization capacity of osteoblasts

Our knowledge of primary bone marrow edema (BME) of the knee is still limited. A major contributing factor is that it shares several radiological findings with a number of vascular, traumatic, and inflammatory conditions having different histopathological features and etiologies. BME can be primary or secondary. The most commonly associated conditions are osteonecrosis, osteochondritis dissecans, complex regional pain syndrome, mechanical strain such as bone contusion/bruising, micro-fracture, stress fracture, osteoarthritis, and tumor. The etiology and pathogenesis of primary BME are unclear. Conservative treatment includes analgesics, non-steroidal anti-inflammatory drugs, weight-bearing limitations, physiotherapy, pulsed electromagnetic fields, prostacyclin, and bisphosphonates. Surgical treatment, with simple perforation, fragment stabilization, combined scraping and perforation, and eventually osteochondral or chondrocyte transplant, is reserved for the late stages. This retrospective study of a cohort of patients with primary BME of the knee was undertaken to describe their clinical and demographic characteristics, identify possible risk factors, and assess treatment outcomes. We reviewed the records of 48 patients with primary BME of the knee diagnosed on MRI by two radiologists and two orthopedists. History, medications, pain type, leisure activities, smoking habits, allergies, and environmental factors were examined. Analysis of patients’ characteristics highlighted that slightly overweight middle-aged female smokers with a sedentary lifestyle are the typical patients with primary BME of the knee. In all patients, the chief symptom was intractable day and night pain (mean value, 8.5/10 on the numerical rating scale) with active as well as passive movement, regardless of BME extent. Half of the patients suffered from thyroid disorders; indeed, the probability of having a thyroid disorder was higher in our patients than in two unselected groups of patients, one referred to our orthopedic center (odds ratio, 18.5) and another suffering from no knee conditions (odds ratio, 9.8). Before pain onset, 56.3% of our cohort had experienced a stressful event (mourning, dismissal from work, concern related to the COVID-19 pandemic). After conservative treatment, despite the clinical improvement and edema resolution on MRI, 93.8% of patients described two new symptoms: a burning sensation in the region of the former edema and a reduced ipsilateral patellar reflex. These data suggest that even though the primary BME did resolve on MRI, the knee did not achieve full healing

Results in patients undergoing total hip arthroplasty (THA) for femoral head osteonecrosis (ON) when compared with primary osteoarthritis (OA) are controversial. Different factors like age, THA type or surgical technique may affect outcome. We hypothesized that patients with ON had an increased revision rate compared with OA. We analysed clinical outcome, estimated the survival rate for revision surgery, and their possible risk factors, in two groups of patients. In this retrospective cohort analysis of our prospective database, we assessed 2464 primary THAs implanted between 1989 and 2017. Patients with OA were included in group 1, 2090 hips; and patients with ON in group 2, 374 hips. In group 2 there were more men (p<0.001), patients younger than 60 years old (p<0.001) and with greater physical activity (p<0.001). Patients with lumbar OA (p<0.001) and a radiological acetabular shape type B according to Dorr (p<0.001) were more frequent in group 1. Clinical outcome was assessed according to the Harris Hip Score and radiological analysis included postoperative acetabular and femoral component position and hip reconstruction. Kaplan-Meier survivorship analysis was used to estimate the cumulative probability of not having revision surgery for different reasons. Univariate and multivariate Cox regression models were used to assess risk factors for revision surgery. Clinical improvement was better in the ON at all intervals. There were 90 hips revised, 68 due to loosening or wear, 52 (2.5%) in group 1, and 16 (4.3%) in group 2. Overall, the survival rate for revision surgery for any cause at 22 years was 88.0 % (95% CI, 82-94) in group 1 and 84.1% (95% CI, 69 – 99) in group 2 (p=0.019). Multivariate regression analysis showed that hips with conventional polyethylene (PE), compared with highly-cross linked PEs or ceramic-on-ceramic bearings, (p=0.01, Hazard Ratio (HR): 2.12, 95% CI 1.15-3.92), and cups outside the Lewinnek´s safe zone had a higher risk for revision surgery (p<0.001, HR: 2.57, 95% CI 1.69-3.91). Modern highly-cross linked PEs and ceramic-on-ceramic bearings use, and a proper surgical technique improved revision rate in patients undergoing THA due to ON compared with OA

Open talus fracture are notoriously difficult to manage and they are commonly associated with a high level of complications including non-union, avascular necrosis and infection. Currently, the management of such injuries is based upon BOAST 4 guidelines although there is no suggested definitive management, thus definitive management is based upon surgeon preference. The key principles of open talus fracture management which do not vary between surgeons, however, there is much debate over whether the talus should be preserved or removed after open talus fracture/dislocation and proceeded to tibiocalcaneal fusion. A review of electronic hospital records for open talus fractures from 2014-2021 returned foureen patients with fifteen open talus fractures. Seven cases were initially managed with ORIF, five cases were definitively managed with FUSION, while the others were managed with alternative methods. We collected patient's age, gender, surgical complications, surgical risk factors and post-treatment functional ability and pain and compliance with BOAST guidelines. The average follow-up of the cohort was four years and one month. EQ-5D-5L and FAAM-ADL/Sports score was used as a patient reported outcome measure. Data was analysed using the software PRISM. Comparison between FUSION and ORIF groups showed no statistically significant difference in EQ-5D-5L score (P = 0.13), FAAM-ADL (P = 0.20), FAAM-Sport (P = 0.34), infection rate (P = 0.55), surgical times (P = 0.91) and time to weight bearing (P = 0.39), despite a higher proportion of polytrauma and Hawkins III and IV fractures in the FUSION group. FUSION is typically used as second line to ORIF or failed ORIF. However, there are a lack of studies that directly compared outcome in open talus fracture patients definitively managed with FUSION or ORIF. Our results demonstrate for the first time, that FUSION may not be inferior to ORIF in terms of patient functional outcome, infection rate, and quality-of-life, in the management of patients with open talus fracture patients. Of note, as open talus fractures have increased risks of complications such as osteonecrosis and non-union, FUSION should be considered as a viable option to mitigate these potential complications in these patients

Arthroscopic management of femoroacetabular impingement (FAI) has become the mainstay of treatment. However, chondral lesions are frequently encountered and have become a determinant of less favourable outcomes following arthroscopic intervention. The aim of this systematic review and meta-analysis was to assess the outcomes of hip arthroscopy (HA) in patients with FAI and concomitant chondral lesions classified as per Outerbridge. A systematic search was performed using the PRISMA guidelines on four databases including MEDLINE, EMBASE, Cochrane Library and Web of Science. Studies which included HA as the primary intervention for management of FAI and classified chondral lesions according to the Outerbridge classification were included. Patients treated with open procedures, for osteonecrosis, Legg-Calve-Perthes disease, and previous ipsilateral hip fractures were excluded. From a total of 863 articles, twenty-four were included for final analysis. Demographic data, PROMs, and radiological outcomes and rates of conversion to total hip arthroplasty (THA) were collected. Risk of bias was assessed using ROBINS-I. Improved post-operative PROMs included mHHS (mean difference:-2.42; 95%CI:-2.99 to −1.85; p<0.001), NAHS (mean difference:-1.73; 95%CI: −2.23 to −1.23; p<0.001), VAS (mean difference: 2.03; 95%CI: 0.93-3.13; p<0.001). Pooled rate of revision surgery was 10% (95%CI: 7%-14%). Most of this included conversion to THA, with a 7% pooled rate (95%CI: 4%-11%). Patients had worse PROMs if they underwent HA with labral debridement (p=0.015), had Outerbridge 3 and 4 lesions (p=0.012), concomitant lesions of the femoral head and acetabulum lesions (p=0.029). Reconstructive cartilage techniques were superior to microfracture (p=0.042). Even in concomitant lesions of the femoral head and acetabulum, employing either microfracture or cartilage repair/reconstruction provided a benefit in PROMs (p=0.027). Acceptable post-operative outcomes following HA with labral repair/reconstruction and cartilage repair in patients with FAI and concomitant moderate-to-severe chondral lesions, can be achieved. Patients suffering from Outerbridge 3 and 4 lesions, concomitant acetabular rim and femoral head chondral lesions that underwent HA with labral debridement, had worse PROMs. Reconstructive cartilage techniques were superior to microfracture. Even in concomitant acetabular and femoral head chondral lesions, employing either microfracture or cartilage repair/reconstruction was deemed to provide a benefit in PROMs

Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis. In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment

The human amniotic membrane (hAM), derived from the placenta, possesses a low (nay inexistant) immunogenicity and exerts an anti-inflammatory, anti-fibrotic, antimicrobial, antiviral and analgesic effect. It is a source of stem cells and growth factors promoting tissue regeneration. hAM acts as an anatomical barrier with adequate mechanical properties (permeability, stability, elasticity, flexibility, resorbability) preventing the proliferation of fibrous tissue and promoting early neovascularization of the surgical site. Cryopreservation and lyophilization, with sometimes additional decellularization process, are the main preservation methods for hAM storage. We examined the use of hAM in orthopaedic and maxillofacial bone surgery, specially to shorten the induced membrane technique (Gindraux, 2017). We investigated the cell survival in cryopreserved hAM (Laurent, 2014) and the capacity of intact hAM of in vitro osteodifferentiation (Gualdi, 2019). We explored its in vivo osteogenic potential in an ectopic model (Laurent, 2017) and, with Inserm U1026 BioTis, in a calvarial defect (Fenelon, 2018). Still piloted by U1026, decellularization and/or lyophilization process were developed (Fenelon, 2019) and, processed hAM capacities was assessed for guided bone regeneration (Fenelon 2020) and induced membrane technique (Fenelon, 2021) in mice. We reported a limited function of hAM for bone defect management. In this light, we recognized medication-related osteonecrosis of the jaw (MRONJ) as appropriate model of disease to evaluate hAM impact on both oral mucosa and bone healing. We treated height compassionate patients (stage II, III) with cryopreserved hAM. A multicentric randomized clinical study (PHRC-I 2020 funding) will be soon conducted in France (regulatory and ethical authorization in progress)

Introduction. Osteonecrosis of the knee encompasses three conditions; spontaneous osteonecrosis of the knee, secondary osteonecrosis (ON) and post-arthroscopic ON. Early stage lesions can be managed by non-operative measures that include protected weight-bearing and analgesia. The aim of this study was to report the experience of the authors in managing early stages of knee ON by analysing the functional outcome and need for surgical intervention. Methods. All patients treated for osteonecrosis of the knee between 1st August 2001 and 1st April 2014 were prospectively collected. Treatment consisted of touch-down weight bearing for four to six weeks. The cases were retrospectively reviewed. MR imaging was evaluated for the stage of disease according to Koshino's Classification system, the condyles involved and the time taken for resolution. Tegner Activity Scale, VAS pain, Lysholm, WOMAC and IKDC scores were recorded at presentation and final follow up. Results. 51 cases were treated for knee ON at our centre; 40 cases of SONK, seven secondary ON and four post-arthroscopic ON. Of the seven cases of secondary osteonecrosis; 5 were secondary to self-reported high ethanol intake and two secondary to corticosteroid treatment. The mean age of the group was 56.9 years and 68.7% were male. The medial femoral condyle was the most commonly affected (54.9%). 86% reported resolution of clinical symptoms and a statistically significant improvement was reported in all functional outcome measures. Four patients required total knee arthroplasty; three in the post-arthroscopic group within 15 months and one following ON secondary to corticosteroids performed at 5 months. Conclusion. Early stage spontaneous osteonecrosis of the knee can be managed successfully without surgery if diagnosed early. Although secondary and post-arthroscopic ON seem to be more resistant. Larger studies are required to confirm or refute this. Level of Evidence. IV – a case series. Conflict of Interests. The authors confirm that they have no relevant financial disclosures or conflicts of interest. Ethical approval was not sought as this was a systematic review

Introduction and Objective. Mesenchymal stem cells (MSC) are attractive candidates for bone regeneration approaches. Benefits of MSC therapy are mainly attributed to paracrine effects via soluble factors, exerting both immunoregulatory and regenerative actions. Encapsulation of MSC in hydrogels prepared with extracellular matrix (ECM) proteins has been proposed as a strategy to enhance their survival and potentiate their function after implantation. Functional activity of MSC can be regulated by the physical and mechanical properties of their microenvironment. In this work, we investigated whether matrix stiffness can modulate the crosstalk between MSC encapsulated in collagen hydrogels with macrophages and osteoblasts. Materials and Method. Collagen hydrogels with a final collagen concentration of 1.5, 3 and 6 mg/mL loaded with human MSC were prepared. Viscoelastic properties of hydrogels were measured in a controlled stress rheometer. Cell distribution into the hydrogels was examined using confocal microscopy and the levels of the immunomodulatory factors interleukin-6 (IL-6) and prostaglandin E. 2. (PGE. 2. ) released by MSC were quantified by immunoassays. To determine the effect of matrix stiffness on the immunomodulatory potential of MSC, human macrophages obtained from healthy blood were cultured in media conditioned by MSC in hydrogels. The involvement of IL-6 and PGE. 2. in MSC-mediated immunomodulation was investigated employing neutralizing antibodies. Finally, the influence of soluble factors released by MSC in hydrogels on bone-forming cells was studied using osteoblasts obtained from trabecular bone explants from patients with osteonecrosis of the femoral head during total hip arthroplasty. Results. MSC loaded in hydrogels containing varying concentrations (1.5, 3 and 6 mg/mL) of collagen were viable. Rheology measurements determined that the hydrogel stiffness increased with increasing collagen concentration. Encapsulation of MSC into hydrogels barely affected their storage modulus values. MSC acquired a three-dimensional (3D) arrangement in all hydrogels and showed a more elongated shape in hydrogels with higher stiffness. The secretion of IL-6 and PGE. 2. by MSC in hydrogels increased with increasing matrix stiffness. Media conditioned by MSC encapsulated in stiffer hydrogels decreased TNF-α levels secreted by macrophages to a higher extent than media conditioned by MSC in softer hydrogels. This effect was partially mediated by PGE. 2. Finally, our preliminary results indicated that factors released by MSC in hydrogels regulated osteoblast-mediated mineralisation and this effect was dependent on hydrogel stiffness. Conclusions. Our data indicate that matrix stiffness of collagen hydrogels regulates the production of soluble factors by MSC and their paracrine actions on macrophages and osteoblasts

Osteonecrosis of the femoral head is a complex pathologic process with many aetiological factors. Factors most often mentioned in the literature are mechanical disruption (hip trauma or surgery), steroid use, smoking, haemoglobinopathies and hyperlipidaemia. 1. Our case depicts a rare association of crack cocaine related to osteonecrosis of the femoral head which has never been reported in the available literature. Case Report: A 32 year old man was referred to our Orthopaedic clinic with right hip pain. He had a 9 pack-year history of cigarette smoking and had also smoked crack cocaine between ages 20 to 28; shortly after this the hip pain started. He denied antecedent injury. He had undergone a steroid injection into his right ankle abroad for swelling one year before referral, which was after onset of hip pain. MRI of his hip previously performed abroad had been normal. The patient had an indoor job and was otherwise fit and well. On examination he had reduced of movement in his right hip with 5–10 degrees of fixed flexion deformity. Plain radiography demonstrated cyst formation and sclerosis of both femoral heads. Repeat MRI confirmed bilateral osteonecrosis, worse on the right with risk of head collapse. The patient underwent bilateral core decompressions. Subsequent follow-up demonstrated a mobile patient with no need for arthroplasty and he was discharged after two years. Osteonecrosis is caused by the coagulation of the intra-osseous microcirculation leading to thrombosis formation and eventual reduction in osseous blood supply. Steroid use is associated with increased risk of osteonecrosis to the femoral head, however in these cases the patients often undergo either direct local or systemic infiltration of steroid. In this case steroid was administered after symptoms began to a far distant site and therefore cannot be the cause. Cigarette smoking is also known to cause osteonecrosis. Our patient had smoked cigarettes for fourteen years without problems, and it was after he ceased to smoke crack cocaine that his symptoms began. Cocaine blocks voltage-gated sodium-channels causing vasospasm. It is known to cause nasal and facial bone osteonecrosis due to its common intranasal method of delivery. We postulate that in this case crack cocaine was a synergistic factor towards development of femoral head osteonecrosis