Aims. The aim of this study is to determine the predictors of overall survival (OS) and predictive factors of poor prognosis of conventional high-grade osteosarcoma of the limbs in a single-centre in South Africa. Methods. We performed a retrospective cross-sectional analysis to identify the prognostic factors that predict the OS of patients with histologically confirmed high-grade conventional osteosarcoma of the limbs over ten years. We employed the Cox proportional regression model and the Kaplan-Meier method for statistical analysis. Results. This study comprised 77 patients at a three-year minimum follow-up. The predictors of poor OS were: the median age of ≤ 19 years (hazard ratio (HR) 0.96; 95% confidence interval (CI) 0.92 to 0.99; p = 0.021); median duration of symptoms ≥ five months (HR 0.91; 95% CI 0.83 to 0.99; p < 0.037); metastasis at diagnosis (i.e. Enneking stage III) (HR 3.33; 95% CI 1.81 to 6.00; p < 0.001); increased alkaline phosphatase (HR 3.28; 95% CI 1.33 to 8.11; p < 0.010); palliative treatment (HR 7.27; 95% CI 2.69 to 19.70); p < 0.001); and amputation (HR 3.71; 95% CI 1.12 to 12.25; p < 0.032). In contrast, definitive surgery (HR 0.11; 95% CI 0.03 to 0.38; p < 0.001) and curative treatment (HR 0.18; 95% CI 0.10 to 0.33; p < 0.001) were a protective factor. The Kaplan-Meier median survival time was 24 months, with OS of 57.1% at the three years. The projected five-year event-free survival was 10.3% and OS of 29.8% (HR 0.76; 95% CI 0.52 to 1.12; p = 0.128). Conclusion. In this series of high-grade conventional osteosarcoma of the appendicular skeleton from South Africa, 58.4% (n = 45) had detectable metastases at presentation; hence, an impoverished OS of five years was 29.8%. Large-scale future research is needed to validate our results. Cite this article: Bone Jt Open 2024;5(3):210–217

Aims. To describe the epidemiology of acetabular fractures including patient characteristics, injury mechanisms, fracture patterns, treatment, and mortality. Methods. We retrieved information from the Swedish Fracture Register (SFR) on all patients with acetabular fractures, of the native hip joint in the adult skeleton, sustained between 2014 and 2020. Study variables included patient age, sex, injury date, injury mechanism, fracture classification, treatment, and mortality. Results. In total, 2,132 patients with acetabular fractures from the SFR were included in the study. The majority of the patients were male (62%) and aged over 70 years old (62%). For patients aged > 70 years, the 30-day mortality was 8% and one-year mortality 24%. For patients aged ≤ 70 years, the 30-day mortality was 0.2% and one-year mortality 2%. Low-energy injuries (63%) and anterior wall fractures (20%) were most common. Treatment was most often non-surgical (75%). Conclusion. The majority of patients who sustain an acetabular fracture are elderly (> 70 years), of male sex, and the fracture most commonly occurs after a simple, low-energy fall. Non-surgical treatment is chosen in the majority of acetabular fracture patients. The one-year mortality for elderly patients with acetabular fracture is similar to the mortality after hip fracture, and a similar multidisciplinary approach to care for these patients should be considered. Cite this article: Bone Jt Open 2023;4(9):652–658

Introduction:. Distal femoral replacement is recognised as the optimum treatment for malignant distal femoral tumours. Aseptic loosening is known to be a major cause for failure in these implants. Studies have indicated that the HA coated collar promotes osteointegration and bony in growth. This study compares long term aseptic loosening in implants with HA coated collars to those without in the immature skeleton. Objectives:. To assess the effect of HA coated collars on aseptic loosening in extendable distal femoral replacement prosthesis in the immature skeleton. Methods:. All paediatric patients undergoing distal femoral replacement with extendable prosthesis were retrospectively reviewed between 1980–2003. A total of 32 patients were reviewed. 24 patients underwent distal femoral replacement with extendable prostheses without a HA coated collar. This cohort was compared to 18 patients who were treated with an extendable prosthesis with a HA coated collar between 2001–03. Average follow up in patients without a collar was 10.1 yrs (6–18) and 8.1 yrs in those with a collar (4–11). All patients with identified infection were excluded. Radiographs taken at last follow-up were analysed for loosening. Results:. Thirty-one patients were treated for primary osteosarcoma and one for a histiocytoma. Average age at operation was 13 yrs for both groups (non-collared 6–17, collared 4–11). Three of 24 patients in the non-collared cohort underwent revision compared to 1 of 18 in the collared group. The cause of revision in the collared group was infection. One patient in each cohort died within 5 years of surgery. Mean loosening score at last follow up for the non-collared group was 11.2 compared to 2.5 for the collared group with a p value of <0.05 (Mann Whitney-U). Conclusions:. Aseptic loosening is a major cause of failure for distal femoral replacement prosthesis. HA coated collars have been shown to promote osteointegration. Little comparable data exists between collared and non-collared extendable prosthesis in the immature skeleton. Our data demonstrates that HA coated collars significantly reduce long term loosening in the immature skeleton

Purpose: We conducted a review of the Leeds Regional Bone Tumour Registry for primary bone tumours of the axial skeleton since establishment in 1958 until year 2000 to analyze the incidence of primary tumours of the axial skeleton and to record their site of occurrence, sex distribution, survival and pathology. Method: Primary tumours of the axial skeleton are particularly rare, accounting for between 4% and 13% of published series of primary bone tumours. The Leeds Bone Tumour Registry was reviewed and a total of 2750 cases of bone tumours and tumour-like cases were analyzed. Consultants in orthopaedic surgery, neurosurgery, oncology and pathology in North and West Yorkshire and Humberside contribute to the Registry. Results: Primary bone tumours of the axial skeleton constitute only 126 of the 2,750 cases (4.6%). Chordoma was the most frequent tumour in the cervical and sacral regions, while the most common diagnosis overall was myeloma. Osteosarcoma ranked third. Mean age of presentation was 42 years. Pain was the most common presenting symptom, occurring in 95% of malignant and 76% of benign tumours. Neurological involvement occurred in 52% of malignant tumours and usually meant a poor prognosis,. Conclusions: The establishment of Bone Tumour Registries is the only way that sufficient data on large numbers of these rare tumours can be accumulated to provide a valuable and otherwise unavailable source of information for research, education and clinical follow-up

Purpose: Reconstruction of long bones with significant loss of bone stock is a major challenge particularly if the gap is greater than 5 cm. Complementary bone resection is often necessary. A conventional cancellous graft may be used when loss of bone substance is not too extensive, but when the defect extends over several centimeters a vascularised bone graft with a microanastomsed fibular graft may be indicated. This technique is widely used for the lower limb but rarely applied for the forearm. The purpose of this work was to examine the modalities and report our experience. Material and methods: This retrospective study included six microvascularised free fibular grafts performed to reconstruct the forearm bones after massive loss of bone stock. The mean age of the five men and one woman was 34 years. Bone loss (mean 10 cm, range 6 – 18 cm) involved the radius in five cases and the ulna in one. All six patients were victims of crush injuries with open fractures and expulsion of part of the forearm skeleton. Initial treatment included debridement, wound closure, and temporary external fixation. The fibular graft was performed eight weeks (mean) after trauma in five patients and six months after trauma in the sixth patient who also had multiple autologous cancellous grafts which left a nonunion of the ulna and an 18 cm defect. The Meyer method using a saphenous loop was used for vessel anastomosis in five cases. A vascularised fibular bypass was used in one. Osteosynthesis was achieved with screw or plate fixation. Results: Bone healing was achieved in all patients four to six months after grafting. Mean follow-up was three years (range 1–5). There were no secondary fractures. Mean flexion-extension of the elbow was 100° at last follow-up. Mean pronation-supination was 100°. Discussion and conclusion: Free fibular transfer enabled reconstruction of the forearm skeleton after massive bone loss. The vascularised graft shortened time to bone healing for these extensive defects with a mechanical quality superior to that obtained with conventional non-vascularised grafts. These vascularised grafts can be indicated for infected nonunion because the vascularised graft favours antibiotic diffusion

The aim of this paper is to present our experience from the surgical treatment of lower limb fractures in the developing skeleton with the use of bio-absorbable PLLA implants as a means of internal fixation. From 1997 until 2002, twenty-three patients (15 boys and 8 girls, ages ranging from 7 to 15 years old, mean of 12 years) who had suffered from 30 lower limb fractures were operated on in our department, with the use of PLLA screws as a means of internal fixation that followed the standard open reduction procedure. We surgically treated 20 tibial fractures (distal metaphysis:1,medial malleolar:6,distal epiphysis lesions:9,tibial spine:2, lateral tibial condyle:1, tibial shaft:1), 8 fibular fractures (distal metaphysis:2, distal epiphysis lesions:5, fibular shaft:1), one transtrochanteric fracture and 1 patellar fracture. All patients were operated on under constant radiographic control. A cast was applied, post-operatively, to all patients, for a period of 3–4 weeks. Gradual and assisted weight-bearing and ambulation, was commencing immediately after the cast removal. All patient’s (with the exception of 1 case of delayed callus formation) post-operative period was completely normal. However, follow-up revealed the development of osteolytic lesions (bone absorption cysts) in 3 of our patients. All lesions were located in the border between epiphysis and metaphysis, at the exact position were the PLLA screws had been placed. The use of PLLA implants in the treatment of fractures renders unnecessary a second operation for the removal of the osteosynthesis’ material. Nevertheless, we should be quite reluctant when deciding to use the PLLA screws in the treatment of these fractures in the developing skeleton, especially of the lower limbs, were the applied weight bearing forces are quite powerful

Introduction: A retrospective analysis was performed to determine the oncological outcome of patients with Ewing’s sarcoma of the spine treated with combined chemotherapy and radiotherapy for definitive local control. Materials and Methods: Fifteen patients were identified from the Scottish Bone Tumour Registry with a histologically confirmed Ewing’s sarcoma affecting the axial skeleton. All case notes and imaging were retrospectively reviewed. Results: Primary vertebral Ewing’s sarcoma accounted for 8.3% of all malignant spinal lesions in our registry. The mean age was 17.8 years (between 4 and 39 years). There was a male predilection with 9 male and 6 female patients. Site was evenly distributed between cervical (4), dorsal (5) and lumbosacral (6) regions. Progressively worsening back pain was the first symptom in all the patients. Satisfactory imaging studies were available in all with plain radiographs (15), bone scan (11), CT-scan (12) and MR Scan (9) patients. Biopsy was performed in 11 patients and surgical treatment was carried out in 3 patients including curettage (2) and excision with bone grafting (1). All patients were treated with adjuvant radiotherapy while 87% also received adjuvant chemotherapy. Seven patients were alive with no evidence of disease at a mean 6 year follow-up. Six patients died of metastatic disease, one due to local recurrence and one with persistent primary disease. The mean follow-up time was 65 months (median 28 months; ranging from 12 to 218 months). Conclusions: Primary vertebral Ewing’s sarcoma comprised 8.3% of our National Registry’s primary malignant spinal lesions. Progressive vertebral pain in the late second decade and male gender should raise the suspicion of Ewing’s sarcoma. Ewing’s sarcoma of the spine treated with combined chemotherapy and radiotherapy for definitive local control achieved a 45% five year survival

Purpose: The supracondylar fractures of the distal humerus are the second most frequent fractures of the developing skeleton. Also their immediate and late complications are very often. The aim of this study is to describe their neurological complications. Material – methods: In our department 178 children were admitted with supracondylar fracture of the distal humerus during the period 1998–2002. Their age ranged from 2 to 16 years of age (the average was 7 years old, 63 girls and 115 boys). Forty-six patients were treated conservatively and 132 surgically. Neurological complications were appeared in 18 patients that had, according to Gartland classification, II and III type fractures. Manipulations for closed reduction had been made to 6 of them. Neurological deficit of the median nerve appeared to 10 patients, of the radial nerve to 6 patients and of ulnar nerve to 2 patients. The treatment of the fractures was surgical (open reduction, internal fixation with Kirschner wires and immobilization with a long arm cast for 4 weeks). The treatment of the neurological complications was conservative (free mobilization of the elbow was followed after the removal of the arm cast and Kirschner’s wires). Results: The results of the conservative treatment of the neurological complications of the supracondylar fractures of the distal humerus were excellent and the surgical exploration on the injured nerve was not necessary on any patient. The function of the nerves recovered completely in 2–3 months after the elbow’s fracture. Conclusion: The prognosis on the neurological complications of the upper limbs due to supracondylar fracture of the distal humerus is very good. They are successfully treated conservatively and the surgical exploration on the injured nerve is rarely necessary

Bone metastases from renal cell carcinoma are aggressive, osteolytic lesions that often require operative intervention for fracture prophylaxis, fracture fixation or palliation. The lesions are hypervascular and intraoperative bleeding is a serious challenge for the orthopaedic surgeon. The purpose of this study was to determine the efficacy of preoperative tumour embolization in reducing blood loss during operative management of renal cell carcinoma metastases to bone. Patients were identified from a prospectively accumulated database (1996–2006). Inclusion criteria included operative management for renal cell metastasis to the pelvis or appendicular skeleton. Patients that were not embolised preoperatively due to renal insufficiency or obesity were excluded. Embolizations were performed the day of surgery by an interventional radiologist. Post-embolization runs were used to determine the percentage of blood flow reduction to the tumour. Variables analyzed included patient age, gender, location of tumour, surgical procedure, surgical time, number of units of packed red blood cells (PRBC) transfused, estimated intraoperative blood loss (EBL) and percentage embolised according to the post-embolization run. Student’s t-test was used to determine the effects of percentage embolization on EBL and number of units of transfused PRBCs. Thirty-five cases (twenty-eight patients) met the inclusion criteria. There were twenty males and eight females with an average age of sixty-five years (range, forty-three to eighty-nine years). The most common metastatic sites were the femur (nineteen cases), humerus (seven cases) and pelvis (six cases). There were ten cases of intramedullary nailing and twenty-five cases of tumor resection and reconstruction. Average surgical time was 4.5 hours (range, 0.75–10 hours) and average EBL was 1.5 litres (range, 0.25–12 litres). Embolization that successfully blocked at least 75% of the blood flow to the tumour significantly decreased surgical EBL (3.2 vs 0.6 litres, P< 0.05) and units of PRBCs transfused (5.6 vs 1.9, P=0.05) compared to those that did not. Two embolization-associated complications occurred including one case of toe gangrene and one case of muscle ischemia. Preoperative embolization significantly reduces blood loss and red blood cell transfusions resulting from surgical stabilization of renal cell metastases to bone. Close communication between the orthopaedic surgeon and interventional radiologist is imperative to maximise these benefits

Skeletal sequels of traumatisms, diseases or surgery often lead to bone defects that fail to self-repair. Although the gold standard for bone reconstruction remains the autologous bone graft (ABG), it however exhibits some drawbacks and bone substitutes developed to replace ABG are still far for having its bone regeneration capacity. Herein, we aim to assess a new injectable allogeneic bone substitute (AlloBS) for bone reconstruction. Decellularized and viro-inactivated human femoral heads were crushed then sifted to obtain cortico-spongious powders (CSP). CSP were then partly demineralized and heated, resulting in AlloBS composed of particles consisting in a mineralized core surrounded by demineralized bone matrix, engulfed in a collagen I gelatin. Calvarial defects (5mm in diameter, n=6/condition) in syngeneic Lewis1A rats were filled with CSP, AlloBS±TBM (total bone marrow), BCP (biphasic calcium phosphate)±TBM or left unfilled (control). After 7 weeks, the mineral volume/total volume (MV/TV) ratios were measured by µCT and Movat's pentachrome staining were performed on undemineralized frontal sections. The MV/TV ratios in defects filled with CSP, AlloBS or BCP were equivalent, whereas the MV/TV ratio was higher in AlloBS+TBM compared to CSP, AlloBS or BCP (p<0.01; Mann-Whitney). Histological analyses exhibited a collagen-rich matrix in all the defects, and osteoid at the surface of all implanted biomaterials. Our data indicates that AlloBS is a promising candidate for bone reconstruction, with ease of manipulation, injectability and substantial osteogenic capacity. Further experiments in larger animal models are under consideration to assess whether AlloBS may be a relevant clinical alternative to ABG.

Bone reconstruction in pediatric oncology always has to face two major problems: the frequent unavailability of small prosthetic tools and the difficulty in finding bone allografts of adequate size.

Aim of this work is to present the research lines in this field, currently active in our institution to improve the planning and the results of reconstructive tumor surgery in children. Starting from patient’s CT data sets, subject-specific 3D models of bone segments can be created and compared with the similar models obtained by the CT analysis of massive allografts stored in the Rizzoli Bone Bank.

In the same time the computer modelling technologies allow the development of three-dimensional environment, where the surgeon can navigate and exploit both artificial (prostheses, metallic plates and screws) or biological tools (bone allografts or autografts).

The presented method has been utilized with success in 10 children (mean age 8, range 4–13) that underwent a skeletal reconstruction of the limbs in the last year (proximal humerus 1, diaphyseal humerus 1, total humerus 1, distal radius 1, proximal femur 3, diaphyseal femur 1, proximal tibia 1, diaphyseal tibia

The primary aim of this study was to compare the clinical outcomes of osteoid osteoma (OO) between the group of patients with the presence of nidus on biopsy samples from radiofrequency ablation (RFA) with those without nidus. Secondly, we aimed to examine other factors that may affect the outcomes of OO reflecting our experience as a tertiary orthopaedic oncology centre. We retrospectively reviewed 88 consecutive patients diagnosed with OO treated with RFA between November 2005 and March 2015, consisting of 63 males (72%) and 25 females (28%). Sixty-six patients (75%) had nidus present in their biopsy samples. Patients’ mean age was 17.6 years (4-53). Median duration of follow-up was 12.5 months (6-20.8). Lesions were located in the appendicular skeleton in seventy-nine patients (90%) while nine patients (10%) had an OO in the axial skeleton. Outcomes assessed were based on patients’ pain alleviation (partial, complete, or no pain improvement) and the need for further interventions. Pain improvement in the patient group with nidus in histology sample was significantly better than the group without nidus (OR 7.4, CI 1.35-41.4, p=0.021). The patient group with nidus on biopsy demonstrated less likelihood of having a repeat procedure compared to the group without nidus (OR 0.092, CI 0.016-0.542, p=0.008). Our study showed significantly better outcomes in pain improvement in appendicular lesions compared to the axially located lesions (p = 0.005). Patients with spinal lesions tend to have relatively poor pain relief than those with appendicular or pelvic lesions (p=0.007). Patients with nidus on histology had better pain alleviation compared to patients without nidus. The histological presence of nidus significantly reduces the chance of repeat interventions. The pain alleviation of OO following RFA is better in patients with appendicular lesions than spinal or axially located lesions

Total joint replacement (TJR) was one of the most revolutionary breakthroughs in joint surgery. The majority studies had shown that most implants could last about 25 years, anyway, there is still variation in the longevity of implants. In US, for all the hip revisions from 2012 to 2017 in the United States, 12.0% of the patients were diagnosed as aseptic loosening. Variable studies have showed that any factor that could cause a systemic or partial bone loss, might be the risk of periprosthetic osteolysis and aseptic loosening. Breast cancer is the most frequent malignancy in women, more than 2.1 million women were newly diagnosed with breast cancer, 626,679 women with breast cancer died in 2018. It's been reported that the mean incidence of THA was 0.29% for medicare population with breast cancer in USA, of which the incidence was 3.46% in Norwegian. However, the effects of breast cancer chemotherapy and hormonotherapy, such as aromatase inhibitors (AI), significantly increased the risk of osteoporosis, and had been proved to become a great threat to hip implants survival. In this case, a 46-year-old female undertook chemotherapy and hormonotherapy of breast cancer 3 years after her primary THA, was diagnosed with aseptic loosening of the hip prosthesis. Her treatment was summarized and analyzed. Breast cancer chemotherapy and hormonotherapy might be a threat to the stability of THA prosthesis. More attention should be paid when a THA paitent occurred with breast cancer. More studies about the effect of breast cancer treatments on skeleton are required

Anatomically, bone consists of building blocks called osteons, which in turn comprise a central canal that contains nerves and blood vessels. This indicates that bone is a highly innervated and vascularized tissue. The function of vascularization in bone (development) is well-established: providing oxygen and nutrients that are necessary for the formation, maintenance, and healing. As a result, in the field of bone tissue engineering many research efforts take vascularization into account, focusing on engineering vascularized bone. In contrast, while bone anatomy indicates that the role of innervation in bone is equally important, the role of innervation in bone tissue engineering has often been disregarded. For many years, the role of innervation in bone was mostly clear in physiology, where innervation of a skeleton is responsible for sensing pain and other sensory stimuli. Unraveling its role on a cellular level is far more complex, yet more recent research efforts have unveiled that innervation has an influence on osteoblast and osteoclast activity. Such innervation activities have an important role in the regulation of bone homeostasis, stimulating bone formation and inhibiting resorption. Furthermore, due to their anatomical proximity, skeletal nerves and blood vessels interact and influence each other, which is also demonstrated by pathways cross-over and joint responses to stimuli. Besides those closely connected sytems, the immune system plays also a pivotal role in bone regeneration. Certain cytokines are important to attract osteogenic cells and (partially) inhibit bone resorption. Several leukocytes also play a role in the bone regeneration process. Overall, bone interacts with several systems. Aberrations in those systems affect the bone and are important to understand in the context of bone regeneration. This crosstalk has become more evident and is taken more into consideration. This leads to more complex tissue regeneration, but may recapitulate better physiological situations

The Cierny and Mader classification assists with decision-making in the management of osteomyelitis by strafying the host status and the pathoanatomy of disease. However the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08– 8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistical significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time

Introduction. The Cierny and Mader classification assists with decision-making by stratifying host status and the pathoanatomy of the disease. However, the anatomical type IV represents a heterogenous group with regards to treatment requirements and outcomes. We propose that modification of the Cierny and Mader anatomical classification with an additional type V classifier (diffuse corticomedullary involvement with an associated critical bone defect) will allow more accurate stratification of patients and tailoring of treatment strategies. Materials & Methods. A retrospective review of 83 patients undergoing treatment for Cierny and Mader anatomical type IV osteomyelitis of the appendicular skeleton at a single centre was performed. Results. Risk factors for the presence of a critical bone defect were female patients (OR 3.1 (95% CI 1.08–8.92)) and requirement for soft tissue reconstruction (OR 3.35 (95% CI 1.35–8.31)); osteomyelitis of the femur was negatively associated with the presence of a critical bone defect (OR 0.13 (95% CI 0.03–0.66)). There was no statistically significant risk of adverse outcomes (failure to eradicate infection or achieve bone union) associated with the presence of a critical-sized bone defect. The median time to bone union was ten months (95% CI 7.9–12.1 months). There was a statistically significant difference in the median time to bone union between cases with a critical bone defect (12.0 months (95% 10.2–13.7 months)) and those without (6.0 months (95% CI 4.8–7.1 months)). Conclusions. This study provided evidence to support the introduction of a new subgroup of the Cierny and Mader anatomical classification (Type V). Using a standardised approach to management, comparable early outcomes can be achieved in patients with Cierny and Mader anatomical type V osteomyelitis. However, to achieve a successful outcome, there is a requirement for additional bone and soft tissue reconstruction procedures with an associated increase in treatment time

The burden of metastatic disease presenting with axial skeleton lesions is exponentially rising predominantly due to advances in oncological therapies. A large proportion is these lesions are located in the proximal femora, which given its unique biomechanical architecture is problematic. These patients are frequently comorbid and require prompt and concise decision making regarding their orthopaedic care in line with recent British Orthopaedic Association guidelines. We present data detailing the outcomes for patients with proximal femoral metastatic disease referred and treated over a three year period in an Regional Cancer Centre. We retrospectively reviewed a prospectively maintained database of all patients referred for discussion at MDT with axial skeletal metastatic disease. From this we isolated patients with femoral disease. Demographic data along with primary tumour and metastatic disease site were assessed. Treatment regimens were analysed and compared. Finally predicted and actual mortality data was collated. 331 patients were referred over the analysed time period, of which 99 had femoral disease. 66% of patients were managed conservatively with serial monitoring while 34% underwent operative treatment. 65% of those received an intramedullary fixation while 35% had arthroplasty performed. There was a 51:49 split male to female with Prostate, Lung and Breast being the predominant primary tumours. Concurrent spinal metastatic disease was noted in 62% of patients while visceral mets were seen in 37%. Mortality rate was 65% with an average prognosis of 388 days (1.06years) while average mortality was noted within 291 days (0.8 years). Proximal femoral metastatic disease accounts for a large volume of the overall mets burden. There is an overall tendency towards conservative management and of those requiring surgery IM nailing was the treatment of choice. The data would indicate that outcomes for these patients are guarded and on average worse than those predicted

Introduction. Promoting bone mass homeostasis keeps skeleton away from osteoporosis. a-Ketoglutarate (a-KG) is an indispensable intermediate of tricarboxylic acid cycle (TCA) process for cellular energy production. a-KG mitigates cellular senescence, tissue degeneration, and oxidative stress. We investigated whether a-KG affected osteoblast activity or osteoporosis development. Method. Serum and bone specimens were biopsied from 26 patients with osteoporosis or 24 patients without osteoporosis who required spinal surgery. Ovariectomized or aged mice were fed 0.25% or 0.75% a-KG in drinking water for 8 – 12 weeks ad libitum. Bone mineral density, trabecular/cortical bone microarchitecture, mechanical strength, bone formation, and osteoclastic erosion were investigated using mCT, material testing device, in vivo calcein labelling, and TRAP histochemical staining. Serum a-KG, osteocalcin, and TRAP5b levels were quantified using ELISA kits. Bone-marrow mesenchymal cells and macrophages were incubated osteogenic and osteoclastogenic media. Histone H3K27me3 levels and enrichment were investigated using immunoblotting and chromatin precipitation-PCR. Result. Serum a-KG levels in patients with osteoporosis were less than controls; and were correlated with T-scores of hips (R2 = 0.6471, P < 0.0001) and lumbar spine (R2 = 0.7235, P < 0.001) in osteoporosis (AUC = 0.9941, P < 0.001). a-KG supplement compromised a plethora of osteoporosis signs in ovariectomized or aged mice, including bone mass loss, trabecular bone microarchitecture deterioration, and mechanical strength loss. It elevated serum osteocalcin levels and decreased serum TRAP5b. a-KG preserved caclein-labelling bone formation and repressed osteoclast resorption. It reversed osteogenic differentiation of bone-marrow stromal cells and reduced osteoclast formation in ovariectomized mice. Mechanically, a-KG attenuated H3K27 hypermethylation and Runx2 transcription repression, improving mineralized matrix production in osteogenic cells. Conclusion. Decreased serum a-KG is correlated with human and murine osteoporosis. a-KG reverses bone loss by repressing histone methylation in osteoblasts. This study highlighted a-KG supplement as a new biochemical option for protecting osteoporosis

Fatty marrow and bone loss are prominent pathologic features of osteoporosis. DNA hypermethylation shifts mesenchymal stem cells towards adipocytes impairing bone formation. Brown adipocytes produce growth factors advantageous to osteogenesis, whereas white adipocytes secrete pro-inflammatory cytokines deleterious to bone homeostasis. We assess DNA methylation inhibitor action to brown and white adipocyte formation in marrow fat of osteoporotic skeletons. Osteoporotic skeletons in mice were induced by glucocorticoid, ovariectomy or ageing. Marrow adipose volume and bone structure were quantified using OsO4 contrast-μCT imaging. Brown and white adipocytes were probed using immunostaining, RT-PCR and primary bone-marrow mesenchymal stem cell cultures. Abundant marrow fat and spare trabecular bone existed in osteoporotic skeletons. Osteoporosis increased expressions of general adipogenic markers PPARγ2 and FABP4 and white adipocyte markers TCF21 and HOXc9, whereas expressions of brown adipocyte markers PGC-1α and UCP-1 and osteogenic markers Runx2 and osteocalcin were significantly decreased. Number of UCP-1 immunostaining-positive brown adipocytes also reduced in osteoporotic bone. In vitro, DNA methylation inhibitor 5'-aza-deoxycystidine significantly increased brown adipocyte formation and osteogenic differentiation and mitigated dexamethasone-induced white adipocyte formation in mesenchymal stem cells. 5'-aza-deoxycystidine control of brown adipogenesis and white fat formation appeared to be regulated by increasing Wnt3a/β-catenin and reducing Dkk1. Disintegrated brown adipocyte and white fat cell differentiation contribute to osteoporosis pathogenesis. Maintaining DNA hypomethylation promotes Wnt signalling and brown adipocyte differentiation facilitating osteogenic differentiation. This study shed a new light to the contribution of brown adipocytic cells to bone metabolism during osteoporosis