Introduction

Pin-tract infections are a common problem in orthopaedic surgery, which limits the time an external fixator or Taylor spatial frame can be applied to a patient. The purpose of our study is to evaluate the ability of a novel implant surface coating — cationic steroid antibiotic (CSA)-44 — to delay or prevent the onset of these infections. This coating mimics endogenous antimicrobial peptides of the innate immune system and has been shown to effectively eradicate biofilms as well as prevent infection and stimulate healing of open, contaminated fractures.

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.

There has been evidence of association between femoral shaft fractures and prolonged bisphosphonate therapy. We present a case series of bisphosphonate-associated fractures and invaluable lessons we have learnt.

Over the last three years at our unit we have collected a case series of eight patients who have had atypical femoral fractures whilst on bisphosphonate therapy. We present illustrative cases, a summary of key findings, and invaluable lessons we have learnt.

There was a long period of prodromal pain for two years before incomplete fractures developed. We speculate this is a warning sign of impending fracture. This may have been prevented with screening. Between incomplete fracture and complete fracture there was a short window of one month. Five patients presented with complete fracture, and three with thigh pain +/- evidence of incomplete fracture. Of the latter group all but one went on to develop complete fractures. The one patient who did not progress died six years after diagnosis. Of those five patients who presented with initial complete fracture, three patients recall thigh pain before fracture on further questioning. Despite being diaphyseal femoral fractures, there is a higher risk of neck of femur fractures in this patient cohort (both patients with initial interlocked nails subsequently developed neck of femur fractures soon after and were revised to cephalomedullary nails). Excluding one death from unrelated cause, only one patient has signs of complete fracture healing. All other patients are still receiving follow-up (mean 490 days). Three patients reported bilateral symptoms (pain). Two had had bilateral symptoms for one year. Both had visible incomplete fractures on further radiographic scrutiny; one underwent prophylactic cephalomedullary nailing, one was managed with active surveillance.

We suggest that improved pain and radiographic changes of cortical healing may be misleading and should not be relied upon. Cephalomedullary nailing is the treatment of choice in these fractures due to higher risk of neck of femur fractures in this cohort. We suggest prompt prophylactic cephalomedullary nailing when radiographic incomplete fractures are identified due to a short window before progression to complete fracture, and the need to consider contralateral prophylactic nailing in patients describing bilateral symptoms. We speculate that thigh pain is a warning sign of impending fracture and fracture-progression can be prevented with appropriate screening.

Optimal surgical management of proximal humeral fractures remains controversial. We report our experience and the study on our surgical technique for proximal humeral fractures and fracture-dislocations using locking plates in conjunction with calcium sulphate augmentation and tuberosity repair using high strength sutures. We used the extended deltoid-splitting approach for fracture patterns involving displacement of both lesser and greater tuberosities and for fracture-dislocations.

We retrospectively analysed 22 proximal humeral fractures in 21 patients. 10 were male and 11 female with an average age of 64.6 years (Range 37 to 77). Average follow-up was 24 months. Fractures were classified according to Neer and Hertel systems. Pre-operative radiographs and CT scans in three and four-part fractures were done to assess the displacement and medial calcar length for predicting the humeral head vascularity. According to the Neer classification, there were 5 two-part, 6 three-part, 5 four-part fractures and 6 fracture-dislocations (2 anterior and 4 posterior). Results were assessed clinically with DASH scores, modified Constant & Murley scores and serial post-operative radiographs.

The mean DASH score was 16.18 and modified Constant & Murley score was 64.04 at the last follow-up. 18 out of 22 cases achieved good clinical outcome. All the fractures united with no evidence of infection, failure of fixation, malunion, tuberosity failure, avascular necrosis or adverse reaction to calcium sulphate bone substitute. There was no evidence of axillary nerve injury. The CaSO4 bone substitute was replaced by normal appearing trabecular bone texture at an average of 6 months in all patients.

Physical activity is a key determinant of bone mass and health, however during adulthood and ageing there appears to be a decrease in the ability to respond positively to exercise which is variable between individuals. While exercise is known to protect against the osteopo-rotic process with modest increases in BMD the exact cellular and molecular responses are poorly understood.

We have studied the effect of mechanical stimulation on bone histomorphometric parameters, osteocyte viability and gene expression in human trabecular bone maintained in a 3D bioreactor.

Trabecular bone cores were prepared from femoral head tissue removed from patients undergoing total hip arthroplasty and maintained in the bioreactor system for 3 (n= 4 patients), 7 (n=5 patients) or 28 days (n=1 patient). Cores (n=3 per patient) were either frozen directly on preparation (T0), placed in the bioreactor system and subjected to Mechanical stimulation (3000 μstrain in jumping exercise waveform repeated at 1Hz for 5 minutes daily) or maintained in the bioreactor system with no mechanical stimulation as control. After the experimental period total cell numbers, cell viability and apoptosis were determined in un-decalcified cryosections at specific distances throughout the bone cores by nuclear staining (DAPI), lactate dehydrogenase activity (LDH) and Nick Translation Assay respectively. Consecutive sections were collected and RNA extracted for gene expression analysis.

Mechanical stimulation was shown to increase Bone Formation Rate (BFR) as determined by Calcein label/ distance to bone surface in the 28 day experiment (BFR mcm/day Control 0.01 ± 0.0035 vs Load 0.055 ± 0.0036 p=0.0022). Expression of bone formation markers such as Alkaline Phosphatase and Collagen Type I was shown to increase in all patients however there was an individual variation in the response of Osteopontin to mechanical stimulation as determined by quantitative real time PCR expression analysis. Numbers of viable osteocytes at T0 varied between individual patients however viability was significantly increased and apoptosis decreased in association with mechanical stimulation compared to control in all patient samples examined (p to 0.021). Our data tend to support animal model findings relating to the osteocyte saving effects of exercise and provide an insight into the molecular detail of the exercise response in human bone.

Over 1 million fractures occur each year in the UK. Approximately 5-10% of these fractures have problems with healing. The treatments used for these patients often have a poor outcome and are associated with increased morbidity and disability. Application of synthetic peptides such as thrombin degradation peptide (TP508) has been shown to accelerate fracture repair in a closed rat femoral fracture model. Controlled release of TP508 using microspheres has been shown to enhance repair of articular cartilage defects and stimulate bone formation in segmental defects in rabbits. The aim of this study was to determine whether TP508 could bring about healing in an established fracture non-union model.

A validated rat model of fracture non-union was used. The model was created and left for 8 weeks in order to represent a clinically equivalent model of a non union of a fracture. Rats were randomised into two treatment groups receiving 10microg and 1microg doses of TP508 diluted in 50microL of microspheres and delivered directly to the non union site using percutaneous injection 8 weeks after surgery. The control group received no treatment. At 16 weeks post-surgery, osseous bridging was assessed both radiographically and histologically.

Radiographically there was no difference between the control and two treatment groups. However, histomor-phometric analysis demonstrated that bone formation increased by 43.9% in animals that received high dose of TP508 compared to the control animals. The analysis also indicated that administration of the low dose of TP508 increased the amount of bone formation compared to the control by 9.9 %.

Administration of TP508 has been shown to enhance healing of segmental defects in both critically and noncritically sized defects. However, in our model which is an established fracture non-union model, TP508 did not manage to achieve full osseous union. It has been suggested that the action of this peptide is concentration and environment dependent possibly indicating that TP508 might be less effective when administered in a chronic situation such as that associated with the established non-union fracture. However, even in this sub-optimal situation an increased amount of bone formation was observed.

Introduction: Oxidative stress occurs when reactive oxygen species (ROS) are produced faster than they can be removed by cellular defence mechanisms contributing to ageing, many chronic diseases, such as atherosclerosis, RA, Parkinson and Alzheimer’s disease and skeletal pathologies. Here we address the impact of ROS on the viability of early osteogenic precursors in the bone marrow and study the influence of estrogen on this interaction. Cells have a number of mechanisms to protect themselves from ROS, which are constantly being formed in the cell through normal metabolic pathways, such as Vitamin E, C and estrogen. Estrogen has been shown to prevent intracellular accumulation of peroxide and to attenuate oxidant-induced death of neuronal and endothelial cells. In addition, it contributes significantly to bone turnover and relieves postmenopausal symptoms. This study has focused on the potential anti-oxidant properties of estrogen against oxidative on bone marrow stromal cells. stress induced by H₂O₂

Methods: Primary bone marrow stromal cells were pre-treated with several different doses between 10⁻⁶M – 10⁻⁸M of estrogen prior to H₂O₂ administration at 0.08–0.4 mM 30% (v/v) for 2–24h. The cellular production of ROS was determined by using the free radical indicator DCFH-DA. Apoptosis was determined by morphological criteria.

Results: H₂O₂ induced an increase in apoptosis of osteoprogenitor cells (p< 0.05). Determination of apoptosis and cell number by nuclear staining, indicated that pre-treatment of bone marrow stromal cells with 17-beta estradiol reduced the apoptotic response induced by H₂O₂ (p< 0.05) and restored cell number to control levels. In order to test the anti-oxidant activity of estrogen, the dye DCFH-DA was introduced in a cell free system in the presence or absence of 17-beta estradiol and H₂O₂. The same experiment was repeated in the presence of bone marrow stromal cells. H₂O₂ increased both intracellularly and extracellularly oxidant activity and estradiol has the capacity of modifying this activity both inside and outside the cell.

Discussion: These data demonstrate the ability of estrogen, used at physiological doses, to block oxidant-induced apoptosis of osteoprogenitor cells. Estrogen appears to reduce the generation of ROS in these cells. These data could have important implications on the maintenance of osteogenic stem cells during fractures, ageing and disease.