We have developed a novel technique to analyse bone, using imaging mass cytometry (IMC) without the constraints of using immunofluorescent histochemistry. IMC can measure the expression of over 40 proteins simultaneously, without autofluorescence. We analysed mitochondrial respiratory chain (RC) protein deficiencies in human bone which are thought to contribute to osteoporosis with increasing age.

Osteoporosis is characterised by reduced bone mineral density (BMD) and fragility fractures. Humans accumulate mitochondrial mutations and RC deficiency with age and this has been linked to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of 30 onwards, coincidently the age BMD begins to decline. Mitochondria contain their own genome which accumulates somatic variants at around 10 times the rate of nuclear DNA. Once these mutations exceed a threshold, RC deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model expresses a proof-reading deficient version of PolgA, a mtDNA polymerase. These mice accumulate mutations 3-5 times higher than wild-type mice showing enhanced levels of age-related osteoporosis and RC deficiency in osteoblasts.

Bone samples were analysed from young and old patients, developing a protocol and analysis framework for IMC in bone tissue sections to analyse osteoblasts in-situ for RC deficiency.

Samples from the femoral neck of 10 older healthy volunteers aged 40 – 85 were compared with samples from young patients aged 1-19. We have identified RC complex I defect in osteoblasts from 6 of the older volunteers, complex II defects in 2 of the older volunteers, complex IV defect in just 1 older volunteer, and complex V defect in 4 of the older volunteers.

These observations are consistent with the PolgD257A/D257A mouse-model and suggest that RC deficiency, due to age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis.

Background

There is significant variation and inconsistencies in the current advice and information delivered to patients undergoing total hip replacement (THR). The aim of this study was to assess a locally developed web-based electronic resource system for patients undergoing total hip replacement (THR) surgery to see if this improves and standardises the content, structure, and delivery of information delivered to patients prior to and after surgery.

The pathogenesis of falling bone mineral density (BMD) as a universal feature of advancing age is poorly understood¹. Frequently culminating in the development of osteoporosis, the process is attributable to more than 500,000 fragility fractures occurring every year in the UK Such injuries are associated with great levels of morbidity, mortality and a £3.5 billion cost to the healthcare economy².

With age, humans are known to accumulate somatic mitochondrial DNA (mtDNA) mutations in mitotic and post mitotic tissue, and stem cell precursors³. Compelling evidence in recent years, particularly that provided by animal models suggests that these mutations are intrinsic to the ageing process^4–6. We provide evidence for the first time that mitochondrial dysfunction contributes significantly to the failure of bone homeostasis and falling BMD.

We have utilised a mouse model that accumulates mtDNA mutations at 3–5 times the rate of normal mice, consequently ageing and developing osteoporosis prematurely⁷, to clearly demonstrate that osteoblasts are vulnerable to mtDNA mutations. We have developed a new quadruple immunofluorescent assay to show that mitochondrial respiratory chain dysfunction occurs in osteoblasts as a consequence (p < 0.0001). We show that this mitochondrial dysfunction is associated with reduced BMD in female and male mice by 7 (p = 0.003) and 11 (p = 0.0003) months of age respectively. Using osteoblasts derived from mesenchymal stem cells extracted from male and female mice with mitochondrial dysfunction aged 4, 7 and 11 months, we demonstrate a vastly reduced capacity to produce new mineralised bone in vitro when compared to wild type cell lines (p < 0.0001). Exercise was found to have no beneficial effect on osteoblast and whole bone phenotype in this mouse model. It is likely that mtDNA mutations accumulating over a longer time period in human ageing have significantly detrimental effects on bone biology and diminishing BMD.

Background: Perioperative red cell salvage may be of use in cases where significant blood loss is likely. The purpose of this investigation was to see if its use in revision hip surgery led to a reduction in homologous blood transfusion requirement.

Methods: 48 patients were identified who had undergone revision hip surgery with the use of a Cell Saver device for perioperative autologous transfusion. Patients were individually matched to control patients who had undergone revision hip surgery without the Cell Saver. Patients were matched for age, sex and eight operative variables, which were chosen to indicate the type of revision surgery and possible level of blood loss, to ensure that the groups were comparable. Total homologous transfusion requirement in both groups was recorded as well as pre and post-operative haemoglobin levels.

Results: The groups were well matched for age, sex and operative variables. The total homologous transfusion requirement was significantly lower in the Cell Saver group than the control group (mean 2.6 v 6.4 units of packed cells respectively, p 0.0006). There was no difference in pre-operative haemoglobin between the groups but it was lower in the Cell Saver group post-operatively (Cell Saver 10.1g/dl v Control 10.6g/dl, p 0.06). There was no difference in length of operation.

Conclusions: Use of perioperative red cell salvage was associated with significantly lower homologous transfusion requirement. This is the first study looking at the use of perioperative red cell salvage in revision hip surgery with matching of patients on the basis of operative variables. A cost analysis shows that use of the Cell Saver has significant financial advantage in these patients.

Introduction and Aims: Despite comprehensive literature on knee arthroplasty outcomes there is a paucity of data on patient satisfaction and functional outcomes. We have examined patient satisfaction, function, and time to return to sport and activities of daily living.

Method: A retrospective cohort study using self-assessment forms reviewed all patients who had undergone an Oxford uni-compartmental knee replacement in one centre from 2000 to 2003 at a minimum one-year post-surgery. One hundred and fifty patients with 183 UKRs were reviewed. Twenty-two had bilateral surgery. The cohort contained 76 males and 74 females of mean age 71.5 years (range 52–90). Patients were assessed using the Oxford knee score and a further score of how ‘normal’ their knee felt. Physical activity was assessed according to Grimby’s scale. Sporting activity was assessed with regards to pre- and post-operative frequency, time taken to return to sport, and pain during and after exercise. Time to return to work was also noted.

Results: Mean Oxford knee score for males was 21.6 (range 12–43, SD 8.25) and females 22.8 (range 12–54, SD 9.78). Mean Grimby’s score for males was 4.1 (range 1–6, SD 1.2) and for females 3.6 (range 1–6, SDI.2). Mean time to return to walking as exercise was 7.9 weeks (range 1–47.6, SD 8.9), to swimming was 10 weeks (range 1–34.6, SD 9.9), to cycling 11.8 weeks (range 1–34.7, SD 11) to lawn bowling 24.5 weeks (range 4–104, SD 26.2) and golf 12.3 weeks (range 3–33.3, SD8.73). Return to sport, activities of daily living and return to work positively correlated to the patients’ perception of how ‘normal’ their knee felt.

Conclusion: This study observes activity levels and times to return to ADLs, work and sport that is a guide for patient education and post-operative expectation. When compared to a recent study of total knee arthroplasty patients from our institution the uni-compartmental patients were more satisfied and more active. Patients were more active pre-operatively and post-operatively, they were less likely to give up sport following surgery.

Introduction This study was conducted in order to evaluate the patterns of utilization of arthroscopic knee debridement for the treatment of degenerative arthritis and the five years outcome following an initial arthroscopic procedure at our institution.

Methods This is a retrospective study on all patients with degenerative arthritis of the knee who had their first arthroscopic debridement between 1992 and 1995, and had a follow-up of at least five years or ended up with total knee replacement (TKR). Patients with other prior surgery to the knee were excluded. The patients were divided into four groups based on the first arthroscopic finding using the Outerbridge grading system (Stage I: Softening, II: Fibrillation, III: Fragmentation, IV: Eburnation). The clinical status following the first arthroscopy and during the last follow-up were evaluated. The duration between the first arthroscopic debridement and TKR were also taken into account. Two hundred and two cases were included in the study which consists of 114 male and 88 female with mean age of 58.7 years. The mean follow-up was 5.4 years. There were 15 cases in stage I, 96 in stage II, 58 in stage III and 33 in stage IV.

Results Following the first arthroscopic debridement, 93.7% of patients in stage I and II became asymptomatic compared to 26.4% in stage III and in IV where 60.4% still presented with recurrent symptoms. On the last follow-up, 18.9% in stage I and II had total knee replacement done compared to 78.0% in stage III and IV. The mean duration between the first arthroscopic debridement and TKR was 8.6 years in stage II, 3.3 years in stage III and 1.5 years in stage IV.

Conclusions This study has shown that given the proper selection of patients and the correct stage of degenerative arthritis, arthroscopic debridement can still be a successful palliative, temporizing treatment for the osteoarthritic knee. It is of utmost importance that the patient’s pre-operative expectations have to be clearly objectified.

The effect of screw geometry on the pullout strength of Anterior Cruciate Ligament [ACL] reconstruction is well documented. Most research has looked at the effect of screw length and diameter, however other factors such as the degree of taper may also be important. Tapered screws should in theory be associated with increased pullout strength. This has not been demonstrated either clinically or in vitro before. The aim of this study was to compare the pullout strength of ACL reconstruction with a parallel against a tapered screw.

A parallel and tapered screw were manufactured which were identical in all other respects. Sixty superficial digital flexors from the hind legs of sheep were harvested. The tendons were paired and combined to form a quadruple tendon reconstruction of approximately 7mm diameter as measured with graft sizer. An ACL reconstruction was performed on the proximal tibia of 30 bovine knees, which had been harvested in right and left knee pairs, using the quadruple tendon. Fifteen reconstructions were fixed using tapered screws and fifteen with non-tapered screws. The insertion torque of both tapered and non tapered screws were recorded using an instrumented torque screwdriver. The reconstructions were mounted in an Instron materials testing machine with an x-ray bearing system to eliminate horizontal forces, to ensure that the forces were all directed along the line of the tibial tunnel. The maximum pullout strengths were recorded in each case. Five knee pairs were subjected to bone densitometry scanning to ensure that any difference in pull out strength was not due to changes in bone density between right and left knee pairs.

Results indicated that there was no difference between right and left knee pairs [p = 0.58] and that tapered screws were associated with significantly higher pull-out strengths [p=0.007] and insertion torques [p = 0.001].