A. Hamish R. W. Simpson

Osmolarity influences chondrocyte death in wounded articular cartilage

BACKGROUND Mechanical injury results in chondrocyte death in articular cartilage. The purpose of the present study was to determine whether medium osmolarity affects chondrocyte death in injured articular cartilage. METHODS Osteochondral explants (n = 48) that had been harvested from the metacarpophalangeal joints of three-year-old cows were exposed to media with varying osmolarity (0 to 480 mOsm) for ninety seconds to allow in situ chondrocytes to respond to the altered osmotic environment. Explants were then wounded with a scalpel through the full thickness of articular cartilage, incubated in the same media for 2.5 hours, and transferred to 340-mOsm Dulbeccos Modified Eagle Medium (control medium) with further incubation for seven days. The spatial distribution of in situ chondrocyte death, percentage cell death, and marginal cell death at the wounded cartilage edge were compared as a function of osmolarity and time (2.5 hours compared with seven days) with use of confocal laser scanning microscopy. RESULTS In situ chondrocyte death was mainly localized to the superficial tangential zone of injured articular cartilage for the range of medium osmolarities (0 to 480 mOsm) at 2.5 hours and seven days. Therefore, a sample of articular cartilage from the superficial region (which included the scalpel-wounded cartilage edge) was studied with use of confocal laser scanning microscopy to compare the effects of osmolarity on percentage and marginal cell death in the superficial tangential zone. Compared with the control explants exposed to 340-mOsm Dulbeccos Modified Eagle Medium, percentage cell death in the superficial tangential zone was greatest for explants exposed to 0-mOsm (distilled water) and least for explants exposed to 480-mOsm Dulbeccos Modified Eagle Medium at 2.5 hours (13.0% at 340 mOsm [control], 35.5% at 0 mOsm, and 4.3% at 480 mOsm; p <or= 0.02 for paired comparisons) and seven days (9.9% at 340 mOsm [control], 37.7% at 0 mOsm, and 3.5% at 480 mOsm; p <or= 0.01 for paired comparisons). Marginal cell death in the superficial tangential zone decreased with increasing medium osmolarity at 2.5 hours (p = 0.001) and seven days (p = 0.002). There was no significant change in percentage cell death from 2.5 hours to seven days for explants initially exposed to any of the medium osmolarities. CONCLUSIONS Medium osmolarity significantly affects chondrocyte death in wounded articular cartilage. The greatest chondrocyte death occurs at 0 mOsm. Conversely, increased medium osmolarity (480 mOsm) is chondroprotective. The majority of cell death occurs within 2.5 hours, with no significant increase over seven days.

Comparative outcomes of total hip and knee arthroplasty: a prospective cohort study

Purpose The comparative outcome of primary hip and knee arthroplasty is not well understood. This study aimed to investigate the outcome and satisfaction of these procedures and determine predictive models for 1 year patient outcome with a view to informing surgical management and patient expectations. Study design Prospective cohort study of all primary hip and knee arthroplasty procedures performed at the Royal Infirmary of Edinburgh between January 2006 and November 2008. General health (SF-12) and joint specific function (Oxford Score) was assessed pre-operatively and at 6 and 12 months post-operatively. Patient satisfaction was assessed at 12 months. Results 1410 total hip arthroplasty (THA) and 1244 total knee arthroplasty (TKA) procedures were assessed. Oxford Score improved by 4.9 points more in THA patients than in TKA patients. SF-12 physical scores were on average 2.7 points greater in the THA patients at one year. Satisfaction was also greater (91%) following THA compared with TKA (81%). Regression modelling was not able to predict individual patient outcome; however, mean pre-operative Oxford Scores were found to be strong predictors of mean post-operative Oxford Scores for each procedure. Age, gender and pre-operative general health scores did not influence these models. Conclusions Both THA and TKA confer substantial improvement in patient outcome; however, greater joint specific, general health and satisfaction scores are reported following THA. This difference is physical in nature. Regression models are presented that can be applied to predict mean hip/knee arthroplasty outcome based on preoperative values.

The importance of lag screw position for the stabilization of trochanteric fractures with a sliding hip screw: A subject-specific finite element study†

Using finite element analysis, we compared the biomechanical performance of a CT scan‐based three‐part trochanteric fracture model (31‐A2 in the AO classification) stabilized with a sliding hip screw for nine different positions of the lag screw (3 × 3 arrangement, from anterior to posterior and from inferior to superior). Our results showed that the volume of bone susceptible to yielding in the head and neck region is the lowest for inferior positions and increases as the lag screw is moved superiorly. Overall, for this specific subject, the models less likely to lead to cut‐out are the ones corresponding to inferior middle and inferior posterior positions of the lag screw. In our study, the tip‐apex distance (TAD) was anti‐correlated with the risk of cut‐out, as quantified by the volume of bone susceptible to yielding, which suggests that a TAD >25 mm cannot be considered to be an accurate predictor of lag screw cut‐out. Further clinical studies investigating lag screw cut‐out should attempt to find more reliable predictors of cut‐out that should better reflect the biomechanics and subject‐specificity of the femoral head.

Does screw-bone interface modelling matter in finite element analyses?

The effect of screw-bone interface modelling strategies was evaluated in the setting of a tibial mid-shaft fracture stabilised using locking plates. Three interface models were examined: fully bonded interface; screw with sliding contact with bone; and screw with sliding contact with bone in an undersized pilot hole. For the simulation of the last interface condition we used a novel thermal expansion approach to generate the pre-stress that the bone would be exposed to during screw insertion. The study finds that the global load-deformation response is not influenced by the interface modelling approach employed; the deformation varied by less than 1% between different interaction models. However, interface modelling is found to have a considerable impact on the local stress-strain environment within the bone in the vicinity of the screws. Frictional and tied representations did not have significantly different peak strain values (<5% difference); the frictional interface had higher peak compressive strains while the tied interface had higher tensile strains. The undersized pilot hole simulation produced the largest strains. The peak minimum principal strains for the frictional interface were 26% of those for the undersized pilot hole simulation at a load of 770 N. It is concluded that the commonly used tie constraint can be used effectively when the only interest is the global load-deformation behaviour. Different contact interface models, however, alter the mechanical response around screw holes leading to different predictions for screw loosening, bone damage and stress shielding.

Occurrence and Treatment of Bone Atrophic Non-Unions Investigated by an Integrative Approach

Recently developed atrophic non-union models are a good representation of the clinical situation in which many non-unions develop. Based on previous experimental studies with these atrophic non-union models, it was hypothesized that in order to obtain successful fracture healing, blood vessels, growth factors, and (proliferative) precursor cells all need to be present in the callus at the same time. This study uses a combined in vivo-in silico approach to investigate these different aspects (vasculature, growth factors, cell proliferation). The mathematical model, initially developed for the study of normal fracture healing, is able to capture essential aspects of the in vivo atrophic non-union model despite a number of deviations that are mainly due to simplifications in the in silico model. The mathematical model is subsequently used to test possible treatment strategies for atrophic non-unions (i.e. cell transplant at post-osteotomy, week 3). Preliminary in vivo experiments corroborate the numerical predictions. Finally, the mathematical model is applied to explain experimental observations and identify potentially crucial steps in the treatments and can thereby be used to optimize experimental and clinical studies in this area. This study demonstrates the potential of the combined in silico-in vivo approach and its clinical implications for the early treatment of patients with problematic fractures.

The relative incidence of fracture non-union in the Scottish population (5.17 million): a 5-year epidemiological study

Objectives In the UK there are approximately 850 000 new fractures seen each year. Rates of non-union of 5–10% of fractures have been suggested, the cost to the National Health Service of treating non-union has been reported to range between £7000 and £79 000 per person yet there are little actual data available. The objective of this epidemiological study therefore is for the first time to report the rates of fracture non-union. Design A cross-sectional epidemiological study. Setting The population of Scotland. Participants All patient admissions to hospital in Scotland are coded according to diagnosis. These data are collected by (and were obtained from) Information Services Department Scotland. Those who have been coded for a bone non-union between 2005 and 2010 were included in the study. No patients were excluded. Population data were obtained from the Registrar General for Scotland. Outcome measure The number of fracture non-unions per 100 000 population of Scotland according to age, sex and anatomical distribution of non-union. Results 4895 non-unions were treated as inpatients in Scotland between 2005 and 2010, averaging 979 per year, with an overall incidence of 18.94 per 100 000 population per annum. The distribution according to gender was 57% male and 43% female. The overall peak incidence according to age was between 30 and 40 years. The mean population of Scotland between 2005 and 2010 was 5 169 140 people. Conclusion Fracture non-union in the population as a whole remains low at less than 20 per 100 000 population and peaks in the fourth decade of life. Further research is required to determine the risk of non-union per fracture according to age/sex/anatomical distribution. .

Chondrocyte Death in Mechanically Injured Articular Cartilage―The Influence of Extracellular Calcium

Calcium is thought to be an important regulator of chondrocyte death associated with articular cartilage injury. Our objective was to determine the influence of extracellular calcium on chondrocyte death following mechanical injury. Using a surgically relevant model of sharp mechanical injury (with a scalpel) and confocal laser scanning microscopy (CLSM), in situ chondrocyte death was quantified within the full thickness of articular cartilage as a function of medium calcium concentration and time (2.5 h and 7 days). Exposure of articular cartilage to calcium‐free media (∼0 mM) significantly reduced superficial zone chondrocyte death after mechanical injury compared with exposure to calcium‐rich media (2–20 mM, ANOVA at 2.5 h, p = 0.002). In calcium‐rich media, although the extent of chondrocyte death increased with increasing medium calcium concentration, cell death remained localized to the superficial zone of articular cartilage over 7 days (ANOVA, p < 0.05). However, in calcium‐free media, there was an increase in chondrocyte death within deeper zones of articular cartilage over 7 days. The early (within hours) chondroprotective effect in calcium‐free media suggests that the use of joint irrigation solutions without added calcium may decrease chondrocyte death from mechanical injury during articular surgery. The delayed (within days) increase in chondrocyte death in calcium‐free media supports the use of calcium supplementation in media used during cartilage culture for tissue engineering or transplantation.

Bone properties affect loosening of half-pin external fixators at the pin–bone interface

INTRODUCTION Local bone yielding at the pin-bone interface of external fixation half-pins has been known to initiate fixator loosening. Deterioration of bone properties due to ageing and disease can lead to an increase in the risk of pin loosening. This study determines the extent, locations and mechanics of bone yielding for unilateral external fixation systems at the tibial midshaft with changes in age-related bone structure and properties. The study also evaluates the effect of the number of pins used in the fixation system and use of titanium pins (in place of steel) on bone yielding. METHODS We employ nonlinear finite element (FE) simulations. Strain-based plasticity is used to simulate bone yielding within FE analyses. Our analyses also incorporate contact behaviour at pin-bone interfaces, orthotropic elasticity and periosteal-endosteal variation of bone properties. RESULTS The results show that peri-implant yielded bone volume increases by three times from young to old-aged cases. The use of three, rather than two half-pins (on either side of the fracture), reduces the volume of yielded bone by 80% in all age groups. The use of titanium half-pins resulted in approximately 60-65% greater volumes of yielded bone. CONCLUSIONS We successfully simulate half-pin loosening at the bone-implant interface which has been found to occur clinically. Yielding across the full cortical thickness may explain the poor performance of these devices for old-aged cases. The models are able to identify patients particularly at risk of half-pin loosening, who may benefit from alternative fixator configurations or techniques such as those using pre-tensioned fine wires.

Investigation of factors affecting loosening of ilizarov ring‐wire external fixator systems at the bone‐wire interface

The potential for peri‐implant bone yielding and subsequent loosening of Ilizarov ring‐wire external fixation systems was investigated using non‐linear finite element (FE) analyses. A strain‐based plasticity model was employed to simulate bone yielding. FE models also incorporated contact behavior at the wire‐bone interface, orthotropic elasticity, and periosteal‐endosteal variation of bone properties. These simulations were used to determine the extent and location of yielding with change in age‐related bone structure and properties for the bone‐Ilizarov construct at the tibial midshaft. At critical wire‐bone interfaces, the predicted volume of yielded bone with four wires (on either side of the fracture) was ∼40% of that with two wires. Old‐aged cases showed considerably greater bone yielding at the wire‐bone interface than young cases (1.7–2.2 times greater volumes of yielded bone). The volume of yielded bone at all wire‐bone interfaces decreased with an increase in wire pre‐tension. The absence of continuous through‐thickness yielding offers an explanation for the clinical observation that Ilizarov ring‐wire fixation can provide stable fracture fixation even in bone with high porosity.

The risk of non-union per fracture: current myths and revised figures from a population of over 4 million adults

Background and purpose — Fracture non-union remains a major clinical problem, yet there are no data available regarding the overall risk of fractures progressing to non-union in a large population. We investigated the rate of non-union per fracture in a large adult population. Methods — National data collected prospectively over a 5-year period and involving just under 5,000 non-unions were analyzed and compared to the incidence of fracture in the same period. Results and interpretation — The overall risk of non-union per fracture was 1.9%, which is considerably less than previously believed. However, for certain fractures in specific age groups the risk of non-union rose to 9%. As expected, these higher rates of non-union were observed with tibial and clavicular fractures, but—less expectedly—it was in the young and middle-aged adults rather than in the older and elderly population. This study is the first to examine fracture non-union rates in a large population according to age and site, and provides more robust (and lower) estimates of non-union risk than those that are frequently quoted.