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Bone & Joint Research
Vol. 9, Issue 1 | Pages 1 - 14
1 Jan 2020
Stewart S Darwood A Masouros S Higgins C Ramasamy A

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion.

Cite this article: Bone Joint Res 2019;9(1):1–14.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_7 | Pages 24 - 24
1 May 2018
Spurrier E Masouros S Clasper J
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Spinal fractures are common following underbody blast. Most injuries occur at the thoracolumbar junction, and fracture patterns suggest the spine is flexed at the moment of injury. However, current mechanistic descriptions of vertebral fractures are based on low energy injuries, and there is no evidence to correlate fracture pattern with posture at the loading rates seen in blast injury.

The T12-L1 segment of 4 human spines was dissected to preserve the paraspinal ligaments and potted in polymethylmecrylate. The specimens were impacted with a 14 kg mass at 3.5m/s in a drop tower; two specimens were impacted in neutral posture, one in flexion, and one in extension. A load cell measured the load history. CT scans and dissection identified the injury patterns.

Each specimen sustained a burst fracture. The neutral specimens demonstrated superior burst fractures, the flexed specimen demonstrated a superior burst fracture with significant anterior involvement, and the extended specimen showed a posterior vertebral body burst fracture.

At high loading rates, the posture of the spine at the moment of injury appears to affect the resulting fracture. This supports understanding the behaviour of the spine in blast injury and will allow improved mitigation system design in the future.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_7 | Pages 26 - 26
1 May 2018
Webster C Masouros S Clasper J
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Severe military pelvic trauma has a high mortality rate with previous work identifying an association between pelvic fracture and traumatic amputation (TA) of the lower limb (LL). Research has also identified casualties with this combination of injuries as the potential ‘future unexpected survivors’, however, most casualties die early from exsanguination, often before medical interventions can be performed. Therefore targeting injury prevention or mitigation might be the route to increased survivorship. This study investigates this combination of injury and identifies targets for preventative techniques. A search of the JTTR from 2003 to 2014 identified all patients with TA and all pelvic fractures. Of 989 casualties with LL TAs, 19% had an associated pelvic fracture, and this was associated with a 56% mortality rate compared to 24% without. Both pubic symphysis and sacroiliac separation alike were associated positively with traumatic amputation (p < 0.01). The combination of pelvic instability and TA had a mortality rate of 52%. We hypothesise that pelvic fracture may share a mechanistic link with TA, meaning fracture may occur as a consequence of the force and direction of the TA, and it may be possible to direct mitigation strategies at this injury in order to improve survival rates.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_7 | Pages 20 - 20
1 May 2018
Bonner T Masouros S Newell N Ramasamy A Hill A West A Clasper J Bull A
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The lower limbs of vehicle occupants are vulnerable to severe injuries during under vehicle explosions. Understanding the injury mechanism and causality of injury severity could aid in developing better protection. Therefore, we tested three different knee positions in standing occupants (standing, knee in hyper-extension, knee flexed at 20˚) of a simulated under‐vehicle explosion using cadaveric limbs in a traumatic blast injury simulator; the hypothesis was that occupant posture would affect injury severity.

Skeletal injuries were minimal in the cadaveric limbs with the knees flexed at 20˚. Severe, impairing injuries were observed in the foot of standing and hyper‐extended specimens. Strain gauge measurements taken from the lateral calcaneus in the standing and hyper-extended positions were more than double the strain found in specimens with the knee flexed position. The results in this study demonstrate that a vehicle occupant whose posture incorporates knee flexion at the time of an under‐vehicle explosion is likely to reduce the severity of lower limb injuries, when compared to a knee extended position.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_8 | Pages 14 - 14
1 Jun 2015
Webster C Masouros S Gibb I Clasper J
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Conflict in Afghanistan demonstrated predominantly lower extremity and pelvi-perineal trauma secondary to Improvised Explosive Devices (IEDs). Mortality due to pelvic fracture (PF) is usually due to exsanguination. This study group comprised 169 military patients who sustained a PF and lower limb injury. There were 102 survivors and 67 fatalities (39% mortality). Frequent fracture patterns were a widened symphysis (61%) and widening of the sacroiliac joints (SIJ) (60%). Fatality was 20.7% for undisplaced SIJs, 24% for unilateral SIJ widening and 64% fatality where both SIJs were disrupted, demonstrating an increase in fatality rate with pelvic trauma severity. A closed pubic symphysis was associated with a 19.7% mortality rate versus 46% when widened. Vascular injury was present in 67% of fatalities, versus 45% of survivors. Of PFs, 84% were associated with traumatic amputation (TA) of the lower limb. Pelvic fracture with traumatic lower limb amputation presents a high mortality. It is likely that the mechanism of TA and PF are related, and flail of the lower limb(s) is the current hypothesis. This study prompts further work on the biomechanics of the pelvic-lower limb complex, to ascertain the mechanism of fracture. This could lead to evidence-based preventative techniques to decrease fatalities.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_8 | Pages 11 - 11
1 Jun 2015
McMenemy L Masouros S Stapley S Clasper J
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Military personnel operating on high speed marine craft are exposed to Whole-Body Vibration (WBV). Additionally planing craft operate at speeds with minimal contact of the hull with warer making the crew vulnerable to mechanical shock. An association between Low Back Pain (LBP) and exposure to WBV has been extensively reported in civilian literature. LBP is reported by military personnel operating on planing craft leading to downgrades and potential discharge. There is a clear need to understand the impact prolonged exposure has on our population operating these craft. We performed a bibliographical search of the PubMed database for records using a combination of keywords. Abstracts were screened for relevance and references cited in retrieved papers reviewed. There is no consensus in the literature on the potentially pivotal pathological process behind the association. Evidence from professional driving suggests current safe operating exposure levels require review to protect against long-term damage however with little evidence concerning the unique environment in which boats crews operate, the parity of these environments require investigation to allow direct comparison. Due to the prevalence of LBP in this population a need exists to establish the pathological process and add to the evidence base driving safe operating exposure levels.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_9 | Pages 2 - 2
1 May 2014
Spurrier E Singleton J Masouros S Clasper J
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Improvised Explosive Device (IED) attacks on vehicles have been a significant feature of recent conflicts. The Dynamic Response Index (DRI), developed for predicting spinal injury in aircraft ejection, has been adopted for testing vehicles in underbelly blast. Recent papers suggest that DRI is not accurate in blast conditions. We suggest that the distribution of blast and ejection injuries is different.

A literature review identified the distribution of spinal fractures in aircraft ejection incidents. A Joint Theatre Trauma Registry search identified victims of mounted IED blast with spinal fractures. The distribution of injuries in the two groups was compared using the Kruskall Wallis test.

329 fractures were identified in ejector seat incidents; 1% cervical, 84% thoracic and 16% lumbar. 245 fractures were identified in victims of mounted blast; 16% cervical, 34% thoracic and 50% lumbar. There was no significant similarity between the two (p=1). There was no statistically significant difference between the distribution of fractures in blast survivors versus fatalities.

The difference between blast and ejection injury patterns suggests that injury prediction models for ejection should not be extrapolated to blast mechanisms and that new models need to be developed.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_26 | Pages 16 - 16
1 Jun 2013
Bonner T Newell N Pullen A Bull A Masouros S
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Characterising material properties of ligaments is essential in the analysis of human morbidity and mortality of low-speed sporting accidents, high-speed road traffic accidents, and very high-speed battlefield injuries. At lower strain rates the elastic modulus and ultimate stress increase relative to strain rate, although very high strain rate testing has not been performed to date.

A porcine stifle joint lateral collateral ligament experiment was conducted that simulated the strain rates that occur during across a full range of different human knee ligament injuries. Tensile testing was performed at five strain rates, each an order of magnitude apart, in the range 100–104%/s. Seven specimens were tested at each rate. Three loading techniques were used: 1) screw-driven, 2) servo-hydraulic, 3) drop weight rig with tensile impact adaptor. Cross sectional area was measured by counting pixels on a standardized digital photograph of an alginate-paste cast of the mid-substance of each sample. Strain was measured directly from the mid-substance of each ligament by high-speed video extensometry. Stress-strain curves were produced and used to quantify the elastic modulus, failure strain and ultimate stress at each strain rate.

Across the range of strain rates, elastic modulus increased from 288 to 905 MPa (p< 0.05), and ultimate stress increased from 39.9 to 77.3 MPa (p< 0.05). A relationship between strain rate and both, elastic modulus and ultimate stress was identified. Strain rate sensitivity was not observed at very fast strain rates.

Ligament strength increases when strain rates are high. These data provide an explanation for very high strain rate failure of ligaments under extreme loading conditions, that can be considered protective of bone fracture, such as can be seen in traumatic through knee amputations in blast injuries.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_21 | Pages 9 - 9
1 Apr 2013
Ramasamy A Masouros S Phillip R Gibb I Bull A Clasper J
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Background

The conflict in Afghanistan has been epitomised by the emergence of the Improvised Explosive Device (IEDs). Improvements in protection and medical treatments have resulted in increasing numbers of casualties surviving with complex lower extremity injuries. To date, there has been no analysis of foot and ankle blast injuries as a result of IEDs. Therefore the aims of this study are to report the pattern of injury and determine which factors were associated with a poor clinical outcome.

Methods

Using a prospective trauma registry, UK Service Personnel who sustained lower leg injuries following an under-vehicle explosion between Jan 2006 and Dec 2008 were identified. Patient demographics, injury severity, the nature of lower limb injury and clinical management was recorded. Clinical endpoints were determined by

need for amputation and

need for ongoing clinical output at mean 33.0 months follow-up.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_8 | Pages 15 - 15
1 Feb 2013
Ramasamy A Masouros S Newell N Bonner T West A Hill A Clasper J Bull A
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Current military conflicts are characterised by the use of the Improvised Explosive Device (IED). Improvements in personal protection, medical care and evacuation logistics have resulted in increasing numbers of casualties surviving with complex musculoskeletal injuries, often leading to life-long disability. Thus, there exists an urgent requirement to investigate the mechanism of extremity injury caused by these devices in order to develop mitigation strategies. In addition, the wounds of war are no longer restricted to the battlefield; similar injuries can be witnessed in civilian centres following a terrorist attack.

Key to mitigating such injuries is the ability to deconstruct the complexities of an explosive event into a controlled, laboratory-based environment. In this study, an anti-vehicle underbelly injury simulator, capable of recreating in the laboratory the impulse from an anti-vehicle (AV) explosion, is presented and characterised. Tests were then conducted to assess the simulator's ability to interact with human cadaveric legs. Two mounting conditions were assessed, simulating a typical seated and standing vehicle passenger using instrumented cadaveric lower limbs.

This experimental device, will now allow us (a) to gain comprehensive understanding of the load-transfer mechanisms through the lower limb, (b) to characterise the dissipating capacity of mitigation technologies, and (c) to assess the biofidelity of surrogates.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_8 | Pages 14 - 14
1 Feb 2013
Bonner T Singleton J Masouros S Gibb I Kendrew J Clasper J
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Counter-insurgency warfare in recent military operations has been epitomised by the use of Improvised Explosive Devices (IED) against coalition troops. Emerging patterns of skeletal fractures, limb amputations and organ injuries, which are caused by these weapons have been described over recent years. This paper describes a retrospective case series of knee dislocations caused by IEDs in recent conflict.

Data was obtained about military personnel from 2006 to 2011, who had sustained a knee dislocation while serving in Afghanistan from a prospectively gathered database, the Joint Theatre Trauma Registry (JTTR), maintained by the Academic Department of Military Emergency Medicine, Royal Centre for Defence Medicine. The diagnosis of knee dislocation and its associated skeletal injuries was assessed by review of all relevant plain radiographs, computed tomography scans and magnetic resonance images. The mechanism of injury, incidence of vascular injuries and other skeletal injuries was recorded.

During the study period, 23 casualties sustained a knee dislocation caused by an IED. Four casualties had an associated popliteal vascular injury. Eleven injuries were caused in enclosed spaces, and 10 injuries caused by IEDs out in the open. Anterior dislocations were common in the group caused in enclosed spaces. 19/20 patients had at least one other skeletal fracture.

Knee dislocations represent an uncommon but important diagnosis in modern warfare. Urgent and careful assessment for any associated vascular injuries or other skeletal injuries may help ensure timely treatment and promote future recovery. Mitigation against knee dislocation may be possible in the enclosed environment because of the predictable pattern of injury.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_1 | Pages 56 - 56
1 Jan 2013
Ramasamy A Hill A Masouros S Gibb I Phillip R Bull A Clasper J
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The conflict in Afghanistan has been epitomised by the emergence of the Improvised Explosive Device(IEDs). Improvements in medical treatments have resulted in increasing numbers of casualties surviving with complex lower extremity injuries. To date, there has been no analysis of foot and ankle blast injuries as a result of IEDs. Therefore the aims of this study are to firstly report the pattern of injury and secondly determine which factors were associated with a poor clinical outcome in order to focus future research.

Using a prospective trauma registry, UK Service Personnel who sustained lower leg injuries following an under-vehicle explosion between Jan 2006 and Dec 2008 were identified. Patient demographics, injury severity, the nature of lower limb injury and clinical management was recorded. Clinical endpoints were determined by (i)need for amputation and (ii)need for ongoing clinical output at mean 33.0 months follow-up.

63 UK Service Personnel (89 injured limbs) were identified with lower leg injuries from explosion. 50% of casualties sustained multi-segmental injuries to the foot and ankle complex. 26(29%) limbs required amputation, with six amputated for chronic pain 18 months following injury. Regression analysis revealed that hindfoot injuries, open fractures and vascular injuries were independent predictors of amputation.

Of the 69 limbs initially salvaged, the overall infection rate was 42%, osteomyelitis 11.6% and non-union rates was 21.7%. Symptomatic traumatic osteoarthritis was noted in 33.3% salvaged limbs. At final follow-up, 66(74%) of injured limbs had persisting symptoms related to their injury, with only 9(14%) fit to return to their pre-injury duties.

This study demonstrates that foot and ankle injuries from IEDs are frequently associated with a high amputation rate and poor clinical outcome. Although, not life-threatening, they remain a source of long-term morbidity in an active population. Primary prevention of these injuries remain key in reducing the injury burden.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXII | Pages 3 - 3
1 Jul 2012
Bonner T Eardley W Newell N Masouros S Gibb I Matthews J Clasper J
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Circumferential pelvic binders have been developed to allow rapid closure of the pelvic ring in unstable fracture patterns. Despite evidence to support the use of pelvic binders, there is a paucity of clinical data regarding the effect of binder position on symphyseal diastasis reduction.

All patients presenting to the UK's military hospital in Afghanistan who survived and underwent pelvic radiography were reviewed. Cases were identified by retrospective assessment of all digital plain pelvic radiographs performed between January 2008 and July 2010. All radiographs and CT images were assessed to identify the presence of any pelvic fracture. Patients were grouped into three categories according to the vertical level of the buckle: superior to the trochanters (high), inferior to the trochanters (low) and at the level of the trochanters (troch). Diastasis reduction was measured in patients with Anterior-Posterior Compression (APC) grades II and III, or Combined Mechanical Injuries(CMI). Comparison of diastasis reduction between the high and troch groups was assessed by an independent samples Student's t-test.

We identified 172 radiographs where the metallic springs in the buckle of a SAM Pelvic Sling were clearly visible. The binders were positioned at the trochanteric level in 50% of radiographs. A high position was the commonest site of inaccurate placement (37%). In the patients with fractures and an open diastasis, the mean pelvic diastasis gap was 2.75 times greater in the high group compared to the trochanteric level (mean difference 22 mm) (p < 0.01).

Application of pelvic binders superior to the greater trochanters is commonplace and associated with inadequate fracture reduction, which is likely to delay cardiovascular recovery in these significantly injured casualties.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 11 | Pages 1524 - 1528
1 Nov 2011
Bonner TJ Eardley WGP Newell N Masouros S Matthews JJ Gibb I Clasper JC

The aim of this study was to assess the accuracy of placement of pelvic binders and to determine whether circumferential compression at the level of the greater trochanters is the best method of reducing a symphyseal diastasis.

Patients were identified by a retrospective review of all pelvic radiographs performed at a military hospital over a period of 30 months. We analysed any pelvic radiograph on which the buckle of the pelvic binder was clearly visible. The patients were divided into groups according to the position of the buckle in relation to the greater trochanters: high, trochanteric or low. Reduction of the symphyseal diastasis was measured in a subgroup of patients with an open-book fracture, which consisted of an injury to the symphysis and disruption of the posterior pelvic arch (AO/OTA 61-B/C).

We identified 172 radiographs with a visible pelvic binder. Five cases were excluded due to inadequate radiographs. In 83 (50%) the binder was positioned at the level of the greater trochanters. A high position was the most common site of inaccurate placement, occurring in 65 (39%). Seventeen patients were identified as a subgroup to assess the effect of the position of the binder on reduction of the diastasis. The mean gap was 2.8 times greater (mean difference 22 mm) in the high group compared with the trochanteric group (p < 0.01).

Application of a pelvic binder above the level of the greater trochanters is common and is an inadequate method of reducing pelvic fractures and is likely to delay cardiovascular recovery in these seriously injured patients.


Orthopaedic Proceedings
Vol. 90-B, Issue SUPP_II | Pages 359 - 359
1 Jul 2008
Smith C Masouros S Hill A Bull A Wallace A Amis A
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The aim of this work was to define the tensile material properties of the glenoid labrum. Previous SEM studies of the labrum have observed three definitive layers, with a densely packed circumferentially orientated collagen core layer. The glenoid labrum from ten cadaveric shoulders were dissected out and divided into eight equal sections. Each section was cut to produce specimens from the core layer using a microtome and a specifically designed cryo-clamp resulting in uniform specimens with dimensions of 1mm x 1mm x 8mm. All of the tensile testing was performed within a controlled-environment unit of 38°C and 100% relative humidity. Each specimen was precycled to a quasi-static state to alleviate the effects of deep-freezing, prior to final testing. The elastic modulus was calculated for each specimen before and after a 5-minute period of stress relaxation and before failure initiation. The mean age of the specimens was 61 years (range 47–70). Load to failure was 2.7N (1.0–7.0). The mean modulus was 10.2MPa (3.0–22.3) before stress relaxation, 18.0MPa (5.8–36.7) immediately after stress relaxation and 22.3MPa (8.4–66.4) before failure initiation. The 1 and 2 o’clock specimens had lower moduli than the 4 and 5 o’clock specimens (p=0.01). These results can aid in explaining the differing pathologies encountered around the circumference of the labrum. The high moduli at the 4 and 5 o’clock positions may reflect the ability of this portion of the labrum to accommodate forces and thus resist anteroinferior subluxation. The lower moduli at the 1 and 2 o’clock positions suggest that this portion of the labrum is less apt to accommodate tension; this might explain the higher incidence of labral foramen observed in this area and the anatomical variant of the Buford complex.