Abstract

Abstract

With information about a patient's bone mechanical properties orthopaedic operations could be optimised to reduce intra- and post-operative complications. However, there is currently no reliable method of measuring a patient's bone mechanical properties in vivo. We have previously investigated microindentation, using a 1.5mm diameter spherical indenter tip, and found no correlation between these measurements and compression testing measurements. We hypothesised that by using a larger diameter indenter tip we would closer match bone millimetre-scale mechanical properties.

20 bone samples were taken from 20 patients undergoing hip replacement surgery. The samples were machined from the femoral neck calcar cortical bone into 6×3×3mm parallelepiped specimens, aligned with the osteons along the long axis. The samples were micro-computed tomography (CT) scanned to calculate porosity. Microindentation was performed using a 6mm diameter, sapphire, spherical indenter tip. 12 indentations were performed in a grid and the reduced moduli were calculated using the Oliver-Pharr method. Compression testing was then performed to failure and the apparent elastic modulus was calculated for each sample.

A moderate correlation was found between the indentation reduced moduli and compression testing elastic moduli (r=0.52, r2=0.275, p=0.018). In addition, a moderate correlation was found between the indentation reduced moduli and CT-measured porosity (r=0.5, r2=0.251, p=0.025) and a strong correlation was found between compression testing moduli and porosity (r=0.75, r2=0.568, p<0.001).

Using large-tip spherical microindentation, indentation reduced moduli correlated significantly with compression testing apparent elastic moduli in these 20 cortical bone specimens. Microindentation using a large, spherical indenter tip may predict the mechanical properties of bone at the millimetre length scale and shows promise as a potential future clinical decision aid in surgery.

Objectives

The ability to determine human bone stiffness is of clinical relevance in many fields, including bone quality assessment and orthopaedic prosthesis design. Stiffness can be measured using compression testing, an experimental technique commonly used to test bone specimens in vitro. This systematic review aims to determine how best to perform compression testing of human bone.

Objectives

Bisphosphonates (BP) are the first-line treatment for preventing fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate is associated with over-suppression of remodelling and accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA) scanning may show a gain in bone density, the impact of this class of drug on mechanical properties remains unclear. We therefore sought to quantify the mechanical strength of bone treated with BP (oral alendronate), and correlate data with the microarchitecture and density of microcracks in comparison with untreated controls.

Objectives

Microindentation has the potential to measure the stiffness of an individual patient’s bone. Bone stiffness plays a crucial role in the press-fit stability of orthopaedic implants. Arming surgeons with accurate bone stiffness information may reduce surgical complications including periprosthetic fractures. The question addressed with this systematic review is whether microindentation can accurately measure cortical bone stiffness.

Introduction

The increase in revision joint replacement surgery and fractures of bone around orthopaedic implants may be partly addressed by keeping bone healthy around orthopaedic implants by inserting implants with mechanical properties closer to the patient's bone properties. We do not currently have an accurate way of calculating a patient's bone mechanical properties. We therefore posed a simple question: can data derived from a micro-indenter be used to calculate bone stiffness?

Introduction

Bisphosphonates (BP) are the first-line therapy for preventing osteoporotic fragility fractures. However, concern regarding their efficacy is growing because bisphosphonate use is associated with over-suppression of remodeling. Animal studies have reported that BP therapy is associated with accumulation of micro-cracks (Fig. 1) and a reduction in bone mechanical properties, but the effect on humans has not been investigated. Therefore, our aim was to quantify the mechanical strength of bone treated with BP, and correlate this with the microarchitecture and density of micro-damage in comparison with untreated osteoporotic hip-fractured and non-fractured elderly controls.

Bones are thought to become fragile with advancing age due to a loss of mass and structure. However, there are important aspects of bone fragility and fracture that cannot be explained simply by a loss of bone: 30% of all patients told they have healthy bone based on bone mineral density (BMD) measurements go on to fracture.

It has been suggested that increased fracture risk might also be due to ageing at the nanoscale, which might deteriorate the overall mechanical properties of a bone. However, it is not clear how mechanics at the level of the collagen-mineral matrix relate to mechanical properties of the whole bone, or whether nano-mechanics contribute to fracture risk. In order to answer these questions our group is developing state of the art methods for analysing the structure and function of the collagen mineral matrix under loading.

To image the collagen mineral matrix we obtained beam time on a synchrotron particle accelerator at the Diamond Light Source (Didcot, UK). Electrons are accelerated to near light speed by powerful electromagnets, then slowed to create high energy monochromatic X-Ray beams. Through a combination of X-Ray computed tomography and X-Ray diffraction we have been able to image the collagen/mineral matrix. Furthermore, using in situ loading experiments it has been possible to visualise collagen fibrillar sliding and mineral crystal structure.

Our group is analysing how age related changes in nano-structure affect bone mechanical behaviour. As well as comparing fragility fracture patients with ‘healthy’ age matched controls to investigate whether ageing at the nano-scale could increase fracture risk. We are also assessing the effect of common treatments for bone fragility (e.g. bisphosphonate) on nano-mechanics.

Unfortunately the expense and high radiation dose associated with synchrotron imaging prevents the technology from being adapted for patients. Therefore the next step will be to identify and test tools that can be used to indirectly assess bone chemistry and mechanical properties at point of care (e.g. laser spectroscopy and indentation). The data could be used to improve the diagnosis, monitoring and treatment of bone fragility.

Osteoporosis is a global health issue with 200 million people suffering worldwide and it is a common condition in the elderly. Bisphosphonates including alendronate and risendronate are considered as the first line treatment for osteoporosis. However, there is increasing evidence that bisphosphonate (BP) therapy is associated with atypical fractures. Animal studies have reported a dose-dependent association between the duration of BP therapy and the accumulation of micro-damage. We tested the hypothesis that hip fracture patients treated with BP exhibited greater micro-damage density than untreated fracture and ‘healthy’ aging non-fracture controls.

Trabecular bone cores from patients treated with BP were compared with patients who had not received any treatment for bone metabolic disease (ethics reference: R13004). Non-fractured cadaveric femora from individuals with no history of bone metabolic disease were used as controls. Cores were imaged in high spatial resolution (∼1.3µm) using Synchrotron X-ray tomography (Diamond Light Source Ltd.) A novel classification system was devised to characterise features of micro-damage in the Synchrotron images: micro-cracks, diffuse damage and perforations. Synchrotron micro-CT stacks were visualised and analysed using ImageJ, Avizo and VGStudio MAX.

Our findings show that the BP group had the highest micro-damage density across all groups. The BP group (7.7/mm³) also exhibited greater micro-crack density than the fracture (4.3/mm³) and non-fracture (4.1/mm³) controls. Furthermore, the BP group (1.9/mm³) demonstrated increased diffuse damage when compared to the fracture (0.3/mm³) and non-fracture (0.8/mm³) controls. In contrast, the BP group (1.9mm³) had fewer perforations than fracture (3.0/mm³) and non-fracture controls (3.9/mm³).

BP inhibits bone remodelling, thereby reducing the number of perforated trabeculae, but over-suppression leads to micro-damage accumulation. Accumulated damage could weaken the trabecular bone in the femoral head and neck, increasing the risk of a fracture during a trip or fall.

The increase in revision joint replacement surgery and fractures of bone around orthopaedic implants may be partly addressed by keeping bone healthy around orthopaedic implants by inserting implants with mechanical properties closer to the patient's bone properties. We do not currently have an accurate way of calculating a patient's bone mechanical properties. We are therefore investigating whether microindentation can accurately calculate bone stiffness.

We received ethical approval to retrieve femoral heads and necks from patients undergoing hip replacement surgery for research. Cortical bone from the medial calcar region of the femoral neck was cut into 3×3×6mm cuboid specimens. Micro-indentation testing was performed in the direction of loading of the bone using a MicroMaterials indenter. The samples were kept hydrated and were not fixed or polished. From the unloading curve after indentation, the elastic modulus was calculated, using the Oliver- Pharr method. To assess which microindentation machine settings most precisely calculate the elastic modulus we varied the loading and unloading rates, load and indenter tip shape.

The most precise results were obtained by using a spherical indenter tip (rather than Berkovich tip), high load (10N), a loading rate of 100 mN/s and unloading rate of 300 mN/s with a pause of 60 seconds at maximum load and multiple load cycles with constant loads. Using these settings the mean elastic modulus over 12 cycles of testing was 13.0 GPa (+/- 2.47).

By using a spherical indenter tip and fast unloading it was possible to get precise apparent modulus values. By unloading as fast as possible the effects of bone viscoelastic properties are minimised. By using a spherical indenter tip, plastic deformation at the tip is minimised (compared to the Berkovich tip). We are performing further standard compression tests on the samples to verify the accuracy of the indentation tests.

Most glenoid implants rely on centrally located large fixation features to avoid perforation of the glenoid vault in its peripheral regions [1]. Upon revision of such components there may not be enough bone left for the reinsertion of an anatomical prosthesis, resulting in a large cavity that resembles a sink hole. Multiple press-fit small pegs would allow for less bone resection and strong anchoring in the stiffer and denser peripheral subchondral bone [2], whilst producing a more uniform stress distribution and increased shear resistance per unit volume [3] and avoiding the complications from the use of bone cement. This study assessed the best combination of anchoring strength, assessed as the ratio between push in and pull out forces (Pin/Pout), and spring-back, measured as the elastic displacement immediately after insertion, for five different small press-fitted peg configurations (Figure 1, left) manufactured out of UHMWPE cylinders (5 mm diameter and length).

16 specimens for each configuration were tested in two types of Sawbones solid bone substitute: hard (40 PCF, 0.64 g/cm3, worst-case scenario of Pin) and soft (15 PCF, 0.24 g/cm3, worst-case scenario of spring-back and Pout). Two different interference-fits, Ø, were studied by drilling holes with 4.7 mm and 4.5 mm diameter (Ø 0.3 and Ø 0.5, respectively). A maximum Pin per peg of 50 N was defined, in order to avoid fracture of the glenoid bone during insertion of multiple pegs. The peg specimens were mounted into the single-axis screw-driven Instron through a threaded fixture. A schematic of the experimental set up is made available (Figure 1, centre). The peg was pushed in vertically for a maximum of 5 mm at a 1 mm/s rate, under displacement control, recording Pin. The spring-back effect was assessed by switching to load control and reducing the load to zero. The peg was then pulled out at a rate of 1 mm/s, recording Pout. The test profile is depicted in Figure 1 (right).

Average Pout/Pin, spring back (in mm) and force-displacement curves for all 80 specimens tested are shown in Figure 2. These were split into groups according to the type of bone substitute and interference-fit, with the right column showing the average values for the Pin. High repeatability among samples of the same configuration tested is noted. Configurations #1, #3 and #5 all exceed the maximum Pin per peg for at least one type of bone. Configuration #2 has the lowest Pin of all (best thread aspect ratio), followed by configuration #4 (thinner threads). The peg configurations #4 and #2 had the highest Pin/Pout. The peg configurations with lowest spring-back after insertion were configuration #2 and #4. Interference fit of Ø 0.3 mm was shown to reduce Pin below maximum limit of 50 N without great influence in spring-back.

Common post-operative problems in shoulder arthroplasty such as glenoid loosening and joint instability can be reduced by improvements in glenoid design shape, material choice and fixation method [1]. Innovation in shoulder replacement is usually carried out by introducing incremental changes to functioning implants [2], possibly overlooking other successful design combinations.

We propose an automated framework for parametric analysis of implant design in order to efficiently assess different possible glenoid configurations. Parametric variations of reference geometries of a glenoid implant were automatically generated in SolidWorks. The different implants were aligned and implanted with repeatability using Rhino. The glenoid-bone models were meshed in Abaqus, and boundary conditions and loading applied via a custom-made Python script. Finally, another MATLAB script integrated and automated the different steps, extracted and analysed the results.

This study compared the influence of reference shape (keel vs. 2-pegged) and material on the von Mises stresses and tensile and compressive strains of glenoid components with bearing surface thickness and fixation feature width of 3, 4, 5 or 6 mm. A total of 96 different glenoid geometries were implanted into a bone cube (E = 300 MPa, ν = 0.3). Fixed boundary conditions were applied at the distal surface of the cube and a contact force of 1000 N was distributed between the central nodes on the bearing surface. The implants were assigned UHMWPE (E = 1 GPa, ν = 0.46), Vitamin E PE (E = 800 MPa, ν = 0.46), CFR-PEEK (E = 18 GPa, ν = 0.41) or PCU (E = 2 GPa, ν = 0.38) material properties and the bone-implant surface was tied (Figure 1). The von Mises stresses, compressive and tensile strains for the different models were extracted. The influence of design parameters in the mechanical environment of the implant could be assessed. In this particular example, the 95^th percentile values of the tensile and compressive strains induced by modifications in reference shape could be evaluated for all the different geometries simultaneously in form of radar plots. 2-pegged geometries (green) consistently produced lower tensile and compressive strains than the keeled (blue) configurations (Figure 2). Vitamin E PE and PCU glenoids also produced lower maximum von Mises stresses values than CFR-PEEK and UHMWPE designs (Figure 3).

The developed method allows for simple, direct, rapid and repeatable comparison of different design features, material choices or fixation methods by analysing how they influence the mechanical environment of the bone surrounding the implant. Such tool can provide invaluable insight in implant design optimisation by screening through multiple potential design modifications at an early design evaluation stage and highlighting the best performing combinations. Future work will introduce physiological bone geometries and loading, a wider variety of reference geometries and fixation features, and look at bone/interface strength and osteointegration predictions.

Laboratory experiments and computational models were used to predict bone-implant micromotion and bone strains induced by the cemented and cementless Biomet Oxford medial Unicompartmental Knee Replacement (UKR) tibial implants.

Introduction and Aims: Locking plates represent a major change in the way we stabilise fractures. The distal radius Locking Compression Plate (LCP, Synthes) theoretically enables palmar plating of dorsally comminuted and intra-articular wrist fractures. All current methods (Dorsal plates, K wires and external fixators) have considerable disadvantages. This is the first study to assess the clinical and biomechanical results of this new implant.

Method: We created a synthetic bone fracture model to compare three plates (the LCP, Buttress and Pi). We tested 24 plates, eight in each group, using the Instrom biomechanical testing machine, axially loading the model to 200 Newtons for 500 cycles. The results show significantly less displacement for the LCP plate (p< 0.05).

Results: Early clinical results are reported following a prospective study of the LCP plate to stabilise dorsally comminuted and intra-articular. The average age was 32 years. We report our results at an average follow-up of six months (range four to nine months). There were no complications. The Gartland & Werley scores were at least satisfactory in all patients and good in 75%.

Conclusion: Both our biomechanical and early clinical results support the clinical use of the palmarly applied LCP for intra-articular and dorsally comminuted wrist fractures.

Surgical joint stabilisation can be achieved by ligamentous plication or thermal shrinkage, and as such, we hypothesized that there is no difference in mechanical and morphological properties after reduction of laxity in ligaments treated by either technique.

Methods: 30 mature female rabbits underwent either ‘thermal’ treatment of their left medial collateral ligament (MCL) using a bipolar radiofrequency probe, or plication with two 4/O non-absorbable sutures following division along its midsubstance and loaded positioning of the free ends. After 12 weeks convalescence, the animals were euthanised and MCL complexes were procured from left and contralateral knees to undergo viscoelastic (creep) testing, quantitative Transmission Electron Microscopy (TEM) and immunohistochemistry. The TEM data was quantified by two data procurement protocols; computational analysis and manual graticule.

Mean creep strain in both thermal (1.85 +/− 0.32%) and plicated ligaments (1.92+/−0.36%) was almost twice that of the control (1.04+/−0.15%), although there was no difference between treatment modalities. Similar findings were seen in the thermal (1.77+/−0.45%), plication (1.85+/−0.40%) and control groups (0.92+/−0.20%) for viscoplastic deformation. However, collagen morphological parameters of all three groups were significantly different (p< 0.001). The thermal ligaments demonstrated predominantly small fibrils, whilst the plicated group displayed an intermediate distribution of heterogenous fibrils. Immunohistochemistry followed by TEM revealed a sparse random distribution of alpha-smooth muscle actin staining fibroblasyts in both thermal and plicated groups. There was an insignificant difference in computational and manual procurement methods (p=0.84).

Susceptibility to creep, and residual deformation after recovery, is similar after thermal shrinkage or plication, although inferior to intact ligaments. However, the plicated results suggest remodeling on a pre-existing fibrillar scaffold, yet the thermal group demonstrated histomorphometry similar to scar tissue, suggesting de novo synthesis. The absence of contractile myofibroblasts suggests that these cells may have an insignificant role in regulation of matrix tension during healing.

Radio frequency (RF) electrothermal capsulorrhaphy has potential to enhance the results of arthroscopic stabilisation. However, early clinical reports have shown variable results when compared with open stabilisation. Numerous experiments have shown that the mechanical properties of thermally treated tissue are mechanically inferior to normal tissue during the early phase of remodelling. Ultimately, the real issue is how thermally treated tissue compares with tissue shortened by surgical plication, as would occur in an open procedure.

Using a validated technique the tibial insertion of the medial collateral ligament (MCL) of the knee was shifted proximally to induce abnormal laxity in 30 mature NZ White rabbits. Bipolar RF shrinkage was applied to the MCL in 15 rabbits, while in the remainder the MCL was surgically transected and plicated with a nonabsorbable suture. Unlimited mobilisation was permitted until euthanasia at 12 weeks after surgery. Bone-ligament-bone complexes were harvested and underwent low-load (viscoelastic) and high-load (tensile failure) analysis on an Instron mechanical testing apparatus. Specimens from intact MCLs were also collected for polarised light microscopy and transmission electron micrography. Quantitative analysis of collagen fibril morphology was performed on the TEM images.

There were no significant complications postoperatively. In both groups there was evidence of ligament healing and remodelling with a thin layer of scar tissue surrounding the MCL. Preliminary analysis has demonstrated that the cross-sectional area of the thermally treated MCLs was increased compared with the plicated MCLs. Somewhat surprisingly, the plicated group had greater vascularity and cellularity in the healing zone than the thermal group. Although crimp patterns remained disorganised in both groups, the collagen matrix appeared more organised in the thermal group.

These results support the concept that the thermally denatured matrix may act as a scaffold for rapid remodelling of the MCL, resulting in a larger mass of ‘scar’ tissue at the site of shrinkage. Since scar tissue following surgical transection is known to be materially inferior to normal ligament tissue, the increased volume in the thermal group may confer an advantage in structural terms. Mechanical testing is presently underway in our laboratory to determine this issue.