Improvement in bone strength parameters. The role of strontium ranelate

Strontium ranelate (SR) is a novel anti-osteoporotic agent approved for the treatment of postmenopausal osteoporosis. SR appears to reduce bone resorption by decreasing osteoclast differentiation and activity, and to stimulate bone formation by increasing replication of pre-osteoblast cells, leading to increased matrix synthesis. The effect of SR on bone strength indices has been investigated in several animal models, including intact female and male rats, ovariectomized rats, after rat limb immobilization and in monkeys. In intact female rats, SR significantly improved bone mechanical properties of vertebrae and midshaft femur. The improvement in bone mechanical properties was characterized by an increase in maximal load and in energy to failure, which was due to an increment in plastic energy. These results suggest that new bone formed following strontium ranelate treatment is able to withstand greater deformation before fracture. Moreover, in ovariectomized rats, a model that resembles postmenopausal osteoporosis, 1-year exposure to strontium ranelate significantly prevented alteration of bone mechanical properties of vertebrae in association with a partial preservation of the trabecular microarchitecture. Finally after limb immobilization SR prevented microarchitectual deterioration, while no significant alteration was observed in crystal characteristics and degree of mineralization after SR administration in monkeys.     

Biomechanical comparison of locking plate and crossing metallic and absorbable screws fixations for intra-articular calcaneal fractures

The locking plate and percutaneous crossing metallic screws and crossing absorbable screws have been used clinically to treat intra-articular calcaneal fractures, but little is known about the biomechanical differences between them. This study compared the biomechanical stability of calcaneal fractures fixed using a locking plate and crossing screws. Three-dimensional finite-element models of intact and fractured calcanei were developed based on the CT images of a cadaveric sample. Surgeries were simulated on models of Sanders type III calcaneal fractures to produce accurate postoperative models fixed by the three implants. A vertical force was applied to the superior surface of the subtalar joint to simulate the stance phase of a walking gait. This model was validated by an in vitro experiment using the same calcaneal sample. The intact calcaneus showed greater stiffness than the fixation models. Of the three fixations, the locking plate produced the greatest stiffness and the highest von Mises stress peak. The micromotion of the fracture fixated with the locking plate was similar to that of the fracture fixated with the metallic screws but smaller than that fixated with the absorbable screws. Fixation with both plate and crossing screws can be used to treat intra-articular calcaneal fractures. In general, fixation with crossing metallic screws is preferable because it provides sufficient stability with less stress shielding.     

A 3D computational simulation of fracture callus formation: influence of the stiffness of the external fixator

The stiffness of the external fixation highly influences the fracture healing pattern. In this work we study this aspect by means of a finite element model of a simple transverse mid-diaphyseal fracture of an ovine metatarsus fixed with a bilateral external fixator. In order to simulate the regenerative process, a previously developed mechanobiological model of bone fracture healing was implemented in three dimensions. This model is able to simulate tissue differentiation, bone regeneration, and callus growth. A physiological load of 500 N was applied and three different stiffnesses of the external fixator were simulated (2300, 1725, and 1150 N/mm). The interfragmentary strain and load sharing mechanism between bone and the external fixator were compared to those recorded in previous experimental works. The effects of the stiffness on the callus shape and tissue distributions in the fracture site were also analyzed. We predicted that a lower stiffness of the fixator delays fracture healing and causes a larger callus, in correspondence to well-documented clinical observations.     

A Functional GTPase Domain,but not its Transmembrane Domain,is Required for Function of the SRP Receptor β-subunit

The signal recognition particle and its receptor (SR) target nascent secretory proteins to the ER. SR is a heterodimeric ER membrane protein whose subunits, SRα and SRβ, are both members of the GTPase superfamily. Here we characterize a 27-kD protein in Saccharomyces cerevisiae (encoded by SRP102) as a homologue of mammalian SRβ. This notion is supported (a) by Srp102p''s sequence similarity to SRβ; (b) by its disposition as an ER membrane protein; (c) by its interaction with Srp101p, the yeast SRα homologue; and (d) by its role in SRP-dependent protein targeting in vivo. The GTP-binding site in Srp102p is surprisingly insensitive to single amino acid substitutions that inactivate other GTPases. Multiple mutations in the GTP-binding site, however, inactivate Srp102p. Loss of activity parallels a loss of affinity between Srp102p and Srp101p, indicating that the interaction between SR subunits is important for function. Deleting the transmembrane domain of Srp102p, the only known membrane anchor in SR, renders SR soluble in the cytosol, which unexpectedly does not significantly impair SR function. This result suggests that SR functions as a regulatory switch that needs to associate with the ER membrane only transiently through interactions with other components.     

Cosserat micromechanics of human bone: strain redistribution by a hydration sensitive constituent

Experimental determination of the strain distribution in prismatic, square cross-section bars of human compact bone in torsion disclosed nonclassical effects associated with the microstructure. Specifically, in wet bone at small strain, significant deviations from the classically predicted strain distribution were observed. The measured strain distribution in wet bone followed predictions based on Cosserat (micropolar) elasticity. In dry bone, the strain distribution was very close to the prediction of classical elasticity. The interaction between Haversian osteons and the cement substance between them was hypothesized to be the principal mechanism for the phenomena. To evaluate this hypothesis, additional specimens were subjected to prolonged torsional load and the cement lines were observed by reflected light microscopy. Localized deformation at the cement lines was observed, but it was less than values reported earlier for bovine plexiform bone.     

Are plasticity models required to predict relative risk of lag screw cut-out in finite element models of trochanteric fracture fixation?

Using a finite element model of unstable trochanteric fracture stabilized with a sliding hip screw, the benefits of two plasticity-based formulations, Drucker–Prager and crushable foam, were evaluated and compared to the commonly used linear elastic model of trabecular bone in order to predict the relative risk of lag screw cut-out for five distinct load cases. The crushable foam plasticity formulation leads to a much greater strain localization, in comparison to the other two models, with large plastic strains in a localized region. The plastic zone predicted with Drucker–Prager is relatively more diffuse. Linear elasticity associated with a minimum principal strain criterion provides the smallest volume of elements susceptible to yielding for all loading modes. The region likely to undergo plastic deformation, as predicted by the linear elastic model, is similar to that obtained from plasticity-based formulations, which indicates that this simple criterion provides an adequate estimate of the risk of cut-out.     

Mechanical analysis of a rodent segmental bone defect model: The effects of internal fixation and implant stiffness on load transfer

Segmental bone defect animal models are often used for evaluating the bone regeneration performance of bone substituting biomaterials. Since bone regeneration is dependent on mechanical loading, it is important to determine mechanical load transfer after stabilization of the defect and to study the effects of biomaterial stiffness on the transmitted load. In this study, we assess the mechanical load transmitted over a 6 mm femur defect that is stabilized with an internal PEEK fixation plate. Subsequently, three types of selective laser melted porous titanium implants with different stiffness values were used to graft the defect (five specimens per group). In one additional group, the defect was left empty. Micro strain gauges were used to measure strain values at four different locations of the fixation plate during external loading on the femoral head. The load sharing between the fixation plate and titanium implant was highly variable with standard deviations of measured strain values between 31 and 93% of the mean values. As a consequence, no significant differences were measured between the forces transmitted through the titanium implants with different elastic moduli. Only some non-significant trends were observed in the mean strain values that, consistent with the results of a previous finite element study, implied the force transmitted through the implant increases with the implant stiffness. The applied internal fixation method does not standardize mechanical loading over the defect to enable detecting small differences in bone regeneration performances of bone substituting biomaterials. In conclusion, the fixation method requires further optimization to reduce the effects of the operative procedure and make the mechanical loading more consistent and improve the overall sensitivity of this rat femur defect model.     

Spontaneous myocardial calcium oscillations: overview with emphasis on ryanodine and caffeine

All mammalian cardiac preparations exhibit the capacity for periodic spontaneous Ca2+ release from the sarcoplasmic reticulum (SR) (Ca2+ oscillations). The occurrence of such oscillations in unstimulated preparations and their periodicity depend on the species and the Ca2+ load on the cell. When the spontaneous frequency of these oscillations exceeds the rate of external simulation, they appear between stimulated contractions and impart a variable Ca2+-dependent component of diastolic tonus and a propensity for extrasystoles and arrhythmias to occur; these diastolic oscillations can also affect systolic function as well. Although enhancing the spontaneous frequency of Ca2+ release, caffeine depresses the oscillation amplitude, whereas ryanodine suppresses both frequency and amplitude. Detailed studies of oscillation characteristics and of the different effects of caffeine and ryanodine on them may provide an understanding of and may be useful for modeling SR Ca2+ uptake and release in intact preparations.     

Harvest of patellar tendon (bone-tendon-bone) autograft for ACL reconstruction significantly alters surface strain in the human patella

The purpose of this study was to measure the effect of bone-patellar tendon-bone autograft harvest for anterior cruciate ligament (ACL) reconstruction on the surface strain of the human patella. Through progressive removal of bone from the patella, three different defect shapes as well as the intact patella were tested in each of seven knees. Maximum principal strain and corresponding principal direction were determined from each of three gages around the defect for the four conditions (intact plus three defect shapes). There were no statistically significant differences in overall average surface strain between any of the defect shapes. Following graft harvest, overall average strain (all three defects combined) increased in the patella both medial (15 percent increase) and lateral (34 percent increase) to the defect, while decreasing in the region directly proximal (22 percent decrease) to the harvest site compared to the intact patella. A statistically significant 7.5 deg shift of principal direction from longitudinal toward a more transverse (lateral-superior to medial-inferior) direction was observed in the medial region when a shallow-dome defect was made. We conclude that removal of a bone block from the anterior, inferior part of the patella induces a significant redistribution of the surface strain. This results in greater local strain adjacent to the upper border of the bone block increasing the risk for patella fracture. This effect may be of importance in various complications known to occur after ACL reconstruction.     

Evaluation of the mechanical properties and clinical application of nickel–titanium shape memory alloy scaphoid arc nail

To investigate the mechanical and biomechanical properties of nickel–titanium (Ni–Ti) shape memory alloy scaphoid arc nail (NT‐SAN) fixator as well as study the surgical method of treating carpal scaphoid fractures and evaluate its clinical efficacy. (1) Static and dynamic bending tests with embedded axial bending fixture were conducted to study the mechanical properties. (2) To evaluate biomechanical strength and fatigue, 32 scaphoid samples were classified into four groups to perform the fixation rigidity test: intramedullary Kirschner fixation (group A), Kirschner straddle nail fixation (group B), screw nail fixation (group C), and NT‐SAN fixation (group D). Next, 24 scaphoid waist fracture models were classified to conduct fatigue experiments as follows: Kirschner straddle nail fixation (group E), screw nail fixation (group F), and NT‐SAN fixation (group G). (3) The Krimmer score chart was used for clinical evaluations. (1) NT‐SAN showed excellent mechanical performance and a long lifespan. (2) NT‐SAN was fixated with a strong intensity and an anti‐fatigue outcome. (3) Ninety‐eight interviewed patients were satisfied with the therapeutic effects of the arc nail (satisfaction rate: 95.92%). The designed strength and hardness of NT‐SAN corresponded with the anatomical characteristics of the scaphoid, and the designed mechanical properties met the biomechanical requirements of a scaphoid fracture. The fatigue strength can meet the requirements of bone healing after the scaphoid fracture. Clinical trials on NT‐SAN scaphoid fracture treatment have shown that the surgery is simple and the clinical results are satisfactory. The therapeutic level of NT‐SAN is III; thus, it is worth promoting.     

Biomechanical comparison of conventional and anatomical calcaneal plates for the treatment of intraarticular calcaneal fractures – a finite element study

Initial stability is essential for open reduction internal fixation of intraarticular calcaneal fractures. Geometrical feature of a calcaneal plate is influential to its endurance under physiological load. It is unclear if conventional and pre-contoured anatomical calcaneal plates may exhibit differently in biomechanical perspective. A Sanders’ Type II-B intraarticular calcaneal fracture model was reconstructed to evaluate the effectiveness of calcaneal plates using finite element methods. Incremental vertical joint loads up to 450 N were exerted on the subtalar joint to evaluate the stability and safety of the calcaneal plates and bony structure. Results revealed that the anatomical calcaneal plate model had greater average structural stiffness (585.7 N/mm) and lower von Mises stress on the plate (774.5 MPa) compared to those observed in the conventional calcaneal plate model (stiffness: 430.9 N/mm; stress on plate: 867.1 MPa). Although both maximal compressive and maximal tensile stress and strain were lower in the anatomical calcaneal plate group, greater loads on fixation screws were found (average 172.7 MPa compared to 82.18 MPa in the conventional calcaneal plate). It was noted that high magnitude stress concentrations would occur where the bone plate bridges the fracture line on the lateral side of the calcaneus bone. Sufficient fixation strength at the posterolateral calcaneus bone is important for maintaining subtalar joint load after reduction and fixation of a Sanders’ Type II-B calcaneal fracture. In addition, geometrical design of a calcaneal plate should worth considering for the mechanical safety in practical usage.     

Reasons why dynamic compression plates are inferior to locking plates in osteoporotic bone: a finite element explanation

While locking plate fixation is becoming increasingly popular for complex and osteoporotic fractures, for many indications compression plating remains the standard choice. This study compares the mechanical behaviour of the more recent locking compression plate (LCP) device, with the traditional dynamic compression plates (DCPs) in bone of varying quality using finite element modelling. The bone properties considered include orthotropy, inhomogeneity, cortical thinning and periosteal apposition associated with osteoporosis. The effect of preloads induced by compression plating was included in the models. Two different fracture scenarios were modelled: one with complete reduction and one with a fracture gap. The results show that the preload arising in DCPs results in large principal strains in the bone all around the perimeter of the screw hole, whereas for LCPs large principal strains occur primarily on the side of the screw proximal to the load. The strains within the bone produced by the two screw types are similar in healthy bone with a reduced fracture gap; however, the DCP produces much larger strains in osteoporotic bone. In the presence of a fracture gap, the DCP results in a considerably larger region with high tensile strains and a slightly smaller region with high compressive strains. These findings provide a biomechanical basis for the reported improved performance of locking plates in poorer bone quality.     

A customized fixation plate with novel structure designed by topological optimization for mandibular angle fracture based on finite element analysis

Background

The purpose of this study was to design a customized fixation plate for mandibular angle fracture using topological optimization based on the biomechanical properties of the two conventional fixation systems, and compare the results of stress, strain and displacement distributions calculated by finite element analysis (FEA).

Methods

A three-dimensional (3D) virtual mandible was reconstructed from CT images with a mimic angle fracture and a 1 mm gap between two bone segments, and then a FEA model, including volume mesh with inhomogeneous bone material properties, three loading conditions and constraints (muscles and condyles), was created to design a customized plate using topological optimization method, then the shape of the plate was referenced from the stress concentrated area on an initial part created from thickened bone surface for optimal calculation, and then the plate was formulated as “V” pattern according to dimensions of standard mini-plate finally. To compare the biomechanical behavior of the “V” plate and other conventional mini-plates for angle fracture fixation, two conventional fixation systems were used: type A, one standard mini-plate, and type B, two standard mini-plates, and the stress, strain and displacement distributions within the three fixation systems were compared and discussed.

Results

The stress, strain and displacement distributions to the angle fractured mandible with three different fixation modalities were collected, respectively, and the maximum stress for each model emerged at the mandibular ramus or screw holes. Under the same loading conditions, the maximum stress on the customized fixation system decreased 74.3, 75.6 and 70.6% compared to type A, and 34.9, 34.1, and 39.6% compared to type B. All maximum von Mises stresses of mandible were well below the allowable stress of human bone, as well as maximum principal strain. And the displacement diagram of bony segments indicated the effect of treatment with different fixation systems.

Conclusions

The customized fixation system with topological optimized structure has good biomechanical behavior for mandibular angle fracture because the stress, strain and displacement within the plate could be reduced significantly comparing to conventional “one mini-plate” or “two mini-plates” systems. The design methodology for customized fixation system could be used for other fractures in mandible or other bones to acquire better mechanical behavior of the system and improve stable environment for bone healing. And together with SLM, the customized plate with optimal structure could be designed and fabricated rapidly to satisfy the urgent time requirements for treatment.

     

Subject-specific finite element models implementing a maximum principal strain criterion are able to estimate failure risk and fracture location on human femurs tested in vitro

No agreement on the choice of the failure criterion to adopt for the bone tissue can be found in the literature among the finite element studies aiming at predicting fracture risk of bones. The use of stress-based criteria seems to prevail on strain-based ones, while basic bone biomechanics suggest using strain parameters to describe failure. The aim of the present combined experimental-numerical study was to verify, using subject-specific finite element models able to accurately predict strains, if a strain-based failure criterion could identify the failure patterns of bones. Three cadaver femurs were CT-scanned and subsequently fractured in a clinically relevant single-stance loading scenario. Load-displacement curves and high-speed movies were acquired to define the failure load and the location of fracture onset, respectively. Subject-specific finite element models of the three femurs were built from CT data following a validated procedure. A maximum principal strain criterion was implemented in the finite element models, and two stress-based criteria selected for comparison. The failure loads measured were applied to the models, and the computed risks of fracture were compared to the results of the experimental tests. The proposed principal strain criterion managed to correctly identify the level of failure risk and the location of fracture onset in all the modelled specimens, while Von Mises or maximum principal stress criteria did not give significant information. A maximum principal strain criterion can thus be defined a suitable candidate for the in vivo risk factor assessment on long bones.     

The influence of acetabular cup material on pelvis cortex surface strains, measured using digital image correlation

Acetabular cup loosening is a late failure mode of total hip replacements, and peri-prosthetic bone deterioration may promote earlier failure. Preservation of supporting bone quality is a goal for implant design and materials selection, to avoid stress shielding and bone resorption. Advanced polymer composite materials have closer stiffness to bone than metals, ceramics or polymers, and have been hypothesised to promote less adverse bone adaptation. Computer simulations have supported this hypothesis, and the present study aimed to verify this experimentally.A composite hemi-pelvis was implanted with Cobalt Chromium (CoCr), polyethylene (UHMWPE) and MOTIS^®carbon-fibre-reinforced polyether etherketone (CFR-PEEK) acetabular cups. In each case, load was applied to the implanted pelvis and Digital Image Correlation (DIC) was used for surface strain measurement. The test was repeated for an intact hemi-pelvis. Trends in implanted vs. intact bone principal strains were inspected to assess the average principal strain magnitude change, allowing comparison of the potential bone responses to implantation with the three cups.The CFR-PEEK cup was observed to produce the closest bone strain to the intact hip in the main load path, the superior peri-acetabular cortex (+12% on average, R²=0.84), in comparison to CoCr (+40%, R²=0.91) and UHWMPE cups (?26%, R²=0.94). Clinical observations have indicated that increased periacetabular cortex loading may result in reduced polar cancellous bone loading, leading to longer term losses in periprosthetic bone mineral density. This study provides experimental evidence to verify previous computational studies, indicating that cups produced using materials with stiffness closer to cortical bone recreate physiological cortical bone strains more closely and could, therefore, potentially promote less adverse bone adaptation than stiffer press-fitted implants in current use.     

Evaluating a suitable level of model complexity for finite element analysis of the intact acetabulum

To enable large-scale multi-factorial finite element (FE) studies, the FE models used must be as computationally efficient as is feasible, while maintaining a suitable level of definition. The present study seeks to find an optimum level of model complexity for use in such large-scale studies by investigating which model attributes are most influential over the chosen model outputs of principal stress and strain in the intact acetabulum. A multi-factorial sensitivity study was carried out using 128 FE models, representing combinations of the following variables: bone stiffness distribution, imposed muscle loading, boundary condition location, hip joint contact conditions and patient's bone anatomy. The relative sensitivity of each input factor was analysed, and it was concluded that the optimum level of model definition must include CT-dependent trabecular bone properties and a sliding interface at the hip joint. It was found that it was not essential to describe the ligamentous sacroiliac and pubic symphysis joints; these could be rigidly fixed in space; and for the normal walking load case, muscle forces may be neglected. It was also concluded that a variety of bone anatomies should be included in a multi-factorial analysis if results are to be inferred for a wider population.     

Strain shielding in proximal tibia of stemmed knee prosthesis: experimental study

Theoretical concerns about the use of cemented or press-fit stems in revision total knee arthroplasty (TKA) include stress shielding with adverse effects on prosthesis fixation. Revision TKA components are commonly stemmed to protect the limited autogenous bone stock remaining. Revision procedures with the use of stems can place abnormal stresses through even normal bone by their constrained design, type of materials and fixation method and may contribute for bone loss. Experimental quantification of strain shielding in the proximal synthetic tibia following TKA is the main purpose of the present study. In this study, cortical bone strains were measured experimentally with tri-axial strain gauges in synthetic tibias before and after in vitro knee surgery. Three tibias were implanted with cemented and press-fit stem augments and solely with a tibial tray (short monobloc stem) of the P.F.C. Sigma Modular Knee System. The difference between principal strains of the implanted and the intact tibia was calculated for each strain gauge position. The results demonstrated a pronounced strain-shielding effect in the proximal level, close to tibial tray with the cemented stem augment. The press-fit stem presented a minor effect of strain shielding but was more extensively throughout the stem. An increase of strains closely to the distal tip of the cemented and the press-fit stem augment was observed. This suggests for a physiological condition, a potential effect of bone resorption at the proximal region for the cemented stem augment. The localized increase of strains in stems tip can be related with the clinical finding of the pain, at the end of stem after revision TKA.     

A rigorous method for evaluation of the 6D compliance of external fixators

External fixators are standard devices to stabilize bone fractures and their compliance aims at producing an interfragmentary motion that promotes rapid and successful healing. While evaluation of their axial compliance is a routine test, the quantification and interpretation of their full 6 × 6 compliance matrix is an extensive and delicate task. In this context, the objective of this study was to develop, validate and demonstrate the potential of a rigorous method to quantify their 6 × 6 compliance matrix. An experimental system was developed to apply six independent static forces and moments to an external fixator in the field of view of two infrared cameras quantifying the induced motion. The system was then tested with a calibration structure which compliance could be calculated analytically and numerically. Finally, the system was applied to compare three configurations of a commercial external wrist fixator. The results of the method proved to be reproducible and highly consistent with the linear elasticity theory in the physiological range of small deformations. A rigorous method for evaluation of the 6D compliance becomes therefore available for research in mechanobiology of fracture healing by external fixation.     

Biodegradable Implants in the Fixation of Physeal Fractures in Cats and Dogs

In a preclinical and a clinical study physeal fractures of cats and dogs were fixated with biodegradable implants. The preclinical part consisted of 4 cats with experimental physeal fractures of the distal femurs and the clinical part of 6 cats and 8 dogs with different physeal fractures. All fractures were fixated with selfreinforced polyglycolic acid (PGA) implants of different sizes. No external support was applied after the fixation. All cats and dogs used their operated legs during the first postoperative week and they could walk without lameness in 6 weeks. The fracture healed without delay or malformations. The retardations of the growth of the physeal regions were considered minimal.     

Strain energy in the femoral neck during exercise

Physical activity is recommended to mitigate the incidence of hip osteoporotic fractures by improving femoral neck strength. However, results from clinical studies are highly variable and unclear about the effects of physical activity on femoral neck strength. We ranked physical activities recommended for promoting bone health based on calculations of strain energy in the femoral neck. According to adaptive bone-remodeling theory, bone formation occurs when the strain energy (S) exceeds its homeostatic value by 75%. The potential effectiveness of activity type was assessed by normalizing strain energy by the applied external load. Tensile strain provided an indication of bone fracture. External force and joint motion data for 15 low- and high-load weight-bearing and resistance-based activities were used. High-load activities included weight-bearing activities generating a ground force above 1 body-weight and maximal resistance exercises about the hip and the knee. Calculations of femoral loads were based on musculoskeletal and finite-element models. Eight of the fifteen activities were likely to trigger bone formation, with isokinetic hip extension (ΔS=722%), one-legged long jump (ΔS=572%), and isokinetic knee flexion (ΔS=418%) inducing the highest strain energy increase. Knee flexion induced approximately ten times the normalized strain energy induced by hip adduction. Strain and strain energy were strongly correlated with the hip-joint reaction force (R²=0.90–0.99; p<0.05) for all activities, though the peak load location was activity-dependent. None of the exercises was likely to cause fracture. Femoral neck mechanics is activity-dependent and maximum isokinetic hip-extension and knee-flexion exercises are possible alternative solutions to impact activities for improving femoral neck strength.