Bone remodeling effects is a significant issue in predicting long term stability of hip arthroplasty. It has been frequently observed around the femoral components especially with the implantation of prosthesis stem. Presence of the stiffer materials into the femur has altering the stress distribution and induces changes in the architecture of the bone. Phenomenon of bone resorption and bone thickening are the common reaction in total hip arthroplasty (THA) which leading to stem loosening and instability. The objectives of this study are (i) to develop inhomogeneous model of lower limbs with hip osteoarthritis and THA and (ii) to predict the bone resorption behavior of lower limbs for both cases. Biomechanical evaluations of lower limbs are established using the finite element method in predicting bone remodeling process. Lower limbs CT-based data of 79 years old female with hip osteoarthritis (OA) are used in constructing three dimensional inhomogenous models. The FE model of lower limbs was consisted of sacrum, left and right ilium and both femur shaft. Bond between cartilage, acetabulum and femoral head, sacrum and ilium were assumed to be rigidly connected. The inhomogeneous material properties of the bone are determined from the Hounsfield unit of the CT image using commercial biomedical software. A load case of 60kg body weight was considered and fixed at the distal cut of femoral shaft. For THA lower limbs model, the left femur which suffering for hip OA was cut off and implanted with prosthesis stem. THA implant is designed to be Titanium alloy and Alumina for stem and femoral ball, respectively. Distribution of young modulus of cross-sectional inhomogeneous model is presented in Fig. 2 while model of THA lower limbs also shown in Fig. 2. Higher values of young modulus at the outer part indicate hard or cortical bone. Prediction of bone resorption is discussed with the respect of bone mineral density (BMD). Changes in BMD at initial age to 5 years projection were simulated for hip OA and THA lower limbs models. The results show different pattern of stress distribution and bone mineral density between hip OA lower limbs and THA lower limbs. Stress is defined to be dominant at prosthesis stem while femur experienced less stress and leading to bone resorption. Projection for 5 years follow up shows that the density around the greater tronchanter appears to decrease significantly

Recently, concerns arose over the medial tibial bone resorption of a novel cobalt-chromium (CoCr) implant. This study aimed to investigate the effects of tibial component material, design, and patient factors on periprosthetic bone resorption and to determine its association with clinical outcomes after total knee arthroplasty (TKA). A total of 462 primary TKAs using five types of implants were included. To evaluate tibial periprosthetic bone resorption, we assessed radiolucent lines (RLL) and change in bone mineral density at the medial tibial condyle (BMDMT). Factors related to bone resorption were assessed using regression analysis. Clinical outcomes were also evaluated with respect to periprosthetic bone resorption. Compared to titanium (Ti) implants, CoCr implants showed a higher incidence of complete RLL (23.1% vs. 7.9% at two years post-TKA) and a greater degree of BMDMT reduction. However, there was no significant difference between the implants made of the same material. Increased medial tibial bone resorption was associated with male sex, osteoporosis, larger preoperative varus deformity, longer follow-up period, and lower body mass index. The periprosthetic bone resorption was not associated with clinical outcomes including changes in range of motion and WOMAC score. Furthermore, no cases warranted additional surgery. Periprosthetic bone resorption was associated with implant material but not with implant design. Moreover, patient factors were related to the medial tibial bone resorption post-TKA. However, the periprosthetic bone resorption was not associated with short-term clinical outcomes. We contend that researchers should incorporate integrative considerations when developing and assessing novel implants

Introduction. Revision total knee arthroplasy (TKA) has been often used with a metal block augmentation for patients with poor bone quality. However, bone resorption beneath metal block augmentation has been still reported and little information about the reasons of the occurrence of bone resorption is available. The aim of the current study is to identify a possibility of the potential occurrence of bone resorption beneath metal block augmentation, through evaluation of strain distribution beneath metal block augmentation in revision TKA with metal block augmentation, during high deep flexion. Materials and Method. LOSPA, revision TKA with a metal block augmentation (Baseplate size #5, Spacer size #5, Stem size Φ9, L30, Augment #5 T5) was considered in this study. For the test, the tibia component of LOSPA was implanted to the tibia sawbone (left, #3401, Sawbones EuropeAB, Malmö, Sweden), which was corresponded to a traditional TKR surgical guideline. The femoral component of LOSPA was mounted to a customized jig attached to the Instron 8872 (Instron, Norwood, MA, USA), which was designed specially to represent the angles ranged from 0° to 140° with consideration of a rollback of knee joint (Figure. 1). Here, a compressive load of 1,600N (10N/s) was applied for each angle. Strain distribution was then measured from rossete strain gauge (Half Bridge type, CAS, Seoul, Korea) together (Figure 1). Results and Discussions. The strain distribution on the cortical bone of the tibia was shown in Figure 2. The results showed that the strains on the posterior region were gradually increased from extension to high deep of the knee joint and generally larger than the other regions. In contrast to the results on the posterior region, the strains on the medial region were gradually decreased after 60° or 90° flexion position and relatively lower than the other regions. Particularly, the strains on the medial region were generally lower than 50–100 µstrain, which is known as critical value range able to inducing bone resorption, during high deep flexion. This fact indicate that a possibility of the potential bone resorption occurrence in revision TKA used with a metal block augmentation may be relatively increased in patients who are frequently exposed to a personal lifestyle history with the loading conditions of the high flexion. This study may be valuable by identifying for the first time a possibility of the potential bone resorption occurrence through evaluation of the strain distribution beneath metal block augmentation in revision TKA used with a metal block augmentation during high deep flexion. Conclusion. A possibility of the potential bone resorption occurrence in revision TKA used with a metal block augmentation may be dependent on loading patterns applied on the knee joint related to personal lifestyle history. Particularly, it may be relatively increased in patients who are frequently exposed to a personal lifestyle history with the loading conditions of the high flexion. Acknowledgements. This study was supported by a grant from the New Technology Product Evaluation Technical Research project, Ministry of Food and Drug Safety (MFDS), Republic of Korea

Introduction. Stress shielding is one of the major concerns of load bearing implants (e.g. hip prostheses). Stiff implants cause stress shielding, which is thought to contribute to bone resorption1. On the contrary, low-stiffness implants generate high interfacial stresses that have been related to pain and interfacial micro-movements². Different attempts have been made to reduce these problems by optimizing either the stem design3 or using functionally graded implants (FGI) where the stem's mechanical properties are optimized4. In this way, new additive manufacturing technologies allow fabricating porous materials with well-controlled mesostructure, which allows tailoring their mechanical properties. In this work, Finite Element (FE) simulations are used to develop an optimization methodology for the shape and material properties of a FGI hip stem. The resorbed bone mass fraction and the stem head displacement are used as objective functions. Methodology. The 2D-geometry of a femur model (Sawbones®) with an implanted Profemur-TL stem (Wright Medical Technology Inc.) was used for FE simulations. The stem geometry was parameterized using a set of 8 variables (Figure 1-a). To optimize the stem's material properties, a grid was generated with equally spaced points for a total of 96 points (Figure 1-b). Purely elastic materials were used for the stem and the bone. Two bone qualities were considered: good (Ecortical=20 GPa, Etrabecular=1.5 GPa) and medium (Ecortical=15 GPa, Etrabecular=1 GPa). Poisson ratio was fixed to v=0.3. Loading corresponded to stair climbing. Hip contact force along with abductors, vastus lateralis and vastus medialis muscles were considered5 for a bodyweight of 847 N. The resorbed bone mass fraction was evaluated from the differences in strain energy densities between the intact bone and the implanted bone2. The displacement of the load point on the femoral head was computed. The optimization problem was formulated as the minimization of the resorbed bone mass fraction and the head displacement. It was solved using a genetic algorithm. Results. For the Profemur-TL design, bone resorption was around 36% and 56% for good and medium bone qualities, respectively (Fig. 2). The corresponding head displacements were 11.75 mm and 21.19 mm. Optimized solutions showed bone resorption from 15% to 26% and from 44% to 65% for good and medium bone qualities, respectively. Corresponding head displacements ranged from 11.85 mm to 12.25 mm and from 16.9 mm to 22.6 mm. Conclusion. The obtained set of solutions constitutes an improvement of the implant performance for this functionally graded implant (FGI) compared to the original implant for both bone qualities. From these simulations, the final solution for the FGI could be chosen based on manufacturing restrictions or another performance indicator

INTRODUCTION. Bone resorption around hip stems, in particular periprosthetic bone loss, is a common observation post-operatively. A number of factors influence the amount of bone loss over time and the mechanical environment following total hip replacement (THR) is important; conventional long stem prostheses have been shown to transfer loads distally, resulting in bone loss of the proximal femur. More conservative, short stems have been recently introduced to attempt to better replicate the physiological load distribution in the femur. The aim of this study was to evaluate the bone mineral density (BMD) change over time, in a femur implanted with either a short or a long stem. METHODS. Finite element models of two implants, a short (Minihip, Corin, UK) and long (Metafix, Corin, UK) hip stem were used to simulate bone remodeling under a physiological load condition (stair climbing). The magnitudes and directions of the muscle forces and joint reaction force were obtained from Heller et al (2001, 2005). An unimplanted femur was also simulated. A strain-adaptive remodelling theory (Scannel & Prendergast 2009) was utilised to simulate remodelling in the bone after virtual implantation. COMSOL Multiphysics software was used for the analysis. The strain component of the remodelling stimulus was strain energy density per unit mass. This was calculated in the continuum model from the strain energy density, and apparent density. Bone mass was adapted using a site-specific approach in an attempt to return the local remodelling stimulus to the equilibrium stimulus level (calculated from the unimplanted femur). The minimal inhibitory signal proposed by Frost (1964), was included in the model and described by a ‘lazy zone’, where no bone remodelling occurred. The three dimensional geometry of the femur was constructed from computed tomography data of the donor (female, 44 years old, right side). Elemental bone properties were assigned from the Hounsfield Unit values of the CT scans. The elastic modulus of the bone was assumed to be isotropic and was determined using a relationship to the apparent bone density (Frost 1964, Rho 1995). The Poisson's ratio for the bone regions varied between 0.2 and 0.32 depending on the apparent density of the bone (Stulpner 1997). The period of implantation analysed was 2 years. The muscle forces and joint contact loads applied were ramped linearly from zero to full load over a period of two weeks, representing the estimated post operative rest period of a patient. RESULTS AND DISCUSSION. The overall percentage BMD change observed for Gruen zones 1 through to 7, were −14%, +4%, +40%, +12%, +4%, 0%, 12% respectively at 2 years for the Minihip. The corresponding overall percentage BMD change observed for Gruen zones 1 through to 7 for the Metafix were −8%, −2%, 18%, 26%, +12%, −9%, −42% respectively (Figure 1,2). CONCLUSIONS. Considerably more bone resorption occurs in Gruen zone 7 with the long stem. Long stem designs distrupt the mechanical environment more than short stems, and lead to a greater bone mineral reduction over time

A common location for radius fracture is the proximal radial head. With the arm in neutral position, the fracture usually happens in the anterolateral quadrant (Lacheta et al., 2019).

If traditional surgeries are not enough to induce bone stabilization and vascularization, or the fracture can be defined grade III or grade IV (Mason classification), a radial head prosthesis can be the optimal compromise between bone saving and recovering the “terrible triad”.

A commercially available design of radial head prosthesis such as Antea (Adler Ortho, Milan, Italy) is characterized by flexibility in selecting the best matching size for patients and induced osteointegration thanks to the Ti-Por^® radial stem realized by 3D printing with laser technique (Figure 1). As demonstrated, Ti-Por^® push-out resistance increased 45% between 8 −12 weeks after implantation, hence confirming the ideal bone-osteointegration. Additional features of Antea are: bipolarity, modularity, TiN coating, radiolucency, hypoallergenic, 10° self-aligning.

The osteointegration is of paramount importance for radius, in fact the literature is unfortunately reporting several clinical cases for which the fracture of the prosthesis happened after bone-resorption. Even if related to an uncommon activity, the combination of mechanical resistance provided by the prosthesis and the stabilization due to the osteointegration should cover also accidental movements.

Based upon Lacheta et al. (2019), after axial compression-load until radii failure, all native specimens survived a compression-load of 500N, while the failure happened for a mean compression force of 2560N.

The aim of this research study was to test the mechanical resistance of a radial head prosthesis obtained by 3D printing. In detail, a finite element analysis (FEA) was used to understand the mechanical resistance of the core of the prosthesis and the potential bone fracture induced in the radius with simulated bone- resorption (Figure 2a). The critical level was estimated at the height for which the thickness of the core is the minimum (Figure 2b).

Considered boundary conditions:

- Full-length prosthesis plus radius out of the cement block equal to 60mm (Figure 2a);

Figure 3 shows the results in terms of maximum stress on the core of the prosthesis and the risk of fracture (Schileo et al., 2008).

According to the obtained results, the radial head prosthesis shows promising mechanical resistance despite of the simulated bone-resorption for all applied loads except for 2560N. The estimated mechanical limit for the material in use is 200MPa. The risk of fracture is in agreement with the experimental findings (Lacheta et al. (2019)), in fact bone starts to fail for the minimum reported failure load, but only for osteoporotic conditions.

The presented FEA aimed at investigating the behavior of a femoral head prostheses made by 3D printing with simulated bone-resorption. The prosthesis shows to be a skilled solution even during accidental loads.

For any figures or tables, please contact the authors directly.

Peri-prosthetic osteolysis and subsequent aseptic loosening is the most common reason for revising total hip replacements. Wear particles originating from the prosthetic components interact with multiple cell types in the peri-prosthetic region resulting in an inflammatory process that ultimately leads to peri-prosthetic bone loss. These cells include macrophages, osteoclasts, osteoblasts and fibroblasts. The majority of research in peri-prosthetic osteolysis has concentrated on the role played by osteoclasts and macrophages. The purpose of this review is to assess the role of the osteoblast in peri-prosthetic osteolysis.

In peri-prosthetic osteolysis, wear particles may affect osteoblasts and contribute to the osteolytic process by two mechanisms. First, particles and metallic ions have been shown to inhibit the osteoblast in terms of its ability to secrete mineralised bone matrix, by reducing calcium deposition, alkaline phosphatase activity and its ability to proliferate. Secondly, particles and metallic ions have been shown to stimulate osteoblasts to produce pro inflammatory mediators in vitro. In vivo, these mediators have the potential to attract pro-inflammatory cells to the peri-prosthetic area and stimulate osteoclasts to absorb bone. Further research is needed to fully define the role of the osteoblast in peri-prosthetic osteolysis and to explore its potential role as a therapeutic target in this condition.

Cite this article: Bone Joint J 2013;95-B:1021–5.

Hip and knee arthroplasty (HKA) are two of the most successful orthopaedic procedures. However, one major complication necessitating revision surgery is osteolysis causing aseptic loosening of the prosthesis. JAK-STAT has been demonstrated to influence bone metabolism and can be regulated by microRNA (miRNA). Adult patients with osteolysis or aseptic loosening undergoing revision HKA were recruited. Age and gender matched patients undergoing primary hip or knee arthroplasty were our controls. Samples of bone, tissue and blood were collected and RNA isolation was performed. The best quality samples were used for RNA-sequencing. Data analysis was performed using RStudio and Galaxy to identify differentially expressed genes. Western blotting of IL6 was used to confirm protein expression. Five circulating miRNA were identified which had 10 differentially expressed genes in bone and 11 differentially expressed genes in tissue related to the JAK-STAT pathway. IL6 in bone and EpoR in bone were highly significant and IL6 in tissue, MPL in bone, SOCS3 in tissue, JAK3 in bone and SPRED1 in bone were borderline significant. Western blot results demonstrated up-expression of IL6 in bone tissue of revision patients. Periprosthetic osteolysis and aseptic loosening can be attributed to miRNA regulation of the JAK-STAT pathway in osteoblasts and osteoclasts, leading to increased bone resorption. These findings can be used for further experiments to determine utility in the clinical setting for identifying diagnostic markers or therapeutic targets

Paget's disease of bone (PDB) is characterised by increased bone resorption and development of an erratic bone structure that is highly fragile and susceptible to fracture. In addition, altered joint biomechanics lead to arthritis, more often in the hip and pelvis, resulting in disability and a Total hip Arthroplasty (THA) may be required. THA in PDB is associated with more complications compared to normal population. There is no consensus on the type of arthroplasty that performs better in people with PDB. To our knowledge, there is no meta-analysis in literature on this rare problem. We undertook a systematic review and meta-analysis to compare the effectiveness of cemented versus cementless THA in patients with PDB. PRISMA guidelines were followed. Search strings were generated based on Boolean operators for identification of the reference articles. 31 studies were included overall. Revision rate was lower in the cementless group compared to the cemented group (chi square=4.36, p=0.04), aseptic loosening was lesser in the cementless group compared to the cemented group (chi square=4.13, p=0.04). The type of the arthroplasty did not affect the infection rate (chi square=2.51, p=0.11), pre and post op Harris Hip Score showed statistically significant difference, but there was no difference between types of arthroplasty. We conclude that THA with uncemented components is better and provided lower revision and aseptic loosening when compared to cemented groups in patients with PDB

Shoulder arthroplasty is effective at restoring function and relieving pain in patients suffering from glenohumeral arthritis; however, cortex thinning has been significantly associated with larger press-fit stems (fill ratio = 0.57 vs 0.48; P = 0.013)1. Additionally, excessively stiff implant-bone constructs are considered undesirable, as high initial stiffness of rigid fracture fixation implants has been related to premature loosening and an ultimate failure of the implant-bone interface2. Consequently, one objective which has driven the evolution of humeral stem design has been the reduction of stress-shielding induced bone resorption; this in-part has led to the introduction of short stems, which rely on metaphyseal fixation. However, the selection of short stem diametral (i.e., thickness) sizing remains subjective, and its impact on the resulting stem-bone construct stiffness has yet to be quantified. Eight paired cadaveric humeri (age = 75±15 years) were reconstructed with surgeon selected ‘standard’ sized and 2mm ‘oversized’ short-stemmed implants. Standard stem sizing was based on a haptic assessment of stem and broach stability per typical surgical practice. Anteroposterior radiographs were taken, and the metaphyseal and diaphyseal fill ratios were quantified. Each humerus was then potted in polymethyl methacrylate bone cement and subjected to 2000 cycles of compressive loading representing 90º forward flexion to simulate postoperative seating. Following this, a custom 3D printed metal implant adapter was affixed to the stem, which allowed for compressive loading in-line with the stem axis (Fig.1). Each stem was then forced to subside by 5mm at a rate of 1mm/min, from which the compressive stiffness of the stem-bone construct was assessed. The bone-implant construct stiffness was quantified as the slope of the linear portion of the resulting force-displacement curves. The metaphyseal and diaphyseal fill ratios were 0.50±0.10 and 0.45±0.07 for the standard sized stems and 0.50±0.06 and 0.52±0.06 for the oversized stems, respectively. Neither was found to correlate significantly with the stem-bone construct stiffness measure (metaphysis: P = 0.259, diaphysis: P = 0.529); however, the diaphyseal fill ratio was significantly different between standard and oversized stems (P < 0.001, Power = 1.0). Increasing the stem size by 2mm had a significant impact on the stiffness of the stem-bone construct (P = 0.003, Power = 0.971; Fig.2). Stem oversizing yielded a construct stiffness of −741±243N/mm; more than double that of the standard stems, which was −334±120N/mm. The fill ratios reported in the present investigation match well with those of a finite element assessment of oversizing short humeral stems3. This work complements that investigation's conclusion, that small reductions in diaphyseal fill ratio may reduce the likelihood of stress shielding, by also demonstrating that oversizing stems by 2mm dramatically increases the stiffness of the resulting implant-bone construct, as stiffer implants have been associated with decreased bone stimulus4 and premature loosening2. The present findings suggest that even a small, 2mm, variation in the thickness of short stem humeral components can have a marked influence on the resulting stiffness of the implant-bone construct. This highlights the need for more objective intraoperative methods for selecting stem size to provide guidelines for appropriate diametral sizing. For any figures or tables, please contact the authors directly

Bone is a connective tissue that undergoes constant remodeling. Any disturbances during this process may result in undesired pathological conditions. A single nucleotide substitution (596T-A) in exon eight which leads to a M199K mutation in human RANKL was found to cause osteoclast-poor autosomal recessive osteopetrosis (ARO). Patients with ARO cannot be cured by hematopoietic stem cell transplantation and, without proper treatments, will die in their early age. To date, how this mutation alters RANKL function has not been characterized. We thus hypothesized that hRANKL M199 residue is a structural determinant for normal RANKL-RANK interaction and osteoclast differentiation. By sharing our findings, we aim to achieve an improved clinical outcome in treating bone-related diseases such as osteoporosis, ARO and osteoarthritis. Site-directed mutagenesis was employed to create three rat RANKL mutants, replacing the methionine 200 (human M199 equivalent residue) with either lysine (M200K), alanine (M200A) or glutamic acid (M200E). Recombinant proteins were subsequently purified through affinity chromatography and visualized by Coomassie blue staining and western blot. MTS was carried out before osteoclastogenesis assay in vitro to measure the cellular toxicity. Bone resorption pit assay, immuno-fluorescent staining, luciferase reporter assay, RT-PCR, western blot and calcium oscillation detection were also conducted to explore the biological effect of rRANKL mutants. Computational modeling, thermal Shift Assay, western blot and protein binding affinity experiments were later carried out for structural analyses. rRANKL mutants M200K/A/E showed a drastically reduced ability to induce osteoclast formation and did not demonstrate features of competitive inhibition against wild-type rRANKL. These mutants are all incapable of supporting osteoclastic polarization and bone resorption or activating RANKL-induced osteoclast marker gene transcription. Consistently, they were unable to induce calcium flux, and also showed a diminished induction of IκBa degradation and activation of NF-kB and NFATc1 transcriptional activity. Furthermore, the transcriptional activation of the antioxidant response element (ARE) crucial in modulating oxidative stress and providing cytoprotection was also unresponsive to stimulation with rM200s. Structural analyses showed that rM200 is located in a hydrophobic pocket critical for protein folding. Thermal shift and western blot assays suggested that rM200 mutants formed unstructured proteins, with disturbed trimerisation and the loss of affinity to its intrinsic receptors RANK and OPG. Taken together, we first demonstrates the underlying cause of M199-meidated ARO in a cellular and molecular level by establishing a phenotype in BMMs similar to observed in human samples. Further investigation hints the structural significance of a hydrophobic pocket within the TNF-like region. Combined with pharmaceutical studies on small-molecule drugs, this finding may represent a therapeutic target motif for future development of anti-resorptive treatments

The triple taper polished cemented stem (C-stem, DePuy) was developed to promote calcar loading, and reduce proximal femoral bone resorption and aseptic loosening. We aimed to evaluate the changes in peri-prosthetic bone mineral density using Dual Energy X-ray Absorbtiometry (DEXA) after total hip arthroplasty (THA) using the C-stem prosthesis. One hundred and three patients were recruited voluntarily through and single institution for THA. The prosthesis used was the triple-taper polished cemented C-Stem (De Puy, Warsaw, Indiana, USA). DEXA scans were performed pre- operatively, then at day for, three months, nine months, 18 months and 24 months post-operativley. Scans were analysed with specialised software (Lunar DPX) to measure bone mineral density (BMD) in all seven Gruen zones at each time interval. Changes in calcar BMD were also correlated with patient age, sex, surgical approach, pre-operative BMD and post-operative mobility to identify risk factors for periprosthetic bone resorption. One hundred and three patients underwent 103 primary THA over a five-year period (98 osteoarthritis; 5 AVN). No femoral components were loose at the two year review and none were revised. The most marked bone resorption occured in Gruen zones 1 and 7, and was best preserved in zone 5. BMD decreased rapidly in all zones in the first three months post-operatively, after which the rate of decline slowed substantially. BMD was better preserved medially (zones 6 and 5) than laterally (zones 2 and 3) at 24 months. There was delayed recovery of BMD in all zones except zones 4 and 5. High pre-operative T-scores (>2.0) in the spine, ipsilateral and contralateral femoral neck were associated with the higher post-operative BMD and less bone resorption at all time intervals in Gruen zone 7. Pre-operative osteopenia and osteoporosis were associated with low BMD and accelerated post-operative bone resorption in zone 7. Patients whose mobility rendered them housebound had lower post-operative BMD, and accelerated post-operative BMD loss in zone 7 when compared to non-housebound patients. Females had a lower post-operative BMD and greater loss of BMD in zone 7. Patient age and surgical approach did not effect post-operative BMD or rate of bone resorption in zone 7. The triple-taper femoral stem design did not show an increase in periprosthetic bone density at the proximal femur at two years post-operative. Calcar bone resorption is accelerated by low pre-operative BMD, poor post-operative mobility, and in females. Age and surgical approach do not have significant effects on calcar bone remodelling

Introduction. Reinforcement ring with allograft bone is commonly used for acetabular reconstruction of bone defects because it can achieve stable initial fixation of the prosthesis. It is not clear whether the allograft bone can function as a viable host bone and provide long-standing structural support. The purpose of this study was to assess to long-term survival of the reinforcement rings and allograft bone incorporation after acetabular revisions. Methods. We retrospectively reviewed 39 hips (37 patients) who underwent reconstruction of the acetabulum with a Ganz reinforcement ring and allograft bone in revision total hip arthroplasty. There were 18 females and 19 males with a mean age of 55.9 years (35–74 years). The minimum postoperative follow-up period was 10 years (10∼17 years). We assessed the acetabular bone defect using the Paprosky's classification. We determined the rates of loosening of the acetabular reconstructions, time to aseptic loosening, integration of the allograft bone, resorption of the allograft bone, and survival rate. Aseptic loosening of the acetabular component was defined as a change in the cup migration of more than 5 mm or a change in the inclination angle of more than 5° or breakage of the acetabular component at the time of the follow-up. Graft integration was defined as trabecular remodelling crossing the graft-host interface. Resorption of the allograft bone was classified as minor (<1/3), moderate (1/3–1/2) or severe (>1/2). Kaplan-Meier survivorship analysis was performed for aseptic loosening of the acetabular component. The results. The acetabular bone defects were classified as follows: 8 type II hips (4 type IIB, 4 type IIC), and 31 type III hips (17 type IIIA, 14 type IIIB). Fourteen (35.9%) of 39 hips was defined as aseptic loosening of an acetabular component. Loosening was more frequent in type IIIB (57.1%) than in type IIIA hips (29.4%). Mean time to aseptic loosening of the acetabular reconstructions was 6.3 years in type IIIA and from 5 years in type IIIB defects, respectively. Allograft bone incorporation was satisfactory in 66.7% of hips. There was minor bone resorption in 14.3% and moderate bone resorption in 10.2%. In 9 hips (23.1%), severe resorption of the allograft bone was observed and early component loosening was observed in these cases. The survival rate of acetabular component at 10 years of follow-up was 63.6% (95% confidence interval, 49–77%) with aseptic loosening as endpoints. Conclusions. The long-term survival rate of acetabular revision using the reinforcement ring and allograft bone in the reconstruction of severe acetabular bone defects was unsatisfactorily low due to loosening of acetabular components. Because of unfavorable graft incorporation into a host bone, an alternative component and structural support may be employed in the reconstruction of severe acetabular bone defects

INTRODUCTION. It is generally accepted that strong hammering is necessary for the press fit fixation of a joint prosthesis. In this regard, large stress must remain within bone tissues for a long period. This residual stress is, however, some different from the feasible mechanical stimuli for bone tissues because that is stationary, continuous and directed from within outward unlike physiological conditions. The response on this residual stress, which may induce the disorder of the fixation of implant, has not been discussed, yet. In the present study, we designed an experimental method to exert a stationary load from inside of a femur of a rat by inserting a loop spring made from a super elastic wire of titanium alloy. Response of the femur was assessed by bone morphology mainly about the migration of the wire into the bone twelve weeks after the implantation. MATERIALS AND METHODS. We developed a method using a loop spring made of super elastic wire of titanium alloy, which can maintain sufficient magnitude of stress in a rat femur during the experimental period. The loop spring was fabricated with a wire of 0.4 mm diameter before the quenching process. Eleven Wistar rats of ten weeks old were used for the experiments. The loop spring was inserted the right femur, as shown in Figure 1. The left femur was remained intact. The compressive load was added from within outward of bone marrow when the spring was compressed with the insertion into a bone marrow of a rat femur, as shown in Figure 2. The average contact stress was calculated by dividing the elastic force by the spring and bone contact area. The contact stress was distributed from 62 to 94 MPa, which are sufficiently lower than the yield stress of cortical bone [1]. The assessment of bone morphology around the implanted loop spring was performed by micro-CT imaging after the twelve weeks of cage activity. RESULTS. To assess the migration of the spring in the femur, we measured the distance from the endocortical surface to the periphery of the spring, on the micro CT image, as shown in Figure 3. Apparent migration of the spring wire was observed on nine specimens among the eleven. Deep migration over 0.3 mm was observed at three cases. DISCUSSION. The migration of the wire in cortical bone was accompanied with the bone resorption on the surface of the wire toward outside. Therefore, the present findings suggest that stationary load at the implant surface can induce endosteal bone resorption and prosthesis dislocation and protrusion. CONCLUSION. We developed a method for configuring a stationary stress field in a rat femur using a loop spring with the super elasticity. It was found that stationary stress about 70 MPa can induce bone resorption

Total shoulder arthroplasty (TSA) is an effective treatment for end-stage glenohumeral arthritis. The use of high modulus uncemented stems causes stress shielding and induces bone resorption of up to 63% of patients following TSA. Shorter length stems with smaller overall dimensions have been studied to reduce stress shielding, however the effect of humeral short stem varus-valgus positioning on bone stress is not known. The purpose of this study was to quantify the effect of humeral short stem varus-valgus angulation on bone stresses after TSA. Three dimensional models of eight male cadaveric humeri (mean±SD age:68±6 years) were created from computed tomography data using MIMICS (Materialise, Belgium). Separate cortical and trabecular bone sections were created, and the resulting bone models were virtually reconstructed three times by an orthopaedic surgeon using an optimally sized short stem humeral implant (Exactech Preserve) that was placed directly in the center of the humeral canal (STD), as well as rotated varus (VAR) or valgus (VAL) until it was contacting the cortex. Bone was meshed using a custom technique which produced identical bone meshes permitting the direct element-to-element comparison of bone stress. Cortical bone was assigned an elastic modulus of 20 GPa and a Poisson's ratio of 0.3. Trabecular bone was assigned varying stiffness based on CT attenuation. A joint reaction force was then applied to the intact and reconstructed humeri representing 45˚ and 75˚ of abduction. Changes in bone stress, as well as the expected bone response based on change in strain energy density was then compared between the intact and reconstructed states for all implant positions. Both varus and valgus positioning of the humeral stem altered both the cortical and trabecular bone stresses from the intact states. Valgus positioning had the greatest negative effect in the lateral quadrant for both cortical and trabecular bone, producing greater stress shielding than both the standard and varus positioned implant. Overall, the varus and standard positions produced values that most closely mimicked the intact state. Surprisingly, valgus positioning produced large amounts of stress shielding in the lateral cortex at both 45˚ and 75˚ of abduction but resulted in a slight decrease in stress shielding in the medial quadrant directly beneath the humeral resection plane. This might have been a result of direct contact between the distal end of the implant and the medial cortex under loading which permitted load transfer, and therefore load-reduction of the lateral cortex during abduction. Conversely, when the implant was placed in the varus angulation, noticeable departures in stress shielding and changes in bones stress were not observed when compared to the optimal STD position. Interestingly, for the varus positioned implant, the deflection of the humerus under load eliminated the distal stem-cortex contact, hence preventing distal load transfer thus precluding the transfer of load

Introduction. Total shoulder arthroplasty (TSA) is an effective treatment to restore shoulder function and alleviate pain in the case of glenohumeral arthritis [1]. Stress shielding, which occurs when bone stress is reduced due to the replacement of bone with a stiffer metallic implant, causes bone resorption of up to 9% of the humeral cortical thickness following TSA [2]. Shorter length stems and smaller overall geometries may reduce stress shielding [3], however the effect of humeral head backside contact with the resection plane has not yet been fully investigated on bone stress. Therefore, the purpose of this study was to quantify the effect of humeral head contact conditions on bone stresses following TSA. Methods. 3D models of eight male left cadaveric humeri (68±6 years) were generated from CT data using MIMICS. These were then virtually prepared for reconstruction by an orthopaedic surgeon to accept a short-stem humeral implant (Exactech Equinoxe® Preserve) that was optimally sized and placed centrally in the humeral canal. The humeral head was positioned in the inferior-medial position such that contact was achieved on the medial cortex, and no contact existed on the lateral cortex. Three different humeral head backside contact conditions were investigated (Figure 1); full backside contact (FULL), contact with only the inferior-medial half of the resection (INF), and contact with only the superior-lateral half of the resection (SUP). Cortical bone was assigned an elastic modulus of 20 GPa and a Poisson's ratio of 0.3. Trabecular bone was assigned varying stiffness based on CT attenuation [4]. A joint reaction force was then applied representing 45˚ and 75˚ of abduction [5]. Changes in bone stress, as well as the expected bone response based on change in strain energy density [6] was then compared between the intact and reconstructed states. Results. For cortical bone, the full backside contact altered bone stress by 28.9±5.5% compared to intact, which was significantly less than the superior (37.0±3.9%, P=0.022) and inferior (53.4±3.9%, P<0.001) backside contact conditions. Similar trends were observed for changes in trabecular bone stress relative to the intact state, where the full backside contact altered bone stress by 86.3±27.9% compared to intact, compared to the superior and inferior contact conditions, which altered bone stress by 115.2±45.0% (P=0.309) and 197.4±80.2% (P=0.024), respectively. In terms of expected bone response, both the superior and inferior contact resulted in an increase in bone volume with resorbing potential compared to the full contact (Figure 2). Discussion and Conclusions. The results of this study show that full humeral head backside contact with the humeral resection plane is preferable for short stem humeral TSA implants with the head in the inferior-medial position. As expected, the superior contact typically increased resorption potential in the medial quadrant due to the lack of load transfer, however interestingly the inferior contact increased resorption potential in both the lateral and medial quadrants. Analysis of implant micromotion showed that medial liftoff of the implant occurred, which resulted in a lack of load transfer in the most medial aspect of the resection plane. For any figures or tables, please contact the authors directly

Background. Stemless prostheses are recognized to be an effective solution for anatomic total shoulder arthroplasty (TSA) while providing bone preservation and shortest operating time. Reverse shoulder arthroplasty (RSA) with stemless has not showed the same effectiveness, as clinical and biomechanical performances strongly depend on the design. The main concern is related to stability and bone response due to the changed biomechanical conditions; few studies have analyzed these effects in anatomic designs through Finite Element Analysis (FEA), however there is currently no study analyzing the reverse configuration. Additionally, most of the studies do not consider the effect of changing the neck-shaft angle (NSA) resection of the humerus nor the proper assignment of spatial bone properties to the bone models used in the simulations. The aim of this FEA study is to analyze bone response and primary stability of the SMR Stemless prosthesis in reverse with two different NSA cuts and two different reverse angled liners, in bone models with properties assigned using a quantitative computed tomography (QCT) methodology. Methods. Sixteen fresh-frozen cadaveric humeri were modelled using the QCT-based finite element methodology. The humeri were CT-scanned with a hydroxyapatite phantom to allow spatial bone properties assignment [Fig. 1]. Two implanted SMR stemless reverse configurations were considered for each humerus: a 150°-NSA cut with a 0° liner and a 135°-NSA cut with a 7° sloped liner [Fig. 2]. A 105° abduction loading condition was simulated on both the implanted reverse models and the intact (anatomic) humerus; load components were derived from previous dynamic biomechanical simulations on RSA implants for the implanted stemless models and from the OrthoLoad database for the intact humeri. The postoperative bone volume expected to resorb or remodel [Fig. 3a] in the implanted humeri were compared with their intact models in sixteen metaphyseal regions of interest (four 5-mm thick layers parallel to the resection and four anatomical quadrants) by means of a three-way repeated measures ANOVA followed by post hoc tests with Bonferroni correction. In order to evaluate primary stability, micromotions at the bone-Trabecular Titanium interface [Fig. 3b] were compared between the two configurations using a Wilcoxon matched-pairs signed-rank test. The significance level α was set to 0.05. Results. With the exception of the most proximal layer (0.0 – 5.0 mm), the 150°-NSA configuration showed overall a statistically significant lower bone volume expected to resorb (p = 0.011). In terms of bone remodelling, the 150°-NSA configuration had again a better response, but fewer statistically significant differences were found. Regarding micromotions, there was a median decrease (Mdn = 3.2 μm) for the 135°-NSA configuration (Mdn = 40.3 μm) with respect to the 150°-NSA configuration (Mdn = 43.5 μm) but this difference was non-significant (p = 0.464). Conclusions. For the analyzed SMR Stemless configurations, these results suggest a reduction in the risk of bone resorption when a 0° liner is implanted with the humerus cut at 150°. The used QCT-based methodology will allow further investigation, as this study was limited to one single design and load case. For any figures or tables, please contact the authors directly

Aims

This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

The inflammatory cascade associated with prosthetic implant wear debris, in addition to diseases such as rheumatoid arthritis and periodontitis, it is shown to drastically influence bone turnover in the local environment. Ultimately, this leads to enhanced osteoclastic resorption and the suppression of bone formation by osteoblasts causing implant failure, joint failure, and tooth loosening in the respective conditions if untreated. Regulation of this pathogenic bone metabolism can enhance bone integrity and the treatment bone loss. The current study used novel compounds that target a group of enzymes involved with the epigenetic regulation of gene expression and protein function, histone deacetylases (HDAC), to reduce the catabolism and improve the anabolism of bone material in vitro. Human osteoclasts were differentiated from peripheral blood monocytes and cultured over a 17 day period. In separate experiments, human osteoblasts were differentiated from human mesenchymal stem cells isolated from bone chips collected during bone marrow donations, and cultured over 21 days. In these assays, cells were exposed to the key inflammatory cytokine involved with the cascade of the abovementioned conditions, tumour necrosis factor-α (TNFα), to represent an inflammatory environment in vitro. Cells were then treated with HDAC inhibitors (HDACi) that target the individual isoforms previously shown to be altered in pathological bone loss conditions, HDAC-1, −2, −5 and −7. Analysis of bone turnover through dentine resorptive measurements and bone mineral deposition analyses were used to quantify the activity of bone cells. Immunohistochemistry of tartrate resistant acid phosphatase (TRAP), WST-assay and automated cell counting was used to assess cell formation, viability and proliferation rates. Real-time quantitative PCR was conducted to identify alterations in the expression of anti- and pro-inflammatory chemokines and cytokines, osteoclastic and osteoblastic factors, in addition to multiplex assays for the quantification of cytokine/chemokine release in cell supernatant in response to HDACi treatments in the presence or absence of TNFα. TNFα stimulated robust production of pro-inflammatory cytokines and chemokines by PBMCs (IL-1β, TNFα, MCP1 and MIP-1α) both at the mRNA and protein level (p < 0 .05). HDACi that target the isoforms HDAC-1 and −2 in combination significantly suppressed the expression or production of these inflammatory factors with greater efficacy than targeting these HDAC isoforms individually. Suppression of HDAC-5 and −7 had no effect on the inflammatory cascade induced by TNFα in monocytes. During osteoclastic differentiation, TNFα stimulated the size and number of active cells, increasing the bone destruction observed on dentine slices (p < 0 .05). Targeting HDAC-1 and −2 significantly reduced bone resorption through modulation of the expression of RANKL signalling factors (NFATc1, TRAF6, CatK, TRAP, and CTR) and fusion factors (DC-STAMP and β3-integerin). Conversely, the anabolic activity of osteoblasts was preserved with HDACi targeting HDAC-5 and −7, significantly increasing their mineralising capacity in the presence of TNFαthrough enhanced RUNX2, OCN and Coll-1a expression. These results identify the therapeutic potential of HDACi through epigenetic regulation of cell activity, critical to the processes of inflammatory bone destruction

Polyethylene wear-debris induced inflammatory osteolysis is known as the main cause of aseptic loosening and long term revision total hip arthroplasty. Although recent reports suggest that antioxidant impregnated ultra-high molecular weight polyethylene (UHMWPE) wear-debris have reduce the osteolytic potential in vivo when compared to virgin UHMWPE, little is known about if and/or how PE rate of oxidation affects osteolysis in vivo. We hypothesized that oxidized UHMWPE particles would cause more inflammatory osteolysis in a murine calvarial bone model when compared to virgin UHMWPE. Male C57BL/6 eight weeks old received equal amount of particulate debris overlaying the calvarium of (n=12/group): sham treatment (no particles), 2mg (6,75×107 particles/mg) of endotoxin-free UHMWPE particles (PE) or of endotoxin-free highly oxidized-UHMWPE (OX) particles. In vivo osteolysis was assessed using high resolution micro-CT and inflammation with L-012 probe dependent luminescence. At day 10, calvarial bone was examined using high resolution micro-CT, histomorphometric, immunohistochemistry analyses and qRT-PCR to assess OPG, RANK, RANK-L, IL-10, IL-4, IL-1b and TRAP genes expression using the protocol defined by individual TaqManTM Gene Expression Assays Protocol (Applied Biosystems). In vivo inflammation was significantly higher in the OX (1.60E+06 ± 8.28E+05 photons/s/cm2) versus PE (8.48E+05 ± 3.67E+05) group (p=0.01). Although there was a statistically significant difference between sham (−0.27% ± 2.55%) and implanted (PE: −9.7% ± 1.97%, and OX: − 8.38% ± 1.98%) groups with regards to bone resorption (p=0.02), this difference was not significant between OX and PE (p = 0.14). There was no significant difference between groups regarding PCR analyses for OPG, RANK, RANK-L, IL-10, IL-4, IL-1b and TRAP (p = 0.6, 0.7, 0.1, 0.6, 0.3, 0.4, 0.7 respectively). Bone volume density was significantly decreased in PE (13.3%±1.2%) and OX (12.2%±1.2%) groups when compared to sham (15%±0.9%) (p < 0 .05). Histomorphometric analyses showed a significantly decreased Bone Thickness/Tissue Thickness ratio in the implanted group (0.41±0.01 mm and 0.43±0.01 mm) compared to sham group (0.69± 0.01) (p < 0 .001). However, there were no significant difference between OX and PE (p = 0.2). Our findings suggest that oxidized UHMWPE particles display increased inflammatory potential. Results were not significant regarding in vivo or ex vivo osteolysis. As antioxidant-diffused UHMWPE induce less inflammation activity in vivo, the mechanism by which they cause reduced osteolysis requires further investigation