Aims

Disorders of bone integrity carry a high global disease burden, frequently requiring intervention, but there is a paucity of methods capable of noninvasive real-time assessment. Here we show that miniaturized handheld near-infrared spectroscopy (NIRS) scans, operated via a smartphone, can assess structural human bone properties in under three seconds.

Osteoarthritis (OA) is a chronic degenerative joint disease with cartilage degeneration, subchondral bone sclerosis, synovial inflammation and osteophyte formation. Sensory nerves play an important role in bone metabolism and in the progression of inflammation. This study explored the effects of capsaicin-induced sensory nerve denervation on OA progression in mice. This study was approved by the Institutional Animal Care and Use Committee. OA was induced via destabilization of the medial meniscus (DMM). Sensory denervation was induced by subcutaneous injection of capsaicin (90mg/kg) one week prior to DMM. One week after capsaicin injection, sensory denervation in the tibia was confirmed by immunofluorescent staining with calcitonin gene-related peptide (CGRP)-specific antibodies. Four weeks after DMM, micro-CT scans, histological analysis and RT-PCR tests were performed to evaluate OA progression. Statistical analysis was performed using SPSS 13. P values of less than 0.05 were considered statistically significant. Subcutaneous injection of capsaicin successfully induced tibial sensory denervation (n=3), which aggravated OA by increasing subchondral bone resorption. The Osteoarthritis Research Society International (OARSI) score of the capsaicin+DMM group (n=8) (11.81±2.92) was significantly higher (P=0.003) than the score of the vehicle+DMM group (n=8) (8.31±1.80). The BV/TV of the tibial subchondral bone in the capsaicin+DMM group (n=8) was 55.67%±3.08, which was significantly lower (P < 0 .001) than in the vehicle+DMM group (n=8) (86.22%±1.92). In addition, the level of expression of somatostatin in the capsaicin+DMM group (n=8) was lower than in the vehicle+DMM group (n=8) (P=0.007). Capsaicin-induced sensory denervation increased tibial subchondral bone resorption, reduced the expression of somatostatin and eventually exacerbated the existing cartilage degeneration in mice. Despite capsaicin is often used clinically to relieve OA pain, its safety is still controversial according to the OARSI guidelines for the non-surgical management of knee osteoarthritis. The findings of our study suggest that application of capsaicin, although effective in relieving pain, may accelerate the progression of existing OA

Introduction. UHMWPE particle-induced osteolysis is one of the major causes of arthroplasty revisions. Recent in vitro findings have suggested that UHMWPE wear particles containing vitamin-E (VE) may have reduced functional biologic activity and decreased potential to cause osteolysis (Bladed C. L. et al, JBMR B 2012 and 2013). This is of significant importance since VE-stabilized cross-linked UHMWPEs were recently introduced for clinical use, and there is no in vivo data determining the effects of wear debris. In this study we hypothesized that particles from VE-stabilized, radiation cross-linked UHMWPE (VE-UHMWPE) would cause reduced levels of osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Methodology. Study groups were the following: 1). Radiation cross-linked VE-UHMWPE (0.8% by weight) diffused after 100 kGy; 2). Radiation cross-linked virgin UHMWPE (virgin UHMWPE); 3). Sham controls. Particle generation and implantation: UHMWPE was sent to Bioengineering Solutions (Oak Park, IL) for particle generation. After IACUC approval, C57BL/6 mice (n=12 for each group) received equal amount of particulate debris (3mg) overlying the calvarium and were euthanized after 10 days. Micro-CT scans: High resolution micro-CT scans were performed using a set voltage of 70 kV and current of 70 µA. Topographical Grading Scale: Each calvarial bone was blindly scored using the following scale: 0=No osteolysis, defined as intact bone; 1=Minimal osteolysis, affecting 1/3 or less of the bone area; 2=Moderate osteolysis, affecting at least 2/3 of the bone area; 3=Severe osteolysis, defined as completely osteolytic bone. Histology: H&E and TRAP staining was done on tissue to confirm micro-CT findings and quantify osteoclasts. Statistical Analysis: Inter-rater analysis was done using Cohen's kappa analysis. An inter-rater coefficient >0.65 was considered as high inter-rater agreement. Comparison between groups was made using one-way ANOVA with post hoc Bonferroni correction for multiple comparisons. Correlations are reported as Spearman's rho. P-value<0.05 was considered statistically significant. Results. More than 83% of the VE-UHMWPE and more than 85% of the virgin UHMWPE particles measured less than 1 µm in mean particle size. There was a statistically significant greater level of osteolysis visualized on the topographical grading scale in calvaria implanted with virgin UHMWPE wear particles. Micro-CT findings were confirmed histologically (Fig. 1). A greater amount of inflammatory tissue overlaying the calvaria was observed in the virgin UHMWPE group when compared to both shams and VE-UHMWPE groups. Post hoc analysis revealed significant difference between VE-UHMWPE and virgin UHMWPE for the topographical osteolysis grading score (p=0.002) but no difference in osteoclast counts (p=0.293). Discussion and Conclusion. This is the first in vivo study reporting the effects of clinically-relevant UHMWPE particles generated from a VE-UHMWPE implant that is in current clinical use. These results suggest that VE-UHMWPE particles have reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model. Arthroplasty procedures using VE-UHMWPE might be less susceptible to peri-prosthetic loosening caused by wear debris

Purpose. Previous retrieval studies demonstrate increased tibial baseplate roughness leads to higher polyethylene backside wear in total knee arthroplasty (TKA). Micromotion between the polyethylene backside and baseplate is affected by the locking mechanism design and can further increase backside wear. This study's purpose was to examine modern locking mechanisms influence, in the setting of both polished and non-polished tibial baseplates, on backside tibial polyethylene damage and wear. Methods. Five TKA models were selected with different tibial baseplate and/or locking mechanism designs. Six retrieval tibial polyethylenes from each TKA model were matched based on time in vivo (TIV), age at TKA revision, BMI, gender, number of times revised, and revision reason. Two observers visually assessed each polyethylene. Primary outcomes were visual damage scores, individual visual damage modes, and linear wear rates determined on micro-computed tomography (micro-CT) scan in mm/year. Demographics were compared by one-way ANOVA. Damage scores, damage modes, and linear wear were analyzed by the Kruskal-Wallis test and Dunn's multiple comparisons test. Results. There were no differences among the groups based on TIV (p=0.962), age (p=0.609), BMI (p=0.951), gender, revision number, or reason for revision. There was a significant difference across groups for visual total damage score (p=0.031). The polished tibial design with a partial peripheral capture locking mechanism and anterior constraint demonstrated a significantly lower score compared to one of the non-polished tibial designs with a complete peripheral-rim locking mechanism (13.0 vs. 22.0, p=0.019). Otherwise, mean total damage scores were not significant between groups. There were identifiable differences among the groups based on abrasions (p=0.006). The polished design with a tongue-in-groove locking mechanism demonstrated a significantly higher score compared to one of the designs with a non-polished baseplate (5.83 vs. 0.83, p=0.016). Only the two designs with non-polished baseplates demonstrated dimpling (5.67 and 8.67), which was significant when compared against all other groups (p<0.0001), but not against each other (p>0.99). No other significant differences were identified when examining burnishing, cold flow, scratching, or pitting. No polyethylene components exhibited embedded debris or delamination. There was a significant difference among groups for linear wear on micro-CT scanning (p=0.003). Two of the polished baseplate designs, one with the partial peripheral rim capture and one with the tongue-in-groove locking mechanism, demonstrated significantly lower wear rates than the non-polished design with a complete peripheral-rim locking mechanism (p=0.008 and p=0.032, respectively). There were no other differences in wear rates between groups. Conclusions. Total damage scores and wear rates were similar between all groups except when comparing two of the polished TKA designs to one of the non-polished baseplate designs. The other TKA model with a non-polished tibial baseplate had similar damage scores and wear rates to the polished designs, likely due to its updated locking mechanism. Dimpling was specific for non-polished tibial baseplates while abrasions were identified in the design with a tongue-in-groove locking mechanism. Our study showed even in the setting of a non-polished tibial baseplate, modern locking mechanisms can decrease backside damage and wear similar to that of other current generation TKA designs. For any figures or tables, please contact authors directly (see Info & Metrics tab above).

Introduction. Mechanical property relationships used in the computational modeling of bones are most often derived using mechanical testing of normal cadaveric bone. However, a significant percentage of patients undergoing joint arthroplasties exhibit some form of pathologic bone disease, such as osteoarthritis. As such, the objective of this study was to compare the micro-architecture and apparent modulus (E. app. ) of humeral trabecular bone in normal cadaveric specimens and bone extracted from patients undergoing total shoulder arthroplasty. Methods. Micro-CT scans were acquired at 20 µm spatial resolution for humeral heads from non-pathologic cadavers (n=12) and patients undergoing total shoulder arthroplasty (n=10). Virtual cylindrical cores were extracted along the medial-lateral direction. Custom-code was used to generate micro finite element models (µFEMs) with hexahedral elements. Each µFEM was assigned either a homogeneous tissue modulus of 20 GPa or a heterogeneous tissue modulus scaled by CT- intensity. Simulated compression to 0.5% apparent strain was performed in the medial-lateral direction. Morphometric parameters and apparent modulus-bone volume fraction relationships were compared between groups. Results. Comparing morphometric parameters, arthroplasty patients had significantly larger bone volume fractions (p = .023) and mean trabecular separation (p = .031), but no significant differences in mean trabecular thickness (p = .060) or trabecular number (p = .178). Variations were observed in the fit curves between normal and arthroplasty cases, with normal bone being best fit by power relationships, and arthroplasty bone exhibiting a more linear relationship. There was no significant difference in mean apparent modulus for homogeneous tissue moduli (p = .060) but was a significant difference for heterogeneous tissue moduli (p = .038). DISCUSSION. Consistent with previously developed relationships that map apparent mechanical properties, normal cadaveric bone was best fit by a power relationship with an exponential coefficient over 2. However, the apparent modulus- volume fraction relationship in the arthroplasty patient bone exhibited a more linear relationship. These results suggest that the architectural and mechanical properties of normal cadaveric and arthroplasty patient trabecular bone are not equal. Since these relationships are used to map apparent mechanical properties to computational models, these preliminary results suggest that relationships derived from cadaveric normal bone may map the apparent mechanical properties differently than patients who undergo arthroplasty. Additional samples added to this dataset will allow for mechanical property relationships to be developed that account for these bone mechanical property variations. This has the potential to greatly improve the computational modeling of patients undergoing arthroplasty procedures and computational models that are used to design and improve shoulder arthroplasty components

Introduction. The use of Additive Manufacturing (AM) to 3D print titanium implants is becoming widespread in orthopaedics, particularly in producing cementless porous acetabular components that are either custom-made or off-the-shelf; the primary design rationale for this is enhanced bony fixation by matching the porosity of bone. Analysis of these retrieved components can help us understand their performance; in this study we introduce a non-destructive method of the retrieval analysis of 3D printed implants. Material and methods. We examined 11 retrieved 3D printed acetabular cups divided into two groups: “custom-made” (n = 4) and “off-the-shelf” (n = 7). A macroscopic visual analysis was initially performed to measure the area of tissue ongrowth. High resolution imaging of each component was captured using a micro-CT scanner and 3D reconstructed models were used to assess clinically relevant morphometric features of the porous structure: porosity, porous structure thickness, pore size and strut thickness. Optical microscopy was also used as a comparison with microCT results. Surface morphology and elemental composition of the implants were investigated with a Scanning Electron Microscope (SEM) coupled with an Energy Dispersive X-ray Spectroscope (EDS). Statistical analysis was performed to evaluate possible differences between the two groups. Results. We found a spread of tissue coverage, median of 81% (23 – 95), with a trend with time in situ. Custom implants showed a higher spread of porosity, with median value of 74.11% (67.94 – 81.01), due to the presence of differently designed porous areas. Off-the-shelf cups had median porosity of 72.49% (66.67 – 73.07), but there was no significant difference between the two groups (p = 0.164). There was a significant difference in the thickness of the porous structure of the two groups, which were 3.918 mm (3.688 – 4.102) and 1.289 mm (1.235 – 1.364), respectively (p = 0.006). SEM output showed specific morphological features of 3D printed object; EDS analysis suggested that no chemical modifications occurred in vivo, with elemental ratios (Ti/Al = 14; Ti/V = 21; Al/V = 1.51) comparable to previously published results. Conclusion. This is one of the first retrieval studies of 3D printed orthopaedic implants. We introduced a method for the investigation of these components and micro-CT scanning enabled the non-destructive assessment of the porous structure. This work represents the first step in understanding the performance of 3D printed implants

We sought to determine what dimensional changes occurred from wear testing of a total knee implant, as well as whether any changes developed within the polyethylene subsurface. Three fixed bearing implants underwent wear simulator testing to 6.1 million cycles. Gravimetric analysis and micro-CT scans were performed pre-test, mid-test, and post-test. Wear volume and surface deviations were greater during 0–3.2 million cycles (91±12 mm. 3. ) than from 3.2–6.1 million cycles (52±18 mm. 3. ). Deviations (wear and creep) occurred across all surfaces of the tibial inserts, including the articular surface, backside surface, sides, and locking mechanism. No subsurface changes were found. The micro-CT results were a useful adjunct to gravimetric analysis, better defining the dimensional changes that occurred with testing and ruling out subsurface fatigue

Introduction. Trabecular bone transmits loads to the cortical shell and is therefore most active in bone remodeling. This remodeling alters trabecular material strength thereby changing the bending stiffness. Accounting for trabecular material heterogeneity has been shown to improve empirical-µFEM correlations by allowing for more realistic trabecular bending stiffness. In µFEMs to reduce computation time, region averaging is often used to scale image resolution. However, region averaging not only alters trabecular architecture, but inherently alters the CT-intensity of each trabeculae. The effect of CT-intensity variations on computationally derived apparent modulus (E. app. ) in heterogenous µFEMs has not been discussed. The objectives of this study were to compare trabecular E. app. among i) hexahedral and tetrahedral µFEMs, ii) µFEMs generated from 32 µm, 64 µm, and 64 µm down-sampled from 32 µm µ-CT scans, and iii) µFEMs with homogeneous and heterogeneous tissue moduli. Methods. Fourteen cadaveric scapulae (7 male; 7 female) were micro-CT scanned at two spatial resolutions (32 µm & 64 µm). Virtual bone cores were extracted from the glenoid vault, maintaining a 2:1 aspect ratio, to create µFEMs from the 32 µm, 64 µm, and down-sampled 64 µm scans. Custom code was used to generate µFEMs with 8-node hexahedral elements (HEX8), while maintaining the bone volume fraction (BV/TV) of each HEX8 32 µm model (BV/TV=0.24±0.10). Each virtual core was also generated as a 10-node tetrahedral (TET10) µFEM. All µFEMs were given either a homogeneous tissue modulus of 20 GPa, or a heterogeneous tissue modulus scaled by CT-intensity. All FEMs were constrained with identical boundary conditions and compressed to 0.5% apparent strain. The apparent modulus of each model was compared. Results. Comparing error in mean E. app. , TET10 32 µm µFEMs with a homogeneous tissue modulus had an error of 7%, and a heterogeneous tissue modulus an error of 1%. Larger errors occurred for both down-sampled and scanned 64 µm µFEMs with both homogeneous and heterogeneous tissue moduli. The error in E. app. as a function of trabecular thickness (Tb.Th*) was larger for µFEMs generated from 64 µm scans, than the down-sampled 64 µm µFEMs. The errors were lowest for Tb.Th* greater than 0.225 mm and for µFEMs generated with heterogeneous tissue moduli. The error in E. app. as a function of volume fraction (BV/TV) was lowest above 0.225 for µFEMs with both homogeneous and heterogeneous tissue moduli and hexahedral and tetrahedral elements. Error was lower for the down-sampled 64 µm µFEMs versus scanned 64 µm µFEMs. DISCUSSION. This study compared the E. app. of linear isotropic µFEMs generated with hexahedral or tetrahedral elements from 32 µm, 64 µm, or down-sampled 64 µm µ-CT scans, with a homogeneous or heterogeneous tissue modulus. It was found that except at the highest spatial resolution, tetrahedral elements underestimate E. app. Down-sampling to half the original scan spatial resolution is not equivalent in E. app. to FEMs generated from scans at that spatial resolution, and both models underestimate the E. app. of the highest spatial resolution models. In general, accounting for trabecular material heterogeneity decreased errors in E. app.

The primary stability of an uncemented femoral total knee replacement component is provided by press-fit forces at the bone-implant interface. This press-fit is achieved by resecting the bone slightly larger than the inner dimensions of the implant, resulting in a so-called interference fit. Previous animal studies have shown that an adequate primary stability is required to minimize micromotions at the bone-implant interface to achieve bone-ingrowth, which provides the secondary (long-term) fixation. It is assumed that during implantation a combination of elastic and plastic deformation and abrasion of the bone will occur, but little is known about what happens at the bone-implant interface and how much interference fit eventually is achieved. Purpose of this study was therefore to assess the actual and effective interference fit and the amount of bone damage during implantation of an uncemented femoral knee component. In this study, five cadaveric distal femora were prepared and femoral knee components were implanted by an experienced surgeon. Micro-CT scans and conventional CT-scans were obtained pre- and post-implantation for geometrical measurements and to measure bone mineral density. In addition, the position of the implant with respect to the bone was determined by optical scanning of the reconstructions (Figure.1). By measuring the differences in surface geometry, assessments were made of the cutting error, the actual interference fit, the amount of bone damage, and the effective interference fit. Our analysis showed an average cutting error of 0.67± 0.17 mm, which pointed mostly towards bone under-resections. We found an average actual AP interference fit of 1.48± 0.27 mm, which was close to the nominal value of 1.5 mm. We observed combinations of bone damage and elastic deformation in all bone specimens (Figure. 2), which showed a trend to be related with bone density. Higher bone density tended to lead to lower bone damage and higher elastic deformation (Figure. 3). The results of the current study indicate different factors that interact while implanting an uncemented femoral knee component. This knowledge can be used to fine-tune design criteria of femoral components and obtain adequate primary stability for all patients in a more predictable way

Orthopaedic reconstruction procedures to combat osteoarthritis, inflammatory arthritis, metabolic bone disease and other musculoskeletal disorders have increased dramatically, resulting in high demand on the advancement of bone implant technology. In the past, joint replacement operations were commonly performed primarily on elderly patients, in view of the prosthesis survivorship. With the advances in surgical techniques and prosthesis technology, younger patients are undergoing surgeries for both local tissue defects and joint replacements. This patient group is now more active and functionally more demanding after surgery. Today, implanted prostheses need to be more durable (load-bearing), they need to better match the patient's original biomechanics and be able to survive longer. Additive manufacturing (AM) provides new possibilities to further combat the problem of stress-shielding and promote better bone remodelling/ingrowth and thus long term fixation. This can be accomplished by matching the varying strain response (stiffness) of trabecular or subchondral bone locally at joints. The purpose of this research is therefore to determine whether a porous structure can be produced that can match the required behaviour and properties of trabecular bone regardless of skeletal location and can it be incorporated into a long-term implant. A stochastic structure visually similar to trabecular bone was designed and optimised for AM (Figure 1) and produced over a range of porosities in multiple materials, Stainless Steel 316, Titanium (Grade 23 – Ti6Al4V ELI) and Commercially Pure Titanium (Grade 2) using a Renishaw AM250 metal additive manufacturing system. Over 150 cylindrical specimens were produced per material and subjected to a compression test to determine the specimens' Elastic Modulus (Stiffness) and Compressive Yield Strength. Micro-CT scans and gravimetric analysis were also performed to determine and validate the specimens' porosity. Results were then graphed on a Strength vs. Stiffness Ashby plot (Figure 2) comparing the values to those of trabecular bone in the tibia and femur. It was found that AM can produce porous structures with an elastic modulus as low as 100 MPa up to 2.7 GPa (the highest stiffness investigated in this study). Titanium structures with a stiffness <500MPa had compressive strengths towards the bottom range of similar stiffness trabecular bone. Between 500 MPa − 1 GPa Titanium AM porous structures match the compressive strength of equivalent stiffness trabecular bone and from 1 GPa − 2 GPa the Ti structures exceed the strength of equivalent stiffness trabecular bone up to ∼2.5 times and consequently increase by a power law. These results show that AM can produce structures with similar stiffness to trabecular bone over a range of skeletal locations whilst matching or exceeding the compressive strength of bone. The results have not yet taken into account fatigue life with the fatigue life of these types of structures tending to be between 0.1 – 0.4 of their compressive strength. This means that a titanium porous structure would need to be 2.5 – 10 times stiffer or stronger than the portion of trabecular bone it is replacing. This data is highly encouraging for AM manufactured, bone stiffness matched implant technology

Introduction. Osteoarthritis continues to be a major cause of pain and disability. The pathological processes leading to the end-stage of joint degeneration remain poorly understood. Advances in radiological imaging have the potential to improve understanding of the structural and functional changes observed in OA. The aim of this study was to describe the microarchitecture of the femoral head in osteoarthritis. Methods. Twenty osteoarthritic femoral heads underwent micro-computed tomography scanning at 30µm. Four parameters of micro-architecture and structure were determined: bone volume ratio (BV:TV), trabecular thickness, structural model index and degree of anisotropy. The femoral head was divided into 27 cubic volumes of interest. Analysis of variance (ANOVA) was used to assess differences between regions. Cystic and sclerotic changes were assessed qualitatively. Results. There was marked heterogeneity in the density and architecture throughout the head. The greatest density and trabecular thickness was found in a central core that extended from the medial calcar to the physeal scar (ANOVA p< 0.001). This region also correlated with the greatest degree of anisotropy (DA=2.4, p< 0.001), plate-like trabeculae (SMI=−0.22, p< 0.001). All osteophytes exhibited a radially orientated trabecular pattern, in close relation to the superior and inferior nutrient foramina in the region of the physeal scar. Cartilage eburnation was associated with loss of the normal subchondral structure of radially-orientated trabeculae and replacement by thickened lamellar bone. Discussion. This study demonstrated marked structural heterogeneity at the 30 µm resultion and the micro-architectural changes associated osteophytes, cysts and sclerosis. The elucidation of the osseous microstructure can clarify the interaction between geometry and function in OA. Further work is necessary to relate this to underlying pathogenic process to determine the temporal sequence of microarchitectural changes

Introduction. In vitro findings (Bladed CL et al. ORS 2011 and J Biomed Mater Res B Appl Biomater, 2012) have suggested that UHMWPE wear particles containing vitamin-E (VE) may have reduced functional biologic activity and decreased osteolytic potential. Currently, there is no in vivo data determining the effects of wear debris from this new generation of implants. In this study we hypothesized that particles from VE-stabilized, radiation cross-linked UHMWPE (VE-UHMWPE) would cause reduced levels of osteolysis in a murine calvarial bone model when compared to virgin gamma irradiated cross-linked UHMWPE. Methods. Study groups: 1). Radiation cross-linked VE-UHMWPE, 0.8% by weight, diffused after 100 kGy; 2). Radiation cross-linked virgin UHMWPE (virgin UHMWPE); 3). Shams. Particle generation and implantation: UHMWPE was sent to Bioengineering Solutions for particle generation. After IACUC approval, C57BL/6 mice (n = 12 for each group) received 3 mg of particulate debris overlying the calvarium and euthanized after 10 days. Micro-CT scans: Performed using an X-Tek-HMX-ST-225 with 70 kV voltage and 70 μA current. Topographical Grading Scale: Each calvarial bone was blindly scored with the following scale: 0 = No osteolysis, defined as intact bone; 1 = Minimal osteolysis, affecting 1/3 or less of the bone area; 2 = Moderate osteolysis, affecting at least 2/3 of the bone area; 3 = Severe osteolysis, defined as completely osteolytic bone. Histology H&E and TRAP staining was performed. Statistical Analysis: Inter-rater analysis was performed using Cohen's kappa analysis. Inter-rater coefficient >0.65 was considered as high inter-rater agreement. Comparison between groups was made using one-way ANOVA with post hoc Bonferroni correction for multiple comparisons. Correlations are reported as Spearman's rho. A p-value<0.05 was considered statistically significant. Results. More than 83% of the VE-UHMWPE and more than 85% of the virgin UHMWPE particles measured less than 1 μm in mean particle size. There was a statistically significant greater level of osteolysis visualized on the topographical grading scale in calvaria implanted with virgin UHMWPE wear particles. The micro-CT findings were confirmed histologically (Fig. 1). A greater amount of inflammatory tissue overlaying the calvaria was observed in the virgin UHMWPE group when compared to both shams and VE-UHMWPE groups. Post hoc analysis revealed significant difference between VE-UHMWPE and virgin UHMWPE for the topographical osteolysis grading score (p = 0.002) but no difference in osteoclast count (p = 0.293). Discussion/Conclusion. This is the first in vivo study reporting the effects of clinically-relevant UHMWPE particles generated from a VE-UHMWPE implant that is in current clinical use. These results suggest that VE-UHMWPE particles have reduced osteolysis potential in vivo when compared to virgin, highly cross-linked UHMWPE in a murine calvarial bone model

Sclerostin is a negative regulator of osteoblast differentiation and bone formation. Expressed by osteocytes, it acts through antagonising the Wnt/â-catenin pathway and/or BMP activity. Distraction osteogenesis, used for limb lengthening and reconstruction, can be complicated by disuse osteopenia and poor healing response, both of which would benefit from pro anabolic therapy. We examined the effects of Sclerostin Antibody (Scl-AbIII, Amgen Inc.,) in a rat model of distraction osteogenesis. A femoral osteotomy was stabilized with an external fixator in male Sprague Dawley rats. After a week of latency, the gap was distracted twice daily for 14 days to a total of 7 mm. Saline or Scl-Ab was administered twice weekly throughout the distraction period and up to 4, 6 or 8 weeks post commencement of distraction. Three groups were examined: Saline, Continuous Scl-Ab throughout the study (C Scl-Ab), and Delayed Scl-Ab with commencement of Scl-Ab after distraction (D Scl-Ab). Regenerate bone mineral content (BMC), determined by DEXA, was increased 36% at 4 weeks and 86% at 6 weeks with C Scl-Ab, resulting in a 65% increase in bone mineral density (BMD) at 6 weeks, compared with Saline (p<0.01). D Scl-Ab treatment showed a 41% increase in BMC and a 31% increase in BMD compared with Saline at 6 weeks (p<0.05). At 8 weeks, C Scl-Ab remained significantly increased over Saline (72% in BMC; 60% in BMD). Micro-CT scans of the regenerate revealed increases in bone volume of 88% with C Scl Ab and 65% with D Scl-Ab compared with Saline at 6 weeks (p<0.05). By 8 weeks, these increases were 36% for C Scl-Ab (p<0.05) and 37% for D Scl-Ab compared with Saline (p<0.01). Importantly, mean moment of inertia was increased over two-fold in both Scl-Ab groups at 6 weeks compared with Saline (p<0.05). Histology at 6 weeks confirmed micro-CT data with 85–88% increases in bone volume/tissue volume (BV/TV) in the regenerate with both C Scl-Ab and D Scl-Ab compared with Saline (p<0.05). Analysis of bone formation at 6 weeks revealed increases in mineral apposition rate of 56% in C Scl-Ab and 52% in D Scl-Ab compared with Saline (p<0.05). Scl-Ab treatment increased bone formation in this model of distraction osteogenesis, resulting in a larger regenerate callus (increased BMC and BV/TV). We expect further studies to reveal increases in mechanical strength. Scl-Ab may hold promise as a therapeutic to accelerate regenerate formation and consolidation in distraction osteogenesis for limb reconstruction