Validation of the Chicken Femur as a Model for the Human Metacarpal: An In-Vitro Analysis.

Background: The aim of this study was to evaluate the chicken femur as a laboratory model for the human metacarpal by comparing the bone microarchitecture and mechanical properties of chicken femurs to human cadaveric metacarpals. Methods: Sixteen fresh chicken femora and 20 fresh frozen cadaveric human metacarpals were imaged using a micro computed tomography scanner. The bones were then mechanically tested using four-point-bending and torsional testing. Results: There were no significant differences in macroscopic features between chicken femora and human metacarpals, including overall length, external radius, internal radius, cortical width and cross-sectional area of the diaphyseal cortex (p > 0.05). There were no significant differences in the trabecular number and spacing in the distal metaphysis of both groups (p > 0.05). The diaphysis and proximal metaphysis did not share any microarchitectural similarities. Four-point bending tests resulted in significantly higher yield forces, ultimate force, failure points and stiffness in human metacarpals (p < 0.05). Torsion tests resulted in significant higher ultimate torque and torsional rigidity in human metacarpals (p < 0.05). Conclusions: The chicken femur has structural and biomechanical differences to the fresh frozen human metacarpal despite the similarity in their macroscopic features.

Critical Examination of Methods to Determine Tibiofemoral Kinematics and Tibial Contact Kinematics Based on Analysis of Fluoroscopic Images.

Goals of knee replacement surgery are to restore function and maximize implant longevity. To determine how well these goals are satisfied, tibial femoral kinematics and tibial contact kinematics are of interest. Tibiofemoral kinematics, which characterize function, is movement between the tibia and femur whereas tibial contact kinematics, which is relevant to implant wear, is movement of the location of contact by the femoral implant on the tibial articular surface. The purposes of this review article are to describe and critique relevant methods to guide correct implementation. For tibiofemoral kinematics, methods are categorized as those which determine (1) relative planar motions and (2) relative three-dimensional (3D) motions. Planar motions are determined by first finding anterior-posterior (A-P) positions of each femoral condyle relative to the tibia and tracking these positions during flexion. Of the lowest point (LP) and flexion facet center (FFC) methods, which are common, the lowest point method is preferred and the reasoning is explained. 3D motions are determined using the joint coordinate system (JCS) of Grood and Suntay. Previous applications of this JCS have resulted in motions which are largely in error due to "kinematic crosstalk." Requirements for minimizing kinematic crosstalk are outlined followed by an example, which demonstrates the method for identifying a JCS that minimizes kinematic crosstalk. Although kinematic crosstalk can be minimized, the need for a JCS to determine 3D motions is questionable based on anatomical constraints, which limit varus-valgus rotation and compression-distraction translation. Methods for analyzing tibial contact kinematics are summarized and validation of methods discussed.

A Controlled Variable Study of the Biomechanical Properties of the Proximal Femur before and after Cancellous Bone Removal.

OBJECTIVE: The biomechanical characteristics of proximal femoral trabeculae are closely related to the occurrence and treatment of proximal femoral fractures. Therefore, it is of great significance to study its biomechanical effects of cancellous bone in the proximal femur. This study examines the biomechanical effects of the cancellous bone in the proximal femur using a controlled variable method, which provide a foundation for further research into the mechanical properties of the proximal femur. METHODS: Seventeen proximal femoral specimens were selected to scan by quantitative computed tomography (QCT), and the gray values of nine regions were measure to evaluated bone mineral density (BMD) using Mimics software. Then, an intact femur was fixed simulating unilateral standing position. Vertical compression experiments were then performed again after removing cancellous bone in the femoral head, femoral neck, and intertrochanteric region, and data were recorded. According to the controlled variable method, the femoral head, femoral neck, and intertrochanteric trabeculae were sequentially removed based on the axial loading of the intact femur, and the displacement and strain changes of the femur samples under axial loading were recorded. Gom software was used to measure and record displacement and strain maps of the femoral surface. RESULTS: There was a statistically significant difference in anteroposterior displacement of cancellous bone destruction in the proximal femur (p < 0.001). Proximal femoral bone mass explained 77.5% of the strength variation, in addition proximal femoral strength was mainly affected by bone mass at the level of the upper outer, lower inner, lower greater trochanter, and lesser trochanter of the femoral head. The normal stress conduction of the proximal femur was destroyed after removing cancellous bone, the stress was concentrated in the femoral head and lateral femoral neck, and the femoral head showed a tendency to subside after destroying cancellous bone. CONCLUSION: The trabecular removal significantly altered the strain distribution and biomechanical strength of the proximal femur, demonstrating an important role in supporting and transforming bending moment under the vertical load. In addition, the strength of the proximal femur mainly depends on the bone density of the femoral head and intertrochanteric region.

Stromal Lineage Precursors from Rodent Femur and Tibia Bone Marrows after Hindlimb Unloading: Functional Ex Vivo Analysis.

Rodent hindlimb unloading (HU) model was developed to elucidate responses/mechanisms of adverse consequences of space weightlessness. Multipotent mesenchymal stromal cells (MMSCs) were isolated from rat femur and tibia bone marrows and examined ex vivo after 2 weeks of HU and subsequent 2 weeks of restoration of load (HU + RL). In both bones, decrease of fibroblast colony forming units (CFU-f) after HU with restoration after HU + RL detected. In CFU-f and MMSCs, levels of spontaneous/induced osteocommitment were similar. MMSCs from tibia initially had greater spontaneous mineralization of extracellular matrix but were less sensitive to osteoinduction. There was no recovery of initial levels of mineralization in MMSCs from both bones during HU + RL. After HU, most bone-related genes were downregulated in tibia or femur MMSCs. After HU + RL, the initial level of transcription was restored in femur, while downregulation persisted in tibia MMSCs. Therefore, HU provoked a decrease of osteogenic activity of BM stromal precursors at transcriptomic and functional levels. Despite unidirectionality of changes, the negative effects of HU were more pronounced in stromal precursors from distal limb-tibia. These observations appear to be on demand for elucidation of mechanisms of skeletal disorders in astronauts in prospect of long-term space missions.

Computational prediction of the long-term behavior of the femoral density after THR using the Silent Hip stem.

Aseptic loosening due to the progressive periprosthetic bone resorption following total hip replacement is a crucial concern, that causes complications and failure of the arthroplasty surgery. The mismatch in stiffness between the hip implant and the surrounding femoral bone is one of the key factors leading to bone density resorption. This paper aimed to investigate the long-term response of the femoral bone after THR using the Silent Hip stem. For this purpose, a validated thermodynamic-based computational model was used to compute the change in bone density before and after THR. This model incorporated essential factors involved in bone remodeling process, such as mechanical loading, and biochemical affinities. The results of the numerical simulations using 3D finite element analysis were analyzed in five zones of interest qualitatively and quantitatively. Bone density predictions showed notable bone resorption in cervical areas, specifically in zone 1 and zone 5 of -18.7% and -14%, respectively. Conversely, bone formation was observed in the greater trochanter area (zone 2) of +25%. Stress shielding seemed to occur at cervical area due to the reduction in the mechanical loading in this region. Based on the quantitative analysis of the bone density distribution throughout the femoral bone, it appears that the Silent Hip stem achieved less bone resorption compared to conventional hip stem designs reported in the literature, which could be used for active patients.

Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes.

Background: Recently, lineage-tracing studies demonstrated that parathyroid hormone and anti-sclerostin antibody (Scl-Ab) can convert bone lining cells (BLCs) into active osteoblasts. However, BLCs might also be differentiated into other lineages. Here we investigated whether BLCs could differentiate into bone marrow adipocytes (BMAds) and whether Scl-Ab could suppress this process. Methods: Dmp1-CreERt2:mTmG mice were injected with 0.5 mg of 4-hydroxytamoxifen once weekly from postnatal week 4 to week 8. The mice were treated with either vehicle or rosiglitazone for 8 weeks (weeks 12-20). Moreover, they were administered either vehicle or Scl-Ab (50 mg/kg) twice weekly for 4 weeks (weeks 16-20, N = 4-6/group). We chased the GFP+ cells from the endosteal surface to the bone marrow (BM) of the femur. Using immunohistochemical staining, the numbers of perilipin+ or GFP+/perilipin double+ cells in the BM were quantified. In addition, serum N-terminal propeptide of type I procollagen (P1NP) levels were measured at each time point, and bone mass was analyzed at 20 weeks using micro-computed tomography. Results: Scl-Ab administration significantly reversed the decreases in bone parameters induced by rosiglitazone. Plump GFP+ cells, presumably active osteoblasts, and extremely flat GFP+ cells, presumably BLCs, were present on the endosteal surface of the femur at 8 and 12 weeks, respectively, in line with prior findings. When we chased the GFP+ cells, rosiglitazone significantly increased the number of GFP/perilipin double+ BMAds compared to the effects of the vehicle (P < 0.001), and overlapping Scl-Ab administration decreased the number of GFP/perilipin double + BMAd compared to rosiglitazone alone (P < 0.001). In addition, we found that osteoblast lineage cells such as BLCs might express PPARγ on immunohistochemical staining. When rosiglitazone was administered to Rip-Cre:mTmG mice, GFP+ cells were not present on the endosteal surface or in the BM of the femur; however, they were present in the pancreas. Conclusion: BLCs could be sources of BMAds, and rosiglitazone could stimulate the differentiation of osteoblast lineage cells into BMAds. Suppression of the differentiation of osteoblast lineage cells into BMAds might contribute to anabolic effects resulting from the pharmacologic inhibition of sclerostin.

Temporal response of an injectable calcium phosphate material in a critical size defect.

BACKGROUND: Calcium phosphate-based bone graft substitutes are used to facilitate healing in bony defects caused by trauma or created during surgery. Here, we present an injectable calcium phosphate-based bone void filler that has been purposefully formulated with hyaluronic acid to offer a longer working time for ease of injection into bony defects that are difficult to access during minimally invasive surgery. METHODS: The bone substitute material deliverability and physical properties were characterized, and in vivo response was evaluated in a critical size distal femur defect in skeletally mature rabbits to 26 weeks. The interface with the host bone, implant degradation, and resorption were assessed with time. RESULTS: The calcium phosphate bone substitute material could be injected as a paste within the working time window of 7-18 min, and then self-cured at body temperature within 10 min. The material reached a maximum ultimate compressive strength of 8.20 ± 0.95 MPa, similar to trabecular bone. The material was found to be biocompatible and osteoconductive in vivo out to 26 weeks, with new bone formation and normal bone architecture observed at 6 weeks, as demonstrated by histological evaluation, microcomputed tomography, and radiographic evaluation. CONCLUSIONS: These findings show that the material properties and performance are well suited for minimally invasive percutaneous delivery applications.

Systems genetics in diversity outbred mice inform BMD GWAS and identify determinants of bone strength.

Genome-wide association studies (GWASs) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene identification and a strict focus on bone mineral density (BMD). Here, we use Diversity Outbred (DO) mice to directly address these limitations by performing a systems genetics analysis of 55 complex skeletal phenotypes. We apply a network approach to cortical bone RNA-seq data to discover 66 genes likely to be causal for human BMD GWAS associations, including the genes SERTAD4 and GLT8D2. We also perform GWAS in the DO for a wide-range of bone traits and identify Qsox1 as a gene influencing cortical bone accrual and bone strength. In this work, we advance our understanding of the genetics of osteoporosis and highlight the ability of the mouse to inform human genetics.

Can accuracy with the iASSIST navigation be confirmed by assessment? A multi-center prospective randomized controlled trial with independent three-dimensional image assessment.

BACKGROUND: iASSIST is one of the novel accelerometer-based navigation systems for total knee arthroplasty (TKA). Although the accuracy of iASSIST compared with conventional instruments has been reported, such evaluations were performed on two-dimensional (2D) images (X-rays). This multi-center prospective randomized controlled trial aimed to assess component positioning between TKA with and without iASSIST by 3D image assessment, and to clarify whether the iASSIST provides any benefit with regard to alignment accuracy. METHODS: Eighty-three knees with primary knee osteoarthritis were enrolled in this study. iASSIST was used for distal femoral and proximal tibial resection in 42 knees (iA group) and a conventional guide was used in 41 knees (CONV group). At 6 months postoperatively, component alignment was evaluated with 3D images by the independent orthopaedic surgeons, and surgical parameters, range of motion and clinical outcomes were examined. RESULTS: The rate of knees who have the alignment within 3° of neutral compared with the iA group and CONV group were 92.9% (39/42) vs. 87.8% (36/41) for femur and 76.2% (32/42) vs. 56.1% (23/41) for tibia in the coronal plane, respectively, whereas in the sagittal plane, the rate was 85.7% (36/42) vs. 58.5% (24/41) for femur and 83.3% (35/42) vs. 78.0% (32/41) for tibia, respectively. Compared with the CONV group, the iA group had a significantly improved femoral alignment in the sagittal plane (P = 0.006). There were no clinical or patient-reported differences at 6 months postoperatively. CONCLUSIONS: The iASSIST provides technically high accuracy in femoral resection at TKA compared with a conventional procedure.

One year of Football Fitness improves L1-L4 BMD, postural balance, and muscle strength in women treated for breast cancer.

PURPOSE: To examine efficacy of 12 months Football Fitness offered twice per week on bone mineral density (BMD), bone turnover markers (BTM), postural balance, muscle strength, and body composition in women treated for early-stage breast cancer (BC). METHODS: Women treated for early-stage BC were randomized to Football Fitness (FFG, n = 46) or control (CON, n = 22) in a 2:1 ratio for 12 months, with assessments performed at baseline, 6 months and 12 months. Outcomes were total body-, lumbar spine- and proximal femur BMD, total body lean and fat mass, leg muscle strength, postural balance, and plasma amino-terminal propeptide of type 1 procollagen (P1NP), osteocalcin, and C-terminal telopeptide of type 1 collagen (CTX). Intention-to-treat (ITT) analyses and per-protocol analyses (≥50% attendance in FFG) were performed using linear mixed models. RESULTS: Participants in FFG completing the 12-month intervention (n = 33) attended 0.8 (SD = 0.4) sessions per week. Intention to treat analysis of mean changes over 12 months showed significant differences (p<.05) in L1-L4 BMD (0.029 g/cm2 , 95%CI: 0.001 to 0.057), leg press strength (7.2 kg, 95%CI: 0.1 to 14.3), and postural balance (-4.3 n need of support, 95%CI: -8.0 to -0.7) favoring FFG compared to CON. In the per-protocol analyses, L1-L4 and trochanter major BMD were improved (p = .012 and .030, respectively) in FFG compared with CON. No differences were observed between groups in BTMs in the ITT or per protocol analyses. CONCLUSION: One year of Football Fitness training may improve L1-L4 BMD, leg muscle strength, and postural balance in women treated for early-stage breast cancer.

Association of Hydrogen Sulfide with Femoral Bone Mineral Density in Osteoporosis Patients: A Preliminary Study.

BACKGROUND Accumulated evidence has suggested that hydrogen sulfide (H2S) has a role in bone formation and bone tissue regeneration. However, it is unknown whether the H2S content is associated with bone mineral density (BMD) in patients with osteopenia/osteoporosis. MATERIAL AND METHODS In the present study, we aimed to explore the changes of serum H2S in osteopenia and osteoporosis patients. We analyzed femur expression of cystathionine ß synthase (CBS), cystathionine γ lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), which are key enzymes for generating H2S. RESULTS Sixteen (16%) patients had osteopenia, 9 (9%) had osteoporosis, and 75 (75%) had normal BMD. In comparison with patients with normal BMD (controls), the serum levels of H2S were unexpectedly increased in patients with osteopenia and osteoporosis. This increase was much higher in patients with osteoporosis than in those with osteopenia. Serum H2S levels were negatively correlated with femoral BMD, but not lumbar BMD. Interestingly, the expression of CBS and CSE were downregulated in femur tissues in patients with osteoporosis, whereas the expression of 3-MST remained unchanged. Serum phosphorus levels, alkaline phosphatase, hemoglobin, and triglycerides were found to be closely associated with CBS and CSE scores in femur tissues. CONCLUSIONS Serum H2S levels and femur CBS and CSE expression may be involved in osteoporosis pathogenesis.

Posterior tibial slope is a modifiable predictor of relatively large extension gaps in total knee arthroplasty for degenerative osteoarthritis.

BACKGROUND: During total knee arthroplasty (TKA) for osteoarthritis, the sagittal gap imbalance (SGI) with a relatively large extension gap is an important surgical challenge. We determined the predictors of SGI with a relatively large extension gap and evaluated the surgical outcomes of knees with SGI. METHODS: 551 consecutive cases of primary TKA for osteoarthritis were retrospectively reviewed. The cohort was divided into two groups according to the SGI and statistically matched according to baseline characteristics via the inverse probability of treatment weighting method. Multiple linear and logistic regression analyses were performed to determine the predictors of sagittal gap difference (SGD) and SGI. Intergroup differences in clinical and radiological outcomes were analyzed. RESULTS: Of all the knees included, 8.5% (n = 45) presented with SGI with a relatively large extension gap and required femoral sagittal balancing to manage SGI. The hyperextension angle (HA), preoperative joint line convergence angle (JLCA), and the change in posterior tibial slope (PTS) significantly correlated to SGD and predicted SGI with a relatively large extension gap. SGI group showed significant changes in femoral posterior condylar offset and joint line height compared to those without SGI (1.48 vs -0.45, 1.37 vs -0.51, respectively). Postoperative ROM and knee society knee scores were lower in SGI group. CONCLUSION: Knees requiring sagittal balancing to manage SGI with a relatively large extension gap is not uncommon in TKA for osteoarthritic knees. The change in PTS is an independent and modifiable predictor of SGI.

Nanohydroxyapatite/polyamide 66 crosslinked with QK and BMP-2-derived peptide prevented femur nonunion in rats.

Active interventions should be made to avoid delayed bone union and nonunion during fracture treatment. Nanohydroxyapatite/polyamide 66 (nHA/PA66), a simulated bioactive bone substitute with great biocompatibility and mechanical properties, has been widely used in bone regeneration. However, the limited bioactivity of nHA/PA66 has impeded its further application in tissue engineering. In this study, BMP-2-derived peptide and QK (a VEGF mimetic peptide) were dually grafted to PA66 polymer chains to prepare peptide-decorated HA/PA66-BMP-2-QK scaffolds to enhance bone formation after severe femoral fracture (periosteum scraped off) in SD rats. Fourier transform infrared spectroscopy (FTIR) confirmed that the BMP-2-derived peptide and QK were covalently bonded onto the surface of nHA/PA66. In vitro, BMP-2- and QK-modified scaffolds promoted the adhesion and proliferation ability of rBMSCs. After loading onto peptide-modified scaffolds, both BMP2-derived peptide and QK showed sustainable release and preserved bioactivity, improving the osteogenic differentiation ability of BMSCs. The combined ability of these factors to promote osteogenicity was better than that of a single peptide. Furthermore, the QK released from nHA/PA66-BMP-2-QK scaffolds improved the proliferation and tube formation ability of HUVECs. In vivo, femur nonunion in SD rats was successfully prevented by implanting HA/PA66-BMP-2-QK scaffolds into the fracture gap: the fracture line disappeared, the cortical bone showed continuity, the scaffolds were completely embedded and more vessels formed in the nonunion area than observed in other groups. Overall, the nHA/PA66-BMP-2-QK scaffolds simultaneously facilitated angiogenesis and osteogenesis, providing a promising method for reinforcing bone regeneration in nonunion treatment.

Total knee replacement wear during simulated gait with mechanical and anatomic alignments.

Total knee replacements (TKR) have historically been implanted perpendicular to the mechanical axis of the knee joint, with a commensurate external rotation of the femur in flexion relative to the posterior condylar axis (PCA). Although this mechanical alignment (MA) method has typically offered good long-term survivorship of implants, it may result in alignment of the implant that departs significantly from the native Joint Line (JL) in extension and flexion for a considerable portion of the patient population. There is a growing interest with surgeons to implant TKR components more closely aligned to the natural JL (Anatomic Alignment-AA) of the patient's knee joint to reduce the need for soft tissue releases during surgery, potentially improving knee function and patient satisfaction. Using a previously-validated finite element model of the lower extremity, implant- and alignment-specific loading conditions were developed and applied in a wear experiment via a six-degree-of-freedom joint simulator. MA was defined as 0° Joint Line (JL), 0° varus hip-knee-ankle (HKA) angle, and 3° external femoral rotation. AA was defined as 5° varus JL, 3° varus HKA, and 0° femoral rotation. The experiment returned wear rates of 3.76 ± 0.51 mg/million cycles (Mcyc) and 2.59 ± 2.11 mg/Mcyc for ATTUNE® cruciate-retaining (CR) fixed bearing (FB) in MA and AA, respectively. For ATTUNE posterior-stabilized (PS) FB in AA, the wear rate was 0.97 ± 1.11 mg/Mcyc. For ATTUNE CR rotating platform (RP), the wear rates were 0.23 ± 0.19 mg/Mcyc, 0.48 ± 1.02 mg/Mcyc in MA and AA respectively. Using a two-way ANOVA, it was determined that there was no significantly difference in the wear rates between AA and MA (p = 0.144) nor the wear rate of ATTUNE PS FB in AA significantly different from either ATTUNE CR FB or ATTUNE CR RP.

Metabolic activities affect femur and lumbar vertebrae remodeling, and anti-resorptive risedronate disturbs femoral cortical bone remodeling.

Metabolic activities are closely correlated with bone remodeling and long-term anti-resorptive bisphosphonate treatment frequently causes atypical femoral fractures through unclear mechanisms. To explore whether metabolic alterations affect bone remodeling in femurs and lumbar vertebrae and whether anti-osteoporotic bisphosphonates perturb their reconstruction, we studied three mouse strains with different fat and lean body masses (BALB/c, C57BL6, and C3H mice). These mice displayed variable physical activity, food and drink intake, energy expenditure, and respiratory quotients. Following intraperitoneal calcein injection, double calcein labeling of the femoral diaphysis, as well as serum levels of the bone-formation marker procollagen type-I N-terminal propeptide and the bone-resorption marker C-terminal telopeptide of type-I collagen, revealed increased bone turnover in mice in the following order: C3H > BALB/c ≥ C57BL6 mice. In addition, bone reconstitution in femurs was distinct from that in lumbar vertebrae in both healthy control and estrogen-deficient osteoporotic mice with metabolic perturbation, particularly in terms of femoral trabecular and cortical bone remodeling in CH3 mice. Interestingly, subcutaneous administration of bisphosphonate risedronate to C3H mice with normal femoral bone density led to enlarged femoral cortical bones with a low bone mineral density, resulting in bone fragility; however, this phenomenon was not observed in mice with ovariectomy-induced femoral cortical bone loss. Together, these results suggest that diverse metabolic activities support various forms of bone remodeling and that femur remodeling differs from lumbar vertebra remodeling. Moreover, our findings imply that the adverse effect of bisphosphonate agents on femoral cortical bone remodeling should be considered when prescribing them to osteoporotic patients.

There are isoheight points that measure constant femoral condyle heights along the knee flexion path.

PURPOSE: It is a challenge to evaluate the maintenance of medial and lateral soft tissue balance in total knee arthroplasty (TKA). This study aimed to determine the "isoheight" points and the "isoheight" axis (IHA) that can measure constant medial/lateral condyle heights during flexion of the knee, and compare the IHA with two major anatomical axes, the transepicondylar axis (TEA) and the geometric center axis (GCA). METHODS: Twenty-two healthy human knees were imaged using a combined MRI and dual fluoroscopic imaging system while performing a single-legged lunge (0°-120°). The isoheight points of the medial and lateral femoral condyles were defined as the locations with the least amount of changes in heights during the knee flexion; an IHA is the line connecting the medial and lateral isoheight points. The measured changes of the condyle heights using the IHA were compared with those measured using the TEA and GCA. RESULTS: Overall, the IHA was posterior and distal to the TEA, and anterior to the GCA. The isoheight points measured condyle height changes within 1.2 ± 2.3 mm at the medial and 0.7 ± 3.3 mm at the lateral sides during the knee flexion. Between 0° and 45°, the condyle height changes measured using the GCA (medial: 3.0 ± 1.8 mm, lateral: 2.3 ± 2.0 mm) were significantly larger than those of the IHA and the TEA (p < 0.05). Between 90° and 120°, the changes of the condyle heights measured using the TEA (medial: 5.3 ± 1.8 mm, lateral: 3.3 ± 1.8 mm) were significantly larger than those of the IHA and GCA (p < 0.05). CONCLUSION: There are isoheight points in the medial and lateral femoral condyles that can measure constant heights along the full range of knee flexion and could be used to formulate an "isoheight" axis (IHA) of the femur. The condyle height changes measured by the TEA and GCA were greater than the IHA measurements along the flexion path. These data could be used as a valuable reference to evaluate the condyle height changes after TKA surgeries and help achieve soft tissue balance and optimal knee kinematics along the flexion path. LEVEL OF EVIDENCE: IV.

Regeneration enhanced in critical-sized bone defects using bone-specific extracellular matrix protein.

Extracellular matrix (ECM) products have the potential to improve cellular attachment and promote tissue-specific development by mimicking the native cellular niche. In this study, the therapeutic efficacy of an ECM substratum produced by bone marrow stem cells (BM-MSCs) to promote bone regeneration in vitro and in vivo were evaluated. Fluorescence-activated cell sorting analysis and phenotypic expression were employed to characterize the in vitro BM-MSC response to bone marrow specific ECM (BM-ECM). BM-ECM encouraged cell proliferation and stemness maintenance. The efficacy of BM-ECM as an adjuvant in promoting bone regeneration was evaluated in an orthotopic, segmental critical-sized bone defect in the rat femur over 8 weeks. The groups evaluated were either untreated (negative control); packed with calcium phosphate granules or granules+BM-ECM free protein and stabilized by collagenous membrane. Bone regeneration in vivo was analyzed using microcomputed tomography and histology. in vivo results demonstrated improvements in mineralization, osteogenesis, and tissue infiltration (114 ± 15% increase) in the BM-ECM complex group from 4 to 8 weeks compared to mineral granules only (45 ± 21% increase). Histological observations suggested direct apposition of early bone after 4 weeks and mineral consolidation after 8 weeks implantation for the group supplemented with BM-ECM. Significant osteoid formation and greater functional bone formation (polar moment of inertia was 71 ± 0.2 mm4 with BM-ECM supplementation compared to 48 ± 0.2 mm4 in untreated defects) validated in vivo indicated support of osteoconductivity and increased defect site cellularity. In conclusion, these results suggest that BM-ECM free protein is potentially a therapeutic supplement for stemness maintenance and sustaining osteogenesis.

Patellar component size effects patellar tilt in total knee arthroplasty with patellar resurfacing.

PURPOSE: Patellar component positioning and patellofemoral kinematics are of great importance in total knee arthroplasty (TKA). The factors influencing patellar tilt are femoral rotation and lateral patellar release. However, the effect of patellar component size remains unknown. The aim of this study was to evaluate the intra-operative risk factors for patellar tilt, particularly the effect of the patellar component size. The hypothesis was that increasing the patellar component size would reduce the risk of patellar tilt. METHODS: 878 primary TKAs with patellar resurfacing were included between January 2015 and October 2018. Analysis was performed at 1-year postoperatively on patients categorized into two groups: patellar tilt (PT) and no patellar tilt (NPT). A multivariate analysis was performed for the effect of patellar component size, femoral rotation, femoral overbuilding, patellar thickness and lateral release on patellar tilt risk. Secondary analysis was performed for any difference in clinical outcomes and revision rates between groups. RESULTS: Multivariate analysis showed that increasing the patellar component size decreased the risk of patellar tilt by 37% (p < 0.001). Placing the femoral component at 3° of external rotation decreased the risk of patellar tilt by 67% (p < 0.001). Secondary analysis showed better clinical outcomes in the NPT group, especially regarding global satisfaction, and KSS objective and subjective scores. The revision for any cause was less in the NPT group (p = 0.019). The cause for TKA revision was related to the patellar in 11% of cases in the NPT group and 65% in the PT group (p < 0.001). CONCLUSION: Increased patellar component size and positioning the femoral component in external rotation decreases the risk of patellar tilt, improves clinical outcomes and decreases the rate of surgical revision. LEVEL OF EVIDENCE: III.

Intra-individual variance of bilateral femoro-tibial leg rotation: a CT study of 105 healthy subjects.

PURPOSE: In cases of suspected rotational deformity of the lower limb, in particular in post-traumatic malalignment following closed nailing, there is a lack of adequate reference values. Available publications on leg rotation have either small sample sizes or do not include bilateral or whole leg rotation of healthy legs. This study aimed to determine side-specific reference values of lower limb rotation in a large healthy sample. This may be helpful in acute clinical settings as well as for medical expert opinion. METHODS: 226 consecutive bilateral lower limb computed tomography (CT) angiographies were screened. 105 patients (210 legs) were included (40 females, 65 males, mean age 67 ± 12 years). Bilateral axial femoral and tibial rotation alignment were independently measured and overall leg rotation was computed by two methods. Distributions, sex, and side differences were analyzed. RESULTS: Two-sided paired t tests showed significant differences between right and left for all measurements. The left side showed a more pronounced mean anteversion in the femur of 2.2° (p = 0.002) and the right side higher mean external rotation in the tibia of 2.8° (p < 0.001). Overall leg rotation showed 5.1° more mean external rotation on the right side (p < 0.001) with both methods. Absolute side-to-side whole leg rotation difference was 9.5°. Absolute differences between both methods were 3.3°. The variance was high. 23 femora were retroverted, 1 tibia internally rotated, and 9 legs were overall internally rotated. No variables differed between female and male subjects except for femoral version (right p = 0.003 and left p = 0.002). Correlation coefficients were high (rho 0.550-0.934, all p < 0.001). CONCLUSION: There is a significant prevalence of side-to-side asymmetry in femoro-tibial torsion. Although side-to-side differences are not extraordinary, comparative axial femoro-tibial rotation alignment should always be interpreted with caution. LEVEL OF EVIDENCE: Diagnostic, retrospective cohort study, level III.

Epidermal growth factor or platelet-rich plasma combined with induced membrane technique in the treatment of segmental femur defects: an experimental study.

OBJECTIVE: Extensive bone defects remain a therapeutic challenge necessitating alternative surgical approaches with better outcomes. Can increase the effectiveness of PRP or EGF treatment in surgical treatment of large bone defects with Masquelet technique? Aim of this study examined potential therapeutic benefits of the Masquelet technique with induced membranes in combination with platelet-rich plasma (PRP) or epidermal growth factor (EGF) in a rat model of segmental femur defect. METHODS: Three groups each consisting of 20 Sprague-Dawley rats were defined as follows: EGF group, PRP group, and control group. A femoral bone defect was created and filled with antibiotic embedded polymethyl methacrylate. Half of the animals in each group were sacrificed at week 6 and the pseudo-membranes formed were analyzed. In the remaining half, the cement was removed and the space was filled with autograft. After another 6 weeks, the structures formed were examined radiologically, histologically, and biochemically. RESULTS: At week 6, both PRP and EGF groups had significantly higher membrane CD31, TGF-beta, and VEGF levels than controls. At week 12, when compared to controls, PRP and EGF groups had significantly higher membrane CD31 levels and the PRP group had significantly higher membrane TGF levels. Regarding bone tissue levels, PRP and EGF groups had significantly higher VEGF levels and the EGF group had significantly higher BMP levels. In addition, PRP and EGF groups had higher radiological scores than controls. However, the two experimental groups did not differ with respect to any parameter tested in this study. CONCLUSION: Both PRP and EGF seem to be associated with histological, biochemical, and radiological improvements in experimental rat model of Masquelet technique, warranting in further clinical studies. LEVEL OF EVIDENCE: Level 5.