Stiffness of the human foot and evolution of the transverse arch.

The stiff human foot enables an efficient push-off when walking or running, and was critical for the evolution of bipedalism1-6. The uniquely arched morphology of the human midfoot is thought to stiffen it5-9, whereas other primates have flat feet that bend severely in the midfoot7,10,11. However, the relationship between midfoot geometry and stiffness remains debated in foot biomechanics12,13, podiatry14,15 and palaeontology4-6. These debates centre on the medial longitudinal arch5,6 and have not considered whether stiffness is affected by the second, transverse tarsal arch of the human foot16. Here we show that the transverse tarsal arch, acting through the inter-metatarsal tissues, is responsible for more than 40% of the longitudinal stiffness of the foot. The underlying principle resembles a floppy currency note that stiffens considerably when it curls transversally. We derive a dimensionless curvature parameter that governs the stiffness contribution of the transverse tarsal arch, demonstrate its predictive power using mechanical models of the foot and find its skeletal correlate in hominin feet. In the foot, the material properties of the inter-metatarsal tissues and the mobility of the metatarsals may additionally influence the longitudinal stiffness of the foot and thus the curvature-stiffness relationship of the transverse tarsal arch. By analysing fossils, we track the evolution of the curvature parameter among extinct hominins and show that a human-like transverse arch was a key step in the evolution of human bipedalism that predates the genus Homo by at least 1.5 million years. This renewed understanding of the foot may improve the clinical treatment of flatfoot disorders, the design of robotic feet and the study of foot function in locomotion.

The Morphologic Patella Entry Point Into the Proximal Trochlea Is More Lateral in Recurrent Dislocators Than Controls as Measured by Entry Point-Trochlear Groove Angle.

PURPOSE: To create a metric for evaluating the degree of laterality of the patella's entry into the trochlea, the entry point-trochlear groove (EP-TG) angle, and to evaluate if this laterality is associated with recurrent patella instability. METHODS: The time frame of the study was January 2020 to February 2023. The inclusion criteria were patients treated by the senior author (J.P.F.) (with the exception of 2 patients who were treated by another provider at the institution who was aware of the study) who have been diagnosed with recurrent atraumatic patellar dislocations. Controls without knee pathology were selected from the New Mexico Decedent Imaging Database (NMDID). Simpleware ScanIP was used to create 3-dimensional (3D) models of the distal femurs from computed tomography scans. Anteroposterior images of these 3D models were uploaded to a custom EP-TG angle measuring tool. Three measurers used the tool to measure the EP-TG angle of the distal femurs. RESULTS: Twenty-eight patients were included for the recurrent dislocator group. Twenty-four decedents from the NMDID were selected for the control group, each with a left or right knee chosen randomly for measurement. A 1-sided Mann-Whitney U test, used to evaluate whether the recurrent dislocators had higher EP-TG angle values, yielded a P value <.001, demonstrating a high level of significance. A Bayesian mixed-effect model, used to determine how different the EP-TG angles are between the 2 groups, gave a posterior predictive interval of [11.93°, 19.12°] for the EP-TG angle shift of dislocators. The intraclass correlation coefficient was 0.648. CONCLUSIONS: The morphologic entry point of the patella into the proximal trochlea is more lateral in recurrent patella dislocators than in controls. This increased laterality can be measured by the EP-TG angle, which may be useful information for optimizing treatment of recurrent patella instability. LEVEL OF EVIDENCE: Level III, case control study.

Some Offset Restoration Options Can Paradoxically Lead to Decreased Range of Motion in Primary Total Hip Arthroplasty: A 3-Dimensional Computer Simulation Study.

BACKGROUND: In total hip arthroplasty (THA), femoral offset restoration results in optimal biomechanics and range of motion (ROM) without bone-bone impingement. We hypothesized that differences in implant design features significantly affect bone-bone impingement risk in primary THA. METHODS: This retrospective computer simulation study included a cohort of 43 primary robotic arm-assisted THA. Considering sagittal pelvic tilt, we measured the maximum external rotation at 0° hip flexion and the maximum internal rotation at both 90° and 100° hip flexion before any bone-bone impingement occurred. To influence the offset, we included neutral or extended polyethylene liners, neutral or plus prosthetic heads, standard or high-offset stems, and stems with 132° or 127° neck angles. RESULTS: Extended polyethylene liner use resulted in decreased bone-bone impingement for both stems but also decreased prosthetic ROM in hip extension (mean -4.5 to 5°, range -10 to 0°) and hip flexion (mean -3 to 3.7°, range -10 to 0°) due to decreases in head diameter. Using a plus head or different stem offset/neck angle options resulted in either (1) no improvement in ROM (stem 1: 60%; stem 2: 28%) or (2) a paradoxical increase in bone-bone impingement (stem 1 with 127°: 19% and stem 2 with high offset option: 7%). CONCLUSION: Counterintuitively, a subset of patients experience a paradoxical increase in bone-bone impingement when transitioning from standard to high-offset or varus necks due to the pelvic and proximal femoral bone shape. For this group of patients, preoperative personalized 3-dimensional modeling may help guide implant choice for optimizing outcomes.

Using preoperative planning software to assess the effect of head length on prosthetic range of motion in a high-risk population: a three-dimensional modeling study.

PURPOSE: Concurrent use of minus heads with tapered stems in total hip arthroplasty (THA) decreases the prosthetic range of motion (pROM). Three-dimensional preoperative templating can simulate the location of the impingement by taking the hip through a virtual pROM. This enables surgeons to simulate how modifying the type of implant, orientation, and position influences impingement. We hypothesized that CT-based modeling would result in a decrease in the pROM, thereby increasing the risk of impingement when minus heads are used. METHODS: Forty-three patients who underwent robotic-assisted primary THAs were included. Prosthetic head diameter (32/36-mm) and head length (minus/zero/plus) were the predictors. Maximum external rotation at full hip extension and internal rotation at 90° and 100° of flexion prior to prosthetic impingement were the outcome variables. A CT-based preoperative planning software was used for pROM estimation and impingement detection. RESULTS: Significant decreases in pROM were found for both head diameters as the head length decreased and was more pronounced in external rotation during full hip extension (changes of 2.8-3.4° for the 32-mm head and 1.6-2.8° for the 36-mm head (p = 0.00011)). The magnitude of loss in pROM when using a minus head was larger than the gain provided by a plus head in tapered stems (p < 0.0001). CONCLUSION: Head length affects the offset and pROM. When the use of minus heads or smaller heads is indicated, 3D preoperative templating for assessing postoperative pROM and impingement provides surgeons with options to consider alternate surgical plans offering additional assurance and protection from dislocation.

Hip Abduction Can Be Considered the Sole Posterior Precaution Strategy to Lower the Rate of Impingement After Posterior Approach Total Hip Arthroplasty With Large Femoral Head: A Computer Simulation Study.

BACKGROUND: Studies suggest that posterior hip precautions are unnecessary after total hip arthroplasty; however, many surgeons and patients choose to follow these precautions to some extent. In this study, we hypothesized that 20° of hip abduction would be sufficient to prevent impingement and dislocation in motions requiring hip flexion when using larger prosthetic heads (≥36 mm) when the acetabular implant is placed within a reasonable orientation (anteversion:15-25° and inclination: 40-60°). METHODS: Using a robotic hip platform, we investigated the effect of hip abduction on prosthetic and bony impingement in 43 patients. For the flexed seated position, anterior pelvic tilt angles of 10 and 20° were chosen, while anterior pelvic tilt angles of 70 and 90° were chosen for the bending forward position. An additional 10° of hip external rotation and 10 or 20° of hip internal rotation were also added to the simulation. One hip received a 32-mm head; otherwise, 36-, 40-mm, or dual-mobility heads were used. The study power was 0.99, and the effect size was 0.644. RESULTS: In 65% of the cases, bone-bone impingement between the calcar and anterior-inferior iliac spine was the main type of impingement. The absolute risk of impingement decreased between 0 and 16.3% in both tested positions with the addition of 20° hip abduction. CONCLUSION: With modern primary total hip arthroplasty stems (low neck diameter) and an overall acceptable cup anteversion angle, small degrees of hip abduction may be the only posterior hip precaution strategy required to lower the risk of dislocation among patients. Future studies can potentially investigate the concept of personalized hip precautions based on preoperative computer simulations, utilized implants, hip-spine relations, and final implant orientation.

The Enthesopathy of XLH Is a Mechanical Adaptation to Osteomalacia: Biomechanical Evidence from Hyp Mice.

A major comorbidity of X-linked hypophosphatemia (XLH) is fibrocartilaginous tendinous insertion site mineralization resulting in painful enthesophytes that contribute to the adult clinical picture and significantly impact physical function. Enthesophytes in Hyp mice, a murine model of XLH are the result of a hyperplastic expansion of resident alkaline phosphatase, Sox9-positive mineralizing fibrochondrocytes. Here, we hypothesized hyperplasia as a compensatory physical adaptation to aberrant mechanical stresses at the level of the entheses interface inserting into pathologically soft bone. To test this hypothesis, we examined the Achilles insertion of the triceps surae developed under normal and impaired loading conditions in Hyp and WT mice. Tensile stiffness, ultimate strength, and maximum strain were measured and compared. Biomechanical testing revealed that under normal loading conditions, despite inserting into a soft bone matrix, both the enthesophyte development (9 weeks) and progression (6-8 months) of Hyp mice were equivalent to the mechanical properties of WT mice. Unloading the insertion during development significantly reduced alkaline phosphatase, Sox9-positive fibrochondrocytes. In WT mice, this correlated with a decrease in stiffness and ultimate strength relative to the control limb, confirming the critical role of mechanical loading in the development of the enthesis. Most significantly, in response to unloading, maximum strain was increased in tensile tests only in the setting of subchondral osteomalacia of Hyp mice. These data suggest that mineralizing fibrochondrocyte expansion in XLH occurs as a compensatory adaptation to the soft bone matrix.

Ibuprofen impairs capsulolabral healing in a rat model of anterior glenohumeral instability.

BACKGROUND: Failure of glenoid labrum and capsular healing after glenohumeral dislocation can lead to persistent shoulder instability. The purpose of this study was to determine the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the healing glenoid labrum and capsule after glenohumeral dislocation in a rat model. METHODS: Sixty-six rats had surgically induced anterior-inferior labral tears and anterior glenohumeral dislocation. Postoperatively, the animals were assigned to either normal (n = 32) or ibuprofen drinking water (n = 31). Animals were euthanized at 2 and 4 weeks postoperatively for biomechanical testing and histologic analysis. RESULTS: The maximum load increased from 2 to 4 weeks after injury in the NSAID groups but not in the control groups. At 2 weeks, the maximum load was lower in the NSAID group compared with the control group. In a matched comparison between injured and uninjured limbs, the maximum load was significantly decreased in the injured limb of the 2-week NSAID group. At 4 weeks, the NSAID group had decreased stiffness compared with the 4-week control group. CONCLUSIONS: In a new rat model of glenohumeral instability, the postinjury administration of ibuprofen resulted in decreased capsulolabral healing. A matched pair analysis of injured to uninjured limbs supported the findings of impaired healing in the NSAID-treated animals. These findings demonstrate that the use of NSAIDs after glenohumeral dislocation may impair capsulolabral healing and should be limited or avoided to optimize glenohumeral stability.

The transcription factor T-box 3 regulates colony-stimulating factor 1-dependent Jun dimerization protein 2 expression and plays an important role in osteoclastogenesis.

Colony-stimulating factor 1 (CSF1) is known to promote osteoclast progenitor survival, but its roles in osteoclast differentiation and mature osteoclast function are less well understood. In a microarray screen, Jun dimerization protein 2 (JDP2) was identified as significantly induced by CSF1. Recent reports indicate that JDP2 is required for normal osteoclastogenesis and skeletal metabolism. Because there are no reports on the transcriptional regulation of this gene, the DNA sequence from -2612 to +682 bp (relative to the transcription start site) of the JDP2 gene was cloned, and promoter activity was analyzed. The T box-binding element (TBE) between -191 and -141 bp was identified as the cis-element responsible for CSF1-dependent JDP2 expression. Using degenerate PCR, Tbx3 was identified as the major isoform binding the TBE. Overexpression of Tbx3 induced JDP2 promoter activity, whereas suppressing Tbx3 expression substantially attenuated CSF1-induced transcription. Suppressing Tbx3 in osteoclast precursors reduced JDP2 expression and significantly impaired RANKL/CSF1-induced osteoclastogenesis. A MEK1/2-specific inhibitor was found to block CSF1-induced JDP2 expression. Consistent with these data, JDP2(-/-) mice were found to have increased bone mass. In summary, CSF1 up-regulates JDP2 expression by inducing Tbx3 binding to the JDP2 promoter. The downstream signaling cascade from activated c-Fms involves the MEK1/2-ERK1/2 pathway. Tbx3 plays an important role in osteoclastogenesis at least in part by regulating CSF1-dependent expression of JDP2.

The remarkable migration of the medial collateral ligament.

The developing cortical surfaces of long bones are sculpted and modeled by periosteal osteoclasts and osteoblasts. These surfaces also receive the insertions of tendons and ligaments, and these insertion sites too are modeled to form the root systems that anchor them into the cortical bone. The regulatory molecules that control modeling are poorly understood, but recent evidence suggests that parathyroid hormone-related protein (PTHrP) participates in this process. PTHrP functions principally as a paracrine regulatory molecule, and is known to be induced by mechanical loading in a number of sites. The most curious example of developmental modeling of the cortex is the migration of insertion sites such as that of the medial collateral ligament (MCL) along the bone surface during long-bone growth. We report here the mechanisms that mediate MCL migration using a combination of genetic, imaging and histological techniques. We describe a MCL migratory complex that comprises two components. The first is the MCL insertion site itself, which is a prototypical fibrous insertion site with coupled osteoclast and osteoblast activities, and its key feature is that it is anchored early in development, well before initiation of the long-bone growth spurt. Above the insertion site the periosteum is excavated by osteoclasts to form a migratory tract; this is mediated by wholly uncoupled osteoclastic bone resorption and remains as an unmineralized canal on the cortical surface in the adult. Load-induction of PTHrP appears to regulate the osteoclastic activity in both the insertion site and migratory tract.

Periosteal PTHrP regulates cortical bone modeling during linear growth in mice.

The modeling of long bone surfaces during linear growth is a key developmental process, but its regulation is poorly understood. We report here that parathyroid hormone-related peptide (PTHrP) expressed in the fibrous layer of the periosteum (PO) drives the osteoclastic (OC) resorption that models the metaphyseal-diaphyseal junction (MDJ) in the proximal tibia and fibula during linear growth. PTHrP was conditionally deleted (cKO) in the PO via Scleraxis gene targeting (Scx-Cre). In the lateral tibia, cKO of PTHrP led to a failure of modeling, such that the normal concave MDJ was replaced by a mound-like deformity. This was accompanied by a failure to induce receptor activator of NF-kB ligand (RANKL) and a 75% reduction in OC number (P ≤ 0.001) on the cortical surface. The MDJ also displayed a curious threefold increase in endocortical osteoblast mineral apposition rate (P ≤ 0.001) and a thickened cortex, suggesting some form of coupling of endocortical bone formation to events on the PO surface. Because it fuses distally, the fibula is modeled only proximally and does so at an extraordinary rate, with an anteromedial cortex in CD-1 mice that was so moth-eaten that a clear PO surface could not be identified. The cKO fibula displayed a remarkable phenotype, with a misshapen club-like metaphysis and an enlargement in the 3D size of the entire bone, manifest as a 40-45% increase in the PO circumference at the MDJ (P ≤ 0.001) as well as the mid-diaphysis (P ≤ 0.001). These tibial and fibular phenotypes were reproduced in a Scx-Cre-driven RANKL cKO mouse. We conclude that PTHrP in the fibrous PO mediates the modeling of the MDJ of long bones during linear growth, and that in a highly susceptible system such as the fibula this surface modeling defines the size and shape of the entire bone.

Fabricating patient-specific 3D printed drill guides to treat femoral head avascular necrosis.

BACKGROUND: Femoral head avascular necrosis (AVN), or death of femoral head tissue due to a lack of blood supply, is a leading cause of total hip replacement for non-geriatric patients. Core decompression (CD) is an effective treatment to re-establish blood flow for patients with AVN. Techniques aimed at improving its efficacy are an area of active research. We propose the use of 3D printed drill guides to accurately guide therapeutic devices for CD. METHODS: Using femur sawbones, image processing software, and 3D modeling software, we created a custom-built device with pre-determined drill trajectories and tested the feasibility of the 3D printed drill guides for CD. A fellowship trained orthopedic surgeon used the drill guide to position an 8 ga, 230 mm long decompression device in the three synthetic femurs. CT scans were taken of the sawbones with the drill guide and decompression device. CT scans were processed in the 3D modeling software. Descriptive statistics measuring the angular and needle-tip deviation were compared to the original virtually planned model. RESULTS: Compared to the original 3D model, the trials had a mean displacement of 1.440 ± 1.03 mm and a mean angle deviation of 1.093 ± 0.749º. CONCLUSIONS: The drill guides were demonstrated to accurately guide the decompression device along its predetermined drill trajectory. Accuracy was assessed by comparing values to literature-reported values and considered AVN lesion size. This study demonstrates the potential use of 3D printing technology to improve the efficacy of CD techniques.

The feasibility of a novel 3D-Printed patient specific cutting guide for extended trochanteric osteotomies.

BACKGROUND: The extended trochanteric osteotomy (ETO) is a surgical technique utilized to expose the intramedullary canal of the proximal femur, protect the soft tissues and promote reliable healing. However, imprecise execution of the osteotomy can lead to fracture, soft tissue injury, non-union, and unnecessary morbidity. We developed a technique to create patient specific, 3D-printed cutting guides to aid in accurate positioning of the ETO and improve osteotomy quality and outcomes. METHODS: Patient specific cutting guides were created based on CT scans using Synopysis Simpleware ScanIP and Solidworks. Custom 3D printed cutting guides were tested on synthetic femurs with foam cortical shells and on cadaveric femurs. To confirm accuracy of the osteotomies, dimensions of the performed osteotomies were compared to the virtually planned osteotomies. RESULTS: Use of the patient specific ETO cutting guides resulted in successful osteotomies, exposing the femoral canal and the femoral stem both in synthetic sawbone and cadaveric testing. In cadaveric testing, the guides allowed for osteotomies without fracture and cuts made using the guide were accurate within 6 percent error from the virtually planned osteotomy. CONCLUSION: The 3D-printed patient specific cutting guides used to aid in ETOs proved to be accurate. Through the iterative development of cutting guides, we found that a simple design was key to a reliable and accurate guide. While future clinical trials in human subjects are needed, we believe our custom 3D printed cutting guide design to be effective at aiding in performing ETOs for revision total hip arthroplasty surgeries.

Off-the-Shelf Tibial Cone Sizes May Not Accommodate All Patients' Bone Morphology and May Lead to Cortical Breaches in Revision Total Knee Arthroplasty: A 3D Modeling Study.

Background: In revision total knee arthroplasty, tibial cones have demonstrated improved longevity and reduced incidence of aseptic loosening. Several currently available "off-the-shelf" (OTS) cone systems may not have sizes to accommodate all patient bone morphologies. Methods: Computed tomographies from one hundred primary total knee arthroplasty patients and dimensions of 4 OTS cones were obtained. Press-fit stems were positioned in 3D tibia models to fit the diaphyseal trajectory. Cones were positioned around the stem at 1, 6, and 13 mm resections measured from the trough of the medial tibial plateau, simulating proximal tibial cuts and bone loss. Tibias were examined for cortical breaching following modeled cone preparation. Results: Increased rate of breaching was observed as size and depth of the cone increased. In 2/49 (4.1%) male and 19/46 (41.3%) female tibias, cones could not be positioned without breaching. No breaches were found in 22/49 (45.0%) male and 5/46 (10.9%) female tibias. For every 1 centimeter increase in patient height, odds of breaching decreased by 12% (odds ratio: 0.88, confidence interval: 0.84, 0.92). For every size increase in cone width, odds of breaching increased by 34% (odds ratio: 1.34, confidence interval: 1.28, 1.47). Placing cones deeper also increased breaching compared to the 1 mm cut. Conclusions: In revision total knee arthroplasty, smaller OTS or custom tibial cones may be needed to fit a patient's proximal tibial geometry. This is especially true in patients not accommodated by the OTS cone sizes we tested, which impacted shorter patients and/or those with substantial bone loss requiring more tibial resection and deeper cone placement. Use of smaller or custom tibial cones should be considered where indicated.

Sustentaculum fracture fixation with lateral plate or medial screw fixation are equivalent.

BACKGROUND: Fixation of sustentaculum tali fractures is important to maintain the biomechanical function of the subtalar joint. A common method of fixation is securing the sustentacular fragment by way of a laterally based locking plate (LP). A medial approach with a single screw (MS) has been proposed as an alternative method of fixation. METHODS: Five pairs of formalin-preserved cadaveric ankles with the subtalar joint and interosseous ligaments intact ("osseous cadavers") and four pairs of fresh-frozen cadaveric ankles with soft-tissue preserved dissected from mid-tibia down ("soft tissue cadavers") were used in the study. The left ankle was randomly assigned to one of the two fixation methods (LP or MS), while the right ankle was the opposite. These same steps for fixation were repeated for six synthetic ankle models. All models were loaded with a body mass of 80 kg. Statistical differences between LP and MS stiffness were determined using a paired t-test in cadavers and un-paired t-tests in synthetic ankles. RESULTS: For osseous cadaveric ankles, LP demonstrated a mean stiffness of 232.95(SD: 59.96) N/mm, while MS was 239.72(SD:131.09) N/mm (p = 0.9293). For soft tissue cadaveric ankles, LP mean stiffness was 133.58(SD:37.84) N/mm, while MS was 134.88(SD:20.75) N/mm (p = 0.9578). For synthetic ankles, LP mean stiffness was 220.40(SD:81.93) N/mm, while MS was 261.50(SD:100.21) N/mm (p = 0.6116). CONCLUSIONS: Across all three models, there was no significant difference between LP and MS methods. Retrospective observational studies are recommended to assess patient outcomes from each of the methods.

Outcomes of Distal Third Femur Fractures in Patients 18 Years and Older: A Pilot Study.

INTRODUCTION: The selection of the most optimal fixation method for fractures of the distal femur, whether intramedullary nail (NL), lateral locking plate (PL), or nail/plate (NP) is not always clear. This study retrospectively evaluates surgical patients with distal femur fractures and introduces a pilot study using cluster analysis to identify the most optimal fracture fixation method for a given fracture type. METHODS: This is a retrospective cohort study of patients 18 years and older with an isolated distal femur fracture who presented to our Level-1 trauma center between January 1, 2012, and December 31, 2022, and obtained NL, PL, or NP implants. Patients with polytrauma and those without at least six months of follow-up were excluded. A chart review was used to obtain demographics, fracture classification, fixation method, and postoperative complications. A cluster analysis was performed. The following factors were used to determine a successful outcome: ambulatory status pre-injury and 6-12 months postoperatively, infection, non-union, mortality, and implant failure. RESULTS: A total of 169 patients met inclusion criteria. No statistically significant association between the fracture classification and fixation type with overall outcome was found. However, patients treated with an NP (n = 14) had a success rate of 92.9% vs only a 68.1% success rate in those treated with a PL (n = 116) (p = 0.106). The most notable findings in the cluster analysis (15 total clusters) included transverse extraarticular fractures demonstrating 100% success if treated with NP (n = 6), 50% success with NL (n=2), and 78.57% success with PL fixation (n=14). NP constructs in complete articular fractures demonstrated success in 100% of patients (n = 5), whereas 77.78% of patients treated with NL (n = 9) and 61.36% of those treated with PL (n = 44). CONCLUSIONS: Plate fixation was the predominant fixation method used for distal third femur fractures regardless of fracture classification. However, NP constructs trended towards improved success rates, especially in complete intraarticular and transverse extraarticular fractures, suggesting the potential benefit of additional fixation with these fractures. Cluster analysis provided a heuristic way of creating patient profiles in patients with distal third femur fractures. However, a larger cohort study is needed to corroborate these findings to ultimately develop a clinical decision-making tool that also accounts for patient specific characteristics.

Biomechanical Impact of Phosphate Wasting on Articular Cartilage Using the Murine Hyp Model of X-linked hypophosphatemia.

Degenerative osteoarthritis (OA) is recognized as an early-onset comorbidity of X-linked hypophosphatemia (XLH), contributing to pain and stiffness and limiting range of motion and activities of daily living. Here, we extend prior findings describing biochemical and cellular changes of articular cartilage (AC) in the phosphate-wasting environment of XLH to determine the impact of these changes on the biomechanical properties of AC in compression and potential role in the etiology of OA. We hypothesize that despite increased proteoglycan biosynthesis, disruption of the mineralized zone of AC impacts the mechanical properties of cartilage that function to accommodate loads and that therapeutic restoration of this zone will improve the mechanical properties of AC. Data were compared between three groups: wild type (WT), Hyp, and Hyp mice treated with calcitriol and oral phosphate. EPIC microCT confirmed AC mineral deficits and responsiveness to therapy. MicroCT of the Hyp subchondral bone plate revealed that treatment improved trabecular bone volume (BV/TV) but remained significantly lower than WT mice in other trabecular microstructures (p < 0.05). Microindentation AC studies revealed that, compared with WT mice, the mean stiffness of tibial AC was significantly lower in untreated Hyp mice (2.65 ± 0.95 versus 0.87 ± 0.33 N/mm, p < 0.001) and improved with therapy (2.15 + 0.38 N/mm) to within WT values. Stress relaxation of AC under compressive loading displayed similar biphasic relaxation time constants (Taufast and Tauslow) between controls and Hyp mice, although Tauslow trended toward slowed relaxation times. In addition, Taufast and Tauslow times correlated with peak load in WT mice (r = 0.80; r = 0.78, respectively), whereas correlation coefficient values for Hyp mice (r = 0.46; r = 0.21) improved with treatment (r = 0.71; r = 0.56). These data provide rationale for therapies that both preserve AC stiffness and recovery from compression. The Hyp mouse also provides unique insight into determinants of structural stiffness and the viscoelastic properties of AC in the progression of OA. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bone marrow sinusoidal endothelial cells are a site of Fgf23 upregulation in a mouse model of iron deficiency anemia.

Iron deficiency is a potent stimulator of fibroblast growth factor 23 (FGF23), a hormonal regulator of phosphate and vitamin D metabolism, that is classically thought to be produced by bone-embedded osteocytes. Here, we show that iron-deficient transmembrane serine protease 6 knockout (Tmprss6-/-) mice exhibit elevated circulating FGF23 and Fgf23 messenger RNA (mRNA) upregulation in the bone marrow (BM) but not the cortical bone. To clarify sites of Fgf23 promoter activity in Tmprss6-/- mice, we introduced a heterozygous enhanced green fluorescent protein (eGFP) reporter allele at the endogenous Fgf23 locus. Heterozygous Fgf23 disruption did not alter the severity of systemic iron deficiency or anemia in the Tmprss6-/- mice. Tmprss6-/-Fgf23+/eGFP mice showed green fluorescence in the vascular regions of BM sections and showed a subset of BM endothelial cells that were GFPbright by flow cytometry. Mining of transcriptomic data sets from mice with normal iron balance revealed higher Fgf23 mRNA in BM sinusoidal endothelial cells (BM-SECs) than that in other BM endothelial cell populations. Anti-GFP immunohistochemistry of fixed BM sections from Tmprss6-/-Fgf23+/eGFP mice revealed GFP expression in BM-SECs, which was more intense than in nonanemic controls. In addition, in mice with intact Tmprss6 alleles, Fgf23-eGFP reporter expression increased in BM-SECs following large-volume phlebotomy and also following erythropoietin treatment both ex vivo and in vivo. Collectively, our results identified BM-SECs as a novel site for Fgf23 upregulation in both acute and chronic anemia. Given the elevated serum erythropoietin in both anemic models, our findings raise the possibility that erythropoietin may act directly on BM-SECs to promote FGF23 production during anemia.

How metal augments, polyethylene thickness and stem length affect tibial baseplate load transfer in revision total knee arthroplasty.

BACKGROUND: It is unclear howmetal augments,polyethylene (PE) liner thickness, and length of cemented stemcontribute to load transferwhen reconstructing uncontained tibial metaphyseal bone loss of Anderson Orthopedic Research Institute (AORI) Type II defects during revision total knee arthroplasty (rTKA).The aimof this study is to understand the impact of these three variableson load transfer through the tibial baseplate. For a fixed defect depth, we hypothesized that there is a particular combination of liner and augment thickness and stem length that minimizes bone stress, reducing the risk of aseptic loosening. METHODS: We conducted a finite element analysis (FEA) to model stresses at the bone-cement interface with different iterations of metal augments, PE liner thicknesses andfully-cemented stems lengths. RESULTS: For a 20 mm tibial defect, constructs with thicker metal augments and thinner polyethylene liners were superior. Constructswith a fully cemented stem further reduced bone stress on the tibial plateau. Bone stress was lowest when a 100 mm fully-cemented stem was used, while stems between 30 mm - 80 mm produced similar results. CONCLUSIONS: When addressing a tibial bone defect of AORI Type II in rTKA, our FEA model demonstrates that surgeons should opt to use the thickest metal augments in combination with afully-cemented stem with an added length of at least 30 mm, which allows for surgical flexibility together with the most stable construct.Our study is notably limited by lack of modeling of knee joint moments, which are important when considering micromotion, bone-implant interface and stem effectiveness.

Three-Dimensional Printing of Models of Patellofemoral Joint Articular Cartilage in Patients With Patella Instability for Observing Joint Congruity.

Three-dimensional (3D) modeling and printing are increasingly used in the field of orthopaedic surgery for both research and patient care. One area where they are particularly helpful is in improving our understanding of the patellofemoral (PF) joint. Heretofore, morphological studies that use 3D models of the PF joint have primarily been based on computed tomography imaging data and thus do not incorporate articular cartilage. Here, we describe a method for creating 3D models of the articular surfaces of the PF joint based on magnetic resonance imaging. Models created using this technique can be used to improve our understanding of the morphology of the articular surfaces of the PF joint and its relationship to joint pathologies. Of particular interest is our finding of articular congruity in printed articular cartilage surfaces of dysplastic PF joints of recurrent patella dislocators.

Fabricating Patient-Specific 3D Printed Drill Guides to Treat Femoral Head Avascular Necrosis.

Background: Femoral head avascular necrosis (AVN), or death of femoral head tissue due to a lack of blood supply, is a leading cause of total hip replacement for non-geriatric patients. Core decompression (CD) is an effective treatment to re-establish blood flow for patients with AVN. Techniques aimed at improving its efficacy are an area of active research. We propose the use of 3D printed drill guides to accurately guide therapeutic devices for CD. Methods: Using femur sawbones, image processing software, and 3D modeling software, we created a custom-built device with pre-determined drill trajectories and tested the feasibility of the 3D printed drill guides for CD. A fellowship trained orthopedic surgeon used the drill guide to position an 8 ga, 230 mm long decompression device in the three synthetic femurs. CT scans were taken of the sawbones with the drill guide and decompression device. CT scans were processed in the 3D modeling software. Descriptive statistics measuring the angular and needle-tip deviation were compared to the original virtually planned model. Results: Compared to the original 3D model, the trials had a mean displacement of 1.440±1.03 mm and a mean angle deviation of 1.093±0.749°. Conclusions: The drill guides were demonstrated to accurately guide the decompression device along its predetermined drill trajectory. Accuracy was assessed by comparing values to literature-reported values and considered AVN lesion size. This study demonstrates the potential use of 3D printing technology to improve the efficacy of CD techniques.