Development of an implantable trapezium carpal bone replacement for measuring in vivo loads at the base of the thumb.

Understanding the loads that occur across musculoskeletal joints is critical to advancing our understanding of joint function and pathology, implant design and testing, as well as model verification. Substantial work in these areas has occurred in the hip and knee but has not yet been undertaken in smaller joints, such as those in the wrist. The thumb carpometacarpal (CMC) joint is a uniquely human articulation that is also a common site of osteoarthritis with unknown etiology. We present two potential designs for an instrumented trapezium implant and compare approaches to load calibration. Two instrumented trapezia designs were prototyped using strain gauge technology: Tube and Diaphragm. The Tube design is a well-established structure for sensing loads while the Diaphragm is novel. Each design was affixed to a 6-DOF load cell that was used as the reference. Loads were applied manually, and two calibration methods, supervised neural network (DEEP) and matrix algebra (MAT), were implemented. Bland-Altman 95% confidence interval for the limits of agreement (95% CI LOA) was used to assess accuracy. Overall, the DEEP calibration decreased 95% CI LOA compared with the MAT approach for both designs. The Diaphragm design outperformed the Tube design in measuring the primary load vector (joint compression). Importantly, the Diaphragm design permits the hermetic encapsulation of all electronics, which is not possible with the Tube design, given the small size of the trapezium. Substantial work remains before this device can be approved for implantation, but this work lays the foundation for further device development that will be required.

Dorsal Subluxation of the First Metacarpal During Thumb Flexion is an Indicator of Carpometacarpal Osteoarthritis Progression.

BACKGROUND: Measurable changes in patients with progression of thumb carpometacarpal (CMC) osteoarthritis (OA) include joint space narrowing, osteophyte formation, subluxation, and adjacent-tissue changes. Subluxation, an indication of mechanical instability, is postulated as an early biomechanical indicator of progressing CMC OA. Various radiographic views and hand postures have been proposed to best assess CMC subluxation, but 3D measurements derived from CT images serve as the optimal metric. However, we do not know which thumb pose yields subluxation that most indicates OA progression. QUESTIONS/PURPOSES: Using osteophyte volume as a quantitative measure of OA progression, we asked: (1) Does dorsal subluxation vary by thumb pose, time, and disease severity in patients with thumb CMC OA? (2) In which thumb pose(s) does dorsal subluxation most differentiate patients with stable CMC OA from those with progressing CMC OA? (3) In those poses, what values of dorsal subluxation indicate a high likelihood of CMC OA progression? METHODS: Between 2011 and 2014, 743 patients were seen at our institutions for trapeziometacarpal pain. We considered individuals who were between the ages of 45 and 75 years, had tenderness to palpation or a positive grind test result, and had modified Eaton Stage 0 or 1 radiographic thumb CMC OA as potentially eligible for enrollment. Based on these criteria, 109 patients were eligible. Of the eligible patients, 19 were excluded because of a lack of interest in study participation, and another four were lost before the minimum study follow-up or had incomplete datasets, leaving 86 (43 female patients with a mean age of 53 ± 6 years and 43 male patients with a mean age of 60 ± 7 years) patients for analysis. Twenty-five asymptomatic participants (controls) aged 45 to 75 years were also prospectively recruited to participate in this study. Inclusion criteria for controls included an absence of thumb pain and no evidence of CMC OA during clinical examination. Of the 25 recruited controls, three were lost to follow-up, leaving 22 for analysis (13 female patients with a mean age of 55 ± 7 years and nine male patients with a mean age of 58 ± 9 years). Over the 6-year study period, CT images were acquired of patients and controls in 11 thumb poses: neutral, adduction, abduction, flexion, extension, grasp, jar, pinch, grasp loaded, jar loaded, and pinch loaded. CT images were acquired at enrollment (Year 0) and Years 1.5, 3, 4.5, and 6 for patients and at Years 0 and 6 for controls. From the CT images, bone models of the first metacarpal (MC1) and trapezium were segmented, and coordinate systems were calculated from their CMC articular surfaces. The volar-dorsal location of the MC1 relative to the trapezium was computed and normalized for bone size. Patients were categorized into stable OA and progressing OA subgroups based on trapezial osteophyte volume. MC1 volar-dorsal location was analyzed by thumb pose, time, and disease severity using linear mixed-effects models. Data are reported as the mean and 95% confidence interval. Differences in volar-dorsal location at enrollment and rate of migration during the study were analyzed for each thumb pose by group (control, stable OA, and progressing OA). A receiver operating characteristic curve analysis of MC1 location was used to identify thumb poses that differentiated patients whose OA was stable from those whose OA was progressing. The Youden J statistic was used to determine optimized cutoff values of subluxation from those poses to be tested as indicators of OA progression. Sensitivity, specificity, negative predictive values, and positive predictive values were calculated to assess the performance of pose-specific cutoff values of MC1 locations as indicators of progressing OA. RESULTS: In flexion, the MC1 locations were volar to the joint center in patients with stable OA (mean -6.2% [95% CI -8.8% to -3.6%]) and controls (mean -6.1% [95% CI -8.9% to -3.2%]), while patients with progressing OA exhibited dorsal subluxation (mean 5.0% [95% CI 1.3% to 8.6%]; p < 0.001). The pose associated with the most rapid MC1 dorsal subluxation in the progressing OA group was thumb flexion (mean 3.2% [95% CI 2.5% to 3.9%] increase per year). In contrast, the MC1 migrated dorsally much slower in the stable OA group (p < 0.001), at only a mean of 0.1% (95% CI -0.4% to 0.6%) per year. A cutoff value of 1.5% for the volar MC1 position during flexion at enrollment (C-statistic: 0.70) was a moderate indicator of OA progression, with a high positive predictive value (0.80) but low negative predictive value (0.54). Positive and negative predictive values of subluxation rate in flexion (2.1% per year) were high (0.81 and 0.81, respectively). The metric that most indicated a high likelihood of OA progression (sensitivity 0.96, negative predictive value 0.89) was a dual cutoff that combined the subluxation rate in flexion (2.1% per year) with that of loaded pinch (1.2% per year). CONCLUSION: In the thumb flexion pose, only the progressing OA group exhibited MC1 dorsal subluxation. The MC1 location cutoff value for progression in flexion was 1.5% volar to the trapezium , which suggests that dorsal subluxation of any amount in this pose indicates a high likelihood of thumb CMC OA progression. However, volar MC1 location in flexion alone was not sufficient to rule out progression. The availability of longitudinal data improved our ability to identify patients whose disease will likely remain stable. In patients whose MC1 location during flexion changed < 2.1% per year and whose MC1 location during pinch loading changed < 1.2% per year, the confidence that their disease would remain stable throughout the 6-year study period was very high. These cutoff rates were a lower limit, and any patients whose dorsal subluxation advanced faster than 2% to 1% per year in their respective hand poses, were highly likely to experience progressive disease. CLINICAL RELEVANCE: Our findings suggest that in patients with early signs of CMC OA, nonoperative interventions aimed to reduce further dorsal subluxation or operative treatments that spare the trapezium and limit subluxation may be effective. It remains to be determined whether our subluxation metrics can be rigorously computed from more widely available technologies, such as plain radiography or ultrasound.

Bone morphological changes of the trapezium and first metacarpal with early thumb osteoarthritis progression.

BACKGROUND: Thumb carpometacarpal osteoarthritis is characterized by osteophyte growth and changes in the curvature of the articular surfaces of the trapezium and first metacarpal. The aim of this longitudinal study was to quantify in-vivo bone morphology changes with osteoarthritis progression. METHODS: The study analyzed an observational dataset of 86 subjects with early thumb osteoarthritis and 22 age-matched asymptomatic controls. CT scans of subjects' affected hands were acquired at enrollment (year 0), and at 1.5, 3, 4.5, and 6-year follow-up visits. Osteoarthritic subjects were classified into stable and progressive groups, as defined by osteophyte volume and the rate of osteophyte growth. Trapezium height, width, and volar facet recession, along with first metacarpal volar beak recession and recession angle, were quantified. FINDINGS: Mean trapezium width increased 12% over six years in the progressive osteoarthritis group. Trapezium volar recession of the progressive osteoarthritis group was significantly greater than stable at enrollment (P < 0.0001) and year 6 (P < 0.0001). The first metacarpal volar beak of the progressive osteoarthritis group recessed significantly faster than stable (P = 0.0004) and control (P = 0.0003). In year 6, volar beak surfaces in subjects with progressive osteoarthritis were flatter with reduced curvature, measuring -8.7 ± 4.0 degrees, compared to the stable osteoarthritis (P < 0.0001) and control groups (P = 0.0003), which maintained nominal curvatures, measuring 0.7 ± 2.5 and 0.2 ± 3.2 degrees, respectively. INTERPRETATION: Our results demonstrate significant recession and reduction in the angle of the first metacarpal volar beak in progressive osteoarthritis. Flattening of the first metacarpal volar beak may have important associations with carpometacarpal joint contact and loading migrations, further propagating osteophyte formation and bony remodeling. This work highlights the volar beak of the first metacarpal as a region of morphology change with disease.

Evaluation of the PROMIS Upper Extremity Against Validated Patient-Reported Outcomes in Patients With Early Carpometacarpal Osteoarthritis.

PURPOSE: Internal consistency, construct, and criterion validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) upper extremity (UE) v1.2 were evaluated in patients with early-stage carpometacarpal (CMC) osteoarthritis (OA). We hypothesized that in patients with early CMC OA, PROMIS UE scores would: (1) be lower than those in asymptomatic controls; (2) correlate with established patient-reported outcomes; (3) correlate with pinch and grip strengths; and (4) not correlate with radiographic disease progression. METHODS: Patients with early CMC OA (modified Eaton stage 0 or 1) and matched asymptomatic control patients completed the PROMIS UE, Australian and Canadian Osteoarthritis Hand Index, and Patient-Rated Wrist-Hand Evaluation at 2 time points. The PROMIS UE's internal consistency was evaluated by Cronbach's alpha, construct validity by Spearman correlation coefficients among the patient-reported outcome measures, and criterion validity using measures of strength. A floor or ceiling effect was indicated if more than 15% of patients achieved the lowest or highest possible score. RESULTS: The PROMIS UE had high internal consistency. Patients with early CMC OA had a lower score than healthy controls (average, 42 vs 54, respectively). We observed moderate to high correlations between the PROMIS UEv1.2, Australian and Canadian Osteoarthritis Hand Index, and Patient-Rated Wrist-Hand Evaluation and good criterion validity when compared to key pinch and grip strengths. The PROMIS UE did not correlate to radiographic disease severity. CONCLUSIONS: The PROMIS UE had a high correlation with Australian and Canadian Osteoarthritis Hand Index and a moderate correlation with Patient-Rated Wrist-Hand Evaluation. The PROMIS UE had high internal consistency and good criterion validity. CLINICAL RELEVANCE: The PROMIS UE is a valid assessment for disability in patients with early CMC OA and can serve as a clinical adjunct to an outcome assessment.

Total Wrist Arthroplasty Alignment and Its Potential Association with Clinical Outcomes.

Purpose There is a lack of quantitative research that describes the alignment and, more importantly, the effects of malalignment on total wrist arthroplasty (TWA). The main goal of this pilot study was to assess the alignment of TWA components in radiographic images and compare them with measures computed by three-dimensional analysis. Using these measures, we then determined if malalignment is associated with range of motion (ROM) or clinical outcomes (PRWHE, PROMIS, QuickDash, and grip strength). Methods Six osteoarthritic patients with a single type of TWA were recruited. Radiographic images, computed tomography images, and clinical outcomes of the wrists were recorded. Using posteroanterior and lateral radiographs, alignment measurements were defined for the radial and carpal components. Radiographic measurements were validated with models reconstructed from computed tomography images using Bland-Altman analysis. Biplanar videoradiography (<1mm and <1 degree accuracy) was used to capture and compute ROM of the TWA components. Linear regression assessed the associations between alignment and outcomes. Results Radiographic measures had a 95% limit-of-agreement (mean difference ± 1.96 × SD) of 3 degrees and 3mm with three-dimensional values, except for the measures of the carpal component in the lateral view. In our small cohort, wrist flexion-extension and radial-ulnar deviation were correlated with volar-dorsal tilt and volar-dorsal offset of the radial component and demonstrated a ROM increase of 3.7 and 1.6 degrees per degree increase in volar tilt, and 10.8 and 4.2 degrees per every millimeter increase in volar offset. The carpal component's higher volar tilt was also associated with improvements in patient-reported pain. Conclusions We determined metrics describing the alignment of TWA, and found the volar tilt and volar offset of the radial component could potentially influence the replaced wrist's ROM. Clinical Relevance TWA component alignment can be measured reliably in radiographs, and may be associated with clinical outcomes. Future studies must evaluate its role in a larger cohort.

The role of scapholunate interosseous, dorsal intercarpal, and radiolunate ligaments in wrist biomechanics.

Rupture to wrist ligaments predisposes the joint to degenerative changes. Scapholunate interosseous ligament (SLIL) rupture, especially when compounded by dorsal intercarpal ligament (DIC) and long radiolunate ligament (LRL) disruption, can cause carpal bone kinematic abnormalities. It is essential to delineate the role of these ligaments and their constraints on wrist range-of-motion (ROM) and center of rotation (COR). Wrist ROM and COR location were determined in 9 specimens using a six degree-of-freedom robotic musculoskeletal simulator in 24 directions of wrist motion for four experimental conditions: intact, and after sequential sectioning of the SLIL, DIC, and LRL. Sectioning the SLIL alone did not change wrist ROM in any direction (p > 0.10), while sectioning the SLIL and both the DIC and LRL caused significant increases in radial deviation, radial-extension, and ulnar-flexion ROM (p < 0.05). The COR of the intact wrist was located between the proximal third and middle third of the capitate, depending on the direction of wrist motion. While SLIL sectioning alone did not affect the COR, subsequent DIC sectioning led to a distal shift of COR in motions involving ulnar-extension relative to the intact condition. Additional sectioning of the LRL caused a proximal shift of COR in motions involving radial-flexion. A proximal shift implies a more dominant role of the radiocarpal joint, while a distal shift of the COR implies an increased role for the midcarpal joint. Understanding the role of ligaments on overall wrist mechanics is critical to devising new treatment strategies to restore wrist function.

Biomechanics of the Distal Radioulnar Joint During In Vivo Forearm Pronosupination.

Background Ulnar variance (UV) and center of rotation (COR) location at the level of the distal radioulnar joint (DRUJ) change with forearm rotation. Nevertheless, these parameters have not been assessed dynamically during active in vivo pronosupination. This assessment could help us to improve our diagnosis and treatment strategies. Questions/purposes We sought to (1) mathematically model the UV change, and (2) determine the dynamic COR's location during active pronosupination. Methods We used biplanar videoradiography to study DRUJ during in vivo pronation and supination in nine healthy subjects. UV was defined as the proximal-distal distance of ulnar fovea with respect to the radial sigmoid notch, and COR was calculated using helical axis of motion parameters. The continuous change of UV was evaluated using a generalized linear regression model. Results A second-degree polynomial with R 2 of 0.85 was able to model the UV changes. Maximum negative UV occurred at 38.0 degrees supination and maximum positive UV occurred at maximum pronation. At maximum pronation, the COR was located 0.5 ± 1.8 mm ulnarly and 0.6 ± 0.8 mm volarly from the center of the ulnar fovea, while at maximum supination, the COR was located 0.2 ± 0.6 mm radially and 2.0 ± 0.5 mm volarly. Conclusion Changes in UV and volar translation of the COR are nonlinear at the DRUJ during pronosupination. Clinical Relevance Understanding the dynamic nature of UV as a function of pronosupination can help guide accurate evaluation and treatment of wrist pathology where the UV is an important consideration. The dynamic behavior of COR might be useful in designing DRUJ replacement implants to match the anatomical motion.

In vivo articular contact pattern of a total wrist arthroplasty design.

Total wrist arthroplasty (TWA) designs suffer from relatively high complication rates when compared to other arthroplasties. Understanding the contact pattern of hip and knee replacement has improved their design and function; however, the in vivo contact pattern of TWA has not yet been examined and is thus the aim of this study. We hypothesized that the center of contact (CoC) is located at the geometric centers of the carpal component and radial component in the neutral posture and that the CoC moves along the principal arcs of curvature throughout primary anatomical motions. Wrist motion and implant kinematics of six patients with the Freedom® total wrist implant were studied during various tasks using biplanar videoradiography. The location of the CoC of the components was investigated by calculating distance fields between the articular surfaces. We found the CoC at the neutral posture was not at the geometric centers but was located 3.5 mm radially on the carpal component and 1.2 mm ulnarly on the radial component. From extension to flexion, the CoC moved 10.8 mm from dorsal to volar side on the carpal component (p < 0.0001) and 7.2 mm from volar to dorsal on the radial component (p = 0.0009). From radial to ulnar deviation, the CoC moved 12.4 mm from radial to ulnar on the carpal component (p < 0.0001), and 5.6 mm from ulnar to radial on the radial component (p = 0.009). The findings of this study may eventually improve TWA success by advancing future designs through a more accurate understating of their kinematic performance in vivo.

Optical motion capture accuracy is task-dependent in assessing wrist motion.

Optical motion capture (OMC) systems are commonly used to capture in-vivo three-dimensional joint kinematics. However, the skin-based markers may not reflect the underlying bone movement, a source of error known as soft tissue artifact (STA). This study examined STA during wrist motion by evaluating the agreement between OMC and biplanar videoradiography (BVR). Nine subjects completed 7 different wrist motion tasks: doorknob rotation to capture supination and pronation, radial-ulnar deviation, flexion-extension, circumduction, hammering, and pitcher pouring. BVR and OMC captured the motion simultaneously. Wrist kinematics were quantified using helical motion parameters of rotation and translation, and Bland-Altman analysis quantified the mean difference (bias) and 95% limit of agreement (LOA). The rotational bias of doorknob pronation, a median bias of -4.9°, was significantly larger than the flexion-extension (0.7°, p < 0.05) and radial-ulnar deviation (1.8°, p < 0.01) tasks. The rotational LOA range was significantly smaller in the flexion-extension task (5.9°) compared to pitcher (11.6°, p < 0.05) and doorknob pronation (17.9°, p < 0.05) tasks. The translation bias did not differ between tasks. The translation LOA range was significantly larger in circumduction (9.8°) compared to the radial-ulnar deviation (6.3°, p < 0.05) and pitcher (3.4°, p < 0.05) tasks. While OMC technology has a wide-range of successful applications, we demonstrated it has relatively poor agreement with BVR in tracking wrist motion, and that the agreement depends on the nature and direction of wrist motion.

Biplanar Videoradiography to Study the Wrist and Distal Radioulnar Joints.

Accurate measurement of skeletal kinematics in vivo is essential for understanding normal joint function, the influence of pathology, disease progression, and the effects of treatments. Measurement systems that use skin surface markers to infer skeletal motion have provided important insight into normal and pathological kinematics, however, accurate arthrokinematics cannot be attained using these systems, especially during dynamic activities. In the past two decades, biplanar videoradiography (BVR) systems have enabled many researchers to directly study the skeletal kinematics of the joints during activities of daily living. To implement BVR systems for the distal upper extremity, videoradiographs of the distal radius and the hand are acquired from two calibrated X-ray sources while a subject performs a designated task. Three-dimensional (3D) rigid-body positions are computed from the videoradiographs via a best-fit registrations of 3D model projections onto to each BVR view. The 3D models are density-based image volumes of the specific bone derived from independently acquired computed-tomography data. Utilizing graphics processor units and high-performance computing systems, this model-based tracking approach is shown to be fast and accurate in evaluating the wrist and distal radioulnar joint biomechanics. In this study, we first summarized the previous studies that have established the submillimeter and subdegree agreement of BVR with an in vitro optical motion capture system in evaluating the wrist and distal radioulnar joint kinematics. Furthermore, we used BVR to compute the center of rotation behavior of the wrist joint, to evaluate the articulation pattern of the components of the implant upon one another, and to assess the dynamic change of ulnar variance during pronosupination of the forearm. In the future, carpal bones may be captured in greater detail with the addition of flat panel X-ray detectors, more X-ray sources (i.e., multiplanar videoradiography), or advanced computer vision algorithms.

Targeted Ptpn11 deletion in mice reveals the essential role of SHP2 in osteoblast differentiation and skeletal homeostasis.

The maturation and function of osteoblasts (OBs) rely heavily on the reversible phosphorylation of signaling proteins. To date, most of the work in OBs has focused on phosphorylation by tyrosyl kinases, but little has been revealed about dephosphorylation by protein tyrosine phosphatases (PTPases). SHP2 (encoded by PTPN11) is a ubiquitously expressed PTPase. PTPN11 mutations are associated with both bone and cartilage manifestations in patients with Noonan syndrome (NS) and metachondromatosis (MC), although the underlying mechanisms remain elusive. Here, we report that SHP2 deletion in bone gamma-carboxyglutamate protein-expressing (Bglap+) bone cells leads to massive osteopenia in both trabecular and cortical bones due to the failure of bone cell maturation and enhanced osteoclast activity, and its deletion in Bglap+ chondrocytes results in the onset of enchondroma and osteochondroma in aged mice with increased tubular bone length. Mechanistically, SHP2 was found to be required for osteoblastic differentiation by promoting RUNX2/OSTERIX signaling and for the suppression of osteoclastogenesis by inhibiting STAT3-mediated RANKL production by osteoblasts and osteocytes. These findings are likely to explain the compromised skeletal system in NS and MC patients and to inform the development of novel therapeutics to combat skeletal disorders.

SHP2 regulates the development of intestinal epithelium by modifying OSTERIX+ crypt stem cell self-renewal and proliferation.

The protein tyrosine phosphatase SHP2, encoded by PTPN11, is ubiquitously expressed and essential for the development and/or maintenance of multiple tissues and organs. SHP2 is involved in gastrointestinal (GI) epithelium development and homeostasis, but the underlying mechanisms remain elusive. While studying SHP2's role in skeletal development, we made osteoblast-specific SHP2 deficient mice using Osterix (Osx)-Cre as a driver to excise Ptpn11 floxed alleles. Phenotypic characterization of these SHP2 mutants unexpectedly revealed a critical role of SHP2 in GI biology. Mice lacking SHP2 in Osx+ cells developed a fatal GI pathology with dramatic villus hypoplasia. OSTERIX, an OB-specific zinc finger-containing transcription factor is for the first time found to be expressed in GI crypt cells, and SHP2 expression in the crypt Osx+ cells is critical for self-renewal and proliferation. Further, immunostaining revealed the colocalization of OSTERIX with OLFM4 and LGR5, two bona fide GI stem cell markers, at the crypt cells. Furthermore, OSTERIX expression is found to be associated with GI malignancies. Knockdown of SHP2 expression had no apparent influence on the relative numbers of enterocytes, goblet cells or Paneth cells. Given SHP2's key regulatory role in OB differentiation, our studies suggest that OSTERIX and SHP2 are indispensable for gut homeostasis, analogous to SOX9's dual role as a master regulator of cartilage and an important regulator of crypt stem cell biology. Our findings also provide a foundation for new avenues of inquiry into GI stem cell biology and of OSTERIX's therapeutic and diagnostic potential.

Proximal-distal shift of the center of rotation in a total wrist arthroplasty is more than twice of the healthy wrist.

Reproduction of healthy wrist biomechanics should minimize the abnormal joint forces that could potentially result in the failure of a total wrist arthroplasty (TWA). To date, the in vivo kinematics of TWA have not been measured and it is unknown if TWA preserves healthy wrist kinematics. Therefore, the purpose of this in vivo study was to determine the center of rotation (COR) for a current TWA design and to compare its location to the healthy wrist. The wrist COR for six patients with TWA and 10 healthy subjects were calculated using biplane videoradiography as the subjects performed various range-of-motion and functional tasks that included coupled wrist motions. An open-source registration software, Autoscoper, was used for model-based tracking and kinematics analysis. It was demonstrated that the COR was located near the centers of curvatures of the carpal component for the anatomical motions of flexion-extension and radial-ulnar deviation. When compared to healthy wrists, the COR of TWAs was located more distal in both pure radial deviation (P < .0001) and pure ulnar deviation (P = .07), while there was no difference in its location in pure flexion or extension (P = .99). Across all coupled motions, the TWA's COR shifted more than two times that of the healthy wrists in the proximal-distal direction (17.1 vs 7.2 mm). We postulate that the mismatch in the COR location and behavior may be associated with increased loading of the TWA components, leading to an increase in the risk of component and/or interface failure.

An Approach to Robotic Testing of the Wrist Using Three-Dimensional Imaging and a Hybrid Testing Methodology.

Robotic technology is increasingly used for sophisticated in vitro testing designed to understand the subtleties of joint biomechanics. Typically, the joint coordinate systems in these studies are established via palpation and digitization of anatomic landmarks. We are interested in wrist mechanics in which overlying soft tissues and indistinct bony features can introduce considerable variation in landmark localization, leading to descriptions of kinematics and kinetics that may not appropriately align with the bony anatomy. In the wrist, testing is often performed using either load or displacement control with standard material testers. However, these control modes either do not consider all six degrees-of-freedom (DOF) or reflect the nonlinear mechanical properties of the wrist joint. The development of an appropriate protocol to investigate complexities of wrist mechanics would potentially advance our understanding of normal, pathological, and artificial wrist function. In this study, we report a novel methodology for using CT imaging to generate anatomically aligned coordinate systems and a new methodology for robotic testing of wrist. The methodology is demonstrated with the testing of 9 intact cadaver specimens in 24 unique directions of wrist motion to a resultant torque of 2.0 N·m. The mean orientation of the major principal axis of range of motion (ROM) envelope was oriented 12.1 ± 2.7 deg toward ulnar flexion, which was significantly different (p < 0.001) from the anatomical flexion/extension axis. The largest wrist ROM was 98 ± 9.3 deg in the direction of ulnar flexion, 15 deg ulnar from pure flexion, consistent with previous studies [1,2]. Interestingly, the radial and ulnar components of the resultant torque were the most dominant across all directions of wrist motion. The results of this study showed that we can efficiently register anatomical coordinate systems from CT imaging space to robotic test space adaptable to any cadaveric joint experiments and demonstrated a combined load-position strategy for robotic testing of wrist.

Osteophyte volume calculation using dissimilarity-excluding Procrustes registration of archived bone models from healthy volunteers.

Osteophytes are associated with later stage osteoarthritis and are most commonly described using semiquantitative radiographic grading systems. A detailed understanding of osteophyte formation is, in part, limited by the ability to quantify bone pathology. Osteophytes can be quantified relative to pre-osteoarthritic bone, or to the contralateral bone if it is healthy; however, in many cases, neither are available as references. We present a method for computing three-dimensional (3D) osteophyte models using a library of healthy control bones. An existing data set containing the computed tomography scans of 90 patients with first carpometacarpal osteoarthritis (OA) and 46 healthy subjects were utilized. A healthy bone that best fit each OA subject's bone was determined using a dissimilarity-excluding Procrustes registration technique (DEP) that minimized the influence of dissimilar features (ie, osteophytes). The osteophyte model was then computed through Boolean subtraction of the reference bone model from the OA bone model. DEP reference bones conformed significantly better to the OA bones (P < .0001) than by finite difference iterative closest point registration (root mean squared distances, 0.33 ± 0.05 and 0.41 ± 0.16 mm, respectively). The effect of library size on dissimilarity measure was investigated by leave-k-out cross-validation randomly reducing k from 46 to 1. A library of n ≥ 31 resulted in less than 10% difference from the theoretical minimum value. The proposed method enables quantification of osteophytes when the disease-free bone or the healthy contralateral bone is not available for any 3D data set. Quantifying osteophyte formation and growth may aid in understating the associated mechanisms in OA.

Predicting Carpal Bone Kinematics Using an Expanded Digital Database of Wrist Carpal Bone Anatomy and Kinematics.

The wrist can be considered a 2 degrees-of-freedom joint with all movements reflecting the combination of flexion-extension and radial-ulnar deviation. Wrist motions are accomplished by the kinematic reduction of the 42 degrees-of-freedom of the individual carpal bones. While previous studies have demonstrated the minimal motion of the scaphoid and lunate as the wrist moves along the dart-thrower's path or small relative motion between hamate-capitate-trapezoid, an understanding of the kinematics of the complete carpus across all wrist motions remains lacking. To address this, we assembled an open-source database of in vivo carpal motions and developed mathematical models of the carpal kinematics as a function of wrist motion. Quadratic surfaces were trained for each of the 42-carpal bone degrees-of-freedom and the goodness of fits were evaluated. Using the models, paths of wrist motion that generated minimal carpal rotations or translations were determined. Model predictions were best for flexion-extension, radial-ulnar deviation, and volar-dorsal translations for all carpal bones with R 2 > 0.8, while the estimates were least effective for supination-pronation with R 2 < 0.6. The wrist path of motion's analysis indicated that the distal row of carpal bones moves rigidly together (<3° motion), along the anatomical axis of wrist motion, while the bones in the proximal row undergo minimal motion when the wrist moves in a path oblique to the main axes. The open-source dataset along with its graphical user interface and mathematical models should facilitate clinical visualization and enable new studies of carpal kinematics and function. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2661-2670, 2019.

Accuracy of biplane videoradiography for quantifying dynamic wrist kinematics.

Accurately assessing the dynamic kinematics of the skeletal wrist could advance our understanding of the normal and pathological wrist. Biplane videoradiography (BVR) has allowed investigators to study dynamic activities in the knee, hip, and shoulder joint; however, currently, BVR has not been utilized for the wrist joint because of the challenges associated with imaging multiple overlapping bones. Therefore, our aim was to develop a BVR procedure and to quantify its accuracy for evaluation of wrist kinematics. BVR was performed on six cadaveric forearms for one neutral static and six dynamic tasks, including flexion-extension, radial-ulnar deviation, circumduction, pronation, supination, and hammering. Optical motion capture (OMC) served as the gold standard for assessing accuracy. We propose a feedforward tracking methodology, which uses a combined model of metacarpals (second and third) for initialization of the third metacarpal (MC3). BVR-calculated kinematic parameters were found to be consistent with the OMC-calculated parameters, and the BVR/OMC agreement had submillimeter and sub-degree biases in tracking individual bones as well as the overall joint's rotation and translation. All dynamic tasks (except pronation task) showed a limit of agreement within 1.5° for overall rotation, and within 1.3 mm for overall translations. Pronation task had a 2.1° and 1.4 mm limit of agreement for rotation and translation measurement. The poorest precision was achieved in calculating the pronation-supination angle, and radial-ulnar and volar-dorsal translational components, although they were sub-degree and submillimeter. The methodology described herein may assist those interested in examining the complexities of skeletal wrist function during dynamic tasks.

Kinematic Accuracy in Tracking Total Wrist Arthroplasty With Biplane Videoradiography Using a Computed Tomography-Generated Model.

Total wrist arthroplasty (TWA) for improving the functionality of severe wrist joint pathology has not had the same success, in parameters such as motion restoration and implant survival, as hip, knee, and shoulder arthroplasty. These other arthroplasties have been studied extensively, including the use of biplane videoradiography (BVR) that has allowed investigators to study the in vivo motion of the total joint replacement during dynamic activities. The wrist has not been a previous focus, and utilization of BVR for wrist arthroplasty presents unique challenges due to the design characteristics of TWAs. Accordingly, the aims of this study were (1) to develop a methodology for generating TWA component models for use in BVR and (2) to evaluate the accuracy of model-image registration in a single cadaveric model. A model of the carpal component was constructed from a computed tomography (CT) scan, and a model of the radial component was generated from a surface scanner. BVR was acquired for three anatomical tasks from a cadaver specimen. Optical motion capture (OMC) was used as the gold standard. BVR's bias in flexion/extension, radial/ulnar deviation, and pronosupination was less than 0.3 deg, 0.5 deg, and 0.6 deg. Translation bias was less than 0.2 mm with a standard deviation of less than 0.4 mm. This BVR technique achieved a kinematic accuracy comparable to the previous studies on other total joint replacements. BVR's application to the study of TWA function in patients could advance the understanding of TWA, and thus, the implant's success.

SHP2 regulates intramembranous ossification by modifying the TGFß and BMP2 signaling pathway.

SHP2 is a ubiquitously expressed protein tyrosine phosphatase, which is involved in many signaling pathways to regulate the skeletal development. In endochondral ossification, SHP2 is known to modify the osteogenic fate of osteochondroprogenitors and to impair the osteoblastic transdifferentiation of hypertrophic chondrocytes. However, how SHP2 regulates osteoblast differentiation in intramembranous ossification remains incompletely understood. To address this question, we generated a mouse model to ablate SHP2 in the Prrx1-expressing mesenchymal progenitors by using "Cre-loxP"-mediated gene excision and examined the development of calvarial bone, in which the main process of bone formation is intramembranous ossification. Phenotypic characterization showed that SHP2 mutants have severe defects in calvarial bone formation. Cell lineage tracing and in situ hybridization data showed less osteoblast differentiation of mesenchymal cells and reduced osteogenic genes expression, respectively. Further mechanistic studies revealed enhanced TGFß and suppressed BMP2 signaling in SHP2 ablated mesenchymal progenitors and their derivatives. Our study uncovered the critical role of SHP2 in osteoblast differentiation through intramembranous ossification and might provide a potential target to treat craniofacial skeleton disorders.

SHP2 regulates skeletal cell fate by modifying SOX9 expression and transcriptional activity.

Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor (OCP), and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2 (encoded by Ptpn11) affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using "Cre-loxP"-mediated gene excision. SHP2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts. Consistent with these observations, the expression of the master chondrogenic transcription factor SOX9 and its target genes Acan, Col2a1, and Col10a1 were increased in SHP2-deficient chondrocytes, as revealed by gene expression arrays, qRT-PCR, in situ hybridization, and immunostaining. Mechanistic studies demonstrate that SHP2 regulates OCP fate determination via the phosphorylation and SUMOylation of SOX9, mediated at least in part via the PKA signaling pathway. Our data indicate that SHP2 is critical for skeletal cell lineage differentiation and could thus be a pharmacologic target for bone and cartilage regeneration.