Improved responsiveness to change in joint space width over 24-month follow-up: comparison of 3D JSW on weight-bearing CT vs 2D JSW on radiographs in the MOST study.

OBJECTIVE: Radiographic joint space width (JSW) has been a standard for measuring knee osteoarthritis (OA) structural change. Limitations in the responsiveness of this approach might be overcome by instead measuring 3D JSW on weight-bearing CT (WBCT). This study compared the responsiveness of 3D JSW measurements using WBCT with the responsiveness of radiographic 2D JSW. DESIGN: Standing, fixed-flexion knee radiographs (XR) and WBCT were acquired ancillary to the 144- and 168-month Multicenter Osteoarthritis Study visits. Tibiofemoral JSW was measured on both XR and WBCT. Responsiveness to change was defined by the standardized response mean (SRM) for change in JSW (1) at predetermined mediolateral locations (JSWx) on both modalities and (2) in the following subregions measured on WBCT images: central medial and lateral femur (CMF/CLF) and tibia (CMT/CLT), and anterior and posterior tibia (AMT/ALT, PMT/MLT). RESULTS: Baseline and 24-month follow-up JSWx measurements were completed for 265 participants (58.1% women). Responsiveness of 3D JSWx for medial tibiofemoral compartment on coronal WBCT (SRM range: -0.18, -0.24) exceeded that for 2D JSWx (-0.10, -0.16). Responsiveness of 3D JSW subregional mean (-0.06, -0.36) and maximal (-1.14, -1.75) CMF and CMT and maximal CLF/CLT 3D JSW changes were statistically significantly greater in comparison with respective medial and lateral 2D JSWx (P ≤ 0.002). CONCLUSIONS: Subregional 3D JSW on WBCT is substantially more responsive to 24-month changes in tibiofemoral joint structure compared to radiographic measurements. Use of subregional 3D JSW on WBCT could enable improved detection of OA structural progression over a 24-month duration in comparison with measurements made on XR.

Correlations of Medial Joint Space Width on Fixed-Flexed Standing Computed Tomography and Radiographs With Cartilage and Meniscal Morphology on Magnetic Resonance Imaging.

OBJECTIVE: To assess whether medial tibiofemoral joint space width (JSW) on 3-dimensional (3-D) standing computed tomography (SCT) correlates more closely with magnetic resonance imaging cartilage morphology (CM) and meniscal scores than does radiographic 2-D JSW. METHODS: Participants in the Multicenter Osteoarthritis Study, who had standing fixed-flexion posteroanterior knee radiographs, were recruited. Medial tibiofemoral 3-D JSW on SCT and 2-D JSW on fixed-flexion radiographs were compared with medial tibiofemoral cartilage and meniscal morphology using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations between the area of the articular surface with 3-D JSW <2.5 mm on SCT, radiographic minimal 2-D JSW, and the WORMS-CM and meniscal scores were assessed using Spearman's rho. RESULTS: For the 19 participants included (33 knees), mean ± SD age was 66.9 ± 5.4 years, body mass index was 29.5 ± 4.4 kg/m(2) , 42.1% of participants were female, and the Kellgren/Lawrence grades were 0 (21.2%), 1 (36.4%), 2 (18.2%), and 3 (24.2%). The articular surface area with 3-D JSW <2.5 mm on SCT correlated with WORMS-CM scores for the central medial tibia (rs = 0.84, P < 0.001), central medial femur (rs = 0.60, P < 0.007), and posterior medial meniscal tear (rs = 0.39, P < 0.026), as did other cut points for 3-D JSW. Correlations with radiographic minimal 2-D JSW were -0.66, -0.52, and -0.40, respectively, differing from SCT only for tibial cartilage (P = 0.001). CONCLUSION: Greater surface area with a low JSW, measured by SCT, correlates more strongly with the severity of tibial cartilage lesions, while correlating with medial femoral cartilage and meniscal damage to a similar extent as radiographic minimal JSW. SCT may enable valid stratification of participants in clinical trials, through quickly and inexpensively characterizing osteoarthritis features.

Elevated tibiofemoral articular contact stress predicts risk for bone marrow lesions and cartilage damage at 30 months.

OBJECTIVE: As cartilage loss and bone marrow lesions (BMLs) are associated with knee joint pain and structural worsening, this study assessed whether non-invasive estimates of articular contact stress may longitudinally predict risk for worsening of knee cartilage morphology and BMLs. DESIGN: This was a longitudinal cohort study of adults aged 50-79 years with risk factors for knee osteoarthritis. Baseline and follow-up measures included whole-organ magnetic resonance imaging score (WORMS) classification of knee cartilage morphology and BMLs. Tibiofemoral geometry was manually segmented on baseline magnetic resonance imaging (MRI), and three-dimensional (3D) tibiofemoral point clouds were registered into subject-specific loaded apposition using fixed-flexion knee radiographs. Discrete element analysis (DEA) was used to estimate mean and peak contact stresses for the medial and lateral compartments. The association of baseline contact stress with worsening cartilage and BMLs in the same subregion over 30 months was assessed using conditional logistic regression. RESULTS: Subjects (N = 38, 60.5% female) had a mean ± standard deviation (SD) age and body mass index (BMI) of 63.5 ± 8.4 years and 30.5 ± 3.7 kg/m2 respectively. Elevated mean articular contact stress at baseline was associated with worsening cartilage morphology and worsening BMLs by 30 months, with odds ratio (OR) [95% confidence interval (CI)] of 4.0 (2.5, 6.4) and 6.6 (2.7, 16.5) respectively. Peak contact stress also was significantly associated with worsening cartilage morphology and BMLs {1.9 (1.5, 2.3) and 2.3 (1.5, 3.6)}(all P < 0.0001). CONCLUSIONS: Detection of higher contact stress 30 months prior to structural worsening suggests an etiological role for mechanical loading. Estimation of articular contact stress with DEA is an efficient and accurate means of predicting subregion-specific knee joint worsening and may be useful in guiding prognosis and treatment.

Subchondral bone remodeling is related to clinical improvement after joint distraction in the treatment of ankle osteoarthritis.

OBJECTIVE: In osteoarthritis (OA), subchondral bone changes alter the joint's mechanical environment and potentially influence progression of cartilage degeneration. Joint distraction as a treatment for OA has been shown to provide pain relief and functional improvement through mechanisms that are not well understood. This study evaluated whether subchondral bone remodeling was associated with clinical improvement in OA patients treated with joint distraction. METHOD: Twenty-six patients with advanced post-traumatic ankle OA were treated with joint distraction for 3 months using an Ilizarov frame in a referral center. Primary outcome measure was bone density change analyzed on computed tomography (CT) scans. Longitudinal, manually segmented CT datasets for a given patient were brought into a common spatial alignment. Changes in bone density (Hounsfield Units (HU), relative to baseline) were calculated at the weight-bearing region, extending subchondrally to a depth of 8mm. Clinical outcome was assessed using the ankle OA scale. RESULTS: Baseline scans demonstrated subchondral sclerosis with local cysts. At 1 and 2 years of follow-up, an overall decrease in bone density (-23% and -21%, respectively) was observed. Interestingly, density in originally low-density (cystic) areas increased. Joint distraction resulted in a decrease in pain (from 60 to 35, scale of 100) and functional deficit (from 67 to 36). Improvements in clinical outcomes were best correlated with disappearance of low-density (cystic) areas (r=0.69). CONCLUSIONS: Treatment of advanced post-traumatic ankle OA with 3 months of joint distraction resulted in bone density normalization that was associated with clinical improvement.

Acute articular fracture severity and chronic cartilage stress challenge as quantitative risk factors for post-traumatic osteoarthritis: illustrative cases.

Novel biomechanical methods have been developed to objectively measure acute fracture severity (from inter-fragmentary surface area) and chronic contact stress challenge (from patient-specific finite element analysis) in articular fractures. These new methods help clarify the pathomechanics of the development of post-traumatic osteoarthritis, and can contribute directly to the clinical care of patients. In this manuscript, the value of these two new measures is demonstrated in three illustrative tibial plafond fracture cases, in which both metrics are correlated with cartilage status and with patient outcomes at a minimum of two years after injury. These clinical cases demonstrate the utility of new biomechanical variables to advance clinical research and patient care, by providing a basis to predict outcome and select treatment.

Quantification of ankle articular cartilage topography and thickness using a high resolution stereophotography system.

OBJECTIVE: To describe the topography and to measure thicknesses, surface areas and volumes in the cartilage layers of the ankle. METHODS: Twelve cadaveric ankle joints were disarticulated and the cartilage surfaces of each bone were imaged with a highly accurate (+/-2 microm) stereophotography system (ATOS). The cartilage was then dissolved and the subchondral bone imaged. The geometric data were then used to measure the quantitative parameters in each cartilage layer. RESULTS: The mean cartilage volume across the 12 specimens ranged from 0.32+/-0.08 ml for the fibula to 2.44+/-0.48 ml for the talus. The mean thickness of both the talar (1.1+/-0.18 mm) and tibial (1.16+/-0.14 mm) cartilage was significantly thicker than the fibula (0.85+/-0.13 mm). The talus had the greatest mean maximum cartilage thickness (2.38+/-0.4 mm). CONCLUSIONS: The reported stereophotographic technique may be used as an independent gold standard for validation of the accuracy of quantitative cartilage measurements made using magnetic resonance imaging. The thickness distribution maps show that the thickest articular cartilage occurs over the talar shoulders where osteochondral lesions commonly occur and not in the centre of the talar dome as commonly believed.

Nonsteroidal selective glucocorticoid modulators: the effect of C-5 alkyl substitution on the transcriptional activation/repression profile of 2,5-dihydro-10-methoxy-2,2,4-trimethyl-1H-[1]benzopyrano[3,4-f]quinolines.

The preparation and characterization of a series of selective glucocorticoid receptor modulators are described. The preliminary structure-activity relationship of nonaromatic C-5 substitution on the tetracyclic quinoline core showed a preference for small lipophilic side chains. Proper substitution at this position maintained the transcriptional repression of proinflammatory transcription factors while diminishing the transcriptional activation activity of the ligand/glucocorticoid receptor complex. The optimal compounds described in this study were the allyl analogue 18 and cyclopentyl analogue 32. These candidates showed slightly less potent, highly efficacious E-selectin repression with significantly reduced levels of glucocorticoid response element activation in reporter gene assays vs prednisolone. Allyl analogue 18 was evaluated in vivo. An oral dose of 18 showed an ED(50) = 1.7 mg/kg as compared to 1.2 mg/kg for prednisolone in the Sephadex-induced pulmonary eosinophilia model and an ED(50) = 15 mg/kg vs 4 mg/kg for prednisolone in the carrageenan-induced paw edema model.

Impact of exercise on bone health and contraindication of oral contraceptive use in young women.

PURPOSE: The effect of quantified resistance and high impact exercise training on bone mass as modified by age and oral contraceptive (OCont) use in young women was studied. METHODS: Women were categorized by age (18-23 vs 24-31 yr) and OCont use, and were then randomized into either three sessions of resistance exercise plus 60 min.wk-1 of jumping rope or a control group for 24 months. Total body, spine, femoral neck, greater trochanter, Ward's area, and radial bone mineral density (BMD) and/or content (BMC), biochemical markers of bone turnover, dietary intake of calcium, lean body mass, maximal oxygen uptake, and strength were determined at baseline and every 6 months. RESULTS: Total body (TB) BMC percent change from baseline was higher in exercisers compared with nonexercisers at 6 and 24 months. OCont users had lower bone turnover at baseline and a decrease in TBBMC from baseline compared with non-OCont users at 24 months. Spine BMC and BMD decreased in the exercise and OCont group at 6 months and remained significantly below nonexercisers who used oral contraceptives at 2 yr. Femoral neck BMD also decreased in the exercise and oral contraceptive group at 6 months. CONCLUSIONS: Exercise prevented a decline in TBBMC seen in the nonexercisers. On the other hand, exercise in oral contraceptive users prevented the increase observed in the spine of the nonexercise plus OCont group.

Insulin-like growth factor I accelerates functional recovery from Achilles tendon injury in a rat model.

We studied the effects of insulin-like growth factor I on Achilles tendon healing in a rat model. Rats were randomized into groups of six each: sham surgery, transection alone, and transection plus growth factor. Postoperatively, rats treated with growth factor had a significantly smaller maximum functional deficit and a decreased time to functional recovery than rats in the untreated groups. Biomechanical testing revealed no significant differences in the measured parameters between the treated and the untreated groups after transection. To study the mechanism of action, six additional animals received an Achilles tendon injection of the inflammatory agent carrageenan alone and six received carrageenan plus growth factor. Rats treated with growth factor did not show the inflammation-induced functional deficit experienced by the control rats. Spectrometric myeloperoxidase assays on the remaining eight rats after Achilles tendon transection demonstrated no significant difference between the untreated and the growth factor-treated groups, indicating a mechanism other than neutrophil recruitment by which the growth factor limits inflammation. Histologic studies were performed on carrageenan-injected rats at postinjection day 2 and on surgically treated rats at postoperative day 15. No gross histologic differences were seen between untreated and growth factor-treated groups. This study demonstrated that via a possible antiinflammatory mechanism, insulin-like growth factor I reduces maximum functional deficit and accelerates recovery after Achilles tendon injury.

Correlation of wrist ligamentotaxis with carpal distraction: implications for external fixation.

Cadaver forearms were tested to measure carpal bone separation and wrist ligament tension in response to MTS-based incremental wrist distraction. Distraction of 2 mm separated the proximal carpal row from the radius and transmitted an average tension of 8 N. The mid-carpal joint also began to widen at this level of distraction. Distraction of 4 mm resulted in an average tension of 20 N. At this level of distraction, radioscaphoid separation started to exceed radiolunate separation. A transition from low- to high-stiffness response was observed over a range of 4-8 mm distraction for the 12 specimens tested, with an average tension of 80 N associated with 8 mm distraction. Average values of carpal height ratio, revised carpal height ratio, and carpal height index were found to be poor indicators of distraction, owing to their high variability between specimens.

The effect of intercondylar notchplasty on the patellofemoral articulation.

Using pressure-sensitive film, we measured the patellofemoral contact areas and pressures after increasing degrees of notchplasty in eight fresh-frozen cadaveric knee specimens. Each specimen was stabilized on an axial loading frame with physiologic loads applied through the quadriceps tendon at varying flexion angles. The patellofemoral joint was loaded at 90 degrees, 105 degrees and 120 degrees of knee flexion. The same measurements were then obtained after serial notchplasties of 3, 6, and 9 mm. The film was analyzed for contact areas and for contact pressures by densitometry. There was no statistical significance between contact area or pressure after notchplasties of 3, 6, or 9 mm at 90 degrees, 105 degrees, and 120 degrees of knee flexion. These data suggest that routine notchplasty does not affect the patellofemoral articulation.

Displaced intra-articular fractures of the distal radius: the effect of fracture displacement on contact stresses in a cadaver model.

Contact stresses in the wrist were measured after simulating displaced fractures of the lunate fossa in the distal radius of eight human cadaver arms. Osteotomies created displaced lunate fossa fractures of 0, 1, 2, and 3 mm. Contact stresses were measured with Fuji pressure-sensitive film after loads of 100 N were applied to the wrist through wrist flexor and extensor tendons. Mean contact stresses were significantly increased with step-offs of 1 mm or more. Maximum stresses and overloaded areas were significantly increased with step-offs of 2 mm or more. As the magnitude of the fracture displacement increased, there was a shift in the focus of the maximum stresses toward the fracture line. In this model, simulated displaced die-punch fractures created alterations in both the magnitude and location of contact stresses in the wrist joint.

Contact stress distributions in malreduced intraarticular distal radius fractures.

Residual articular incongruity of the distal radius following intraarticular fracture has been correlated with early osteoarthritis (OA) and a poor clinical outcome. We developed a simple in vitro fracture model of the distal radius to investigate the relationship between degree of articular incongruity and the resulting distribution of radiocarpal contact stress. Twelve fresh-frozen cadaver arms were dissected, packets of Fuji Pressensor film were inserted into the wrist, and the wrist was loaded through its flexor and extensor tendons. We created a simple intraarticular fracture that allowed controlled distal radius articular incongruity. Loading trials were performed for the intact distal radius, for a fully reduced case, and for step-offs of 0.4, 1, 2, and 3 mm. Mean contact stress was significantly greater than the anatomically reduced case at only 3 mm of step-off. Contact area was greater than the anatomically reduced case at 0.4, 1, and 2 mm of step-off. The elevations in contact stress that we observed were only modest, suggesting that other factors may be involved in the pathogenesis of radiocarpal OA in the presence of residual articular incongruity.

Physical modelling of hip joint forces in stair climbing.

A test device has been developed and validated to simulate physiologic loading of the hip during stair climbing. Forces about the hip joint were measured in static simulations of stair climbing using simulated extensor, abductor and adductor muscle groups to support the joint. Femoral flexion angle (to model step length and height) and applied hip flexion moment (to model trunk lean) were varied to examine the effects of different loading conditions on the hip. In stair climbing the maximum total joint force was six times body weight at 34 degrees of femoral flexion and 60 N m of hip flexion moment. Joint forces increased with hip flexion moment and varied little with femoral flexion angle, except for the posteriorly directed force. This component, which twists implants about the femoral shaft, increased with femoral flexion angle but changed little with hip flexion moment.

Biomechanical evaluation of cervical spine stabilization methods using a porcine model.

STUDY DESIGN: The biomechanical stability of three different methods of cervical spine stabilization was evaluated in a porcine model. Specimens were tested in flexion, extension, and axial rotation. OBJECTIVES: Our goal was to determine if posterior lateral mass plating after anterior reconstruction provided more stability compared with unicortical or bicortical anterior plate fixation after a simulated corpectomy. SUMMARY OF BACKGROUND DATA: Previous implant biomechanical evaluations use ligamentous and intervertebral disc disruption models under constrained and nonrepetitive loading. This study examines implant performance using a corpectomy model loaded for multiple cycles, allowing for unconstrained motion. METHODS: Twenty-one porcine cervical spines were destabilized with a one-level cervical corpectomy and reconstructed with an anterior methacrylate graft. Each construct was stabilized with either an AO Morscher plate system with unicortical, self-locking screws; a Caspar plate with biocortical screws; or two posterior lateral mass plates. Testing with cyclic loads was performed on an MTS machine in flexion, extension, and axial rotation. RESULTS: There was no statistical difference between the two anterior forms of fixation in flexion, extension, or axial rotation. Posterior lateral mass plating was significantly more stable than either anterior construct. Screw loosening was seen more frequently with bicortical Caspar plating. CONCLUSIONS: After a single-level cervical corpectomy and idealized grafting, all three surgical constructs provided stability equal to or greater than the intact condition in flexion, extension, and axial rotation. In unstable cervical spine injury patterns involving anterior disruption, this study supports the use of anterior grafting combined with posterior lateral mass plating to achieve maximum stability.

Radial instability of the metacarpophalangeal joint of the thumb. A biomechanical investigation.

Human cadaver thumbs were tested to evaluate stability of the radial side of the MP joint. The contributions of the dorsal capsule, radial collateral ligament, accessory collateral ligament, and volar plate were examined with the joint in 0 degrees and 30 degrees of flexion. At 0 degrees flexion, the average joint angulation increased 4 degrees following isolated radial collateral ligament transection and 6 degrees following isolated accessory collateral ligament transection. Release of both the accessory and radial collateral ligaments produced marked instability with joint angulation of at least 46 degrees. The accessory collateral ligament helped to stabilize the extended MP joint. There were no significant contributions to stability from the dorsal capsule and volar plate when the collateral ligaments were intact. In the laboratory setting, radial-side instability of the MP joint of the thumb requires transection of both the proper and accessory radial collateral ligament.