Modification to Mirels scoring system location component improves fracture prediction for metastatic disease of the proximal femur.

BACKGROUND: Correctly identifying patients at risk of femoral fracture due to metastatic bone disease remains a clinical challenge. Mirels criteria remains the most widely referenced method with the advantage of being easily calculated but it suffers from poor specificity. The purpose of this study was to develop and evaluate a modified Mirels scoring system through scoring modification of the original Mirels location component within the proximal femur. METHODS: Computational (finite element) experiments were performed to quantify strength reduction in the proximal femur caused by simulated lytic lesions at defined locations. Virtual spherical defects representing lytic lesions were placed at 32 defined locations based on axial (4 axial positions: neck, intertrochanteric, subtrochanteric or diaphyseal) and circumferential (8 circumferential: 45-degree intervals) positions. Finite element meshes were created, material property assignment was based on CT mineral density, and femoral head/greater trochanter loading consistent with stair ascent was applied. The strength of each femur with a simulated lesion divided by the strength of the intact femur was used to calculate the Location-Based Strength Fraction (LBSF). A modified Mirels location score was next defined for each of the 32 lesion locations with an assignment of 1 (LBSF > 75%), 2 (LBSF: 51-75%), and 3 (LBSF: 0-50%). To test the new scoring system, data from 48 patients with metastatic disease to the femur, previously enrolled in a Musculoskeletal Tumor Society (MSTS) cross-sectional study was used. The lesion location was identified for each case based on axial and circumferential location from the CT images and assigned an original (2 or 3) and modified (1,2, or 3) Mirels location score. The total score for each was then calculated. Eight patients had a fracture of the femur and 40 did not over a 4-month follow-up period. Logistic regression and decision curve analysis were used to explore relationships between clinical outcome (Fracture/No Fracture) and the two Mirels scoring methods. RESULTS: The location-based strength fraction (LBSF) was lowest for lesions in the subtrochanteric and diaphyseal regions on the lateral side of the femur; lesions in these regions would be at greatest risk of fracture. Neck lesions located at the anterior and antero-medial positions were at the lowest risk of fracture. When grouped, neck lesions had the highest LBSF (83%), followed by intertrochanteric (72%), with subtrochanteric (50%) and diaphyseal lesions (49%) having the lowest LBSF. There was a significant difference (p < 0.0001) in LBSF between each axial location, except subtrochanteric and diaphyseal which were not different from each other (p = 0.96). The area under the receiver operator characteristic (ROC) curve using logistic regression was greatest for modified Mirels Score using site specific location of the lesion (Modified Mirels-ss, AUC = 0.950), followed by a modified Mirels Score using axial location of lesion (Modified Mirels-ax, AUC = 0.941). Both were an improvement over the original Mirels score (AUC = 0.853). Decision curve analysis was used to quantify the relative risks of identifying patients that would fracture (TP, true positives) and those erroneously predicted to fracture (FP, false positives) for the original and modified Mirels scoring systems. The net benefit of the scoring system weighed the benefits (TP) and harms (FP) on the same scale. At a threshold probability of fracture of 10%, use of the modified Mirels scoring reduced the number of false positives by 17-20% compared to Mirels scoring. CONCLUSIONS: A modified Mirels scoring system, informed by detailed analysis of the influence of lesion location, improved the ability to predict impending pathological fractures of the proximal femur for patients with metastatic bone disease. Decision curve analysis is a useful tool to weigh costs and benefits concerning fracture risk and could be combined with other patient/clinical factors that contribute to clinical decision making.

Early Changes in Cement-Bone Fixation Using a Novel Rat Knee Replacement Model.

Trabecular resorption from interdigitated regions between cement and bone has been found in postmortem-retrieved knee replacements, but the viability of interdigitated bone, and the mechanism responsible for this bone loss is not known. In this work, a Sprague-Dawley (age 12 weeks) rat knee replacement model with an interdigitated cement-bone interface was developed. Morphological and cellular changes in the interdigitated region of the knee replacement over time (0, 2, 6, or 12 weeks) were determined for ovariectomy (OVX) and Sham OVX treatment groups. Interdigitated bone volume fraction (BV/TV) increased with time for Sham OVX (0.022 BV/TV/wk) and OVX (0.015 BV/TV/wk) group, but the rate of increase was greater for the Sham OVX group (p = 0.0064). Tissue mineral density followed a similar increase with time in the interdigitated regions. Trabecular resorption, when it did occur, started at the cement border with medullary-adjacent bone in the presence of osteoclasts. There was substantial loss of viable bone (~80% empty osteocyte lacunae) in the interdigitated regions. Pre-surgical fluorochrome labels remained in the interdigitated regions, and did not diminish with time, indicating that the bone was not remodeling. There was also some evidence of continued surface mineralization in the interdigitated region after cementing of the knee, but this diminished over time. Statement of clinical significance: Interdigitated bone with cement provides mechanical stability for success of knee replacements. Improved understanding of the fate of the interdigitated bone over time could lead to a better understanding of the loosening process and interventions to prevent loss of fixation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2163-2171, 2019.

Cementing Constrained Liners Into Secure Cementless Shells: A Minimum 15-Year Follow-Up Study.

BACKGROUND: The authors and others have previously described the technique of cementing constrained liners into secure cementless acetabular shells and reported the short-term, average 3.9-year follow-up, using that technique. The purpose of the present study was to report the minimum 15-year follow-up of this same cohort. METHODS: Between 1988 and 2000, 31 consecutive constrained liners of one design were cemented into well-fixed, well-positioned cementless acetabular shells at 3 institutions. Average age at surgery was 72 years (range, 31-91 years). Indications for the procedure were recurrent hip dislocation in 16 cases and intraoperative instability in 15 cases. Patients were evaluated for revision for failure of the device and revision for any reason. RESULTS: At minimum 15-year follow-up, there was 1 patient lost to follow-up. Three hips (9.7%) were revised for failure of the device and 5 hips (16.1%) were revised for any reason. CONCLUSION: At minimum 15-year follow-up, considering the complexity of cases, there was excellent medium-term durability of this construct.

Two- to 4-Year Followup of a Short Stem THA Construct: Excellent Fixation, Thigh Pain a Concern.

BACKGROUND: Short stem cementless femoral components were developed to aid insertion through smaller incisions, preserve metaphyseal bone, and potentially decrease or limit the incidence of thigh pain. Despite some clinical success, the senior author (DDG) believed a higher percentage of his patients who had received a cementless short stem design were experiencing thigh pain, which, coupled with concerns about bone ingrowth fixation, motivated the review of this case series. QUESTIONS/PURPOSES: (1) What is the proportion of patients treated with a short stem cementless THA femoral component that develop thigh pain and what are the hip scores of this population? (2) What are the radiographic results, specifically with respect to bone ingrowth fixation and stress shielding, of this design? (3) Are there particular patient or procedural factors that are associated with thigh pain with this short stem design? METHODS: Two hundred sixty-one primary THAs were performed in 238 patients by one surgeon between November 2010 and August 2012. During this time period, all patients undergoing primary THA by this surgeon received the same cementless short titanium taper stem. Seven patients (eight hips) died and five patients (five hips) were lost to followup, leaving 226 patients (248 hips) with a mean followup of 3 years (range, 2-5 years). Patients rated their thigh pain during activity or rest at final followup on a 10-point visual analog scale. Harris hip scores (HHS) were obtained at every clinic appointment. Thigh pain was evaluated at the final followup or by contacting the patient by phone. Radiographs were evaluated for bone-implant fixation, bone remodeling, and osteolysis. An attempt was made to correlate thigh pain with patient demographics, implant specifications, or radiographic findings. RESULTS: Seventy-six percent of hips (180 of 238) had no thigh pain, 16% of hips (37 of 238) had mild thigh pain, and 9% (21 of 238) had moderate or severe thigh pain. Preoperatively, mean HHS was 47 (SD, 16) and at last followup, mean HHS was 88 (SD, 13). There were two femoral revisions, one for severe thigh pain and the other for infection. All but two components demonstrated bone ingrowth fixation (99%). Femoral stress shielding was mild in 64% of hips (135 of 212), moderate in 0.5% (one of 212), and severe in no hips. There is an inverse linear relationship between age and severity of thigh pain (r = -0.196; p < 0.0024). CONCLUSIONS: Although reliable fixation was achieved and good HHS were attained, the frequency and severity of thigh pain with this short cementless stem were concerning. The surgeon has subsequently abandoned this short stem design and returned to a conventional length stem. Future study direction might investigate the biomechanical grounds for the thigh pain associated with this stem design. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Influence of Ankle Position and Radiographic Projection Angle on Measurement of Supramalleolar Alignment on the Anteroposterior and Hindfoot Alignment Views.

BACKGROUND: Using digitally reconstructed radiographs (DRRs), we determined how changes in the x-ray beam projection angle from the horizon, tibiotalar joint angle, and axial rotation of the foot influenced measurements of the medial distal tibial angle (MDTA) on the anteroposterior (AP) and hindfoot alignment views (HAV). METHODS: Seven cadaver foot-ankle specimens were scanned by computed tomography (CT) at fixed tibiotalar joint positions, ranging from 15 degrees of dorsiflexion to 25 degrees of plantarflexion. DRRs were created from each CT scan to simulate alterations in the horizontal projection angle (0 to 25 degrees) and foot axial rotation (-30 to 30 degrees). The MDTA was measured on each DRR and compared with that quantified on the baseline HAV and AP view. RESULTS: Altering the horizontal projection angle by ≥5 degrees and >10 degrees significantly altered the MDTA for the AP view and the HAV, respectively. Shifting dorsiflexion and plantarflexion caused minor changes in the MDTA that were only statistically significant for the HAV. Axial rotation significantly changed the MDTA on both views, but deviations were more pronounced for the HAV. CONCLUSIONS: Compared with the HAV, the MDTA on the AP view was less sensitive to changes in foot-ankle position. However, increasing the tilt of the x-ray beam from the horizon altered the MDTA on the AP view substantially. CLINICAL RELEVANCE: To avoid misinterpretation of the MDTA, we recommend using the AP view to quantify supramalleolar alignment as it is less sensitive to changes in positioning of the foot-ankle. When acquiring an AP film, the x-ray beam should be directed along the horizon to ensure consistent assessment of the MDTA across patients.

Development of a preliminary pediatric tracheal growth model from magnetic resonance images.

OBJECTIVES/HYPOTHESIS: To develop a growth model of the minimum cross-sectional area of the normal pediatric trachea with measurements from magnetic resonance images (MRIs) to supplement the clinical criteria used to determine if a child with tracheal stenosis needs surgery. STUDY DESIGN: Retrospective imaging review. METHODS: A total of 81 patients were imaged for a variety of clinical reasons and declared to have normal tracheas fully visible in their T1 magnetic resonance image. Regression analysis was used to identify any contribution that age, gender, and z scores for height and weight have in predicting the minimum cross-sectional area of the trachea. RESULTS: The best-fit model for minimum cross-sectional area is: Area = -0.00451*age(4) + 0.177*age(3) - 2.05*age(2) + 12.6*age + 8.02 (area in mm(2) and age in years). Gender and z scores for height and weight did not provide any additional explanation of variance in tracheal size. CONCLUSIONS: Our study demonstrates the potential to create a growth model of the normal trachea based on cross-sectional area of the trachea using MRIs. Even with the relatively small number of patients used to build it, the model has demonstrated some ability to be used as an objective prediction tool when deciding a treatment path for a patient. With continued development of precise, objective measures to diagnose the severity of the tracheal stenosis, more patients can be given early and accurate prognosis and be treated appropriately.

Medial distal tibial angle: comparison between weightbearing mortise view and hindfoot alignment view.

BACKGROUND: The medial distal tibial angle (MDTA) is used to determine ankle alignment. The mortise view is the standard to measure MDTA, but the hindfoot alignment view (HAV) has become popular. The MDTA may vary between views, influencing the choice of surgery. METHODS: The MDTA was compared between the mortise and HAV in 146 ankles. MDTA was correlated to age and sagittal tibial tilt for each view. Differences in MDTA by gender and ethnicity were assessed. Diagnostic agreement (varus, valgus, normal) between views was calculated. Clinical assessment of alignment was determined and percent agreement between clinical and radiographic alignment was quantified. RESULTS: The MDTA measured from the mortise view and HAV radiographs was 89.0 (range, 81 to 96 degrees; SD = 2.8) degrees and 86.0 (range, 73 to 95 degrees; SD = 3.5) degrees, respectively. The MDTA was comparable for both genders for mortise (p = 0.356) and HAV (p = 0.621). The MDTA was comparable in all ethnic groups for mortise view (p = 0.616) and HAV (p = 0.916). Correlation between the measured MDTA and age was not statistically significant for both the mortise (r = 0.118; p = 0.158) and HAV (r = 0.148; p = 0.074). In only 47.3% of all ankles was the radiographic diagnosis of alignment the same between views. Agreement between clinical and radiographic classifications was 60.3% for the mortise view and 52.8% for the HAV. CONCLUSION: Substantial disagreement in primary alignment was found between the mortise and HAV as quantified by the MDTA. Agreement between clinical and radiographic alignment was also poor. CLINICAL RELEVANCE: Advanced imaging such as CT or MRI may better describe ankle alignment.

Cocultures of adult and juvenile chondrocytes compared with adult and juvenile chondral fragments: in vitro matrix production.

BACKGROUND: The use of allogenic juvenile chondrocytes or autologous chondral fragments has shown promising laboratory results for the repair of chondral lesions. HYPOTHESIS: Juvenile chondrocytes would not affect matrix production when mixed with adult chondrocytes or cartilage fragments. STUDY DESIGN: Controlled laboratory study. METHODS: Cartilage sources consisted of 3 adult and 3 juvenile (human) donors. In part 1, per each donor, juvenile chondrocytes were mixed with adult chondrocytes in 5 different proportions: 100%, 50%, 25%, 12.5%, and 0%. Three-dimensional cultures in low-melt agarose were performed. At 6 weeks, biochemical and histologic analyses were performed. In part 2, isolated adult, isolated juvenile, and mixed 3-dimensional cultures (1:1) were performed with chondral fragments (<1 mm), both with low-melt agarose and a hyaluronic acid scaffold. At 2 and 6 weeks, cultures were evaluated with biochemical and histologic analyses. RESULTS: Part 1: Biochemical and histologic analyses showed that isolated juvenile cultures performed significantly better than mixed and isolated adult cultures. No significant differences were noted between mixed cultures (1:1) and isolated adult cultures. Part 2: Biochemical and histologic results at 6 weeks showed that mixed cartilage fragment cultures performed better than isolated adult cultures in terms of proteoglycans/DNA ratio (P = .014), percentage of safranin O-positive cells (P = .012), Bern score (P = .001), and collagen type II. No statistically significant difference was noted between juvenile and mixed cultures. CONCLUSION: Extracellular matrix production of juvenile chondrocytes is inhibited by adult chondrocytes. The addition of juvenile cartilage fragments to adult fragments improves matrix production, with a positive interaction between the 2 sources. CLINICAL RELEVANCE: Even if the underlying mechanisms are still unknown, this study describes the behavior of juvenile/adult cocultures using both chondrocytes and cartilage fragments, with potential for new research and clinical applications.

The potential of human allogeneic juvenile chondrocytes for restoration of articular cartilage.

BACKGROUND: Donor-site morbidity, limited numbers of cells, loss of phenotype during ex vivo expansion, and age-related decline in chondrogenic activity present critical obstacles to the use of autologous chondrocyte implantation for cartilage repair. Chondrocytes from juvenile cadaveric donors may represent an alternative to autologous cells. Hypothesis/ PURPOSE: The authors hypothesized that juvenile chondrocyte would show stronger and more stable chondrogenic activity than adult cells in vitro and that juvenile cells pose little risk of immunologic incompatibility in adult hosts. STUDY DESIGN: Controlled laboratory study. METHODS: Cartilage samples were from juvenile (<13 years old) and adult (>13 years old) donors. The chondrogenic activity of freshly isolated human articular chondrocytes and of expanded cells after monolayer culture was measured by proteoglycan assay, gene expression analysis, and histology. Lymphocyte proliferation assays were used to assess immunogenic activity. RESULTS: Proteoglycan content in neocartilage produced by juvenile chondrocytes was 100-fold higher than in neocartilage produced by adult cells. Collagen type II and type IX mRNA in fresh juvenile chondrocytes were 100- and 700-fold higher, respectively, than in adult chondrocytes. The distributions of collagens II and IX were similar in native juvenile cartilage and in neocartilage made by juvenile cells. Juvenile cells grew significantly faster in monolayer cultures than adult cells (P = .002) and proteoglycan levels produced in agarose culture was significantly higher in juvenile cells than in adult cells after multiple passages (P < .001). Juvenile chondrocytes did not stimulate lymphocyte proliferation. CONCLUSION: These results document a dramatic age-related decline in human chondrocyte chondrogenic potential and show that allogeneic juvenile chondrocytes do not stimulate an immunologic response in vivo. CLINICAL RELEVANCE: Juvenile human chondrocytes have greater potential to restore articular cartilage than adult cells, and may be transplanted without the fear of rejection, suggesting a new allogeneic approach to restoring articular cartilage in older individuals.