Comparable results in total knee arthroplasty using the ROSA knee system versus the conventional technique: A retrospective propensity-matched cohort study.

PURPOSE: Robotic-assisted total knee arthroplasty (RA-TKA) is an increasingly popular alternative that may increase the accuracy of conventional TKA techniques. This study aims to evaluate RA-TKA accuracy and compare its radiographic and clinical outcomes to conventional TKA (cTKA). METHODS: A retrospective examination of patients with bi- or tricompartmental knee osteoarthritis who underwent RA-TKA (RObotic Surgical Assistant system) or cTKA and were prospectively documented in the TKA registry. Accuracy was assessed using standardized radiographic implant position evaluations, namely femoral and tibial coronal angles and femoral and tibial sagittal angles. Baseline demographics, surgery details and 6- and 12-month post-TKA patient-reported outcomes (PROMs; e.g., Oxford Knee Score [OKS] and Core Outcome Measures Index) were compared between RA-TKA and propensity score-matched cTKA patients. RESULTS: Overall correlation between preset and 6-week postoperative angle measurements for RA-TKA was low with significant differences noted only for mean tibial sagittal angles (84.6° [RA-TKA] vs. 82.3° [cTKA]) (p < 0.001). The study groups were demographically similar, although RA-TKA patients had slightly longer operative times and higher blood loss but shorter inpatient stays. There were sustainable improvements in all PROMs already at 6 months, yet RA-TKA patients had significantly higher OKS values over their conventional counterparts at this time point. CONCLUSION: Radiological and clinical outcomes were comparable between RA-TKA and cTKA. The robotic-assisted system demonstrated higher accuracy in the coronal than sagittal plane and RA-TKA patients achieved better short-term outcomes for pain and disability. While both methods are similar in the hands of a skilled surgeon, long-term studies are necessary to establish clear method superiority. LEVEL OF EVIDENCE: Therapeutic, Level III.

Mid-term results of autologous matrix-induced chondrogenesis for large chondral defects in hips with femoroacetabular impingement syndrome.

Aims: The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI). Methods: This single-centre study focused on a cohort of 24 patients with cam- or pincer-type FAI, full-thickness femoral or acetabular chondral lesions, or osteochondral lesions ≥ 2 cm2, who underwent surgical hip dislocation for FAI correction in combination with AMIC between March 2009 and February 2016. Baseline data were retrospectively obtained from patient files. Mid-term outcomes were prospectively collected at a follow-up in 2020: cartilage repair tissue quality was evaluated by MRI using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Patient-reported outcome measures (PROMs) included the Oxford Hip Score (OHS) and Core Outcome Measure Index (COMI). Clinical examination included range of motion, impingement tests, and pain. Results: A total of 12 hips from 11 patients were included (ten males, one female, mean age 26.8 years (SD 5.0), mean follow-up 6.2 years (SD 5.2 months)). The mean postoperative MOCART score was 66.3 (SD 16.3). None of the patients required conversion to total hip arthroplasty. Two patients had anterior impingement. External hip rotation was moderately limited in four patients. There was a correlation between MOCART and follow-up time (rs = -0.61; p = 0.035), but not with initial cartilage damage, age, BMI, or imaging time delay before surgery. PROMs improved significantly: OHS from 37.4 to 42.7 (p = 0.014) and COMI from 4.1 to 1.6 (p = 0.025). There was no correlation between MOCART and PROMs. Conclusion: Based on the reported mid-term results, we consider AMIC as an encouraging treatment option for large cartilage lesions of the hip. Nonetheless, the clinical evidence of AMIC in FAI patients remains to be determined, ideally in the context of randomized controlled trials.

Isolating factors for the prediction of rebound after guided growth with tension band plating for the valgus deformity of the knee.

Purpose: The conditions leading to growth rebound after hemiepiphysiodesis are still poorly understood. This article analyzes the radiographical outcomes after guided growth with tension band plating, using plates in idiopathic genu valgum patients and attempts to generate a predictive model of growth rebound. Methods: Patients with idiopathic genu valgum deformity who received tension band plating were selected for evaluation. We only analyzed coronal plane deformities. Only patients with a long-standing X-ray before tension band plating surgery, a long-standing X-ray at tension band plating removal, and a long-standing X-ray at the latest follow-up after tension band plating removal were considered for this study. The change of mechanical axis deviation between the tension band plating removal and the last follow-up was evaluated for rebound, and ordinal logistic regression was performed to determine the relevant variables for predictive modeling rebound growth. Results: Overall, 100 patients (189 legs) were analyzed. The mean mechanical axis deviation at tension band plating removal was 8.4 mm in varus direction, and the mean mechanical axis deviation at the last follow-up was -3.4 mm (p ≤ 0.001). However, 111 legs (59%) showed rebound growth, 57 (30%) stayed stable, and 21 (11%) showed a continuous correction. Six significant factors significantly influencing rebound were isolated which are clinically relevant: sex, age, baseline mechanical axis deviation, mechanical lateral distal femoral angle, and mechanical medial proximal tibial angle, and mechanical axis deviation correction rate. Mechanical axis deviation correction rate had the highest odds ratios. The machine learning classification model for predicting rebound growth built from the study data showed a misclassification rate of 39%. Conclusion: There was a high rate of rebound growth in this cohort, especially for patients at a young age at implantation. The highest risk factors for rebound growth were male sex, and high correction rates, such as found during peak growth spurt. The proposed classification model needs more data to improve its predictive power before it can be used in clinics. Level of evidence: Level III.

Autologous minced cartilage repair for chondral and osteochondral lesions of the knee joint demonstrates good postoperative outcomes and low reoperation rates at minimum five-year follow-up.

PURPOSE: Minced cartilage is a one-step, autologous procedure with promising short-term results. The aim of the present study was to evaluate mid-term results in a patient cohort with chondral and osteochondral lesions in the knee joint treated with minced cartilage. METHODS: From 2015 through 2016, a total of 34 consecutive patients were treated with a single-step, autologous minced cartilage for knee chondral and osteochondral lesions. Numeric analogue scale (NAS) for pain and knee function were obtained prior to surgery and at 12, 24 and 60 months postoperatively. Secondary outcomes, including Lysholm score, Tegner activity score, and the International Knee Documentation Committee (IKDC) score, were recorded at final follow-up. MRI examinations of patients with unplanned radiological follow-up were analysed using the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score. RESULTS: A total of 28 patients (44.1% females, age at surgery: 29.5 ± 11.5 years) were available at a mean follow-up of 65.5 ± 4.1 months. Mean defect size was 3.5 ± 1.8 cm2. NAS for pain decreased from a median of 7 (range: 2-10) preoperatively to 2 (0-8) postoperatively. NAS knee function improved from a median of 7 (range: 2-10) to 3 (0-7) after five years, respectively. Satisfactory Lysholm (76.5 ± 12.5), IKDC (71.6 ± 14.8) and Tegner activity (4, range 3-9) scores were reported at final follow-up. Of all patients, 21(75%) and 19 (67.9%) reached or exceeded the PASS for the IKDC- and Lysholm score at final follow-up, respectively. The average overall MOCART 2.0 scores for all postoperatively performed MRIs (n = 23) was 62.3 ± 17.4. Four (14.2%) postoperative complications were directly linked to minced cartilage, one (3.5%) of which required revision surgery. CONCLUSION: One-step, autologous minced cartilage repair of chondral and osteochondral lesions of the knee without the necessity for subchondral bone treatment demonstrated good patient-reported outcomes, low complication rates, and graft longevity at mid-term follow-up. Minced cartilage represents a viable treatment option to more traditional cartilage repair techniques even in mid-term. LEVEL OF EVIDENCE: Level III.

Measurement properties of PROMIS short forms for pain and function in patients receiving knee arthroplasty.

BACKGROUND: While there are a few studies on measurement properties of PROMIS short forms for pain and function in patients with knee osteoarthritis, nothing is known about the measurement properties in patients with knee arthroplasty. Therefore, this study examined the measurement properties of the German Patient-Reported Outcomes Measurement Information System (PROMIS) short forms for pain intensity (PAIN), pain interference (PI) and physical function (PF) in knee arthroplasty patients. METHODS: Short forms were collected from consecutive patients of our clinic's knee arthroplasty registry before and 12 months post-surgery. Oxford Knee Score (OKS) was the reference measure. A subsample completed the short forms twice to test reliability. Construct validity and responsiveness were assessed using scale-specific hypothesis testing. For reliability, Cronbach's alpha, intraclass correlation coefficients, and agreement using standard error of measurement (SEMagr) were used. Agreement was used to determine standardised effect sizes and smallest detectable changes (SDC90). Individual-level minimal important change (MIC) was calculated using a method of adjusted prediction. RESULTS: Of 213 eligible patients, 155 received questionnaires, 143 returned baseline questionnaires and 119, 12-month questionnaires. Correlations of short forms with OKS were large (│r│ ≥ 0.7) with slightly lower values for PAIN, and specifically for men. Cronbach's alpha values were ≥ 0.84 and intraclass correlation coefficients ≥ 0.90. SEMagr were around 3.5 for PAIN and PI and 1.7 for PF. SDC90 were around 8 for PAIN and PI and 4 for PF. Follow-up showed a relevant ceiling effect for PF. Correlations with OKS change scores of around 0.5 to 0.6 were moderate. Adjusted MICs were 7.2 for PAIN, 3.5 for PI and 5.7 for PF. CONCLUSION: Our results partly support the use of the investigated short forms for knee arthroplasty patients. The ability of PF to differentiate between patients with high perceived recovery is limited. Therefore, the advantages and disadvantages should be strongly considered within the context of the intended use.

Percutaneous minimal invasive Achilles tendon lengthening improves clinical and radiographic outcomes in severe flexible flatfeet with shortened triceps sureae complex in early childhood: A retrospective study.

BACKGROUND: Severe flexible flatfeet with triceps surae complex shortening are prognostically unfavorable in early childhood and may compromise normal foot development. METHODS: This retrospective, IRB-approved study included 20 children (38 feet) under 6 years with severe flexible flatfeet and triceps surae complex shortening. Treatment included minimally invasive percutaneous achilles tendon lengthening followed by a 4-week cast fixation and corrective orthotic therapy under talo-navicular reposition for at least 6-months. Preoperative weightbearing x-rays and at the last available follow-up included anteroposterior talus-first metatarsal angle and lateral talus pitch, Meary's and talocalcaneal angle and were compared to reference values. ROM, surgeon-rated clinical outcomes and complications/re-interventions were evaluated. RESULTS: Age at surgery was 3.7 years (1.3-5.9 y) and follow-up time was 4.3 years (1.1-8.9 y). No complications occurred. Clinical outcome was good (68 %) to very good (26 %). Ratio of normal angles increased significantly for three angles. Dorsiflexion ROM improved from -5.0 ± 6.8° at baseline to 15.7 ± 7.6°. CONCLUSIONS: With significant improvements in clinical and radiographic outcomes, minimal-invasive percutaneous Achilles tendon lengthening followed by orthotic therapy seems to be a valuable treatment option for selected preschool-aged patients with severe, flexible flatfeet with significantly shortened triceps surae. LEVEL OF EVIDENCE: IV.

Impact of capsular preservation on patient-reported outcomes and complication rates in total hip arthroplasty using the direct anterior approach.

AIMS: It is not known whether preservation of the capsule of the hip positively affects patient-reported outcome measures (PROMs) in total hip arthroplasty using the direct anterior approach (DAA-THA). A recent randomized controlled trial found no clinically significant difference at one year postoperatively. This study aimed to determine whether preservation of the anterolateral capsule and anatomical closure improve the outcome and revision rate, when compared with resection of the anterolateral capsule, at two years postoperatively. METHODS: Two consecutive groups of patients whose operations were performed by the senior author were compared. The anterolateral capsule was resected in the first group of 430 patients between January 2012 and December 2014, and preserved and anatomically closed in the second group of 450 patients between July 2015 and December 2017. There were no other technical changes between the two groups. Patient characteristics, the Charlson Comorbidity Index (CCI), and surgical data were collected from our database. PROM questionnaires, consisting of the Oxford Hip Score (OHS) and Core Outcome Measures Index (COMI-Hip), were collected two years postoperatively. Data were analyzed with generalized multiple regression analysis. RESULTS: The characteristics, CCI, operating time, and length of stay were similar in both groups. There was significantly less blood loss in the capsular preservation group (p = 0.037). The revision rate (n = 3, (0.6%) in the resected group, and 1 (0.2%) in the preserved group) did not differ significantly (p = 0.295). Once adjusted for demographic and surgical factors, the preserved group had significantly worse PROMs: + 0.24 COMI-Hip (p < 0.001) and -1.6 OHS points (p = 0.017). However, the effect sizes were much smaller than the minimal clinically important differences (MCIDs) of 0.95 and 5, respectively). The date of surgery (influencing, for instance, the surgeon's age) was not a significant factor. CONCLUSION: Based on the MCID, the lower PROMs in the capsular preservation group do not seem to have clinical relevance. They do not, however, confirm the expected benefit of capsular preservation reported for the posterolateral approach. Cite this article: Bone Joint J 2022;104-B(7):826-832.

Measurement properties of PROMIS short forms for pain and function in total hip arthroplasty patients.

INTRODUCTION: While the Patient-Reported Outcomes Measurement Information System (PROMIS) is mainly designed for computer adaptive testing, its static short forms (SF) are used when a paper-pencil format is preferred or item banks are not yet translated into the target language. This study examined the measurement properties of the German PROMIS-SF for pain intensity (PAIN), pain interference (PI) and physical function (PF) in total hip arthroplasty (THA) patients. METHODS: SF were collected before and 12 months post-surgery. Higher scores indicate more PAIN, higher PI and better PF. Oxford Hip Score (OHS) was the main reference measure. Six months post-surgery, a subsample completed the SF twice within 14 days to test reliability. RESULTS: Of 172 eligible patients, 147 consented to participate and received questionnaires; 132 (74 males) returned baseline questionnaires (mean age 65.8 ± 10.2 years) and 116, 12-month questionnaires. Forty-five patients provided test-retest data. Correlations of all SF with OHS were large (│r│ ≥ 0.7; confidence intervals did not include 0.50). Cronbach's alpha values were: PAIN, 0.86; PI, 0.93; PF, 0.91. Intraclass correlation coefficients were: PAIN, 0.77; PI, 0.81; PF, 0.69. Standard errors of measurement were: PAIN, 3.8; PI, 2.8; PF, 3.6. Smallest detectable change thresholds were: PAIN, 8.8; PI, 6.6; PF, 8.4. Follow-up data showed a ceiling effect (best score) for PAIN (66%), PI (76%), and PF (66%). SF change scores showed large correlations with OHS change scores (│r│ > 0.6). CONCLUSION: Our results provide some evidence of construct validity, and acceptable reliability and responsiveness of PROMIS-SF for pain and function in THA patients. These SF can thus be considered acceptable for use, although patients' improvement in physical function might be underestimated due to the large follow-up PF score ceiling effects.

Measurement qualities of PROMIS instruments are mainly assessed for computer adaptive testing but not for non-adaptive short questionnaires. As these questionnaires are in use, their measurement properties must also be evaluated. Results from computer adaptive testing cannot simply be transferred.We studied the measurement qualities of the German PROMIS short questionnaires for pain intensity, pain interference and physical function in patients undergoing hip replacement. We wanted to see how these questionnaires perform when compared to the Oxford Hip Score, a standard questionnaire commonly used to test hip-related disability in these patients.The three questionnaires can be considered acceptable for use in hip replacement patients, but some limitations do exist. Patient improvement in physical function might be underestimated because many patients reach the highest possible score and further improvements cannot be measured. Also, any small but important improvement in physical function cannot be distinguished from measurement error in individual patients.

Impact of low bone mass and antiresorptive therapy on antibiotic efficacy in a rat model of orthopedic device-related infection.

A significant proportion of orthopedic devices are implanted in osteoporotic patients, but it is currently unclear how estrogen deficiency and/or exposure to antiresorptive bisphosphonates (BPs) influence orthopedic device-related infection (ODRI), or response to therapy. The aim of this study is to characterize the bone changes resulting from Staphylococcus epidermidis infection in a rodent ODRI model and to determine if ovariectomy (OVX) or BP treatment influences the infection or the success of antibiotic therapy. A sterile or S. epidermidis-contaminated screw was implanted into the proximal tibia of skeletally mature female Wistar rats (n = 6-9 per group). Bone changes were monitored over 28 days using in vivo micro-computed tomography scanning. OVX was performed 12 weeks before screw implantation. The BP zoledronic acid (ZOL) was administered 4 days before screw insertion. A combination antibiotic regimen (rifampin plus cefazolin) was administered from Days 7-21. In skeletally healthy animals, S. epidermidis induced marked changes in bone, with peak osteolysis occurring at Day 9 and woven bone deposition and periosteal mineralization from Day 14 onwards. Antibiotic therapy cleared the infection in the majority of animals (2/9 infected) but did not affect bone responses. OVX did not affect the pattern of infection-induced changes in bone, nor bacterial load, but reduced antibiotic efficacy (5/9 infected). ZOL treatment did not protect from osteolysis in OVX animals, or further affect antibiotic efficacy (5/9 infected) but did significantly increase the bacterial load. This study suggests that both BPs and OVX can influence host responses to bone infections involving S. epidermidis.

The Impact of Heterotopic Ossification on Self-Reported Outcomes After Total Hip Arthroplasty Using the Direct Anterior Approach.

BACKGROUND: Heterotopic ossification (HO) is a known finding after total hip arthroplasty (THA) that potentially affects clinical outcomes. The incidence of HO is related to various factors, including soft-tissue trauma, postoperative medication, surgical approach, and the surgeon's experience. Because use of the direct anterior approach (DAA) is gaining popularity, we aimed (1) to determine the incidence of HO after DAA-THA and (2) to evaluate the impact of HO on patient-reported outcomes (PROs). METHODS: We retrospectively reviewed 401 THAs (67 ± 10 years old, 210 men). The incidence and grade of HO were evaluated using the Brooker classification with anteroposterior and lateral radiographs. PROs were collected with use of the Oxford Hip Score (OHS) and the Core Outcome Measures Index (COMI)-Hip and were correlated with HO grades using generalized multiple regression models. RESULTS: The incidence of HO was 29.9% on the anteroposterior radiographic views (Brooker grade 1, 14.5%; grade 2, 11.1%; grade 3, 2.7%; and grade 4, 0.57%); the lateral radiographic views detected 9% additional HO when compared with the anteroposterior radiographs alone (Brooker grade 1, 8%, and grade 2, 1%). HO was more frequent in men. The American Society of Anesthesiologists (ASA) grade, age in women, and higher body mass index (BMI) in men were associated with higher HO grades. A transverse "bikini" incision was associated with a lower rate (4%) of Brooker grades 3 and 4 HO when compared with a longitudinal incision (12%). A Brooker grade of 0 to 3 HO did not impact outcomes. Only Brooker grade-4 HO was associated with significantly worse PROs; however, pain was not affected. CONCLUSIONS: Low-grade HO after DAA-THA is not uncommon, and its rate is underestimated when anteroposterior radiographic views are evaluated without lateral views. The risk factors for developing HO in our cohort were an ASA grade of >3, male sex (especially with a high BMI), older age in women, and use of longitudinal incisions. With use of the bikini incision, patients had lower rates of severe HO, but mostly senior surgeons with more experience performed their surgery. Age, ASA grade, experience level of the surgeon, and Brooker grade-4 HO all had a significant influence on PROs. Clinically important HO (Brooker grade 4) remains rare after DAA-THR. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Orbital floor repair using patient specific osteoinductive implant made by stereolithography.

The orbital floor (OF) is an anatomical location in the craniomaxillofacial (CMF) region known to be highly variable in shape and size. When fractured, implants commonly consisting of titanium meshes are customized by plying and crude hand-shaping. Nevertheless, more precise customized synthetic grafts are needed to meticulously reconstruct the patients' OF anatomy with better fidelity. As alternative to titanium mesh implants dedicated to OF repair, we propose a flexible patient-specific implant (PSI) made by stereolithography (SLA), offering a high degree of control over its geometry and architecture. The PSI is made of biodegradable poly(trimethylene carbonate) (PTMC) loaded with 40 wt % of hydroxyapatite (called Osteo-PTMC). In this work, we developed a complete work-flow for the additive manufacturing of PSIs to be used to repair the fractured OF, which is clinically relevant for individualized medicine. This work-flow consists of (i) the surgical planning, (ii) the design of virtual PSIs and (iii) their fabrication by SLA, (iv) the monitoring and (v) the biological evaluation in a preclinical large-animal model. We have found that once implanted, titanium meshes resulted in fibrous tissue encapsulation, whereas Osteo-PMTC resulted in rapid neovascularization and bone morphogenesis, both ectopically and in the OF region, and without the need of additional biotherapeutics such as bone morphogenic proteins. Our study supports the hypothesis that the composite osteoinductive Osteo-PTMC brings advantages compared to standard titanium mesh, by stimulating bone neoformation in the OF defects. PSIs made of Osteo-PTMC represent a significant advancement for patients whereby the anatomical characteristics of the OF defect restrict the utilization of traditional hand-shaped titanium mesh.

Spatially matching morphometric assessment of cartilage and subchondral bone in osteoarthritic human knee joint with micro-computed tomography.

OBJECTIVE: The objective of this study was to develop a reproducible and semi-automatic method based on micro computed tomography (microCT) to analyze cartilage and bone morphology of human osteoarthritic knee joints in spatially matching regions of interest. MATERIALS AND METHODS: Tibial plateaus from randomly selected patients with advanced osteoarthritis (OA) who underwent total knee arthroplasty surgery were microCT scanned once fresh and once after staining with Hexabrix. The articular surface was determined manually in the first scan. Total articular surface, defect surface and cartilage surface were computed by triangulation of the cartilage surface and the spatially corresponding subchondral bone regions were automatically generated and the standard cortical bone and trabecular bone morphometric indices were computed. RESULTS: The method to identify cartilage surface and defects was successfully validated against photographic examinations. The microCT measurements of the cartilage defect were also verified by conventional histopathology using safranin O-stained sections. Cartilage thickness and volume was significantly lower for OA condyle compared with healthy condyle. Bone fraction, bone tissue mineral density, cortical density and trabecular thickness differed significantly depending on the level of cartilage damage. CONCLUSION: This new microCT imaging workflow can be used for reproducible quantitative evaluation of articular cartilage damage and the associated changes in subchondral bone morphology in osteoarthritic joints with a relatively high throughput compared to manual contouring. This methodology can be applied to gain better understanding of the OA disease progress in large cohorts.

A doxycycline inducible, adenoviral bone morphogenetic protein-2 gene delivery system to bone.

We report the novel use of a tuneable, non-integrating viral gene delivery system to bone that can be combined with clinically approved biomaterials in an 'off-the-shelf' manner. Specifically, a doxycycline inducible Tet-on adenoviral vector (AdTetBMP-2) in combination with mesenchymal stromal cells (MSCs), fibrin and a biphasic calcium phosphate ceramic (MBCP®) was used to repair large bone defects in nude rats. Bone morphogenetic protein-2 (BMP-2) transgene expression could be effectively tuned by modification of the doxycycline concentration. The effect of adenoviral BMP-2 gene delivery upon bone healing was investigated in vivo in 4 mm critically sized, internally fixated, femoral defects. MSCs were transduced either by direct application of AdTetBMP-2 or by pre-coating MBCP granules with the virus. Radiological assessment scores post-mortem were significantly improved upon delivery of AdTetBMP-2. In AdTetBMP-2 groups, histological analysis revealed significantly more newly formed bone at the defect site compared with controls. Newly formed bone was vascularized and fully integrated with nascent tissue and implanted biomaterial. Improvement in healing outcome was achieved using both methods of vector delivery (direct application vs. pre-coating MCBP). Adenoviral delivery of BMP-2 enhanced bone regeneration achieved by the transplantation of MSCs, fibrin and MBCP in vivo. Importantly, our in vitro and in vivo data suggest that this can be achieved with relatively low (ng/ml) levels of the growth factor. Our model and novel gene delivery system may provide a powerful standardized tool for the optimization of growth factor delivery and release for the healing of large bone defects. Copyright © 2016 John Wiley & Sons, Ltd.

Composite time-lapse computed tomography and micro finite element simulations: A new imaging approach for characterizing cement flows and mechanical benefits of vertebroplasty.

Vertebroplasty has been shown to reinforce weak vertebral bodies and reduce fracture risks, yet cement leakage is a major problem that can cause severe complications. Since cement flow is nearly impossible to control during surgery, small volumes of cement are injected, but then mechanical benefits might be limited. A better understanding of cement flows within bone structure is required to further optimize vertebroplasty and bone augmentation in general. We developed a novel imaging method, composite time-lapse CT, to characterize cement flow during injection. In brief, composite-resolution time-lapse CT exploits the qualities of microCT and clinical CT. The method consists in overlaying low-resolution time-lapse CT scans acquired during injection onto pre-operative high-resolution microCT scans, generating composite-resolution time-lapse CT series of cement flow within bone. In this in vitro study, composite-resolution time-lapse CT was applied to eight intact and five artificially fractured cadaveric vertebrae during vertebroplasty. The time-lapse scans were acquired at one-milliliter cement injection steps until a total of 10 ml cement was injected. The composite-resolution series were then converted into micro finite element models to compute strains distribution under virtual axial loading. Relocation of strain energy density within bone structure was observed throughout the progression of the procedure. Interestingly, the normalized effect of cement injection on the overall stiffness of the vertebrae was similar between intact and fractured specimens, although at different orders of magnitude. In conclusion, composite time-lapse CT can picture cement flows during bone augmentation. The composite images can also be easily converted into finite element models to compute virtual strain distributions under loading at every step of an injection, providing deeper understanding on the biomechanics of vertebroplasty.

Prediction of bone density around orthopedic implants delivering bisphosphonate.

The fixation of an orthopedic implant depends strongly upon its initial stability. Peri-implant bone may resorb shortly after the surgery. This resorption is directly followed by new bone formation and implants fixation strengthening, the so-called secondary fixation. If the initial stability is not reached, the resorption continues and the implant fixation weakens, which leads to implant loosening. Studies with rats and dogs have shown that a solution to prevent peri-implant resorption is to deliver bisphosphonate from the implant surface. The aims of the study were, first, to develop a model of bone remodeling around an implant delivering bisphosphonate, second, to predict the bisphosphonate dose that would induce the maximal peri-implant bone density, and third to verify in vivo that peri-implant bone density is maximal with the calculated dose. The model consists of a bone remodeling equation and a drug diffusion equation. The change in bone density is driven by a mechanical stimulus and a drug stimulus. The drug stimulus function and the other numerical parameters were identified from experimental data. The model predicted that a dose of 0.3 microg of zoledronate on the implant would induce a maximal bone density. Implants with 0.3 microg of zoledronate were then implanted in rat femurs for 3, 6 and 9 weeks. We measured that peri-implant bone density was 4% greater with the calculated dose compared to the dose empirically described as best. The approach presented in this paper could be used in the design and analysis processes of experiments in local delivery of drug such as bisphosphonate.

Osteopenia, decreased bone formation and impaired osteoblast development in Sox4 heterozygous mice.

The transcription factor Sox4 is vital for fetal development, as Sox4(-/-) homozygotes die in utero. Sox4 mRNA is expressed in the early embryonic growth plate and is regulated by parathyroid hormone, but its function in bone modeling/remodeling is unknown. We report that Sox4(+/-) mice exhibit significantly lower bone mass (by dual-energy X-ray absorptiometry) from an early age, and fail to obtain the peak bone mass of wild-type (WT) animals. Microcomputed tomography (muCT), histomorphometry and biomechanical testing of Sox4(+/-) bones show reduced trabecular and cortical thickness, growth plate width, ultimate force and stiffness compared with WT. Bone formation rate (BFR) in 3-month-old Sox4(+/-) mice is 64% lower than in WT. Primary calvarial osteoblasts from Sox4(+/-) mice demonstrate markedly inhibited proliferation, differentiation and mineralization. In these cultures, osterix (Osx) and osteocalcin (OCN) mRNA expression was reduced, whereas Runx2 mRNA was unaffected. No functional defects were found in osteoclasts. Silencing of Sox4 by siRNA in WT osteoblasts replicated the defects observed in Sox4(+/-) cells. We demonstrate inhibited formation and altered microarchitecture of bone in Sox4(+/-) mice versus WT, without apparent defects in bone resorption. Our results implicate the transcription factor Sox4 in regulation of bone formation, by acting upstream of Osx and independent of Runx2.