A novel entity of massive multifocal osteolyses in the elderly.

Osteolyses are common findings in elderly patients and most frequently represent malignant or locally aggressive bone tumors, infection, inflammatory and endocrine disorders, histiocytoses, and rare diseases such as Gorham-Stout syndrome. We here report on a novel entity of massive multifocal osteolyses in both shoulders, the right hip and left knee joint and the dens of an 83-year-old patient not relatable to any previously known etiopathology of bone disorders. The soft tissue mass is of myxoid stroma with an unspecific granulomatous inflammatory process, aggressively destroying extensive cortical and cancellous bone segments and encroaching on articulating bones in diarthrodial large joints. Radiological, nuclear medical, serological, histological, and immunohistochemical analyses were incapable of further classifying the disease pattern within the existing scheme of pathology. Quantitative polymerase chain reaction and next generation sequencing revealed that mutations are not suggestive of any known hereditary or acquired bone disease. Possible treatment options include radionuclide therapy for pain palliation and percutaneous radiation to arrest bone resorption while surgical treatment is inevitable for pathological fractures. This case study shall increase the awareness of the musculoskeletal community and motivate to collect further information on this rare but mutilating disorder.

Locally Directed Recombinant Adeno- Associated Virus-Mediated IGF-1 Gene Therapy Enhances Osteochondral Repair and Counteracts Early Osteoarthritis In Vivo.

BACKGROUND: Restoration of osteochondral defects is critical, because osteoarthritis (OA) can arise. HYPOTHESIS: Overexpression of insulin-like growth factor 1 (IGF-1) via recombinant adeno-associated viral (rAAV) vectors (rAAV-IGF-1) would improve osteochondral repair and reduce parameters of early perifocal OA in sheep after 6 months in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral defects were created in the femoral trochlea of adult sheep and treated with rAAV-IGF-1 or rAAV-lacZ (control) (24 defects in 6 knees per group). After 6 months in vivo, osteochondral repair and perifocal OA were assessed by well-established macroscopic, histological, and immunohistochemical scoring systems as well as biochemical and micro-computed tomography evaluations. RESULTS: Application of rAAV-IGF-1 led to prolonged (6 months) IGF-1 overexpression without adverse effects, maintaining a significantly superior overall cartilage repair, together with significantly improved defect filling, extracellular matrix staining, cellular morphology, and surface architecture compared with rAAV-lacZ. Expression of type II collagen significantly increased and that of type I collagen significantly decreased. Subchondral bone repair and tidemark formation were significantly improved, and subchondral bone plate thickness and subarticular spongiosa mineral density returned to normal. The OA parameters of perifocal structure, cell cloning, and matrix staining were significantly better preserved upon rAAV-IGF-1 compared with rAAV-lacZ. Novel mechanistic associations between parameters of osteochondral repair and OA were identified. CONCLUSION: Local rAAV-mediated IGF-1 overexpression enhanced osteochondral repair and ameliorated parameters of perifocal early OA. CLINICAL RELEVANCE: IGF-1 gene therapy may be beneficial in repair of focal osteochondral defects and prevention of perifocal OA.

Comparison of the scientific performance in hip and knee arthroplasty between the leading continents.

Background: Scientific progress in the field of knee and hip arthroplasty has enabled the preservation of mobility and quality of life in the case of patients with many primary degenerative and (post-) traumatic joint diseases. This comparative study aims to investigate differences in scientific performance between the leading continents in the field of hip and knee arthroplasty. Methods: Using specific search terms all studies published by the scientific leading continents Europe, North America, Asia and Oceania listed in the Web of Science databases were included. All identified publications were analysed and comparative conclusions were drawn regarding the qualitative and quantitative scientific merit of each continent. Results: Europe, followed by North America, Asia, and Oceania, had the highest overall number of publications in the field of arthroplasty. Since 2000, there has been a strong increase in knee arthroplasty publication rate, particular pronounced in Asia. Studies performed and published in North America and those on knee arthroplasty received the highest number of fundings. Publications regarding hip arthroplasty achieved the highest average citation rate. In contradistinction to the others, in North America most funding was provided by private agencies. Conclusion: Although Europe showed the highest total number of publications, authors and institutions, arthroplasty research from North America received greater scientific attention and financial support. Measured by citations, publications on hip arthroplasty attained higher scientific interest and studies on knee arthroplasty received higher economic affection.

Accuracy of Personalized Computed Tomographic 3D Templating for Acetabular Cup Placement in Revision Arthroplasty.

Background: Revision hip arthroplasty presents a surgical challenge, necessitating meticulous preoperative planning to avert complications like periprosthetic fractures and aseptic loosening. Historically, assessment of the accuracy of three-dimensional (3D) versus two-dimensional (2D) templating has focused exclusively on primary hip arthroplasty. Materials and Methods: In this retrospective study, we examined the accuracy of 3D templating for acetabular revision cups in 30 patients who underwent revision hip arthroplasty. Utilizing computed tomography scans of the patients' pelvis and 3D templates of the implants (Aesculap Plasmafit, B. Braun; Aesculap Plasmafit Revision, B. Braun; Avantage Acetabular System, Zimmerbiomet, EcoFit 2M, Implantcast; Tritanium Revision, Stryker), we performed 3D templating and positioned the acetabular cup implants accordingly. To evaluate accuracy, we compared the planned sizes of the acetabular cups in 2D and 3D with the sizes implanted during surgery. Results: An analysis was performed to examine potential influences on templating accuracy, specifically considering factors such as gender and body mass index (BMI). Significant statistical differences (p < 0.001) in the accuracy of size prediction were observed between 3D and 2D templating. Personalized 3D templating exhibited an accuracy rate of 66.7% for the correct prediction of the size of the acetabular cup, while 2D templating achieved an exact size prediction in only 26.7% of cases. There were no statistically significant differences between the 2D and 3D templating methods regarding gender or BMI. Conclusion: This study demonstrates that 3D templating improves the accuracy of predicting acetabular cup sizes in revision arthroplasty when compared to 2D templating. However, it should be noted that the predicted implant size generated through 3D templating tended to overestimate the implanted implant size by an average of 1.3 sizes.

Subgroup analysis of scientific performance in the field of arthroplasty.

Introduction: Arthroplasty is the final treatment option for maintaining mobility and quality of life in many primary degenerative and (post-) traumatic joint diseases. Identification of research output and potential deficits for specific subspecialties may be an important measure to achieve long-term improvement of patient care in this field. Methods: Using specific search terms and Boolean operators, all studies published since 1945 to the subgroups of arthroplasty listed in the Web of Science Core Collection were included. All identified publications were analysed according to bibliometric standards, and comparative conclusions were drawn regarding the scientific merit of each subgroup. Results: Most publications investigated the subgroups of septic surgery and materials followed by approach, navigation, aseptic loosening, robotic and enhanced recovery after surgery (ERAS). In the last 5 years, research in the fields of robotic and ERAS achieved the highest relative increase in publications In contrast, research on aseptic loosening has continued to lose interest over the last 5 years. Publications on robotics and materials received the most funding on average while those on aseptic loosening received the least. Most publications originated from USA, Germany, and England, except for research on ERAS in which Denmark stood out. Relatively, publications on aseptic loosening received the most citations, whereas the absolute scientific interest was highest for the topic infection. Discussion: In this bibliometric subgroup analysis, the primary scientific outputs focused on septic complications and materials research in the field of arthroplasty. With decreasing publication output and the least financial support, intensification of research on aseptic loosening is urgently recommended.

[Innovative image-based planning in musculoskeletal surgery]. / Innovative bildbasierte Operationsplanung in der muskuloskelettalen Chirurgie.

BACKGROUND: For the preparation of surgical procedures in orthopedics and trauma surgery, precise knowledge of imaging and the three-dimensional imagination of the surgeon are of outstanding importance. Image-based, preoperative two-dimensional planning is the gold standard in arthroplasty today. In complex cases, further imaging such as computed tomography (CT) or magnetic resonance imaging is also performed, generating a three-dimensional model of the body region and helping the surgeon in the planning of the surgical treatment. Four-dimensional, dynamic CT studies have also been reported and are available as a complementary tool. DIGITAL AIDS: Furthermore, digital aids should generate an improved representation of the pathology to be treated and optimize the surgeon's imagination. The finite element method allows patient-specific and implant-specific parameters to be taken into account in preoperative surgical planning. Intraoperatively, relevant information can be provided by augmented reality without significantly influencing the surgical workflow.

Comparison of the Accuracy of 2D and 3D Templating for Revision Total Hip Replacement.

INTRODUCTION: Revision hip arthroplasty is a challenging surgical procedure, especially in cases of advanced acetabular bone loss. Accurate preoperative planning can prevent complications such as periprosthetic fractures or aseptic loosening. To date, the accuracy of three-dimensional (3D) versus two-dimensional (2D) templating has been evaluated only in primary hip and knee arthroplasty. METHODS: We retrospectively investigated the accuracy of 3D personalized planning of reinforcement cages (Burch Schneider) in 27 patients who underwent revision hip arthroplasty. Personalized 3D modeling and positioning of the reinforcement cages were performed using computed tomography (CT) of the pelvis of each patient and 3D templates of the implant. To evaluate accuracy, the sizes of the reinforcement cages planned in 2D and 3D were compared with the sizes of the finally implanted cages. Factors that may potentially influence planning accuracy such as gender and body mass index (BMI) were analyzed. RESULTS: There was a significant difference (p = 0.003) in the accuracy of correct size prediction between personalized 3D templating and 2D templating. Personalized 3D templating predicted the exact size of the reinforcement cage in 96.3% of the patients, while the exact size was predicted in only 55.6% by 2D templating. Regarding gender and BMI, no statistically significant differences in planning accuracy either for 2D or 3D templating were observed. CONCLUSION: Personalized 3D planning of revision hip arthroplasty using Burch Schneider reinforcement cages leads to greater accuracy in the prediction of the required size of implants than conventional 2D templating.

Impact of Covid-19 on the global orthopaedic research output.

The pandemic led to a significant change in the clinical routine of many orthopaedic surgeons. To observe the impact of the pandemic on scientific output all studies published in the fields of orthopaedics listed in the Web of Science databases were analysed regarding the scientific merit of the years 2019, 2020, and 2021. Subsequently, correlation analyses were performed with parameters of regional pandemic situation (obtained from WHO) and economic strength (obtained from the World Bank). The investigations revealed that the Covid-19 pandemic led to a decrease in the annual publication rate for the first time in 20 years (2020 to 2021: -5.69%). There were regional differences in the publication rate, which correlated significantly with the respective Covid-19 case count (r = -.77, p < 0.01), associated death count (r = -.63, p < 0.01), and the gross domestic product per capita (r = -.40, p < 0.01) but not with the number of vaccinations (r = .09, p = 0.30). Furthermore, there was a drastic decrease in funding from private agencies (relative share: 2019: 36.43%, 2020: 22.66%, 2021: 19.22%), and a balanced decrease in publication output for research areas of acute and elective patient care. The Covid-19 pandemic resulted in a decline in orthopaedic annual publication rates for the first time in 20 years. This reduction was subject to marked regional differences and correlated directly with the pandemic load and was associated with decreased research funding from the private sector.

Subchondral Drilling Independent of Drill Hole Number Improves Articular Cartilage Repair and Reduces Subchondral Bone Alterations Compared With Debridement in Adult Sheep.

BACKGROUND: Subchondral drilling is an established marrow stimulation technique for small cartilage defects, but whether drilling is required at all and if the drill hole density affects repair remains unclear. HYPOTHESES: Osteochondral repair is improved when the subchondral bone is perforated by a higher number of drill holes per unit area, and drilling is superior to defect debridement alone. STUDY DESIGN: Controlled laboratory study. METHODS: Rectangular full-thickness chondral defects (4 × 8 mm) were created in the trochlea of adult sheep (N = 16), debrided down to the subchondral bone plate without further treatment as controls (no treatment; n = 7) or treated with either 2 or 6 (n = 7 each) subchondral drill holes (diameter, 1.0 mm; depth, 10.0 mm). Osteochondral repair was assessed at 6 months postoperatively by standardized (semi-)quantitative macroscopic, histological, immunohistochemical, biochemical, and micro-computed tomography analyses. RESULTS: Compared with defect debridement alone, histological overall cartilaginous repair tissue quality (P = .025) and the macroscopic aspect of the adjacent cartilage (P≤ .032) were improved after both drilling densities. Only drilling with 6 holes increased type 2 collagen content in the repair tissue compared with controls (P = .038). After debridement, bone mineral density was significantly decreased in the subchondral bone plate (P≤ .015) and the subarticular spongiosa (P≤ .041) compared with both drilling groups. Debridement also significantly increased intralesional osteophyte sectional area compared with drilling (P≤ .034). No other differences in osteochondral repair existed between subchondral drilling with 6 or 2 drill holes. CONCLUSION: Subchondral drilling independent of drill hole density significantly improves structural cartilage repair compared with sole defect debridement of full-thickness cartilage defects in sheep after 6 months. Subchondral drilling also leads to a better reconstitution of the subchondral bone compartment below the defects. Simultaneously, drilling reduced the formation of intralesional osteophytes caused by osseous overgrowth compared with debridement. CLINICAL RELEVANCE: These results have important clinical implications, as they support subchondral drilling independent of drill hole number but discourage debridement alone for the treatment of small cartilage defects. Clinical studies are warranted to further quantify the effects of subchondral drilling in similar settings.

Effects of Recombinant Adeno-Associated Virus-Mediated Overexpression of Bone Morphogenetic Protein 3 on the Chondrogenic Fate of Human Bone Marrow-Derived Mesenchymal Stromal Cells.

Implantation of genetically modified chondrogenically competent human bone marrow-derived mesenchymal stromal cells (hMSCs) is an attractive strategy to improve cartilage repair. The goal of this study was to examine the potential benefits of transferring a sequence coding for the bone morphogenetic protein 3 (BMP-3) that modulates bone and cartilage formation, using recombinant adeno-associated virus (rAAV) vectors on the chondroreparative activities of hMSCs. Undifferentiated and chondrogenically induced primary human MSCs were treated with an rAAV-hBMP-3 construct to evaluate its effects on the proliferative, metabolic, and chondrogenic activities of the cells compared with control (reporter rAAV-lacZ vector) condition. Effective BMP-3 expression was noted both in undifferentiated and chondrogenically differentiated cells in the presence of rAAV-hBMP-3 relative to rAAV-lacZ, stimulating cell proliferation and extracellular matrix (proteoglycans, type-II collagen) deposition together with higher levels of chondrogenic sex-determining region Y-type high-mobility group box 9 (SOX9) expression. rAAV-hBMP-3 also advantageously decreased terminal differentiation, hypertrophy, and osteogenesis (type-I/-X collagen and alkaline phosphatase expression), with reduced levels of osteoblast-related runt-related transcription factor 2 (RUNX-2) transcription factor and ß-catenin (osteodifferentiation mediator) and enhanced parathyroid hormone-related protein expression (inhibitor of hypertrophic maturation, calcification, and bone formation). This study shows the advantage of modifying hMSCs with rAAV-hBMP-3 to trigger adapted chondroreparative activities as a source of improved cells for transplantation protocols in cartilage defects.

rAAV-Mediated Human FGF-2 Gene Therapy Enhances Osteochondral Repair in a Clinically Relevant Large Animal Model Over Time In Vivo.

BACKGROUND: Osteochondral defects, if left untreated, do not heal and can potentially progress toward osteoarthritis. Direct gene transfer of basic fibroblast growth factor 2 (FGF-2) with the clinically adapted recombinant adeno-associated viral (rAAV) vectors is a powerful tool to durably activate osteochondral repair processes. PURPOSE: To examine the ability of an rAAV-FGF-2 construct to target the healing processes of focal osteochondral injury over time in a large translational model in vivo versus a control gene transfer condition. STUDY DESIGN: Controlled laboratory study. METHODS: Standardized osteochondral defects created in the knee joints of adult sheep were treated with an rAAV human FGF-2 (hFGF-2) vector by direct administration into the defect relative to control (reporter) rAAV-lacZ gene transfer. Osteochondral repair was monitored using macroscopic, histological, immunohistological, and biochemical methods and by micro-computed tomography after 6 months. RESULTS: Effective, localized prolonged FGF-2 overexpression was achieved for 6 months in vivo relative to the control condition without undesirable leakage of the vectors outside the defects. Such rAAV-mediated hFGF-2 overexpression significantly increased the individual histological parameter "percentage of new subchondral bone" versus lacZ treatment, reflected in a volume of mineralized bone per unit volume of the subchondral bone plate that was equal to a normal osteochondral unit. Also, rAAV-FGF-2 significantly improved the individual histological parameters "defect filling,""matrix staining," and "cellular morphology" and the overall cartilage repair score versus the lacZ treatment and led to significantly higher cell densities and significantly higher type II collagen deposition versus lacZ treatment. Likewise, rAAV-FGF-2 significantly decreased type I collagen expression within the cartilaginous repair tissue. CONCLUSION: The current work shows the potential of direct rAAV-mediated FGF-2 gene therapy to enhance osteochondral repair in a large, clinically relevant animal model over time in vivo. CLINICAL RELEVANCE: Delivery of therapeutic (hFGF-2) rAAV vectors in sites of focal injury may offer novel, convenient tools to enhance osteochondral repair in the near future.

Analysis of spatial osteochondral heterogeneity in advanced knee osteoarthritis exposes influence of joint alignment.

Osteoarthritis (OA) is considerably affected by joint alignment. Here, we investigate the patterns of spatial osteochondral heterogeneity in patients with advanced varus knee OA together with clinical data. We report strong correlations of osteochondral parameters within individual topographical patterns, highlighting their fundamental and location-dependent interactions in OA. We further identify site-specific effects of varus malalignment on the lesser loaded compartment and, conversely, an unresponsive overloaded compartment. Last, we trace compensatory mechanisms to the overloaded subarticular spongiosa in patients with additional high body weight. We therefore propose to consider and to determine axial alignment in clinical trials when selecting the location to assess structural changes in OA. Together, these findings broaden the scientific basis of therapeutic load redistribution and weight loss in varus knee OA.

Small-Diameter Subchondral Drilling Improves DNA and Proteoglycan Content of the Cartilaginous Repair Tissue in a Large Animal Model of a Full-Thickness Chondral Defect.

This study quantified changes in the DNA content and extracellular matrix composition of both the cartilaginous repair tissue and the adjacent cartilage in a large animal model of a chondral defect treated by subchondral drilling. Content of DNA, proteoglycans, and Type II and Type I collagen, as well as their different ratios were assessed at 6 months in vivo after treatment of full-thickness cartilage defects in the femoral trochlea of adult sheep with six subchondral drill holes, each of either 1.0 mm or 1.8 mm in diameter by biochemical analyses of the repair tissue and the adjacent cartilage and compared with the original cartilage. Only subchondral drilling which were 1.0 mm in diameter significantly increased both DNA and proteoglycan content of the repair tissue compared to the original cartilage. DNA content correlated with the proteoglycan and Type II collagen content within the repair tissue. Significantly higher amounts of Type I collagen within the repair tissue and significantly increased DNA, proteoglycan, and Type I collagen content in the adjacent cartilage were identified. These translational data support the use of small-diameter bone-cutting devices for marrow stimulation. Signs of early degeneration were present within the cartilaginous repair tissue and the adjacent cartilage.

Microfracture for cartilage repair in the knee: a systematic review of the contemporary literature.

PURPOSE: To systematically review and evaluate novel clinical data following microfracture treatment of knee articular cartilage defects. METHODS: A systematic review was performed by searching PubMed, ScienceDirect, and Cochrane Library databases for clinical trials on microfracture treatment, published between 2013 and 2018. Titles, abstracts, and articles were reviewed, and data concerning patient demographics, study design, pre-, intra-, and postoperative findings were extracted. PRISMA guidelines were applied. The methodological quality of the included studies was analyzed by the modified Coleman Methodology Score (CMS), and aggregate data were generated. RESULTS: Eighteen studies including 1830 defects (1759 patients) were included. Of them, 8 (59% of patients) were cohort studies without a comparison group. Overall study quality was moderate (mean total CMS: 64 points), mainly due to low patient numbers, short follow-up periods, lack of control groups and structural repair tissue evaluation, and inhomogeneity in outcome parameters. Microfracture treatment of full-thickness articular cartilage defects (3.4 ± 2.1 cm2) was performed at 43.4 ± 68.0 months of symptom duration. Postoperative assessment at 79.5 ± 27.2 months revealed failure rates of 11-27% within 5 years and 6-32% at 10 years. Imaging analysis was conducted in 10 studies, second-look arthroscopies were reported twice (n = 205 patients) and revealed well integrated fibrocartilaginous repair tissue. CONCLUSIONS: Microfracture provides good function and pain relief at the mid-term and clinically largely satisfying results thereafter. Standardized, high-quality future study designs will better refine optimal indications for microfracture in the context of cartilage repair strategies. LEVEL OF EVIDENCE: This systematic review is based on studies with levels of evidence ranging between I and IV (see results section and Table). Therefore, and according to this journals Instructions for Authors (SYSTEMATIC REVIEWS AND META-ANALYSES are assigned a level of evidence equivalent to the lowest level of evidence used from the manuscripts analysed), level of evidence is IV.