Increased local bone turnover in patients with chronic periprosthetic joint infection.

Aims: The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Methods: Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20). Results: PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp. Conclusion: This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations.

Absolute synovial polymorphonuclear neutrophil cell count as a biomarker of periprosthetic joint infection.

The aim of this study was to evaluate the diagnostic accuracy of the absolute synovial polymorphonuclear neutrophil cell (PMN) count for the diagnosis or exclusion of periprosthetic joint infection (PJI) after total hip (THA) or knee arthroplasty (TKA). In this retrospective cohort study, 147 consecutive patients with acute or chronic complaints following THA and TKA were included. Diagnosis of PJI was established based on the 2018 International Consensus Meeting criteria. A total of 39 patients diagnosed with PJI (32 chronic and seven acute) and 108 patients with aseptic complications were surgically revised. Using receiver operating characteristic curves and calculating the area under the curve (AUC), an optimal synovial cut-off value of 2,000 PMN/µl was determined (AUC 0.978 (95% confidence interval (CI) 0.946 to 1)). Using this cut-off, sensitivity and specificity of absolute synovial PMN count for PJI were 97.4% (95% CI 91.2 to 100) and 93.5% (95% CI 88.9 to 98.1), respectively. Positive and negative predictive value were 84.4% (95% CI 72.7 to 93.9) and 99.0% (95% CI 96.7 to 100), respectively. Exclusion of 20 patients with acute complications improved specificity to 97.9% (95% CI 94.6 to 100). Different cut-off values for THA (< 3,600 PMN/µl) and TKA (< 2,000 PMN/µl) were identified. Absolute synovial PMN count correlated strongly with synovial alpha-defensin (AD) (r = 0.759; p < 0.001). With a positive AD result, no additional PJI could be identified in any case. Absolute synovial PMN count is a widely available, rapid, cost-effective, and accurate marker in PJI diagnostics, whereas synovial AD appears to be a surrogate parameter of absolute synovial PMN count. Despite limitations in the early postoperative phase, wear, and rheumatic diseases in confirming PJI, an absolute synovial PMN count below 2,000/µl is highly suitable for ruling out PJI, with specific cut-off values for THA and TKA.

The Use of Bovine Xenogeneic Bone Graft for Dega Pelvic Osteotomy in Children with Hip Dysplasia: A Retrospective Study of 147 Treated Hips.

BACKGROUNDS: Dega pelvic osteotomy is commonly used to correct acetabular dysplasia in children with open triradiate cartilage. The use of bovine xenogeneic bone graft (Tutobone®) for Dega osteotomy has not been reported so far. This study aimed to determine the clinical and radiological outcome in a large series of children with hip dysplasia who were treated by Dega osteotomy using a bovine xenogeneic block for stabilisation. METHODS: A retrospective, single-centre study was conducted including 101 patients (147 hips) with different underlying diseases. The acetabular angle of Hilgenreiner (AA) and the lateral center-edge angle (LCA) were analysed to quantify the correction of acetabular indices. Graft incorporation was assessed using the Goldberg scoring system. RESULTS: the mean preoperative AA improved from 28.1 (SD: 6.7) to 14.7 (SD: 5.1) after surgery (p < 0.001). The mean preoperative LCA improved from 9.9 (SD: 6.7) to 21.8 (SD: 6.8) postoperatively (p < 0.001). Both indices remained stable at the one-year follow-up examination. Graft incorporation was excellent with a mean Goldberg score of 6.6. Heterotopic ossification occurred in one hip without clinical relevance. Graft-related complications were not noted. CONCLUSIONS: Dega osteotomy using Tutobone® is safe and effective in the treatment of acetabular dysplasia in children independent of the underlying disease.

Pharmacological estrogen administration causes a FSH-independent osteo-anabolic effect requiring ER alpha in osteoblasts.

Postmenopausal osteoporosis is characterized by declining estrogen levels, and estrogen replacement therapy has been proven beneficial for preventing bone loss in affected women. While the physiological functions of estrogen in bone, primarily the inhibition of bone resorption, have been studied extensively, the effects of pharmacological estrogen administration are still poorly characterized. Since elevated levels of follicle-stimulating hormone (FSH) have been suggested to be involved in postmenopausal bone loss, we investigated whether the skeletal response to pharmacological estrogen administration is mediated in a FSH-dependent manner. Therefore, we treated wildtype and FSHß-deficicent (Fshb(-/-)) mice with estrogen for 4 weeks and subsequently analyzed their skeletal phenotype. Here we observed that estrogen treatment resulted in a significant increase of trabecular and cortical bone mass in both, wildtype and Fshb(-/-) mice. Unexpectedly, this FSH-independent pharmacological effect of estrogen was not caused by influencing bone resorption, but primarily by increasing bone formation. To understand the cellular and molecular nature of this osteo-anabolic effect we next administered estrogen to mouse models carrying cell specific mutant alleles of the estrogen receptor alpha (ERα). Here we found that the response to pharmacological estrogen administration was not affected by ERα inactivation in osteoclasts, while it was blunted in mice lacking the ERα in osteoblasts or in mice carrying a mutant ERα incapable of DNA binding. Taken together, our findings reveal a previously unknown osteo-anabolic effect of pharmacological estrogen administration, which is independent of FSH and requires DNA-binding of ERα in osteoblasts.

Metaphyseal fracture healing follows similar biomechanical rules as diaphyseal healing.

It is generally supposed that the pattern of fracture healing in trabecular metaphyseal bone differs from that of diaphyseal fractures. However, few experimental studies to date have been performed, even though clinically many fractures occur in metaphyseal bone. Particularly, the influence of biomechanical factors has not yet been investigated under standardized conditions. Our aim was to correlate the interfragmentary strain (IFS) with the bone-healing outcome in a controlled metaphyseal fracture model in sheep. Twelve sheep received a partial osteotomy in the distal femoral condyle close to the trochlea. The determination of the IFS by in vivo X-ray analyses and a finite element model revealed that the deflection of the osteotomy gap by the patello-femoral force during walking provoked increasing strains of up to 40%. Bone healing was evaluated after 8 weeks by the assessment of the bone mineral density and by histomorphometry in regions of interest that displayed differing magnitudes of IFS. In areas with strains below 5% significantly less bone formation occurred compared to areas with higher strains (6-20%). For strains larger than 20% fibrocartilage layers were observed. Low IFS (<5%) led to intramembranous bone formation, whereas higher strains additionally provoked endochondral ossification or fibrocartilage formation. It is therefore proposed that metaphyseal bone healing follows similar biomechanical principles as diaphyseal healing.

Skeletal analysis and comparison of bog bodies from Northern European peat bogs.

Although numerous bodies were deposited in Western European bogs in the past centuries, few were found and underwent archeological analysis. No studies comparing skeletal structure and mineralization of bog bodies from different ages have been performed to this day. Therefore, the aim of this study was to analyze and compare skeletal features and specifics of the human remains of three bog bodies from the Iron and Middle Ages found in Northern European peat bogs. Demineralization due to the acidic environment in peat bogs was comparably pronounced in all three bodies. Still, the macroscopic state of skeletal preservation was excellent. In addition to contact radiography, we used peripheral quantitative computed tomography to measure cortical bone mineral density. The conservation of skeletal three-dimensional microstructural elements was assessed by high-resolution microcomputed tomography analysis. These techniques revealed severe differences in bone mineral density and enabled us to determine handedness in all three bodies. Additionally, unique skeletal features like intravital bone lesions, immobilization osteoporosis, and Harris lines were found. A deformity of the left femoral head was observed which had the typical appearance of an advanced stage of Legg-Calve-Perthes disease. This study gives detailed insight into the skeletal microstructure and microarchitecture of 800- to 2,700-year-old bog bodies. Skeletal analysis enables us to draw conclusions not only concerning changes in the acidic environment of the bog, but also serves as a diagnostic tool to unravel life circumstances and diseases suffered by humans in the Iron and Middle Ages.