Since the hematopoetic system is located within the bone marrow, it is not surprising that recent evidence has demonstrated the existence of molecular interactions between bone and immune cells. While interleukin 1 (IL-1) and IL-18, two cytokines of the IL-1 family, have been shown to regulate differentiation and activity of bone cells, the role of IL-33, another IL-1 family member, has not been addressed yet. Since we observed that the expression of IL-33 increases during osteoblast differentiation, we analyzed its possible influence on bone formation and observed that IL-33 did not affect matrix mineralization but enhanced the expression of Tnfsf11, the gene encoding RANKL. This finding led us to analyze the skeletal phenotype of Il1rl1-deficient mice, which lack the IL-33 receptor ST2. Unexpectedly, these mice displayed normal bone formation but increased bone resorption, thereby resulting in low trabecular bone mass. Since this finding suggested a negative influence of IL-33 on osteoclastogenesis, we next analyzed osteoclast differentiation from bone marrow precursor cells and observed that IL-33 completely abolished the generation of TRACP⁺ multinucleated osteoclasts, even in the presence of RANKL and macrophage colony-stimulating factor (M-CSF). Although our molecular studies revealed that IL-33 treatment of bone marrow cells caused a shift toward other hematopoetic lineages, we further observed a direct negative influence of IL-33 on the osteoclastogenic differentiation of RAW264.7 macrophages, where IL-33 repressed the expression of Nfatc1, which encodes one of the key transciption factors of osteoclast differentiation. Taken together, these findings have uncovered a previously unknown function of IL-33 as an inhibitor of bone resorption. © 2011 American Society for Bone and Mineral Research.

Background: Impacted bone-grafting with morselized allograft chips is commonly used to reconstruct acetabular bone defects in revision total hip arthroplasty (THA). While the overall clinical outcome of this procedure is described to be excellent, the microstructural basis and histological determinants of allograft incorporation remained to be further elucidated. Methods: The acetabula of 23 individuals with documented previous use of allograft chips during revision THA were explanted post mortem. The time that the allografts were in situ averaged 10.3 ± 4.5 years (range, 1.2 to 19.8 years). The host bone (HB)-allograft bone (AB) interface was characterized using a suite of high-resolution (HR) imaging techniques including HR-peripheral quantitative computed tomography (HR-pQCT), histological analysis, cellular histomorphometry, and scanning electron microscopy. Results: AB could be identified in 16 of the 23 cases. The HB and AB showed overlap (i.e., ingrowth) in 91.3% of the total interface. The mean ingrowth was 2.2 ± 1.0 mm with a maximum of 4.7 ± 2.1 mm. The periphery of the AB showed a tight interconnection with the HB associated with increased bone remodeling indices and increased trabecular thickness. While no association between the time in situ and the ingrowth was observed, the bone defect area was positively associated with the thickness of a fibrosis layer separating the ingrowth zone from the AB. Conclusions: Allograft chips in revision THA form an adequate osseous foundation with successful incorporation through ingrowth of the HB (i.e., osteoconduction). While complete remodeling was not observed, larger defects were associated with fibrosis formation, which may compromise stability. Clinical Relevance: Our study provides the first systematic, multiscale long-term evaluation of chip allograft incorporation in revision THA to underscore its successful clinical use. As larger defects were associated with fibrous ingrowth, structural allografts may be superior for larger defects in terms of long-term outcomes.

Introduction: Several studies have reported good to excellent outcomes of revision total hip arthroplasty (rTHA) using allografts for treating severe acetabular bone defects. However, precise information on the impact of allograft type and reconstruction method is not available. Material and methods: Systematic literature search was performed in Medline and Web of Science including patients with acetabular bone loss classified according to the Paprosky classification who underwent rTHA involving the use of allografts. Studies with a minimum follow-up of 2 years published between 1990 and 2021 were included. Kendall correlation was applied to determine the relationship between Paprosky grade and allograft type use. Proportion meta-analyses with 95% confidence interval (CI) were performed to summarize the success of various reconstruction options, including allograft type, fixation method, and reconstruction system. Results: Twenty-seven studies met the inclusion criteria encompassing 1561 cases from 1491 patients with an average age of 64 years (range 22–95). The average follow-up period was 7.9 years (range 2–22). Structural bulk and morselized grafts were used in equal proportions for all Paprosky acetabular defect types. Their use increased significantly with the type of acetabular defect (r = 0.69, p = 0.049). The overall success rate ranged from 61.3 to 98.3% with a random effect pooled estimate of 90% [95% CI 87–93]. Trabecular metal augments (93% [76–98]) and shells (97% [84–99]) provided the highest success rates. However, no significant differences between reconstruction systems, allograft types and fixation methods were observed (p > 0.05 for all comparisons). Conclusion: Our findings highlight the use of bulk or morselized allograft for massive bone loss independent of Paprosky classification type and indicate similar good mid- to long-term outcomes of the different acetabular reconstruction options using allografts. Clinical trial registration: PROSPERO: CRD42020223093.

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.Cite this article: Bone Joint Res 2023;12(10):644–653.

Background: Physiological reference values for morphological parameters of the hip (MPH) are of clinical importance for the treatment of painful, degenerated or fractured hip joints, as well as to detect morphological deformities, which could result in early osteoarthritis of the hip. Currently, sufficient data for MPH are lacking. Therefore, it remains unclear if age-dependent alterations in adult hip morphology are physiological and if there are side- and gender-dependent differences. The aim of the study was to analyze MPH according to gender, side and age in a large-scaled cohort by CT scans. Methods: A total of 1576 hip joints from 788 patients (female: 257, male: 531; mean age: 58.3 years (±18.9; 18–92 years)) were analyzed by CT. For all hips, acetabular anteversion (AcetAV); lateral centrum edge angle (LCE); acetabular index (AI); femoral neck version (FNV); centrum-collum-diaphyseal angle (CCD); and anterior alpha angle (AαA) were measured. Results: The mean values in this cohort were: AcetAV 20.5° (±6.9); LCE 40.8° (±8.8); AI 0.3° (±5.3); FNV 11.0° (±9.8); CCD 129.9° (±7.4); and AαA 41.2° (±7.7). There was a detectable side-specific difference for AcetAV (p = 0.001); LCE (p < 0.001); CCD (p < 0.001); and AαA (p < 0.001). All the analyzed parameters showed a significant gender-specific difference, except for AI (p = 0.37). There was a significant correlation between age and AcetAV (r = 0.17; p < 0.001); LCE (r = 0.39; p < 0.001); AI (r = −0.25; p < 0.001); CCD (r = −0.15; p < 0.001); and AαA (r = 0.09; p < 0.001), except FNV (p = 0.79). Conclusions: There are side-, gender- and age-specific alterations in hip morphology, which have to be considered in treating hip joint pathologies.