Blood transfusion in elective total hip arthroplasty: can patient-specific parameters predict transfusion?

Aims: Transfusion after primary total hip arthroplasty (THA) has become rare, and identification of causative factors allows preventive measures. The aim of this study was to determine patient-specific factors that increase the risk of needing a blood transfusion. Methods: All patients who underwent elective THA were analyzed retrospectively in this single-centre study from 2020 to 2021. A total of 2,892 patients were included. Transfusion-related parameters were evaluated. A multiple logistic regression was performed to determine whether age, BMI, American Society of Anesthesiologists (ASA) grade, sex, or preoperative haemoglobin (Hb) could predict the need for transfusion within the examined patient population. Results: The overall transfusion rate was 1.2%. Compared to the group of patients without blood transfusion, the transfused group was on average older (aged 73.8 years (SD 9.7) vs 68.6 years (SD 10.1); p = 0.020) and was mostly female (p = 0.003), but showed no significant differences in terms of BMI (28.3 kg/m2 (SD 5.9) vs 28.7 kg/m2 (SD 5.2); p = 0.720) or ASA grade (2.2 (SD 0.5) vs 2.1 (SD 0.4); p = 0.378). The regression model identified a cutoff Hb level of < 7.6 mmol/l (< 12.2 g/dl), aged > 73 years, and a BMI of 35.4 kg/m² or higher as the three most reliable predictors associated with postoperative transfusion in THA. Conclusion: The possibility of transfusion is predictable based on preoperatively available parameters. The proposed thresholds for preoperative Hb level, age, and BMI can help identify patients and take preventive measures if necessary.

Advantages of cone beam computed tomography for evaluation of subchondral insufficiency fractures of the knee compared to MRI.

To determine the diagnostic yield of cone beam computed tomography (CBCT) compared with 3 T magnetic resonance imaging (MRI) for the evaluation of subchondral insufficiency fractures of the knee. Consecutive patients with subchondral insufficiency fractures of the knee examined by 3 T MRI and CBCT of the femoral condyles were reviewed. Two experienced raters graded the lesion severity on 3 T MRI and CBCT images: grade 1: no signs of a subchondral bone lesion; grade 2: subchondral trabecular fracture or cystic changes, but without infraction of the subchondral bone plate; grade 3: collapse of the subchondral bone plate. Ratings were repeated after six weeks to determine reliability. In addition, the bone lesion size was measured as elliptical area (mm2) and compared between CBCT and T1-weighted MRI sequences. Among 30 patients included (43.3% women; mean age: 60.9 ± 12.8 years; body mass index (BMI) 29.0 ± 12.8 kg/m2), the medial femoral condyle was affected in 21/30 patients (70%). The grading of subchondral lesions between MRI and CBCT did not match in 12 cases (40%). Based on MRI images, an underestimation (i.e., undergrading) compared with CBCT was observed in nine cases (30%), whereas overgrading occurred in three cases (10%). Compared to CBCT, routine T1-weighted 3 T sequences significantly overestimated osseus defect zones in sagittal (84.7 ± 68.9 mm2 vs. 35.9 ± 38.2 mm2, p < 0.01, Cohen's d = 1.14) and coronal orientation (53.1 ± 24.0 mm2 vs. 22.0 ± 15.2 mm2, p < 0.01, Cohen's d = 1.23). The reproducibility of the grading determined by intra- and inter-rater agreement was very high in MRI (intra-class correlation coefficient (ICC) 0.78 and 0.90, respectively) and CBCT (ICC 0.96 and 0.96, respectively). In patients with subchondral insufficiency fractures of the knee, the use of CBCT revealed discrepancies in lesion grading compared with MRI. These findings are clinically relevant, as precise determination of subchondral bone plate integrity may influence the decision about conservative or surgical treatment. CBCT represents our imaging modality of choice for grading the lesion and assessing subchondral bone plate integrity. MRI remains the gold standard modality to detect especially early stages.

Influence of variable hinge positioning on coronal and sagittal alignment in uniplanar medial open-wedge high tibial osteotomy.

Purpose: There is a high risk of increasing the posterior tibial slope (PTS) during medially opening-wedge high tibial osteotomy (mowHTO). Most recently, the idea of intentional simultaneous coronal and sagittal correction, using uniplanar cutting techniques has emerged. This study aims to examine the influences of variable hinge positioning and osteotomy gap height on the sagittal and coronal plane. Methods: Twenty uniplanar mowHTOs were performed in standardised (left) solid-foam proximal tibia models. In the different models, hinge position was rotated stepwise by 10°, between 90° (cutting straight medial to lateral) and 0° (cutting straight anterior to posterior) (n = 10). Additionally, gap heights of 5 and 10 mm were produced and analysed. Logistic regression analysis was performed to calculate a predictive regression formula for the relation between gap height, hinge rotation and the changes of medial proximal tibia angle (MPTA), medial and lateral PTS. Results: Between cutting angles of 90 and 20°, the MPTA was mainly influenced by the gap height (0.95° MPTA per 1 mm gap height), but not by the cutting angle. Between 20 and 0°, the MPTA was decreased by 3.6° per 10° of rotation, but not by the gap height. Between cutting angles of 90 and 10°, the PTS was increased linearly by 0.97° per 10° of rotation and by 0.61° per 1 mm gap height. Conclusion: In mowHTO with lateral hinge positions, the MPTA is mainly influenced by gap height. Changes of PTS can be avoided by a straight lateral hinge position. In posterior hinge locations (0-20°), changes of MPTA are mainly caused by hinge rotation, but not by gap height. Level of Evidence: Level III, Case-control study.

Patients with Periprosthetic Femoral Hip Fractures are Commonly Classified as Having Osteoporosis Based on DXA Measurements.

Periprosthetic femoral hip fractures are subject to an increasing incidence and are often considered to be related to osteoporosis. However, there are no available studies that have determined the frequency of osteoporosis in affected patients using gold standard dual-energy X-ray absorptiometry (DXA). In this retrospective comparative study, we analyzed the DXA results of 40 patients with periprosthetic femoral hip fractures who were treated surgically in our department. DXA measurements were performed at the total hip and the lumbar spine to determine bone mineral density T-scores. Data were compared to two age-, sex-, and BMI-matched control groups in which patients underwent DXA prior to aseptic revision surgery for other causes or primary THA (consisting of 40 patients each). The mean T-score in the periprosthetic fracture cohort was significantly lower (- 1.78 ± 1.78) than that of the aseptic revision (- 0.65 ± 1.58, mean difference - 1.13 [95% CI - 1.88 to - 0.37]; p = 0.001) and the primary THA cohort (- 0.77 ± 1.34, mean difference - 1.01 [95% CI - 1.77 to - 0.26]; p = 0.005). Accordingly, osteoporosis was detected more frequently (45%) in the fracture cohort compared to patients undergoing aseptic revision (12.5%) and primary THA (10%). In conclusion, almost half of the patients with periprosthetic femoral hip fractures have osteoporosis according to DXA measurements. A regular assessment of bone health in THA enables identification of patients with osteoporosis who likely benefit from initiation of osteoporosis medication and cemented stem fixation.

A clinical risk score enables early prediction of dissatisfaction 1 year after total knee arthroplasty.

PURPOSE: Dissatisfaction after total knee arthroplasty (TKA) is a prevalent and clinically relevant problem that affects approximately 10%-20% of patients. The aim of this study is to identify factors associated with dissatisfaction 1 year after TKA. METHODS: A total of 236 patients undergoing TKA were included in this prospective cohort study. Demographic data, preoperative clinical parameters (e.g., axial alignment, osteoarthritis severity) and patient-reported outcome measures (PROMs) were collected preoperatively, at 1 month and 1 year after TKA, encompassing the Knee Society Score (KSS) and Knee injury and Osteoarthritis Outcome Score (KOOS). The primary outcome was dissatisfaction 1 year after TKA, defined as ≤20 points on the KSS satisfaction scale. A risk score based on multiple regression and area under the curve (AUC) analyses was calculated to predict dissatisfaction. RESULTS: One year after TKA, 16% of the patients were dissatisfied. Dissatisfied patients were significantly younger (p = 0.023) and had a higher body mass index (BMI) (p = 0.007). No differences were observed in preoperative objective (p = 0.903) and functional KSS (p = 0.346), pain (p = 0.306), osteoarthritis severity (p = 0.358), axial knee alignment (p = 0.984) or psychological distress (p = 0.138). The likelihood of dissatisfaction at 1 year was 3.0, 4.0, 7.4, 4.3 and 2.8 times higher amongst patients aged <63.5 years, with a BMI > 30.1 kg/m2, a KOOSPain < 50%, a KSSFunction < 42 points and a KSSExpectation < 9 points (all at 1 month), respectively. Using these variables, a risk score with a maximum of 7 points was developed, demonstrating a high predictive value for dissatisfaction (AUC: 0.792 [95% confidence interval: 0.700-0.884], p < 0.001). CONCLUSION: Dissatisfaction 1 year after TKA can be predicted by a weighted risk score that includes patient age, BMI, pain, subjective functionality and unmet expectation 1 month postoperatively. Using the risk score, early detection of dissatisfaction has the potential to enable targeted interventions and improve patients' quality of life. LEVEL OF EVIDENCE: Level II, Prognostic study.

Pronounced cortical porosity and sex-specific patterns of increased bone and osteocyte lacunar mineralization characterize the human distal fibula with aging.

The high occurrence of distal fibula fractures among older women suggests a potential link to impaired bone health. Here we used a multiscale imaging approach to investigate the microarchitecture, mineralization, and biomechanics of the human distal fibula in relation to age and sex. Micro-computed tomography was performed to analyze the local volumetric bone mineral density and various microarchitectural parameters of the trabecular and the cortical compartment. Bone mineral density distribution and osteocyte lacunar parameters were quantified using quantitative backscattered electron imaging in periosteal, endocortical, and trabecular regions. Additionally, cortical hardness and Young's modulus were assessed by nanoindentation. While cortical porosity strongly increased with age independent of sex, trabecular microarchitecture remained stable. Notably, nearly half of the specimens showed non-bony hypermineralized tissue located at the periosteum, similar to that previously detected in the femoral neck, with no consistent association with advanced age. Independent of this finding, cortical and trabecular mineralization, i.e., mean calcium content, as well as endocortical tissue hardness increased with age in males but not females. Importantly, we also observed mineralized osteocyte lacunae that increased with age specifically in females. In conclusion, our results indicate that skeletal aging of the distal fibula is signified not only by pronounced cortical porosity but also by an increase in mineralized osteocyte lacunae in females. These findings may provide an explanation for the increased occurrence of ankle fractures in older women.

Alterations in compositional and cellular properties of the subchondral bone are linked to cartilage degeneration in hip osteoarthritis.

OBJECTIVE: The subchondral bone is an emerging regulator of osteoarthritis (OA). However, knowledge of how specific subchondral alterations relate to cartilage degeneration remains incomplete. METHOD: Femoral heads were obtained from 44 patients with primary OA during total hip arthroplasty and from 30 non-OA controls during autopsy. A multiscale assessment of the central subchondral bone region comprising histomorphometry, quantitative backscattered electron imaging, nanoindentation, and osteocyte lacunocanalicular network characterization was employed. RESULTS: In hip OA, thickening of the subchondral bone coincided with a higher number of osteoblasts (controls: 3.7 ± 4.5 mm-1, OA: 16.4 ± 10.2 mm-1, age-adjusted mean difference 10.5 mm-1 [95% CI 4.7 to 16.4], p < 0.001) but a similar number of osteoclasts compared to controls (p = 0.150). Furthermore, higher matrix mineralization heterogeneity (CaWidth, controls: 2.8 ± 0.2 wt%, OA: 3.1 ± 0.3 wt%, age-adjusted mean difference 0.2 wt% [95% CI 0.1 to 0.4], p = 0.011) and lower tissue hardness (controls: 0.69 ± 0.06 GPa, OA: 0.67 ± 0.06 GPa, age-adjusted mean difference -0.05 GPa [95% CI -0.09 to -0.01], p = 0.032) were detected. While no evidence of altered osteocytic perilacunar/canalicular remodeling in terms of fewer osteocyte canaliculi was found in OA, specimens with advanced cartilage degeneration showed a higher number of osteocyte canaliculi and larger lacunocanalicular network area compared to those with low-grade cartilage degeneration. Multiple linear regression models indicated that several subchondral bone properties, especially osteoblast and osteocyte parameters, were closely related to cartilage degeneration (R2 adjusted = 0.561, p < 0.001). CONCLUSION: Subchondral bone properties in OA are affected at the compositional, mechanical, and cellular levels. Based on their strong interaction with cartilage degeneration, targeting osteoblasts/osteocytes may be a promising therapeutic OA approach. DATA AND MATERIALS AVAILABILITY: All data are available in the main text or the supplementary materials.

Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development.

Piezo proteins are mechanically activated ion channels, which are required for mechanosensing functions in a variety of cell types. While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for bone-anabolic processes, there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage. Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis (OA) development. Mice with chondrocyte-specific inactivation of Piezo1 (Piezo1Col2a1Cre), but not of Piezo2, developed a near absence of trabecular bone below the chondrogenic growth plate postnatally. Moreover, all Piezo1Col2a1Cre animals displayed multiple fractures of rib bones at 7 days of age, which were located close to the growth plates. While skeletal growth was only mildly affected in these mice, OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age. Likewise, when OA was induced by anterior cruciate ligament transection, only the chondrocyte inactivation of Piezo1, not of Piezo2, resulted in attenuated articular cartilage degeneration. Importantly, osteophyte formation and maturation were also reduced in Piezo1Col2a1Cre mice. We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes. Finally, we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes. Collectively, our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes, but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

Tranexamic Acid Attenuates the Progression of Posttraumatic Osteoarthritis in Mice.

BACKGROUND: Posttraumatic osteoarthritis (OA) is a common disorder associated with a high socioeconomic burden, particularly in young, physically active, and working patients. Tranexamic acid (TXA) is commonly used in orthopaedic trauma surgery as an antifibrinolytic agent to control excessive bleeding. Previous studies have reported that TXA modulates inflammation and bone cell function, both of which are dysregulated during posttraumatic OA disease progression. PURPOSE: To evaluate the therapeutic effects of systemic and topical TXA treatment on the progression of posttraumatic OA in the knee of mice. STUDY DESIGN: Controlled laboratory study. METHODS: OA was induced via anterior cruciate ligament (ACL) transection on the right knee of female mice. Mice were treated with TXA or vehicle intraperitoneally daily or intra-articularly weekly for 4 weeks, starting on the day of surgery. Articular cartilage degeneration, synovitis, bone erosion, and osteophyte formation were scored histologically. Micro-computed tomography evaluation was conducted to measure the subchondral bone microstructure and osteophyte volume. Cartilage thickness and bone remodeling were assessed histomorphometrically. RESULTS: Both systemic and topical TXA treatment significantly reduced cartilage degeneration, synovitis, and bone erosion scores and increased the ratio of hyaline to calcified cartilage thickness in posttraumatic OA. Systemic TXA reversed ACL transection-induced subchondral bone loss and osteophyte formation, whereas topical treatment had no effect. Systemic TXA decreased the number and surface area of osteoclasts, whereas those of osteoblasts were not affected. No effect of topical TXA on osteoblast or osteoclast parameters was observed. CONCLUSION: Both systemic and topical TXA exerted protective effects on the progression of posttraumatic OA. Drug repurposing of TXA may, therefore, be useful for the prevention or treatment of posttraumatic OA, particularly after ACL surgery. CLINICAL RELEVANCE: TXA might be beneficial in patients with posttraumatic OA of the knee.

Are Synovial Inflammatory Markers Increased in Patients Who Have Aseptic Total Hip Arthroplasty Dislocation Indicated for Revision?

BACKGROUND: Previous studies have speculated on elevated synovial inflammatory markers in patients undergoing surgical revision for total hip arthroplasty (THA) dislocation. However, this assumption is based on small patient series and a full investigation according to International Consensus Meeting (ICM) criteria has not yet been performed. METHODS: Patients who had aseptic THA dislocation indicated for revision surgery were identified retrospectively. Only patients who had available diagnostic workup according to ICM 2018 criteria, including preoperative and intraoperative parameters, were included. For comparison, we analyzed a matched cohort of patients indicated for aseptic THA revision for other conditions. The 2 cohorts each consisted of 55 patients and were not different regarding age, sex, BMI, or implant fixation. RESULTS: There was no difference in synovial white blood cell count (2,238 ± 2,544 versus 2,533 ± 3,448 c/µL; P = .601), alpha-defensin quotient (0.14 ± 0.11 versus 0.19 ± 0.28; P = .207), or polymorphonuclear neutrophil percentage (% PMN) (36.7 ± 22.6 versus 31.3 ± 24.5%; P = .312) between the groups. In the dislocation cohort, 20% of patients had a synovial white blood cell count of 3,000 c/µL or higher, compared with 18% in the control cohort. However, all patients in the dislocation cohort were below the cutoff for alpha-defensin or % PMN. CONCLUSION: In patients who have aseptic THA dislocation, synovial inflammatory markers are not elevated compared with patients undergoing aseptic revision for other complications. A detailed preoperative analysis of synovial inflammatory markers using ICM criteria appears critical in patients who have a THA dislocation to exclude periprosthetic joint infection. LEVEL OF EVIDENCE: Level III, retrospective, comparative study.

Areal bone mineral density is not associated with femoral stem subsidence in patients younger than 70 years undergoing total hip arthroplasty.

INTRODUCTION: Femoral stem subsidence is a known complication after uncemented total hip arthroplasty (THA). The purpose of this study was to determine the frequency of osteoporosis and to investigate the relationship between areal bone mineral density (aBMD) and subsidence in a cohort of patients younger than 70 years. METHODS: One hundred consecutive patients (age 60 ± 6 years; 52 female, 48 male) undergoing uncemented THA using a collarless press fit femoral stem were retrospectively reviewed. Dual-energy X-ray absorptiometry (DXA) was performed preoperatively at the proximal femur and lumbar spine, and if not feasible at these sites, at the distal radius. DXA results were compared to a cohort of 100 patients ≥ 70 years scheduled for cemented THA. Age, sex, and body mass index (BMI), canal flare index (CFI), and canal fill ratio (CFR) were assessed. Analysis of stem subsidence and migration was performed on standardized, calibrated radiographs obtained postoperatively and at follow-up. RESULTS: The frequency of osteoporosis was considerably lower in the study cohort compared to patients ≥ 70 years (7% vs. 19%, p = 0.02). Illustrated by the high CFR (mean 96 ± 4%) in the mid-stem region, a sufficient press fit was achieved. After a mean follow-up of 7.4 months, the mean stem subsidence was 0.9 ± 0.9 mm. Only two patients had subsidence greater than 3 mm, one of whom was morbidly obese and the other diagnosed with severe osteoporosis. There were no correlations between any of the parameters (CFI, CFR, age, sex, BMI) and femoral stem subsidence. In addition, aBMD T-scores showed no correlations with subsidence. CONCLUSION: aBMD by DXA does not appear to be associated with stem subsidence in patients younger than 70 years and with adequate press fit.

Influence of health literacy on health-related quality of life after total hip arthroplasty.

INTRODUCTION: Personal knowledge about the own disease, a key component of health literacy (HL), may have a considerable impact on treatment outcomes. The purpose of this study was to investigate whether the patients' knowledge about the surgical procedure, risks, and aftercare, as well as the satisfaction with the preoperative level of information, has an influence on the health-related quality of life (HRQoL) after primary total hip arthroplasty (THA). MATERIALS AND METHODS: A total of 176 patients (68.3 ± 10.3 years, 60.8% female) were evaluated. HRQoL was assessed prior to surgery as well as one and twelve months after THA using the 12-item Short Form Questionnaire. Following standardized surgical informed consent, HL was assessed preoperatively using a self-constructed quiz score, while information satisfaction was measured with a single-item rating scale. Sociodemographic and clinical characteristics, including pain (VAS), functionality (WOMAC), and psychological distress (PHQ-4), were also assessed at baseline. Multiple linear regression analyses were performed to examine whether HL, satisfaction with information, age, social class, WOMAC, VAS, and PHQ-4 predict HRQoL at one and twelve months post-surgery. RESULTS: The average HL quiz score was 23 ± 5.1 out of a possible 33 points. Social class index significantly influenced HL (p < 0.001). A weak correlation between HL and age (r = 0.23, p = 0.01) and no correlation between HL and psychological distress (p = 0.868) were observed. One month after THA, physical HRQoL was significantly predicted by the WOMAC index (p = 0.031) and subjective satisfaction with information (p = 0.022), but not by HL. After twelve months, only the WOMAC was a significant predictor (p < 0.001) of physical HRQoL. CONCLUSION: Although subjective satisfaction with the patient's preoperative level of information had a significant effect on the physical HRQoL at one month after THA, the influence of osteoarthritis severity outweighed this effect after twelve months. HL had no direct influence on HRQoL. These results suggest that patient satisfaction, rather than knowledge, predicts HRQoL.

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.

Mice heterozygous for an osteogenesis imperfecta-linked MBTPS2 variant display a compromised subchondral osteocyte lacunocanalicular network associated with abnormal articular cartilage.

Missense variants in the MBTPS2 gene, located on the X chromosome, have been associated with an X-linked recessive form of osteogenesis imperfecta (X-OI), an inherited bone dysplasia characterized by multiple and recurrent bone fractures, short stature, and various skeletal deformities in affected individuals. The role of site-2 protease, encoded by MBTPS2, and the molecular pathomechanism underlying the disease are to date elusive. This study is the first to report on the generation of two Mbtps2 mouse models, a knock-in mouse carrying one of the disease-causative MBTPS2 variants (N455S) and a Mbtps2 knock-out (ko) mouse. Because both loss-of-function variants lead to embryonic lethality in hemizygous male mutant mice, we performed a comprehensive skeletal analysis of heterozygous Mbtps2+/N455S and Mbtps2+/ko female mice. Both models displayed osteochondral abnormalities such as thinned subchondral bone, altered subchondral osteocyte interconnectivity as well as thickened articular cartilage with chondrocyte clustering, altogether resembling an early osteoarthritis (OA) phenotype. However, distant from the joints, no alterations in the bone mass and turnover could be detected in either of the mutant mice. Based on our findings we conclude that MBTPS2 haploinsufficiency results in early OA-like alterations in the articular cartilage and underlying subchondral bone, which likely precede the development of typical OI phenotype in bone. Our study provides first evidence for a potential role of site-2 protease for maintaining homeostasis of both bone and cartilage.

Cholesteatoma Severely Impacts the Integrity and Bone Material Quality of the Incus.

Cholesteatoma can lead to progressive destruction of the auditory ossicles along with conductive hearing loss but precise data on the microstructural, cellular, and compositional aspects of affected ossicles are not available. Here, we obtained incus specimens from patients who had cholesteatoma with conductive hearing loss. Incudes were evaluated by micro-computed tomography, histomorphometry on undecalcified sections, quantitative backscattered electron imaging, and nanoindentation. Results were compared with two control groups taken from patients with chronic otitis media as well as from skeletally intact donors at autopsy. The porosity of incus specimens was higher in cholesteatoma than in chronic otitis media, along with a higher osteoclast surface per bone surface. Histomorphometric assessment revealed higher osteoid levels and osteocyte numbers in cholesteatoma incudes. Incudes affected by cholesteatoma also showed lower matrix mineralization compared with specimens from healthy controls and chronic otitis media. Furthermore, the modulus-to-hardness ratio was higher in cholesteatoma specimens compared with controls. Taken together, we demonstrated increased porosity along with increased osteoclast indices, impaired matrix mineralization, and altered biomechanical properties as distinct features of the incus in cholesteatoma. Based on our findings, a possible impact of impaired bone quality on conductive hearing loss should be further explored.

Conservative versus operative treatment of FFP II fractures in a geriatric cohort: a prospective randomized pilot trial.

A clear recommendation regarding treatment strategy of fragility fractures of the pelvic ring is missing. The most typical fracture pattern is a lateral compression type injury with non-displaced fractures of the anterior pubic rami and a unilateral os sacrum fracture (FFP II). We hypothesized that operative treatment would be superior to conservative treatment. From October 2017 to April 2020, a randomized prospective non-blinded trial with n = 39 patients was carried out. Two arms with 17 operative versus 22 conservative cases were created. Inclusion criteria were a posterior pelvic ring fracture FFP type II, age over 60 years and acute fracture (< 3 weeks). Barthel index, pain level (VAS), quality of life (EQ-5D-3L), and Tinetti-Gait Test were determined on admission, at discharge, and after 3, 6, 12 and 24 months. Median follow-up was 12.9 months. The Barthel index (= 0.325), VAS (p = 0.711), quality of life (p = 0.824), and Tinetti-Gait Test (p = 0.913) showed no significant differences between the two groups after 12 months. Two patients switched from the conservative to the operative arm due to persistent immobilization and pain. The one-year mortality rate showed no significant difference (p = 0.175). Our hypothesis that surgical treatment is superior was refuted. No significant benefit was shown in terms of quality of life, mortality and pain levels. The results suggest a more differentiated treatment approach in the future, with initial conservative treatment preferred. A larger multi-center trial is required to confirm these findings.Trial registration: The study was retrospectively registered with the German Clinical Trials Registry (DRKS00013703) on 10/12/2018.

Raman spectroscopy and U-Net deep neural network in antiresorptive drug-related osteonecrosis of the jaw.

OBJECTIVE: Application of an optical method for the identification of antiresorptive drug-related osteonecrosis of the jaw (ARONJ). METHODS: We introduce shifted-excitation Raman difference spectroscopy followed by U-Net deep neural network refinement to determine bone tissue viability. The obtained results are validated through established histological methods. RESULTS: Discrimination of osteonecrosis from physiological tissues was evaluated at 119 distinct measurement loci in 40 surgical specimens from 28 patients. Mean Raman spectra were refined from 11,900 raw spectra, and characteristic peaks were assigned to their respective molecular origin. Then, following principal component and linear discriminant analyses, osteonecrotic lesions were distinguished from physiological tissue entities, such as viable bone, with a sensitivity, specificity, and overall accuracy of 100%. Moreover, bone mineral content, quality, maturity, and crystallinity were quantified, revealing an increased mineral-to-matrix ratio and decreased carbonate-to-phosphate ratio in ARONJ lesions compared to physiological bone. CONCLUSION: The results demonstrate feasibility with high classification accuracy in this collective. The differentiation was determined by the spectral features of the organic and mineral composition of bone. This merely optical, noninvasive technique is a promising candidate to ameliorate both the diagnosis and treatment of ARONJ in the future.

Performance and Hypothetical Impact on Joint Infection Management of the BioFire Joint Infection Panel: a Retrospective Analysis.

Pathogen identification is key in septic arthritis. Culture-based techniques are challenging, especially when patients have been pretreated with antibiotics or when difficult-to-culture bacteria are encountered. The BioFire joint infection assay (BJA) is a multiplex PCR panel which detects 31 of the most prevalent bacterial and fungal pathogens causing septic arthritis. Here, 123 cryoconserved contemporary synovial fluid samples from 120 patients underwent BJA analysis. Results were compared to those of culture-based diagnostics (standard of care [SOC]). Clinical data were collected, and the possible impact of the molecular diagnostic application on patient management was evaluated. Fifteen of 123 synovial fluid cultures grew bacterial pathogens. All on-panel pathogens (9/15) were correctly identified by the BJA. The BJA identified four additional bacterial pathogens in four SOC-negative cases. BJA sensitivity and specificity were 100% (95% confidence interval [CI], 69.2% to 100%) and 100% (95% CI, 96.8% to 100%), respectively. Compared to the SOC, the BJA would have resulted in faster provision of species identification and molecular susceptibility data by 49 h and 99 h, respectively. Clinical data analysis indicates that in BJA-positive cases, faster species ID could have led to timelier optimization of antibiotic therapy. This retrospective study demonstrates high sensitivity and specificity of the BJA to detect on-panel organisms in bacterial arthritis. The usefulness of the BJA in prosthetic-joint infections is limited, as important pathogens (i.e., coagulase negative staphylococci and Cutibacterium acnes) are not covered. Evidence from patient data analysis suggests that the assay might prove valuable for optimizing patient management in acute arthritis related to fastidious organisms or for patients who received antibiotics prior to specimen collection.

Do Clinical Parameters Reflect Local Bone Metabolism in Heterotopic Ossification After Septic or Aseptic THA?

BACKGROUND: Heterotopic ossification (HO) is a common complication after THA. Although current research primarily focuses on treatment and prevention, little is known about the local bone metabolism of HO and clinical contributing factors. QUESTIONS/PURPOSES: We aimed to assess bone remodeling processes in HO using histomorphometry, focusing on the effects of inflammation and prior NSAID treatment. Specifically, we asked: (1) Are HO specimens taken from patients with periprosthetic joint infection (PJI) more likely to exhibit active bone modeling and remodeling than specimens taken at the time of revision from patients without infection? (2) Do clinical or inflammatory serum and synovial parameters reflect the microstructure of and remodeling in both HO entities? (3) Is NSAID treatment before revision surgery associated with altered local bone mineralization or remodeling properties? METHODS: Between June 2021 and May 2022, we screened 395 patients undergoing revision THA at two tertiary centers in Germany. Of those, we considered all patients with radiographic HO as potentially eligible. Based on that, 21% (83 of 395) were eligible; a further 43 were excluded because of an inability to remove the implant intraoperatively (16 patients), insufficient material (11), comorbidities with a major effect on bone metabolism (10), or bone-specific drugs (six), leaving 10% (40) for analysis in this retrospective, comparative study. HO specimens were collected during aseptic (25 patients: 18 male, seven female, mean age 70 ± 11 years, mean BMI 29 ± 4 kg/m 2 ) and septic (15 patients: 11 male, four female, mean age 69 ± 9 years, mean BMI 32 ± 9 kg/m 2 ) revision THA at a mean of 6 ± 7 years after primary implantation and a mean age of 70 ± 9 years at revision. Septic origin (PJI) was diagnosed based on the 2018 International Consensus Meeting criteria, through a preoperative assessment of serum and synovial parameters. To specify the local bone microstructure, ossification, and cellular bone turnover, we analyzed HO specimens using micro-CT and histomorphometry on undecalcified sections. Data were compared with those of controls, taken from femoral neck trabecular bone (10 patients: five female, five male, mean age 75 ± 6 years, mean BMI 28 ± 4 kg/m 2 ) and osteophytes (10 patients: five female, five male, mean age 70 ± 10 years, mean BMI 29 ± 7 kg/m 2 ). The time between primary implantation and revision (time in situ), HO severity based on the Brooker classification, and serum and synovial markers were correlated with HO microstructure and parameters of cellular bone turnover. In a subgroup of specimens of patients with NSAID treatment before revision, osteoid and bone turnover indices were evaluated and compared a matched cohort of specimens from patients without prior NSAID treatment. RESULTS: Patients with aseptic and septic HO presented with a higher bone volume (BV/TV; aseptic: 0.41 ± 0.15, mean difference 0.20 [95% CI 0.07 to 0.32]; septic: 0.43 ± 0.15, mean difference 0.22 [95% CI 0.08 to 0.36]; femoral neck: 0.21 ± 0.04; both p < 0.001), lower bone mineral density (aseptic: 809 ± 66 mg HA/cm 3 , mean difference -91 mg HA/cm 3 [95% CI -144 to -38]; septic: 789 ± 44 mg HA/cm 3 , mean difference -111 mg HA/cm 3 [95% CI -169 to -53]; femoral neck: 899 ± 20 mg HA/cm 3 ; both p < 0.001), and ongoing bone modeling with endochondral ossification and a higher proportion of woven, immature bone (aseptic: 25% ± 17%, mean difference 25% [95% CI 9% to 41%]; septic: 37% ± 23%, mean difference 36% [95% CI 19% to 54%]; femoral neck: 0.4% ± 0.5%; both p < 0.001) compared with femoral neck specimens. Moreover, bone surfaces were characterized by increased osteoblast and osteoclast indices in both aseptic and septic HO, although a higher density of osteocytes was detected exclusively in septic HO (aseptic: 158 ± 56 1/mm 2 versus septic: 272 ± 48 1/mm 2 , mean difference 114 1/mm 2 [95% CI 65 to 162]; p < 0.001). Compared with osteophytes, microstructure and turnover indices were largely similar in HO. The Brooker class was not associated with any local bone metabolism parameters. The time in situ was negatively associated with bone turnover in aseptic HO specimens (osteoblast surface per bone surface: r = -0.46; p = 0.01; osteoclast surface per bone surface: r = -0.56; p = 0.003). Serum or synovial inflammatory markers were not correlated with local bone turnover in septic HO. Specimens of patients with NSAID treatment before revision surgery had a higher osteoid thickness (10.1 ± 2.1 µm versus 5.5 ± 2.6 µm, mean difference -4.7 µm [95% CI -7.4 to -2.0]; p = 0.001), but there was no difference in other osteoid, structural, or cellular parameters. CONCLUSION: Aseptic and septic HO share phenotypic characteristics in terms of the sustained increase in bone metabolism, although differences in osteocyte and adipocyte numbers suggest distinct homeostatic mechanisms. These results suggest persistent bone modeling or remodeling, with osteoblast and osteoclast indices showing a moderate decline with the time in situ in aseptic HO. Future studies should use longitudinal study designs to correlate our findings with clinical outcomes (such as HO growth or recurrence). In addition, the molecular mechanisms of bone cell involvement during HO formation and growth should be further investigated, which may allow specific therapeutic and preventive interventions. CLINICAL RELEVANCE: To our knowledge, our study is the first to systematically investigate histomorphometric bone metabolism parameters in patients with HO after THA, providing a clinical reference for evaluating modeling and remodeling activity. Routine clinical, serum, and synovial markers are not useful for inferring local bone metabolism.