Non-steroidal anti-inflammatory drugs are commonly used to reduce pain and inflammation in orthopaedic patients. Selective cyclooxygenase-2 (COX-2) inhibitors have been developed to minimize drug-specific side effects. However, they are suspected to impair both bone and tendon healing. The objective of this study is to evaluate the effect of COX-2 inhibitor administration on tendon-to-bone healing and prostaglandin E (PGE2) concentration. Thirty-two New Zealand white rabbits underwent reconstructions of the anterior cruciate ligaments and were randomized into four groups: Two groups postoperatively received a selective COX-2 inhibitor (Celecoxib) on a daily basis for 3 weeks, the two other groups received no postoperative COX-2 inhibitors at all and were examined after three or 6 weeks. The PGE2 concentration of the synovial fluid, the osseous integration of the tendon graft at tunnel aperture and midtunnel section, as well as the stability of the tendon graft were examined via biomechanic testing. After 3 weeks, the PGE2 content of the synovial fluid in the COX-2 inhibitor recipients was significantly lower than that of the control group (p = 0.018). At the same time, the COX-2 inhibitor recipients had a significantly lower bone density and lower amount of new bone formation than the control group (p = 0.020; p = 0.028) in the tunnel aperture. At the 6-week examination, there was a significant increase in the PGE2 content within synovial fluid of the COX-2 inhibitor recipients (p = 0.022), whose treatment with COX-2 inhibitors had ended 3 weeks earlier; in contrast, the transplant stability decreased and was reduced by 37% compared to the controls. Selective COX-2 inhibitors cause impaired tendon-to-bone healing, weaken mechanical stability and decrease PGE2 content of the synovial fluid. The present study suggests a reluctant use of COX-2 inhibitors when tendon-to-bone healing is intended.

Background: Minimally invasive sacroiliac-screw (SI-screw) fixation of the pelvis is used in energy trauma (Arbeitsgemeinschaft für Osteosynthesefragen (AO) classified) and fragility fractures (Fragility Fracture of the Pelvis (FFP) classified). However, available clinical data are based on small case series and biomechanical data seem to be contradictory. Methods: The present single center retrospective cohort study investigated percutaneous SI-screw fixation and augmentation over 15 years. Groups were compared concerning the general epidemiological data, mobilization, complication rates, duration of stay, and safety of SI-screw insertion. Multivariable analyses were performed using logistic regression. Results: Between 2005 and March 2020, 448 patients with 642 inserted SI-screws were identified. Iatrogenic neurological impairment was documented in 2.47% and correlated with screw misplacement. There was an increased complication risk in patients with AO type C over patients with AO type B and in FFP II over FFP III/IV patients. Cement-augmented FFP patients showed a 25% reduced stay in hospital and a reduced complication risk. Cement-associated complications were seen in 22% without correlation to neurologic impairment. Conclusions: The present study confirms the safety and usability of percutaneous SI-screw fixation, despite specific risks. Cement augmentation seems to reduce the complication risk in FFP patients and shorten hospital stay for some reasons, without increased specific complications or correlated neurological impairment.

Background: Delayed fracture healing continues to cause significant patient morbidity and an economic burden to society. Biological stimulation of non-unions includes application of recombinant bone morphogenetic protein-2 (rhBMP-2). However, rhBMP-2 use continues to be a matter of controversy as literature shows scarce evidence for treatment effectiveness. Questions: The objective of this study was to evaluate the effectiveness of rhBMP-2 treatment on long bone non-unions measuring union rate and time to union. Furthermore, we assess risk factors for treatment failure. Methods and patients: A total of 91 patients with non-unions of long bones were treated with rhBMP-2 (n = 72) or standard care without BMP (n = 19) at our institution. Patient characteristics, comorbidities, nicotine consumption, and complications were recorded. Bone healing was assessed by plane X-rays and clinical examination. Patients were followed up with for 24 months. Results: Overall, there was significantly faster bone healing after rhBMP-2 application compared to the no-BMP group (p < 0.001; HR = 2.78; 95% CI 1.4–5.6). Union rates differed significantly between rhBMP-2 compared to the no-BMP group (89% vs. 47%; p < 0.001). At the humerus, there was neither a significantly higher union rate in the rhBMP-2 (83%) compared to the no-BMP group (50%) (p = 0.26; n = 12) nor a faster bone healing with a median time of 9 months in both groups (HR = 2.01; 95% CI 0.49–8.61; p = 0.315). The 33 femora treated using rhBMP-2 healed significantly faster than 9 femora in the no-BMP group (HR = 2.93; 95% CI 1.00–8.4; p = 0.023) with significant differences in union rate with 85% and 44%, respectively (p = 0.022). Regarding tibia non-unions, 25 out of 27 (93%) healed with a median of 9 months after rhBMP-2 application with no significant difference in the no-BMP group (33%) in time to union (p = 0.097) but a significantly higher union rate (p = 0.039). There was no effect of comorbidities, age, sex, soft tissue damage, or nicotine use on time to union, union rate, or secondary interventions. Conclusion: Consistent with the literature, overall, significantly higher union rates with reduced time to union were achieved after rhBMP-2 application. Femoral and tibial non-unions in particular seem to profit from rhBMP-2 application.

Background: Currently, there seems to be a paradigm change in the surgical treatment of proximal humeral fractures in patients aged 65 years and older, with a considerable increase in the use of reverse total shoulder arthroplasty (RTSA) compared with angular stable internal fixation (locking plate fixation). However, even among shoulder specialists there is controversy regarding the best treatment strategy. Questions/purposes: To evaluate for (1) a greater risk of in-hospital major adverse events, (2) a greater risk for in-hospital surgical complications, and (3) a greater risk of 30-day mortality, locking plate fixation and RTSA were compared for the treatment of proximal humerus fractures of patients aged 65 years and older after controlling for potentially confounding variables in a large-database analysis. Methods: Health claims data of the largest German insurance company including approximately one-third of the population (26.5 million policyholders) between 2010 and 2018 were analyzed. This database was chosen because of its size, nationwide distribution, and high quality/completeness. In total, 55,070 patients (≥ 65 years of age) treated with locking plate fixation (75% [41,216]) or RTSA (25% [13,854]) for proximal humeral fracture were compared. As primary endpoints, major adverse events (including acute myocardial infarction, stroke, organ failure, resuscitation, and death) and surgical complications (infection, hematoma, loss of reduction, dislocation, and revision surgery) were analyzed. The risk of all endpoints was analyzed with multivariable logistic regression models in the context of comorbidities to address existing group differences. Results: After controlling for potentially confounding variables such as age, sex, and risk profile, RTSA was associated with a higher risk for major adverse events (OR 1.40 [95% CI 1.29 to 1.53]; p < 0.001) and surgical complications (OR 1.13 [95% CI 1.05 to 1.21]; p < 0.01) compared with locking plate fixation. There was no evidence for an increase in mortality (OR 0.98 [95% CI 0.86 to 1.12]; p = 0.81). Conclusion: The increased in-hospital risk for major adverse events and surgical complications may moderate the enthusiasm associated with RTSA for proximal humeral fractures in patients 65 years and older. Treatment decisions should be based on individual risk estimation to avoid potential harmful events. Future studies must include long-term outcomes and quality of life to enlighten these findings in a broader context. Level of Evidence: Level III, therapeutic study.

The goal of this study is to compare mortality, major adverse events, and complication rates after the surgical treatment of proximal humeral fractures with locked plate fixation (LPF) versus reverse total shoulder arthroplasty (RTSA) in elderly patients. Health insurance data from patients aged 65 and above for the period January 2010 to September 2018 were retrospectively evaluated. The median follow-up duration after LPF (40 419 patients) or RTSA (13 552 patients) was 52 months. Hazard ratios adapted to the patients’ risk profiles were determined with the aid of multivariable Cox regression models. The p-values were adjusted using the Bonferroni–Holm method. After adaptation to the patients’ risk profiles, reverse shoulder replacement showed statistically significantly lower mortality (HR 0.92, 95% confidence interval [0.88; 0.95]; p <0.001) and fewer major adverse events (HR 0.92 [0.89; 0.95]; p<0.001). Eight years after surgery, the risk of surgical complications was twice as high for LPF (12.2% [11.9; 12.7]; HR for RTSA versus LPF 0.5 [0.46; 0.55]; p<0.001 for both), with 3.8% [3.6; 4.0] of the patients receiving a secondary RTSA. Surgical complications were more common (p<0.05) in patients with a diagnosis of osteoporosis, obesity, alcohol abuse, chronic polyarthritis, or frozen shoulder. The long-term findings are in agreement with clinical short-term findings from other studies and support the current trend toward more liberal use of reverse shoulder replacements in elderly patients.

Osteoarthritis (OA) is characterized by cartilage degradation that is induced by inflammation. Sterile inflammation can be caused by damage-associated molecular patterns that are released by chondrocytes and activate pattern recognition receptors. We evaluate the role of toll-like receptor-3-activating RNA in the pathogenesis of OA. Toll-like receptor 3 (TLR3) was detected by semiquantitative reverse transcriptase PCR, western blotting and microscopy. Rhodamine-labelled poly(I:C) was used to image uptake in chondrocytes and full-thickness cartilage. The production of IFNβ in chondrocytes after stimulation with poly(I:C) as well as in the synovial fluid of OA patients was measured using ELISA. Chondrocyte apoptosis was chemically induced using staurosporine. Immunohistochemistry was performed to examine TLR3 expression and apoptosis in human and murine OA cartilage. RNA in synovial fluid was quantified by RiboGreen assay. Destabilisation of the medial meniscus was performed in TLR3^−/− and wildtype mice. OA was assessed after eight weeks using OARSI score. TLR3 expression was confirmed by western blot and RT-PCR. Poly(I:C) was internalised by chondrocytes as well as cartilage and caused an increase of IFNβ production in murine (11.46 ± 11.63 (wo) to 108.7 ± 25.53 pg/ml; N = 6) and human chondrocytes (1.88 ± 0.32 (wo) to 737.6 ± 130.5 pg/ml; N = 3; p < 0.001). OA cartilage showed significantly more TLR3-positive (KL0 = 0.22 ± 0.24; KL4 = 6.02 ± 6.75; N ≥ 15) and apoptotic chondrocytes (KL0 = 0.6 ± 1.02; KL4 = 9.78 ± 7.79; N ≥ 12) than healthy cartilage (p < 0.001). Staurosporine-induced chondrocyte apoptosis causes a dose-dependent RNA release (0 ng/ml = 1090 ± 39.1 ng/ml; 1000 ng/ml=2014 ± 160 ng/ml; N = 4; p < 0.001). Human OA synovial fluid contained increased concentrations of RNA (KL0-2 = 3408 ± 1129 ng/ml; KL4 = 4870 ± 1612ng/ml; N ≥ 7; p < 0.05) and IFNβ (KL0-2 = 41.95 ± 92.94 ng/ml; KL3 = 1181 ± 1865ng/ml; N ≥ 8; p < 0.05). TLR3^−/− mice showed reduced cartilage degradation eight weeks after OA induction (OARSI WT = 5.5 ± 0.04; TLR3^−/− = 3.75 ± 1.04; N ≥ 6) which was accompanied by gradually decreasing levels of TUNEL-positive cells (WT = 34.87 ± 24.10; TLR3^−/ = 19.64 ± 7.89) resulting in decreased IFNβ expression (WT = 12.57 ± 5.43; TLR3^−/− = 6.09 ± 2.07) in cartilage (p < 0.05). The release of RNA by apoptotic chondrocytes thus activating TLR3 signalling is one possible way of perpetuating inflammatory cartilage changes. The inhibition of TLR3 could be a possible therapeutic target for OA treatment.