Osteonecrosis of the jaw (ONJ) is a rare but serious adverse event associated with antiresorptive treatment. There is little evidence regarding the incidence of ONJ among patients with osteoporosis who are treated with denosumab versus bisphosphonates (BPs). The aim of this study was to determine the risk of ONJ in a real-world population. Subjects who underwent at least one dual-energy X-ray absorptiometry (DXA) examination were included in the osteoporosis register of the Swiss Society of Rheumatology between January 1, 2015, and September 30, 2019. Statistical analyses included incidence rates, rate ratios, and hazard ratios for ONJ, considering sequential therapies and drug holidays as covariates. Among 9956 registered patients, 3068 (89% female, median age 69 years [63 to 76]) were treated with BPs or denosumab for a cumulative duration of 11,101 and 4236 patient-years, respectively. Seventeen cases of ONJ were identified: 12 in patients receiving denosumab at the time of ONJ diagnosis and 5 in patients receiving oral or intravenous BP therapy. The diagnosis of ONJ was confirmed by independent and blinded maxillofacial surgeons, using the American Association of Oral and Maxillofacial Surgeons case definition of ONJ. The incidence of ONJ per 10,000 observed patient-years was 28.3 in patients receiving denosumab and 4.5 in patients with BP-associated ONJ, yielding a rate ratio of 6.3 (95% confidence interval [CI] 2.1 to 22.8), p < 0.001. Nine of 12 patients who developed ONJ during denosumab treatment had been pretreated with BPs, but none of the 5 patients with BP-related ONJ had previously received denosumab. The risk of ONJ was higher in patients receiving denosumab therapy compared with BPs (hazard ratio 3.49, 95% CI 1.16 to 10.47, p = 0.026). Previous BP therapy before switching to denosumab may be an additional risk factor for ONJ development. © 2021 American Society for Bone and Mineral Research (ASBMR).

Background: Aim of this study was to evaluate the outcomes of endocarditis patients undergoing valve surgery with the Cytosorb^® hemoadsorption (HA) device during cardiopulmonary bypass. Methods: From 2009 until 2019, 241 patients had undergone valve surgery due to endocarditis at the Department of Cardiac Surgery, University Hospital of Basel. We compared patients who received HA during surgery (n = 41) versus patients without HA (n = 200), after applying inverse probability of treatment weighting. Results: In-hospital mortality, major adverse cardiac and cerebrovascular events and postoperative renal failure were similar in both groups. Demand for norepinephrine (88.4 vs. 52.8%; p = 0.001), milrinone (42.2 vs. 17.2%; p = 0.046), red blood cell concentrates (65.2 vs. 30.6%; p = 0.003), and platelets (HA vs. Control: 36.7 vs. 9.8%; p = 0.013) were higher in the HA group. In addition, a higher incidence of reoperation for bleeding (34.0 vs. 7.7 %; p = 0.011), and a prolonged length of in-hospital stay (15.2 (11.8 to 19.6) vs. 9.0 (7.1 to 11.3) days; p = 0.017) were observed in the HA group. Conclusions: No benefits of HA-therapy were observed in patients with infective endocarditis undergoing valve surgery.

Cartilage lesions do not heal spontaneously and predispose to osteoarthritis. Functional cartilage tissues, engineered using autologous chondrocytes, have a therapeutic advantage over conventional cellular therapies in preclinical studies. Here, we tested whether ex vivo maturation of engineered grafts for cartilage repair leads to improved patient benefit. Using autologous nasal chondrocytes (NCs), we tested whether implantation of in vitro–matured NC-tissue-engineered cartilage (N-TEC) versus undifferentiated NC-cell-activated matrices (N-CAM) in focal cartilage lesions would result in a superior clinical outcome. The prospective, randomized, parallel, open-label phase-2 trial ( ClinicalTrials.gov , NCT02673905) enrolled 108 patients in five hospitals from four countries. Patients ranging in age from 30 to 46 years with full-thickness knee cartilage defects (size, 2.7 to 6.0 square centimeters) were equally randomized and treated with N-TEC or N-CAM. The primary preregistered outcome was the overall Knee Injury Osteoarthritis Outcome Score (KOOS) at 24 months. N-TEC, which underwent a longer NC culture time, was phenotypically, structurally, and functionally more like hyaline cartilage than N-CAM. The overall KOOS increased with clinical relevance in both groups compared with preoperative values. KOOS was higher at 24 months for N-TEC [85; interquartile range (IQR), 74 to 91] than for N-CAM (79; IQR, 65 to 85). N-TEC, but not N-CAM, was similarly effective in patients with larger defects or revision surgery. Radiologically, N-TEC resulted in a superior composition of both repair tissue and surrounding cartilage, whereas structural scores were similar. This trial validates the clinical efficacy of NC-based grafts for articular cartilage repair and supports the clinical relevance of engineering mature tissues, even for patients with more challenging cartilage defects.

Summary This registry-based study of 3068 patients with osteoporosis compared the anti-fracture effectiveness of denosumab versus bisphosphonates. Denosumab was associated with significantly greater risk reduction than alendronate or ibandronate for vertebral and any fractures. No difference in fracture risk reduction was found between zoledronate and denosumab. Purpose To analyse the fracture risk of patients with osteoporosis receiving bisphosphonates or denosumab in a real-world setting. Methods This registry-based cohort study evaluated patients taking denosumab, bisphosphonates or both sequentially. Fractures were analysed using rates, rate ratios and hazard ratios (HR), including both therapies as time-varying co-variates. Fracture risk hazards were adjusted (aHR) for baseline T-Scores and trabecular bone score (TBS) and were additionally analysed with inverse probability treatment weighting. Results A total of 3068 patients (89% female; median age at treatment onset, 69 years [63 to 76]) received denosumab (median duration 2.8 years, [2.2 to 4.7]), bisphosphonates (3.4 years, [2.1 to 5.7]) or both sequentially. Thus, 11,078 subject-years were assessed for bisphosphonates (41% alendronate, 36% ibandronate, 23% zoledronate) and 4216 for denosumab. Moreover, 48,375 subject-years were observed before treatment onset, in addition to 2593 years of drug holidays. A total of 1481 vertebral fractures (435 under therapy), 1508 non-vertebral fractures (499 under therapy) and 202 hip fractures (67 under therapy) occurred after age 50. The risks of vertebral, non-vertebral and hip fractures were significantly lower under all bisphosphonates, denosumab and drug holidays than before treatment onset (all p < 0.001). After adjusting for age, baseline T-scores and TBS, denosumab was associated with lower risk than alendronate or ibandronate for vertebral fractures (aHR 0.47 (0.35 to 0.64) and 0.70 [0.53 to 0.91], p < 0.001 and p = 0.009, respectively) and any fractures (aHR 0.62 [0.51 to 0.76] and 0.77 [0.64 to 0.92], p < 0.001 and p = 0.004). With propensity weighting, denosumab was associated with a lower hip fracture risk compared to alendronate (HR 0.54 [0.29 to 0.98], p = 0.044). No difference in fracture risk reduction (vertebral, non-vertebral or hip) was found between zoledronate and denosumab. Conclusions When adjusting for disease severity, denosumab was associated with significantly greater risk reduction than alendronate and ibandronate for vertebral fractures. No difference in fracture risk reduction was found between zoledronate and denosumab.