Association between CDK4/6 inhibitors and drug-related osteonecrosis of the jaw: A pharmacoepidemiological study using the FDA Adverse Events Reporting System.

The most common toxicities associated with cyclin-dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication-related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of "Osteonecrosis of jaw" were detected only in females using palbociclib (cROR025: 2.08). Other signals detected included stomatitis-related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib-induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0025: 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug-related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors.

Natural course of talar avascular necrosis during short-term follow-up and factors associated with Disease progression.

BACKGROUND: This retrospective cohort study aimed to investigate the natural history of talar avascular necrosis (AVN) during short-term outpatient follow-up and to identify the risk factors for progression to collapse and arthritic changes. METHODS: Thirty-four cases of talar AVN from 34 patients (15 males, 19 females) were included. The mean age of the patients was 48.9 years (SD 16.0 years) and the mean follow-up period was 39.5 months (SD 42.0 months). The patients were divided into two groups i.e., progression and non-progression groups. The progression group consisted of those who showed aggravation of the Ficat stage during the follow-up period or advanced arthritis of the ankle joint (Ficat stage 4) at presentation. Demographic data and information regarding BMI, medical comorbidities, trauma history, bilaterality, and location of the lesion (shoulder vs. non-shoulder lesions) were collected. Following the univariate analysis, a binary logistic regression analysis was performed. RESULTS: The location of the talar AVN was the only significant factor (p = 0.047) associated with disease progression. A total of 14.3% (2 of 14) of the central (non-shoulder) talar AVN lesions showed progression, while 50% (10 of 20) of shoulder lesions aggravated during follow-up. Age, sex, bilaterality, medical comorbidities, and trauma history were not associated with progressive talar collapse or subsequent arthritic changes in talar AVN. CONCLUSIONS: Conservative treatment should be considered for a central lesion of the talar AVN because it tends to remain stable without progression. A more comprehensive study with a larger study population is required to establish the surgical indications for talar AVN. LEVEL OF EVIDENCE: Prognostic level III.

Frequency of osteonecrosis in bisphosphonate users submitted to dental procedures: A systematic review.

OBJECTIVE: To determine the frequency of osteonecrosis of the jaw in bisphosphonate users submitted to dental procedures. METHODS: This systematic review searched the sources: MEDLINE, EMBASE, Web of Science, Scopus, and Virtual Health Library, with no restriction on language or publication date. Reviewers, in pairs and independently, selected the studies, extracted their data, and assessed the risk of bias. Meta-analyses were pooled using the DerSimonian and Laird random effects model. RESULTS: A total of 27 studies (5391 participants) were included. The most reported bisphosphonates were zoledronate (n = 17 studies) and alendronate (n = 19) for treating cancers (n = 11) and osteoporosis (n = 16), respectively. Twelve studies were of low methodological quality. The frequency of osteonecrosis was 2.7% (95% CI: 0.9-5.2%) and proved higher for intravenous [6.9% (0.7-17.3%)] than oral [0.2% (0.9-5.2%)] bisphosphonate use. No association between longer treatment duration and greater frequency of osteonecrosis was observed. CONCLUSIONS: Higher frequency of osteonecrosis was observed in intravenous bisphosphonate users submitted to dental extraction. Further studies collecting more detailed information on the bisphosphonates used and of greater methodological rigor are warranted to confirm these findings and better inform prescribers, dental surgeons, and other professionals on risks of bisphosphonate use in this patient group.

Surgical Trends for Managing Knee Osteonecrosis: A 2010 to 2020 United States Nationwide Study.

BACKGROUND: Knee osteonecrosis (ON) is rare, with an estimated incidence of 0.01-0.17 per 1,000 person years. Our study aimed to do the following: 1) quantify total operative procedures with rates normalized to the United States population; 2) compare arthroplasty versus joint-preserving procedural trends; and 3) determine rates of specific operative techniques/demographics in patients aged <50 versus >50 years. METHODS: Using a nationwide database, 8,269 patients diagnosed with knee ON underwent surgical treatment from 2010 to 2020. Documented surgical procedures included total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA), and core decompression. Primary outcomes included procedural utilization with subanalyses comparing arthroplasty versus joint-preserving procedures, and age-stratified by under/over 50 years. Linear regressions were evaluated for trends in procedural volumes over time. RESULTS: From 2010 to 2014, 0.54% of all knee procedures were to treat ON compared to 0.71% from 2015 to 2020 (P < .001). Overall rates of TKA (85.4%) and UKA (10.3%) far exceeded rates of joint preserving procedures (4.3%). Comparing 2010-2014 with 2015-2019, joint-preserving procedures proportionally increased (0.7 to 5.0%, P < .001). Patients <50 years had significantly more joint-preserving procedures (19.5 versus 2.7%). Overall, TKA was the most common procedure (7,062; 85.40%), following by UKA 853; 10.32%) and core decompression (354; 4.28%). CONCLUSION: To our knowledge, this is the first study to characterize surgical trends in management of knee ON. Overall surgical volume for knee ON has continued to increase, outpacing population growth. Patients who have knee ON are most commonly managed with arthroplasty procedures, specifically TKA. Younger aged patients (<50 years) are more likely to undergo joint-preserving procedures, namely core decompression.

Increased Risk of In-Hospital Complications and Costs After Total Hip Arthroplasty for Primary and Secondary Osteonecrosis.

BACKGROUND: An increasing proportion of patients are undergoing total hip arthroplasty (THA) for osteonecrosis (ON). Comorbid conditions and surgical risk factors are known to be greater in ON patients compared with patients who have osteoarthritis (OA) alone. The purpose of our study was to quantify the specific in-hospital complications and resource utilization associated with patients undergoing THA for ON versus OA. METHODS: A large national database was queried to identify patients undergoing primary THA from January 1, 2016 to December 31, 2019. A total of 1,383,880 OA, 21,080 primary ON, and 54,335 secondary ON patients were identified. Demographics, in-hospital complications, costs, lengths of stay, and discharge dispositions for primary and secondary ON cohorts were compared to OA only. Age, race, ethnicity, comorbidities, Medicaid, and income status were controlled with binary logistic regression analyses. RESULTS: The ON patients were often younger, African American or Hispanic, and had more comorbidities. Those undergoing THA for primary and secondary ON had a significantly higher risk of perioperative complications, including myocardial infarction, postoperative blood transfusion, and intraoperative bleeding. Total hospital costs and lengths of stay were significantly higher for both primary ON and secondary ON and both cohorts were less likely to be discharged home. CONCLUSION: While rates of most complications have decreased over recent decades in ON patients undergoing THA, the ON patients still have worse outcomes even when controlling for comorbidity differences. Bundled payment systems and perioperative management strategies for these different patient cohorts should be considered separately.

Did the COVID-19 Pandemic Coincide With an Increase in Osteonecrosis as Indication for Total Hip Arthroplasty in Older Patients?

BACKGROUND: Osteonecrosis of the femoral head is a common indication for total hip arthroplasty (THA). It is unclear to what extent the COVID-19 pandemic has impacted its incidence. Theoretically, the combination of microvascular thromboses and corticosteroid use in patients who have COVID-19 may increase the risk of osteonecrosis. We aimed to (1) assess recent osteonecrosis trends and (2) investigate if a history of COVID-19 diagnosis is associated with osteonecrosis. METHODS: This retrospective cohort study utilized a large national database between 2016 and 2021. Osteonecrosis incidence in 2016 to 2019 was compared to 2020 to 2021. Secondly, utilizing a cohort from April 2020 through December 2021, we investigated whether a prior COVID-19 diagnosis was associated with osteonecrosis. For both comparisons, Chi-square tests were applied. RESULTS: Among 1,127,796 THAs performed between 2016 and 2021, we found an osteonecrosis incidence of 1.6% (n = 5,812) in 2020 to 2021 compared to 1.4% (n = 10,974) in 2016 to 2019; P < .0001. Furthermore, using April 2020 to December 2021 data from 248,183 THAs, we found that osteonecrosis was more common among those who had a history of COVID-19 (3.9%; 130 of 3,313) compared to patients who had no COVID-19 history (3.0%; 7,266 of 244,870); P = .001). CONCLUSION: Osteonecrosis incidence was higher in 2020 to 2021 compared to previous years and a previous COVID-19 diagnosis was associated with a greater likelihood of osteonecrosis. These findings suggest a role of the COVID-19 pandemic on an increased osteonecrosis incidence. Continued monitoring is necessary to fully understand the impact of the COVID-19 pandemic on THA care and outcomes.

Symptomatic osteonecrosis in French survivors of childhood and adolescent leukemia: a clinical and MRI study of LEA cohort.

Osteonecrosis (ON) is a known complication of acute leukemia (AL) management, affecting 1%-10% of young patients and resulting in long-term morbidity. Widespread access to MRI over the past decade has allowed earlier detection and more accurate assessment. This study investigated clinical and MRI features of the 129 (2.5%) patients with symptomatic ON retrospectively recruited from the French LEA (Leucémies de l'Enfant et de l'Adolescent, or child and adolescent leukemias) cohort (n = 4,973). We analyzed data concerning ON risk factors, multifocal involvement, severe lesions detected by MRI, and patient quality of life (QoL). ON patients tended to be >10 years old at the time of AL diagnosis (odds ratio [OR]: 22.46; p < 10-6), female (OR: 1.8; p = 0.002), or treated for relapse (OR: 1.81; p = 0.041). They more frequently suffered from other sequelae (p < 10-6). Most necroses involved weight-bearing joints, and they were multifocal in 69% of cases. Double-blinded review of MRIs for 39 patients identified severe lesions in 14, usually in the hips. QoL of adolescents and adults was poor and permanently impacted after onset of ON. In conclusion, age >10 at time of AL diagnosis, female sex, and relapse occurrence were risk factors for multifocal ON; MRI revealed severe ON in a third of the patients considered; and ON was associated with persistently poor QoL affecting multiple domains. Future studies should include prospective data addressing ON management and seek to identify genetic markers for targeted screening enabling early ON detection and treatment.

Osteonecrosis in paediatric acute lymphoblastic leukaemia: Incidence, risk factors, radiological patterns and evolution in a single-centre cohort.

Osteonecrosis (ON) is a well-known sequela of paediatric acute lymphoblastic leukaemia (ALL) treatment. Incidence differs substantially among studies and the clinical significance of radiological findings is not fully established. We analysed 256 consecutive patients with ALL treated in our Institution between October 2010 and December 2016. Within the cohort, 41 developed ON, with a mean 5-year cumulative incidence of 18.5 (standard error, SE, 5.7)% overall. The mean (SE) 5-year cumulative incidence of ON was 12.7 (2.1)% after censoring upon stem cell transplantation (SCT) and/or relapse. Patients aged ≥10 years and patients allocated to the high-risk stratum had a 10-fold and fivefold higher risk of ON respectively. The risk of ON was more than double in relapsed patients, whereas no significant impact of gender, immunophenotype and SCT was demonstrated. Multiple lesions (median four joints involved per patient) were detected by magnetic resonance imaging in all but one patient, with the knee being the most affected joint. Lesions affecting convex joint surfaces experienced the worst evolution, whereas most lesions on diaphyses and concave surfaces remained radiologically stable or disappeared during follow-up. ON has a high prevalence in paediatric ALL, presenting with multiple lesions. Lesions involving convex surfaces were at higher risk of radiological deterioration.

Post-COVID-19 related osteonecrosis of the jaw (PC-RONJ): an alarming morbidity in COVID-19 surviving patients.

PURPOSE: The recent coronavirus disease (COVID-19) pandemic mainly affects the respiratory system; however, several oral and maxillofacial post-COVID-19 complications have also been observed. This series reports the growing number of osteonecrosis cases associated with post-COVID-19 patients. MATERIALS AND METHODS: This is a retrospective, multi-center case series that reports cases with maxillary osteonecrosis after various periods of SARS-CoV-2 infection in the period between January and August 2021 based on the PROCESS guidelines. RESULTS: Twelve cases were reported with post-COVID-19 manifestation of spontaneous osteonecrosis of the maxillary jaw. Five patients were hospitalized during COVID-19 management and all of the twelve cases had at least one systematic Co-morbidity, and undertake corticosteroids prescription based on the COVID-19 disease treatment protocol. The mean onset of osteonecrosis symptoms appearance was 5.5 ± 2.43 weeks calculated from the day of the negative PCR test. The management was successfully done through surgical debridement and pre and post-operative antibiotics. No anti-fungal medications were prescribed as the fungal culture and the histopathological report were negative. CONCLUSION: Post-COVID-related osteonecrosis of the jaw (PC-RONJ) could be now considered as one of the potential post-COVID-19 oral and maxillofacial complications that occurs unprovokedly and mainly in the maxilla.

Prevalence of and Associations With Avascular Necrosis After Pediatric Sepsis: A Single-Center Retrospective Study.

OBJECTIVES: Avascular necrosis (AVN) is a rare, but serious, complication after sepsis in adults. We sought to determine if sepsis is associated with postillness diagnosis of AVN, as well as potential-associated risk factors for AVN in children with sepsis. DESIGN: Retrospective observational study. SETTING: Single academic children's hospital. PATIENTS: Patients less than 18 years treated for sepsis or suspected bacterial infection from 2011 to 2017. Patients who developed AVN within 3 years after sepsis were compared with patients who developed AVN after suspected bacterial infection and with patients with sepsis who did not develop AVN. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: AVN was determined using International Classification of Diseases, 9th Edition/10th Edition codes and confirmed by chart review. The prevalence of AVN after sepsis was 0.73% (21/2,883) and after suspected bacterial infection was 0.43% (53/12,276; risk difference, 0.30; 95% CI, 0.0-0.63; p = 0.05). Compared with 43 sepsis controls without AVN, AVN in the 21 sepsis cases was associated with being older, having sickle cell disease and malignancy, higher body mass index, unknown source of infection, and low platelet count in the first 7 days of sepsis. Half of sepsis patients were treated with corticosteroids, and higher median cumulative dose of steroids was associated with AVN (23.2 vs 5.4 mg/kg; p < 0.01). Older age at infection (odds ratio [OR], 1.3; 95% CI, 1.1-1.4), malignancy (OR, 8.8; 95% CI, 2.6-32.9), unknown site of infection (OR, 12.7; 95% CI, 3.3-48.6), and minimal platelet count less than 100,000/µL in first 7 days of sepsis (OR, 5.0; 95% CI, 1.6-15.4) were identified as potential risk factors for AVN after sepsis following adjustment for multiple comparisons. CONCLUSIONS: Although rare, sepsis was associated with a higher risk of subsequent AVN than suspected bacterial infection in children. Older age, malignancy, unknown site of infection, and minimum platelet count were potential risk factors for AVN after sepsis.

Risk factors for multi-joint disease in patients with glucocorticoid-induced osteonecrosis.

This study investigated risk factors for osteonecrosis involving multiple joints (MJON) among glucocorticoid-treated patients. The best predictor of MJON was cumulative oral glucocorticoid dose. Risk of MJON was 12-fold higher in patients who had a second risk factor for osteonecrosis. Further research is needed into strategies for prevention of MJON. INTRODUCTION: Osteonecrosis (ON) is a debilitating musculoskeletal condition in which bone cell death can lead to mechanical failure. When multiple joints are affected, pain and disability are compounded. Glucocorticoid treatment is one of the most common predisposing factors for ON. This study investigated risk factors for ON involving multiple joints (MJON) among glucocorticoid-treated patients. METHODS: Fifty-five adults with glucocorticoid-induced ON were prospectively enrolled. MJON was defined as ON in ≥ three joints. Route, dose, duration, and timing of glucocorticoid treatment were assessed. RESULTS: Mean age of enrolled subjects was 44 years, 58% were women. Half had underlying conditions associated with increased ON risk: systemic lupus erythematosus (29%), acute lymphoblastic leukemia (11%), HIV (9%), and alcohol use (4%). Mean daily oral dose of glucocorticoids was 29 mg. Average cumulative oral dose was 30 g over 5 years. The best predictor of MJON was cumulative oral glucocorticoid dose. For each increase of 1,000 mg, risk of MJON increased by 3.2% (95% CI 1.03, 1.67). Glucocorticoid exposure in the first 6 months of therapy, peak dose (oral or IV), and mean daily dose did not independently increase risk of MJON. The risk of MJON was 12-fold in patients who had a second risk factor (95% CI 3.2, 44.4). CONCLUSIONS: Among patients with glucocorticoid-induced ON, cumulative oral dose was the best predictor of multi-joint disease; initial doses of IV and oral glucocorticoids did not independently increase risk. Further research is needed to better define optimal strategies for prevention and treatment of MJON.

Denosumab-related osteonecrosis of the jaw after tooth extraction and the effects of a short drug holiday in cancer patients: a multicenter retrospective study.

Pre-existing inflammation, corticosteroid therapy, periapical periodontitis, longer duration of denosumab therapy, and female sex were significantly associated with an increased risk of denosumab-related osteonecrosis of the jaw after tooth extraction in patients with cancer on oncologic doses of denosumab. A short drug holiday did not protect against this complication. INTRODUCTION: This study retrospectively investigated the relationship between various risk factors, including brief discontinuation of denosumab, and development of denosumab-related osteonecrosis of the jaw (DRONJ) after tooth extraction in patients with cancer who were receiving oncologic doses of this agent. METHODS: Data were collected on demographic characteristics, duration of denosumab therapy, whether or not denosumab was discontinued before tooth extraction (drug holiday), duration of discontinuation, presence of pre-existing inflammation, and whether or not additional surgical procedures were performed. Risk factors for DRONJ after tooth extraction were evaluated by univariate and multivariate analyses. RESULTS: A total of 136 dental extractions were performed in 72 patients (31 men, 41 women) with cancer who were receiving oncologic doses of denosumab. Post-extraction DRONJ was diagnosed in 39 teeth (28.7%) in 25 patients. Tooth extraction was significantly associated with development of DRONJ only in patients with pre-existing inflammation (odds ratio [OR] 243.77), those on corticosteroid therapy (OR 73.50), those with periapical periodontitis (OR 14.13), those who had been taking oncologic doses of denosumab for a longer period (OR 4.69), and in women (OR 1.04). There was no significant difference in the occurrence of DRONJ between patients who had a drug holiday before tooth extraction and those who did not. CONCLUSIONS: These findings suggest that inflamed teeth should be extracted immediately in patients with cancer who are receiving oncologic doses of denosumab. Drug holidays have no significant impact on the risk of DRONJ.

Symptomatic osteonecrosis of the hip and knee in patients with systemic lupus erythematosus: Prevalence, pattern, and comparison of natural course.

OBJECTIVE: Osteonecrosis (ON), also known as avascular necrosis, is characterized by the collapse of the architectural bone structure secondary to the death of the bone marrow and trabecular bone. Osteonecrosis may accompany many conditions, especially rheumatic diseases. Among rheumatic diseases, osteonecrosis is most commonly associated with systemic lupus erythematosus (SLE). We assessed prevalence and distribution pattern of symptomatic ON in patients with SLE and compare the natural courses of hip and knee ON. METHODS: 912 SLE patients admitted between 1981 and 2012 were reviewed. SLE patients with symptomatic ON were retrospectively identified both from the existing SLE/APS database. The prevalence of symptomatic ON was calculated; with ON, the joint involvement pattern was determined by examining the distribution of the joints involved, and then the data about the hip and knee joints were entered in the Kaplan-Meier analysis. Kaplan-Meier methods were used to calculate 5- and 10-year rates of ON-related hip (the hip group) and knee survival (the knee group). RESULTS: Symptomatic ON developed in various joints in 97 of 912 patients with SLE, and the overall prevalence of ON was detected as 10.6%. The mean age at the time of SLE and ON diagnoses were 27.9 ± 9.9 (14-53) and 34.2 ± 11.3 (16-62) years, respectively. The mean duration from diagnosis of SLE to the first development of ON was 70.7± 60.2 (range = 0-216) months. The most common site for symptomatic ON was the hips (68%, n=66), followed by the knees (38%, n = 37). According to Kaplan-Meier analysis, hip and knee joint survival rates associated with 5-year ON were 51% and 88%, and 10-year survival rates were 43% and 84%, respectively. CONCLUSION: We observed that the prevalence of symptomatic ON in patients with SLE was 10.6%. With the estimated 10-year survival rates of 40% versus 84% for the hip and knee joints, respectively, hip involvement may demonstrate a more aggressive course to end-stage osteoarthritis than the knee involvement.

Risk of osteonecrosis in systemic lupus erythematosus: An 11-year Chinese single-center cohort study.

OBJECTIVE: Osteonecrosis (ON), which can lead to physical disability, is a common complication of systemic lupus erythematosus (SLE). The purpose of this study was to determine the prevalence of ON and identify possible risk factors in Chinese SLE patients. METHODS: SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were recruited from the Peking Union Medical College Hospital. The chi-square test (χ2 test) and multivariate regression analyses were used to evaluate risk factors. The Cox proportional-hazards model was used to construct the survival curves and estimate the simultaneous effects of prognostic factors on survival. RESULTS: We consecutively enrolled 1,158 patients, of which 88 patients (7.6%) developed ON. Among ON patients, 57.1% of patients had isolated femoral head necrosis and 42.9% had multiple joint involvement. The mean age of ON patients (24.62 ± 8.89 years) was significantly younger than SLE patients without ON (27.23 ± 10.16 years, p = 0.09). The ON group presented with a much longer disease course (10.68 ± 5.97 years, p < 0.001) and increased incidence of arthritis, kidney, and central nervous system (CNS) involvement (65.9% [p < 0.05], 57.6% [p < 0.05], and 16.5% [p < 0.05], respectively, in the ON group). ON patients were more likely to be treated with glucocorticoid (GC) and to receive a high dose of prednisolone at the initial stage of SLE (p < 0.05). The percentage of patients who received hydroxychloroquine was much higher in the control group (p < 0.001). Cox regression analysis suggested that CNS involvement and GC therapy were two independent risk factors for ON in SLE patients. The presence of anti-phospholipid antibodies (aPLs) was a risk factor for multiple joint necrosis (odds ratio: 6.28, p = 0.009). CONCLUSIONS: ON remains a serious and irreversible complication in SLE. In addition to glucocorticoid therapy, we found that CNS system involvement was a risk factor for ON, while the administration of hydroxychloroquine was a protective factor. The clinical characteristics of multiple site ON patients were distinct from isolated femoral head necrosis patients. The presence of aPLs was a risk factor for multiple site osteonecrosis.

Extrusion of the medial meniscus is a potential predisposing factor for post-arthroscopy osteonecrosis of the knee.

BACKGROUND: Post-arthroscopic osteonecrosis of the knee (PAONK) is a rare condition. No studies have analyzed the relationship between the meniscus extrusion and PAONK. The purpose of this retrospective study is to test a hypothesis that the degree of the medial meniscus (MM) extrusion might be significantly greater in the knees with PAONK than in the matched control knees both before and after the meniscectomy. METHODS: Ten knees with PAONK were detected out of a total of 876 knees which had undergone arthroscopic partial meniscectomy of the MM. Ten matched control knees were randomly selected out of the remaining 866 knees without PAONK. The clinical data of these 20 patients were retrospectively collected from the medical records. To evaluate the location of the menisci on the joint line, Extrusion width and Inner width were defined on a coronal section of magnetic resonance imaging (MRI). The intra- and inter-rater reliability was evaluated by calculating the intra- and inter-class coefficients. Statistical comparisons between the 2 groups were made using the 3 non-parametric tests. RESULTS: Before the meniscectomy, the Extrusion width of the MM (mean 4.7 ± 1.4 mm) was significantly greater than that (3.0 ± 1.3 mm) in the Control group (P = 0.0195). In the MRI taken in a range from 3 to 50 weeks after the meniscectomy, the Extrusion width of the MM (5.9 ± 1.1 mm) in the PAONK group was significantly greater than that (3.4 ± 1.4 mm) in the Control group (P = 0.0009), and the Inner width of the MM (0.6 ± 1.7 mm) in the PAONK group was significantly less than that (3.9 ± 1.0 mm) in the Control group (P = 0.0001). CONCLUSION: A significant relationship was found between the degree of the MM extrusion and the onset of PAONK. This study suggested that the extrusion of the MM is a potential predisposing factor for PAONK.

Type of bone graft and primary diagnosis were associated with nosocomial surgical site infection after high tibial osteotomy: analysis of a national database.

PURPOSE: Although several small-scale studies have reported risk factors for surgical site infection (SSI) after high tibial osteotomy (HTO), no study has collectively analysed risk factors in a large cohort. The present study aimed to clarify the risk factors for SSI after HTO using a national database. METHODS: Data of inpatients who underwent HTO from 2010 to 2017 were obtained from the Diagnosis Procedure Combination database in Japan. Outcome measures were the incidence of SSI and deep SSI after HTO. Associations between SSI and patient data were examined with multivariable logistic regression analysis. RESULTS: Among 12,853 patients who underwent HTO, 195 developed SSI (1.52%) and 50 developed deep SSI (0.39%). Univariate analysis showed that male sex, smoking, and longer anaesthesia duration were associated with higher incidences of SSI, whereas a primary diagnosis of osteonecrosis and use of natural bone grafts were associated with lower incidences. In multivariable analysis, SSI was positively associated with male sex, anaesthesia duration longer than 210 min (vs. 150-210 min), and use of artificial bone graft (vs. natural bone graft). SSI was negatively associated with age ≤ 49 years (vs. 50-59 years) and a primary diagnosis of osteonecrosis (vs. osteoarthritis). CONCLUSION: The present study revealed novel risk factors for SSI after HTO that previous studies have failed to find, including use of artificial bone graft and longer anaesthesia duration; primary diagnosis of osteonecrosis and younger age were novel protective factors. These findings will help surgeons assess risks of SSI after HTO in individual patients. LEVEL OF EVIDENCE: III.

A Study on the Evaluation of a Risk Score of Osteonecrosis of the Femoral Head Based on Survival Analysis.

BACKGROUND: This study aimed at developing a risk score predicting the probability of developing an osteonecrosis of the femoral head (ONFH) in patients with femoral neck fracture within 3 years after closed reduction internal fixation and evaluating its performance, clinical utility, and internal validity. METHODS: A retrospective follow-up study of 378 newly injured femoral neck fracture patients treated with 3 partially threaded parallel cannulated screws in 3 hospitals in Shanghai from March 2013 to January 2017 was performed. The patients were divided into development (n = 284) and validation (n = 94) cohorts. The risk score was constructed by Cox regression analysis in a form of nomogram. The performance and clinical utility were illustrated by box plots, calibration plots, and decision curve analysis. RESULTS: Eighty-three of 378 patients had developed ONFH within 3 years. Garden alignment index, time to surgery, preoperative displace, impaction, and postoperative malposition were used as predictors to construct the risk score in a form of nomogram. In the development and validation cohort, the concordance index was 0.96 and 0.94, respectively; the discrimination slope was 0.51 and 0.47, respectively. In both cohorts, the calibration slopes and intercepts were 1 and 0, respectively. The risk score was clinically useful between the risk threshold of 0% and 88%. The performance and utility in the validation data illustrated good repeatability. CONCLUSION: The risk score had satisfactory discrimination and calibration performance and demonstrated clinical utility with good internal validity. It managed to distinguish high-risk groups for post-traumatic ONFH.

Osteoarthritis and Osteonecrosis in Total Hip Arthroplasty: 90-Day Postoperative Costs and Outcomes.

BACKGROUND: Two common diagnoses for patients undergoing total hip arthroplasty (THA) are osteoarthritis (OA) and osteonecrosis (ON), pathologically different diseases that affect postoperative complication rates. The underlying pathology of ON may predispose patients to a higher rate of certain complications. Previous research has linked ON with higher mortality and revisions, but a comparison of costs and complication rates may help elucidate further risks. This study reports 90-day costs, lengths of stay (LOS), readmission rates, and complication rates between patients undergoing THA for OA and ON. METHODS: The Nationwide Readmissions Database was retrospectively reviewed for primary THAs, with 90-day readmissions assessed from the index procedure. Patients diagnosed with OA (n = 1,577,991) and ON (n = 55,034) were identified. Costs, LOS, and any readmission within 90 days for complications were recorded and analyzed with the chi-square and t-tests. RESULTS: Patients with ON had higher 90-day costs ($20,110.80 vs. 22,462.79, P < .01) and longer average LOS (3.48 vs. 4.49 days, P < .01). Readmission rates within 90 days of index THA were significantly higher among patients with ON (7.7% vs. 13.1%, P < .01). Patients with OA had a lower incidence of 90-day overall complications (4.1 vs. 6.4%, P < .01). CONCLUSIONS: Patients undergoing THA for ON incur higher readmission-related costs and complication rates. Understanding the predisposing factors for increased complications in ON may improve patient outcomes.

Outcomes of Cemented Total Knee Arthroplasty for Secondary Osteonecrosis of the Knee.

BACKGROUND: Secondary osteonecrosis of the knee (SOK) generally occurs in relatively young patients; at advanced stages of SOK, the only viable surgical option is total knee arthroplasty (TKA). We conducted a retrospective study to investigate implant survivorship, clinical and radiographic outcomes, and complications of contemporary cemented bicompartmental TKA with/without patellar resurfacing for SOK. METHODS: Thirty-eight cemented TKAs in 27 patients with atraumatic SOK, mean age 43 years (17 to 65), were retrospectively reviewed. Seventy-four percent had a history of corticosteroid use, and 18% had a history of alcohol abuse. Patellar osteonecrosis was coincidentally found in six knees (16%), and all were asymptomatic without joint collapse. The mean followup was 7 years (2 to 12). Knee Society Score (KSS) and radiographic outcomes were evaluated at 6 weeks, 1 year, then every 2 to 3 years. RESULTS: Ninety-two percent had implant survivorship free from revision with significant improvement in KSS. Causes of revision included aseptic tibial loosening (one), deep infection (one), and instability with patellofemoral issues (one). Four of six cases also with patellar osteonecrosis received resurfacing, including one with periprosthetic patellar fracture after minor trauma, with satisfactory clinical results after conservative treatment. None of the unrevised knees had progressive radiolucent lines or evidence of loosening. An unresurfaced patella, use of a stem extension or a varus-valgus constrained prosthesis constituted 18%, 8% and 3%, respectively. CONCLUSION: Cemented TKAs with selective stem extension in patients with SOK had satisfactory implant survivorship and reliable outcomes. Secondary osteonecrosis of the patella should be carefully evaluated prior to operation.

Long-Term Results of Total Hip Arthroplasty in Young Patients With Osteonecrosis After Allogeneic Bone Marrow Transplantation for Hematological Disease: A Multicenter, Propensity-Matched Cohort Study With a Mean 11-Year Follow-Up.

BACKGROUND: The number of young patients with hematological disease requiring total hip arthroplasty (THA) is expected to increase. We aimed to investigate the long-term THA outcomes in patients with osteonecrosis of the femoral head (ONFH) following allogeneic bone marrow transplantation (BMT) for hematological disease. METHODS: All patients who underwent THA for osteonecrosis after BMT from 1997 to 2012 were identified at 2 institutions. Using propensity scores, 75 THAs in 45 patients were matched for age, gender, body mass index, American Society of Anesthesiologists score, and year of surgery with 75 THAs in 58 patients with idiopathic ONFH without a history of hematological disease (1:1 ratio). The mean age at surgery was 36.7 years and 52% were men. Clinical and radiographic evaluations were performed and clinical scores were obtained at last follow-up. Kaplan-Meier analyses were used to compare survivorship. RESULTS: At a mean follow-up of 10.6 ± 3.5 years, clinical, radiographic, and survivorship outcomes, and the Harris hip scores were similar between both groups. The 13-year survivorship for all-cause revision was 93.4% for the BMT group and 95% for the control group (P = .928). No significant differences were observed between groups in the rates of reoperation (4% vs 5.3%, P = 1.000), 90-day readmission (all 5.3%), or overall mortality (4.4% vs 1.7%, P = .681). No hips had periprosthetic joint infection or septic loosening in either group. Osteolysis occurred in none of the BMT patients and in 2 hips (2.7%) of the control patients (P = .497). CONCLUSION: This large cohort multicenter survey at 11-year follow-up shows that contemporary cementless THA in young hematological disease patients after allogeneic BMT is not associated with a higher risk for surgical complications, revision, reoperation, readmission, and mortality compared to a matched cohort of idiopathic ONFH.