Older age increases the risk of revision and perioperative complications after high tibial osteotomy for unicompartmental knee osteoarthritis

Among various patient risk factors affecting survival after high tibial osteotomy (HTO), the ideal age limit for HTO is unclear. This study was performed to evaluate the effect of age on survival rate and complications after HTO for medial unicompartmental osteoarthritis. Among of 61,145 HTO patients from Korean National Health Insurance database, 41,112 patients underwent the procedure before the age of 60 years (Group A), 13,895 patients between the age of 60 and 65 years (Group B), and 6138 patients after the age of 65 years (Group C). We compared the survival rate in person-years among the three groups from the date of primary surgery until subsequent total knee arthroplasty. Perioperative complications were also recorded. The adjusted hazard ratio (HR) were calculated using the multivariable Cox proportional hazard regression model, adjusting for the potential confounders: age, sex, type of medical insurance, region of residence, hospital type, comorbidities, and Charlson comorbidity index score. The total number of HTO increased 6.5-fold, especially in patients aged > 65 years (by 8.2-fold) from 2008 to 2018. The overall revision rate was 4.2% in Group A, 6.4% in Group B, and 7.3% in Group C. The 5- and 10-year revision rate was significantly lower in Group A (p < 0.001), but no difference between Groups B and C. After adjusting for potential confounders, multivariable regression analysis revealed that revision rate was significantly lower in Group A than Group B (HR: 0.57; p < 0.0001), but no difference between Groups B and C. The incidence of complications was also significantly lower in Group A than in other groups. The inferior survival rate and more perioperative complications after HTO was found in old patients (aged ≥ 60 years) than in young patients. Therefore, the patient age is one of the predicting factors for a high risk of failure after HTO.


Materials and methods
This study was approved by the Institutional Review Board (IRB) of Chonnam National University Hwasun Hospital. The review board waived the requirement for patient consent because the retrospective nature of the study. Data sources. The study population included all patients who underwent HTO in Korea between January 1, 2007 and May 31, 2019. To allow a washout period of 1 year, the index date was set as January 2008 (Fig. 1).
We identified the target cohort by searching for HTO using the surgical procedure code to ensure that cases counted in only one of the registers were included. This retrospective nationwide cohort study used the claims database of the National Health Insurance Service (NHIS; Seoul, South Korea), which covers almost 99% of entire Korean population. Diagnosis was based on the International Classification of Diseases, 10th revision (ICD-10), and the procedure code was based on the Electronic Data Interchange (EDI). The NHIS database of South Korea provides data on the individual identification codes, and the data linked to each code provides information on patient age, sex, diagnosis, hospitalization records, surgical records, medication prescriptions, and local hospital information.
Data collection. The study population included all patients aged 30-90 years who underwent HTO (EDI: N0304) as a primary procedure. Each patient's first additional procedure throughout the study period was also recorded. Patients who had undergone orthopedic surgery during the preceding year (washout period) were excluded to eliminate the influence of previous surgical history. All diagnosis and treatment codes were defined and searched in accordance with the ICD-10 and EDI codes. The first objective of the study was to confirm age-related revision rates; the second objective was to analyze the incidence of unwanted surgery-related complications according to age. We compared survival rates and complications according to age (< 60 years, 60-65 years, > 65 years) by analyzing the conversion to unicompartmental knee arthroplasty (UKA) or total knee arthroplasty (TKA) and evaluating perioperative medical complications. This was approved by the Institutional Review Board of our hospital. The review board waived the requirement for patient consent because the retrospective nature of the study. Statistical analysis. The following baseline characteristics of patients treated with HTO were collected: age, sex, type of insurance, region of residence, hospital type, and comorbidities. These were summarized using descriptive statistics, including proportion, mean, and standard deviation. Differences in continuous variables among age groups (< 60, 60-65, and > 65 years) were evaluated using the Wilcoxon rank-sum test, while categorical variables were compared using the chi-square test. The balance of covariates among groups was evaluated using standardized mean difference (SMD). An SMD of < 0.1 indicated a negligible difference between the groups. In each group, we calculated the person-years from the date of primary surgery until subsequent TKA or UKA. We also recorded perioperative complications. Time to revision surgery was calculated using Kaplan-Meier survival analysis. The adjusted hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazard regression model, adjusting for potential confounders such as age, sex, type of medical insurance, region of residence, hospital type, comorbidities, and Charlson comorbidity index Informed consent. For this type of study, formal consent is not required.

Results
A total of 67,549 patients who underwent HTO during the 11.5-year period from January 2007 to March 2019 were identified. Patients aged < 30 years and > 90 years (n = 410) and those with inappropriate data (n = 50) were excluded. The final target cohort included 61,145 patients who had undergone HTO. Of the 61,145 patients, 41,112 patients underwent the procedure before the age of 60 years (Group A), 13,895 patients underwent the procedure between the age of 60 and 65 years (Group B), and 6138 patients underwent the procedure after the age of 65 years (Group C; Fig. 1). The mean age was 52.6 years in Group A, 62.1 years in Group B, and 70.1 years in Group C (p < 0.001). Group A had a higher proportion of male patients (73.4%) than Groups B and C, which had approximately 77% female patients. Underlying diseases (hypertension, hyperlipidemia, peripheral vascular disease, diabetes mellitus, and depression) were more common in Groups B and C than in Group A ( Table 1).
Type of medical insurance did not differ among the three groups, but there was a difference in city of residence and hospital type. The CCI score was significantly higher in Groups B and C than in Group A. The proportion of patients in Group B or C significantly increased over the 10 years ( Table 1). The number of HTO procedures increased by 6.5-fold, from 1507 in 2008 to 9853 in 2018, while the number of patients undergoing the procedure after the age of 65 years increased by 8.2-fold ( Table 1).
The overall revision rate was 4.2% (CI: 95.1-95.9) in Group A, 6.4% (CI: 94.9-96.5) in Group B, and 7.3% (CI: 94.9-96.5) in Group C. There was a significant difference in the revision rate among the three groups after 5 and 10 years, with Group A showing a significantly lower revision rate than other groups (p < 0.001); however, there was no difference between Groups B and C (p > 0.05; Table 2; Fig. 2A). Moreover, male patients had better survival in all age groups after 5 and 10 years ( Fig. 2B-D).
The number of 10-year revisions per 1000 person-years was 9.5 in Group A, 17.8 in Group B, and 19.1 in Group C (Table 2). Group A had a significantly lower revision rate than Group B (HR: 0.5, 95% CI: 0.46-0.54; p < 0.001); the HR was 0.46 after 5 years and 0.49 after 10 years (Table 3). However, there was no significant difference in the revision rate between Groups B and C. After adjusting for potential confounders, such as age, sex, type of medical insurance type, region of residence, type of hospital, comorbidities, and CCI score, multivariable regression analysis showed that the revision rate was significantly lower in Group A than in Group B (HR: 0.57, 0.53-0.62, p < 0.0001); the HR was 0.53 after 5 years and 0.57 after 10 years (Table 3). However, there was no significant difference in the revision rate between Groups B and C (HR: 0.96, 0.86-1.08; p = 0.53).

Discussion
The range of indications for high tibial osteotomy (HTO) is expanding 1,4 , especially in terms of patient age. There are many studies on the optimal age to perform TKA 27,28 . However, there is no consensus regarding the age limit for HTO. In the present study, data from a nationwide Korean registry were used to compare survival rates and perioperative complications based on age. We included 61,145 patients who underwent HTO and evaluated the revision rate and postoperative complications according to age. The survival rate after HTO was significantly higher in Group A (< 60 years) than other groups (≥ 60 years). Additionally, the incidence of perioperative complications after HTO was higher in patients aged > 65 years than in those aged 60-65 or < 60 years. Therefore, surgeons must carefully consider whether to perform HTO on patients aged ≥ 60 years with medial knee OA. To our knowledge, the present study is the first to evaluate HTO revision rates according to age in a large, validated, nationwide cohort. The number of HTO procedures increased by 6.5-fold during the study period, while the number of patients undergoing the procedure after the age of 65 years increased by 8.2-fold.
One of the most important risk factors for survival after HTO is patient age 9,13,15,16,20,21,25,26,[29][30][31][32] . Although there is no consensus regarding the age limit for HTO, some recent studies have reported no age restriction for successful outcomes after HTO 7,22,23,33,34 . Kuwashima et al. 23 reported excellent overall survival rates of HTO (94.4% and 84.6% at 10 and 15 years, respectively). Their study could not find any statistical significant difference in survival rate after HTO between the two groups divided by the age (≥ 65 years or not). Moreover, Ruangsomboon et al. 19 also reported good survival rate of HTO after 4 year follow-up, and concluded HTO in patient ≥ 60 years had good surgical options for OA with acceptable complication. However, other studies showed higher failure rate in old patients than young patients 12,15,20,25,26,31,35 . Keeenan et al. 15 evaluated the risk factor using a total of 1576 HTO and reported increased incidence of arthroplasty by 8% in each additional year in age patients (relative risk, 1.08). They recommend that careful consideration should be given to patient age when selecting patients for HTO. Similarly, in the present study, patients aged < 60 years had a significantly lower revision rate after HTO than those aged more than 60 years or > 65 years ( www.nature.com/scientificreports/ With regard to perioperative complications after HTO, to our knowledge, the significant adverse outcomes associated with patient age have not been investigated thus far. In the present study, the preoperative incidence of underlying medical diseases was significantly higher in patients aged 60-65 and > 65 years than in those aged < 60 years. In particular, the CCI score was significantly higher in patients aged ≥ 60 years than in those aged < 60 years. As expected, perioperative complications such as CVA, MI, and delirium were significantly less common in patients aged < 60 years than in those aged 60-65 years after adjusting for confounders. Moreover, patients aged > 65 years also had higher incidences of PTE, CVA, MI, ARF, and delirium than those aged  www.nature.com/scientificreports/ 60-65 years. In terms of TKA and UKA, similarly, the results were worse as the patient's age increased. Klasan et al. 36 reported that Post-TKA mortality rate was higher in the elderly group and general complication rate was also higher in the elderly group. Lee et al. 27 revealed that the mortality tended to increase with age. Kennedy et al. 37 grouped the patients by age at UKA (< 55, 55 to < 65, 65 to < 75, 75 +) and the revision rate was not higher in youger patients. Otherwise, the clinical scores had more significant improvement in youger group. Therefore, surgeons should discuss possible perioperative complications with patients or their families before performing HTO.
The strength of the present study is that it used one of the largest datasets (NHIS) worldwide. In Korea, health insurance is mandated by law and covers up to 99% of the population. Using a well-designed statistical technique and multivariate regression analysis, we reduced confounders. In addition, we stratified patients into three age groups (< 60 years, 60-65 years, and > 65 years).
However, the present study has several limitations. First, claims-based studies have inherent problemsdiagnostic and procedure codes can fail to reflect a patient's actual medical history. Second, detailed clinical information of individual patients was not available. Thus, the clinical and functional outcomes could not be compared based on age. Third, in study design, it may be more meaningful to divide the age group of the patient into more than three groups or to find the age that is a cut-off value. However, it was our best option to divide the age groups into three groups which had a relatively high number of surgeries. It was not simple comparison between younger and older patients, and could be more detailed comparison between different age groups. Finally, there were many confounding factors even after considerable adjustment. For example, the severity and extent of knee OA are can be identified radiologically, and therefore, it was not considered in the present study. And many other confounders such as degree of deformity, body mass index and status of activity were not considered in the analysis. Despite these limitations, to our knowledge, the current study is the first large-scale,

Conclusions
The HTO can delay conversion to TKA and can be used as a definitive treatment for knee OA, especially in young patients (aged < 60 years) without serious perioperative complications. And the survival rate was found to be inferior in old patients (aged ≥ 60 years) and more perioperative complications than young patients. Therefore, the patient age is one of the predicting factors for a high risk of failure after HTO.

Data availability
Korean National Health Insurance Claims Data are available on reasonable request. Study protocol, statistical code : available from the author JKS (e-mail, seonbell@jnu.ac.kr). Dataset : de-identified datasets generated and analysed during the present study will be made available by request from the Health Insurance & Assessment Service of Korea at https:// opend ata. hira. or. kr/. After user approaval by the Health Insurance Review and Assessment Service, a remote analysis system (https:// ras. hira. or. kr) can be used by receiving a virtualized ID.