Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Survey of awareness and attitudes to the management of fragility fractures among the membership of the Asia Pacific Orthopaedic Association.

A survey of awareness and attitudes to the management of fragility fractures among the membership of the Asia Pacific Orthopaedic Association conducted in 2022 found considerable variation in care across the region. A Call to Action is proposed to improve acute care, rehabilitation and secondary fracture prevention across Asia Pacific. PURPOSE: Fragility fractures impose a substantial burden on older people and their families, healthcare systems and national economies. The current incidence of hip and other fragility fractures across the Asia Pacific region is enormous and set to escalate rapidly in the coming decades. This publication describes findings of a survey of awareness and attitudes to the management of fragility fractures among the membership of the Asia Pacific Orthopaedic Association (APOA) conducted in 2022. METHODS: The survey was developed as a collaboration between the Asia Pacific Osteoporosis and Fragility Fracture Society and the Asia Pacific Fragility Fracture Alliance, and included questions relating to aspects of care upon presentation, during surgery and mobilisation, secondary fracture prevention, and access to specific services. RESULTS: In total, 521 APOA members completed the survey and marked variation in delivery of care was evident. Notable findings included: Fifty-nine percent of respondents indicated that analgesia was routinely initiated in transit (by paramedics) or within 30 minutes of arrival in the Emergency Department. One-quarter of respondents stated that more than 80% of their patients underwent surgery within 48 hours of admission. One-third of respondents considered non-hip, non-vertebral fractures to merit assessment of future fracture risk. One-third of respondents reported the presence of an Orthogeriatric Service in their hospital, and less than a quarter reported the presence of a Fracture Liaison Service. CONCLUSION: A Call to Action for all National Orthopaedic Associations affiliated with APOA is proposed to improve the care of fragility fracture patients across the region.

Social network associated with depressed mood and sarcopenia among older adults in Taiwan.

BACKGROUND: Social isolation is increasing in aging societies; however, its relationship with depressed mood and sarcopenia is not well studied. This study aims to examine the influence of social network on depressed mood and sarcopenia among community-dwelling older adults in Taiwan. METHODS: We collected data from a sample of 981 older adults residing in the community. These individuals received government-subsidized preventive healthcare services for adults at a district hospital in Taipei in 2021. The social network of the older adults who participated was assessed using the Lubben Social Network Scale, while depressed mood was assessed using the Geriatric Depression Scale. The definition of sarcopenia used in this study was based on the 2019 Asian Working Group for Sarcopenia. RESULTS: According to this study, sarcopenia was present in approximately 15 % of older adults. Multiple logistic regression analysis showed that older adults who had poor social network and did not meet the recommended 150 min of regular physical activity per week were more likely to have depressed mood. Additionally, older adults who were older, underweight, did not engage in regular physical activity, and had poor social network were more likely to have sarcopenia. CONCLUSION: Poor social network was associated with increased risks of depressed mood and sarcopenia among older adults.

Prediction of adverse health outcomes using an electronic frailty index among nonfrail and prefrail community elders.

BACKGROUND: Early recognition of older people at risk of undesirable clinical outcomes is vital in preventing future disabling conditions. Here, we report the prognostic performance of an electronic frailty index (eFI) in comparison with traditional tools among nonfrail and prefrail community-dwelling older adults. The study is to investigate the predictive utility of a deficit-accumulation eFI in community elders without overt frailty. METHODS: Participants aged 65-80 years with a Clinical Frailty Scale of 1-3 points were recruited and followed for 2 years. The eFI score and Fried's frailty scale were determined by using a semiautomated platform of self-reported questionnaires and objective measurements which yielded cumulative deficits and physical phenotypes from 80 items of risk variables. Kaplan-Meier method and Cox proportional hazards regression were used to analyze the severity of frailty in relation to adverse outcomes of falls, emergency room (ER) visits and hospitalizations during 2 years' follow-up. RESULTS: A total of 427 older adults were evaluated and dichotomized by the median FI score. Two hundred and sixty (60.9%) and 167 (39.1%) elders were stratified into the low- (eFI ≤ 0.075) and the high-risk (eFI > 0.075) groups, respectively. During the follow-up, 77 (47.0%) individuals developed adverse events in the high-risk group, compared with 79 (30.5%) in the low-risk group (x2, p = 0.0006). In multivariable models adjusted for age and sex, the increased risk of all three events combined in the high- vs. low-risk group remained significant (adjusted hazard ratio (aHR) = 3.08, 95% confidence interval (CI): 1.87-5.07). For individual adverse event, the aHRs were 2.20 (CI: 1.44-3.36) for falls; 1.67 (CI: 1.03-2.70) for ER visits; and 2.84 (CI: 1.73-4.67) for hospitalizations. Compared with the traditional tools, the eFI stratification (high- vs. low-risk) showed better predictive performance than either CFS rating (managing well vs. fit to very fit; not discriminative in hospitalizations) or Fried's scale (prefrail to frail vs. nonfrail; not discriminative in ER visits). CONCLUSION: The eFI system is a useful frailty tool which effectively predicts the risk of adverse healthcare outcomes in nonfrail and/or prefrail older adults over a period of 2 years.

Objective assessment of the association between frailty and sedentary behavior in older adults: a cross-sectional study.

BACKGROUND: Given the inconsistent findings of the association between frailty and sedentary behavior in older adults, this cross-sectional study investigated the aforementioned association using four different frailty criteria and two sedentary behavior indices in older adults. METHODS: Data from older adults (age ≥ 65 y) who participated in health examinations or attended outpatient integrated clinics at a medical center in Taipei, Taiwan, were collected. Frailty was measured using the modified Fried Frailty Phenotype (mFFP), Clinical Frailty Scale in Chinese Translation (CFS-C), Study of Osteoporotic Fractures (SOF) index, and Clinical Frailty-Deficit Count (CF-DC) index; sedentary behavior was assessed with a waist-worn accelerometer. Adjusted linear regression ascertained the association between frailty and both sedentary behavior outcomes. RESULTS: Among the 214 participants (mean age 80.82 ± 7.14 y), 116 were women. The average total sedentary time and number of sedentary bouts were 609.74 ± 79.29 min and 5.51 ± 2.09 times per day, respectively. Frail participants had a longer total sedentary time (odds ratio [OR]: 30.13, P = .01 and 39.43, P < .001) and more sedentary bouts (OR: 3.50 and 5.86, both P < .001) on mFFP and CFS-C assessments, respectively. The SOF index revealed more sedentary bouts among frail than in robust participants (OR: 2.06, P = .009), without a significant difference in the total sedentary time. Frail participants defined by the CF-DC index were more likely to have frequent sedentary bouts (OR: 2.03, P = .016), but did not have a longer total sedentary time. CONCLUSIONS: Regardless of the frailty criteria adopted, frailty was positively associated with the number of sedentary bouts per day in older adults. A significant correlation between frailty and total sedentary time was detected only with mFFP and CFS-C indices. Further research may target decreasing the sedentary bouts in older adults as a strategy to improve frailty.

Osteoporosis care after hip fracture: Observation from national health insurance database and fracture liaison services.

BACKGROUND: The objective of this research was to report the trend of osteoporosis care after hip fractures from usual care (UC) and to compare the quality of care with those who received fracture liaison services (FLSs). METHODS: Data on osteoporosis care for patients with hip fracture were acquired from the National Health Insurance claims (UC group), and surveys from FLS programs (FLS group). A total of 183,300 patients receiving UC and 3010 patients receiving FLS were studied. For the two groups, common osteoporosis care indicators, such as bone mineral density (BMD) testing rate, antiosteoporosis medication commencement rate, and adherence rate were described. RESULTS: There were 2488 participants (82.7%) in the FLS group who completed Dual-energy X-ray absorptiometry (DXA) in 8 weeks, 155 (5.1%) who finished it between 8 weeks and 1 year. Even in 2018, when the DXA completion rate was at its highest, the completion rate in the UC group was only 23.5%. In terms of medication commencement, 2372 FLS patients (78.8%) received treatment within 3 months. Only 24.9% of the UC patients received antiosteoporosis medication within 3 months. Furthermore, antiosteoporosis medication adherence rate was 92.2% after 1 year and 83.9% after 2 years in the FLS group, but these were only 66.5% and 42.7%, respectively, in the UC group. CONCLUSION: Patients who received FLS had more timely BMD exams, antiosteoporosis medication treatment, and higher adherence to antiosteoporosis therapy than those who received UC. The discrepancy in rates of continuing treatment became more significant over time between both groups.

Eleven years secular trend of the initiation of anti-osteoporosis medications and subsequent fractures in Taiwan: From 2008 to 2018.

BACKGROUND: Osteoporosis is a common metabolic bone disease that benefits from many newly developed anti-osteoporosis medications (AOMs). Reimbursement policies need to allocate medical budgets properly based on evidence-based data. This study aimed to investigate the 11-year secular trend, focusing on older age and males in this adjustment wave of the National Health Insurance reimbursement. METHODS: We adopted a nationwide cohort from Taiwan's National Health Insurance Research Database (NHIRD). Patients undergoing newly initiated AOMs from 2008 to 2018 were included. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. Patients <50 years, pathological fractures, missing data, and two AOMs prescribed were excluded. The real-world trends related to subsequent fragility fracture and death within 1 and 3 years were used to evaluate the potential effects due to revision of reimbursement policies. RESULTS: Of 393,092 patients, among them, 336,229 patients met the criteria, whose mean age ranged from 73.3 to 74.4 years, and nearly 80% were female. Further analysis showed a steady increase of AOMs from 5567 (17.1%) and 8802 (27.0%) in 2008-6697 (18.3%) and 10,793 (29.5%) in 2018 for males and 80+ years respectively. The subsequent fragility fracture within one and three years post AOMs initiation was 5.81% and 11.80% in 2018. CONCLUSION: This study showed an immediate drop in AOMs prescription after the implementation of a new stricter reimbursement policy. It took 5 years to return the annual prescription number.

Constraining in reimbursement criteria and the adherence to anti-osteoporosis medications (AOMs) in Taiwan: Urbanization makes the difference.

BACKGROUND: The Bureau of National Health Insurance in Taiwan implemented a new reimbursement scheme incorporating bone mineral density (BMD) criteria on Jan. 1, 2011. This study aimed to investigate a real-life 11-year secular trend of adherence in new AOMs users and evaluated the change of adherence to AOMs therapy in different urbanization areas after reimbursement criteria were restrained. METHODS: We used Taiwan's National Health Insurance Research Database to identify new AOMs users as our study population. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. The first prescription date of AOMs was defined as the cohort entry date. The adherence rates within one year after initiation were assessed. RESULTS: High adherence (≥75%) in the first year increased markedly after the new reimbursement scheme in 2011, changing from 31.8% in 2008, and 41.7% in 2011 to 54.2% in 2018. On the other hand, low adherence (<25%) decreased from 38.8% in 2008 to 14.6% in 2018. In addition, the switchers increased from 5.9% in 2008 to 9.3% in 2018, indicating a more flexible choice of AOMs. The proportion of high adherence to AOMs was highest in high-urbanization areas, and the proportion increased about two times from 30% in 2008 to 60% in 2018. CONCLUSION: The implementation of new reimbursement criteria in 2011 was associated with increased adherence to AOMs and the increase was most apparent in high-urbanization areas.

Therapeutic ultrasound treatment for the prevention of chronic kidney disease-associated muscle wasting in mice.

Low-intensity pulsed ultrasound (LIPUS) is a kind of therapeutic ultrasound. It can help improve bone fracture repair and soft tissue healing. Our previous study found that LIPUS treatment could halt the chronic kidney disease (CKD) progression in mice; unexpectedly, we observed the improvement of CKD-reduced muscle weights by LIPUS treatment. Here, we further tested the protective potential of LIPUS on CKD-associated muscle wasting/sarcopenia using the CKD mouse models. Mouse models of both unilateral renal ischemia/reperfusion injury (IRI) with nephrectomy and adenine administration were used to induce CKD. LIPUS with condition of 3 MHz, 100 mW/cm2, 20 min/day was applied to the kidney of CKD mice. LIPUS treatment significantly reversed the increased serum BUN/creatinine levels in CKD mice. LIPUS effectively prevented the decrease in grip strength, muscle weight (soleus, tibialis anterior, and gastrocnemius muscles), cross-section areas of muscle fibres, and muscular phosphorylated Akt protein expression by immunohistochemistry, and the increase in muscular atrogenes Atrogin1 and MuRF1 protein expression by immunohistochemistry in CKD mice. These results indicated that LIPUS could help improve weak muscle strength, muscle mass loss, muscle atrophy-related protein expression, and Akt inactivation. LIPUS application may be an alternative non-invasive therapeutic intervention on the management of CKD-associated muscle wasting.

Diurnal pattern of breaks in sedentary time and the physical function of older adults.

BACKGROUND: The association of breaks in sedentary time with outcomes of physical function can vary according to the time of day. We examined the association of the diurnal pattern of breaks in sedentary time with physical function outcomes in older adults. METHODS: A cross-sectional analysis was conducted among 115 older adults (≥60 years). The overall and time-specific breaks (morning: 06:00-12:00; afternoon: 12:00-18:00; evening: 18:00-24:00) in sedentary time were assessed using a triaxial accelerometer (Actigraph GT3X+). A break in sedentary time was defined as at least 1 min where the accelerometer registered ≥100 cpm following a sedentary period. Five physical function outcomes were assessed: handgrip strength (dynamometer), balance ability (single leg stance), gait speed (11-m walking), basic functional mobility (time up and go), and lower-limb strength (five times sit-to-stand). Generalized linear models were used to examine the associations of the overall and time-specific breaks in sedentary time with the physical function outcomes. RESULTS: Participants showed an average of 69.4 breaks in sedentary time during the day. Less frequent breaks in the evening (19.3) were found than that in the morning (24.3) and the afternoon (25.3) (p < 0.05). Breaks in sedentary time during the day were associated with less time on gait speed in older adults (exp (ß) = 0.92, 95% confidence interval [CI] 0.86-0.98; p < 0.01). Time-specific analysis showed that breaks in sedentary time were associated with less time on gait speed (exp (ß) = 0.94, 95% CI 0.91-0.97; p < 0.01), basic functional mobility (exp (ß) = 0.93, 95% CI 0.89-0.97; p < 0.01), and lower-limb strength (exp (ß) = 0.92, 95% CI 0.87-0.97; p < 0.01) in the evening only. CONCLUSION: A break in sedentary time, particularly during the evening, was associated with better lower extremity strength in older adults. Further strategies to interrupt sedentary time with frequent breaks, with an emphasis on evening hours, can be helpful to maintain and improve physical function in older adults.

Effect of isotemporal substitution of sedentary behavior with different intensities of physical activity on the muscle function of older adults in the context of a medical center.

BACKGROUND: Engaging in physical activity and reducing sedentary time in daily life may enable older individuals to maintain muscle mass. This study aimed to investigate the effects of replacing sedentary behavior with light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on the muscle function of older adults at a medical center in Taiwan. METHODS: We recruited 141 older adults (51.1% men; 81.1 ± 6.9 years old) and asked them to wear a triaxial accelerometer on the waist to measure their sedentary behavior and physical activity. Functional performance was assessed based on handgrip strength, Timed Up and Go (TUG) test, gait speed, and five-times-sit-to-stand test (5XSST). Isotemporal substitution analysis was performed to examine the effect of substituting 60 min of sedentary time with 60 min of LPA, MVPA, and combined LPA and MVPA in different proportions. RESULTS: Reallocating 60 min of sedentary behavior per day to LPA was associated with better handgrip strength (Beta [B] = 1.587, 95% confidence interval [CI] = 0.706, 2.468), TUG test findings (B = -1.415, 95% CI = -2.186, -0.643), and gait speed (B = 0.042, 95% CI = 0.007, 0.078). Reallocating 60 min of sedentary behavior per day to MVPA was associated with better gait speed (B = 0.105, 95% CI = 0.018, 0.193) and 5XSST findings (B = -0.060, 95% CI = -0.117, -0.003). In addition, each 5-min increment in MVPA in the total physical activity replacing 60 min of sedentary behavior per day resulted in greater gait speed. Replacing 60 min of sedentary behavior with 30-min of LPA and 30-min of MVPA per day significantly decreased the 5XSST test time. CONCLUSION: Our study indicates that introducing LPA and a combination of LPA and MVPA to specifically replace sedentary behavior may help maintain muscle function in older adults.

Multimorbidity and prior falls correlate with risk of 30-day hospital readmission in aged 80+: A prospective cohort study.

BACKGROUND/PURPOSE: Thirty-day hospital readmission rate significantly raised with advanced age. The performance of existing predictive models for readmission risk remained uncertain in the oldest population. We aimed to examine the effect of geriatric conditions and multimorbidity on readmission risk among older adults aged 80 and over. METHODS: This prospective cohort study enrolled patients aged 80 and older discharged from a geriatric ward at a tertiary hospital, with phone follow-up for 12 months. Demographics, multimorbidity, and geriatric conditions were assessed before hospital discharge. Logistic regression models were conducted to analyse risk factors for 30-day readmission. RESULTS: Patients readmitted had higher Charlson comorbidity index scores, and were more likely to have falls, frailty, and longer hospital stay, compared to those without 30-day readmission. Multivariate analysis revealed that higher Charlson comorbidity index score was associated with readmission risk. Older patients with a fall history within 12 months had a near 4-fold increase in readmission risk. Severe frailty status before index admission was associated with a higher 30-day readmission risk. Functional status at discharge was not associated with readmission risk. CONCLUSION: In addition to multimorbidity, history of falls and frailty were associated with higher hospital readmission risk in the oldest.

Asia-pacific consensus on osteoporotic fracture prevention in postmenopausal women with low bone mass or osteoporosis but no fragility fractures.

Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia-Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics.

Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: 2022 update.

Osteoporosis greatly increases the risk of fractures. Osteoporotic fractures negatively impact quality of life, increase the burden of care, and increase mortality. Taiwan is an area with a high prevalence of osteoporosis. This updated summary of guidelines has been developed by experts of the Taiwan Osteoporosis Association with the intention of reducing the risks of osteoporotic fractures and improving the quality of care for patients with osteoporosis. The updated guidelines compile the latest evidence to provide clinicians and other healthcare professionals with practical recommendations for the prevention, diagnosis, and management of osteoporosis under clinical settings in Taiwan.

Outbreak investigation in a COVID-19 designated hospital: The combination of phylogenetic analysis and field epidemiology study suggesting airborne transmission.

BACKGROUND: Healthcare-associated COVID-19 infections caused by SARS-CoV-2 have increased morbidity and mortality. Hospitals and skilled nursing facilities (SNFs) have been challenged by infection control and management. METHODS: This case study presents an outbreak investigation in a COVID-19-designated hospital and a hospital-based SNF. Real-time polymerase chain reaction (PCR) and other studies were performed on samples obtained from SNF residents, hospital patients, and healthcare workers (HCWs). The results of the laboratory tests and field epidemiological data were analyzed. Genome sequencing and phylogenetic analysis of SARS-CoV-2 were performed to identify the associations between cases. The tracer gas was released and recorded by a thermal imaging camera to investigate the spatial relations within clusters. RESULTS: During the outbreak, 29 COVID-19 infections in 3 clusters were identified through hospital-wide, risk-guided, and symptom-driven PCR tests. This included 12 HCWs, 5 patients, and 12 SNF residents who had been hospitalized for at least 14 days. Serology tests did not identify any cases among the PCR-negative individuals. The phylogenetic analysis revealed that viral strains from the 3 clusters shared a common mutation of G3994T and were phylogenetically related, which suggested that this outbreak had a common source rather than multiple introductions from the community. Linked cases exhibited vertical spatial distribution, and the sulfur hexafluoride release test confirmed a potential airborne transmission. CONCLUSIONS: This report addressed the advantage of a multi-disciplinary team in outbreak investigation. Identifying an airborne transmission within an outbreak highlighted the importance of regular maintenance of ventilation systems.

Urban-rural differences in outcomes and management of vertebral fractures: A real-world observational study.

BACKGROUND: A fracture liaison services (FLSs) and its modified services reduce refractures and mortality and can be cost-effective. Limited studies have addressed whether urban-rural differences exist in vertebral fracture outcomes and management. Therefore, the aims of the study were to investigate any urban-rural differences in refracture, mortality, prescription pattern, and associated factors of vertebral fractures after receiving assistance from an FLSs. METHODS: Baseline characteristics and osteoporosis medication prescription patterns of participants were collected. After 1-year follow-up, mortality, refracture rate, and osteoporosis medication switching and adherence were evaluated. Multivariate logistic regressions were performed to identify baseline correlates on one-year mortality. RESULTS: There was higher mortality rate in the rural group but no urban-rural difference in the 1-year refracture rate after implementation of FLSs and medication management services (MMSs). The types of osteoporosis medications prescribed for both groups were similar, but participants in the rural group were less likely to change their osteoporosis medications during the 1-year follow-up timeframe and with lower adherence rate. The likelihood of being older and having chronic kidney disease, osteoarthritis, and neurological disease was higher in the rural group. CONCLUSION: Our multicomponent services have similar effectiveness in osteoporosis treatment between urban and rural areas. The overall adherence rate was lower in the rural group with higher mortality but no difference in the refracture rate in one year.

Low-dose tributyltin triggers human chondrocyte senescence and mouse articular cartilage aging.

Tributyltin (TBT) is known as an endocrine-disrupting chemical. This study investigated the effects and possible mechanisms of TBT exposure on inducing human articular chondrocyte senescence in vitro at the human-relevant concentrations of 0.01-0.5 µM and mouse articular cartilage aging in vivo at the doses of 5 and 25 µg/kg/day, which were 5 times lower than the established no observed adverse effect level (NOAEL) and equal to NOAEL, respectively. TBT significantly increased the senescence-associated ß-galactosidase activity and the protein expression levels of senescence markers p16, p53, and p21 in chondrocytes. TBT induced the protein phosphorylation of both p38 and JNK mitogen-activated protein kinases in which the JNK signaling was a main pathway to be involved in TBT-induced chondrocyte senescence. The phosphorylation of both ataxia-telangiectasia mutated (ATM) and histone protein H2AX (termed γH2AX) was also significantly increased in TBT-treated chondrocytes. ATM inhibitor significantly inhibited the protein expression levels of γH2AX, phosphorylated p38, phosphorylated JNK, p16, p53, and p21. TBT significantly stimulated the mRNA expression of senescence-associated secretory phenotype (SASP)-related factors, including IL-1ß, TGF-ß, TNF-α, ICAM-1, CCL2, and MMP13, and the protein expression of GATA4 and phosphorylated NF-κB-p65 in chondrocytes. Furthermore, TBT by oral gavage for 4 weeks in mice significantly enhanced the articular cartilage aging and abrasion. The protein expression of phosphorylated p38, phosphorylated JNK, GATA4, and phosphorylated NF-κB-p65, and the mRNA expression of SASP-related factors were enhanced in the mouse cartilages. These results suggest that TBT exposure can trigger human chondrocyte senescence in vitro and accelerating mouse articular cartilage aging in vivo.