Objective:To systematically evaluate the relationship between thiazide diuretics and the risk of hip fracture in the elderly patients.Methods:The relevant databases at home and abroad were searched up to December 31, 2023 and case-control studies and cohort studies on the relationship between thiazide diuretics and the risk of hip fractures in the elderly patients were collected. Quality of the enrolled studies was evaluated by bias risk assessment tool of Newcastle-Ottawa Scale (NOS). RevMan 5.4 software was used for meta-analysis on related outcome indicators, and the effect sizes were odds ratio ( OR) and the 95% confidence interval ( CI). Funnel plots, Egger′s method and Begg′s method were performed using Stata 15.1 software to analyze the inclusion literature for publication bias. Results:A total of 18 studies were enrolled in the study, including 7 case-control studies and 11 cohort studies and involving 175 200 patients in the trial group (thiazide diuretics) and 1 574 989 in the control group (placebo or other medications). All 18 studies scored ≥5 on the NOS (15 articles of high quality and 3 articles of medium quality). The meta-analysis results indicated that the risk of hip fractures in the trial group was lower than that in the control group ( OR=0.82, 95% CI: 0.75-0.89, P<0.001). Subgroup analyses by study type and gender both revealed that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR in case-control studies was 0.78, 95% CI: 0.72-0.84, P<0.001; adjusted OR in cohort studies was 0.83, 95% CI: 0.74-0.93, P=0.002; adjusted OR in female was 0.78, 95% CI: 0.72-0.85, P<0.001; adjusted OR in male was 0.73, 95% CI: 0.68-0.80, P<0.001). The subgroup analysis of 11 large-sample studies (≥2 000 cases) indicated that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR=0.79, 95% CI: 0.72-0.87, P<0.001). However, 6 small-sample studies did not find the similar correlation. A combined analysis of studies that rigorously controlled for confounding factors revealed that thiazide diuretics were associated with a lower risk of hip fractures in the elderly ( OR=0.79, 95% CI: 0.74-0.84, P<0.001), and the combined results showed no heterogeneity ( P=0.72, I2=0%). Conclusions:Thiazide diuretics were associated with a reduced risk of hip fractures in the elderly patients. Based on a comprehensive assessment of the risks and benefits of medication for elderly patients, clinicians may prioritize thiazide diuretics as a component of combination therapy for eligible patients, which may be beneficial in reducing their risk of hip fractures.

Objective:To systematically evaluate the relationship between thiazide diuretics and the risk of hip fracture in the elderly patients.Methods:The relevant databases at home and abroad were searched up to December 31, 2023 and case-control studies and cohort studies on the relationship between thiazide diuretics and the risk of hip fractures in the elderly patients were collected. Quality of the enrolled studies was evaluated by bias risk assessment tool of Newcastle-Ottawa Scale (NOS). RevMan 5.4 software was used for meta-analysis on related outcome indicators, and the effect sizes were odds ratio ( OR) and the 95% confidence interval ( CI). Funnel plots, Egger′s method and Begg′s method were performed using Stata 15.1 software to analyze the inclusion literature for publication bias. Results:A total of 18 studies were enrolled in the study, including 7 case-control studies and 11 cohort studies and involving 175 200 patients in the trial group (thiazide diuretics) and 1 574 989 in the control group (placebo or other medications). All 18 studies scored ≥5 on the NOS (15 articles of high quality and 3 articles of medium quality). The meta-analysis results indicated that the risk of hip fractures in the trial group was lower than that in the control group ( OR=0.82, 95% CI: 0.75-0.89, P<0.001). Subgroup analyses by study type and gender both revealed that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR in case-control studies was 0.78, 95% CI: 0.72-0.84, P<0.001; adjusted OR in cohort studies was 0.83, 95% CI: 0.74-0.93, P=0.002; adjusted OR in female was 0.78, 95% CI: 0.72-0.85, P<0.001; adjusted OR in male was 0.73, 95% CI: 0.68-0.80, P<0.001). The subgroup analysis of 11 large-sample studies (≥2 000 cases) indicated that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR=0.79, 95% CI: 0.72-0.87, P<0.001). However, 6 small-sample studies did not find the similar correlation. A combined analysis of studies that rigorously controlled for confounding factors revealed that thiazide diuretics were associated with a lower risk of hip fractures in the elderly ( OR=0.79, 95% CI: 0.74-0.84, P<0.001), and the combined results showed no heterogeneity ( P=0.72, I2=0%). Conclusions:Thiazide diuretics were associated with a reduced risk of hip fractures in the elderly patients. Based on a comprehensive assessment of the risks and benefits of medication for elderly patients, clinicians may prioritize thiazide diuretics as a component of combination therapy for eligible patients, which may be beneficial in reducing their risk of hip fractures.

Lumican is a member of the small leucine-rich proteoglycan family, which is involved in cell processes related to tumorigenesis and development, such as epithelial-mesenchymal transition, cell proliferation, migration, invasion and adhesion. The expression of Lumican in different tumors is positively or negatively correlated with tumor progression, and can be used as a reference for tumor prognosis and efficacy evaluation. Further study of the correlation and potential mechanism between Lumican and tumor therapy resistance can provide new ideas for predicting clinical therapeutic efficacy.