Objective:To investigate the frailty state transition in the community-dwelling elderly undergoing health check-up, and related influencing factors.Methods:From September to October 2016, 3 833 residents aged ≥ 60 years undergoing health check-up in Xidu Community Health Center were enrolled in this prospective cohort study by multistage random sampling. All participants completed a questionnaire survey, health examinations, and frailty assessments as measured with the Fried frailty phenotype. A second assessment of frailty status was conducted from June to July 2020, the frailty state transition was analyzed by comparison between two assessments of frailty states. Logistic regression was used to analyze the influencing factors related to frailty progression.Results:The final cohort consisted of 3 061 participants. At the entering of the study, the median age of participants was 71.0 years, 41.0% were male, 1 563 (51.1%) were prefrail, and 156 (5.1%) were frail. At the follow-up, the frailty status of 1 304 (42.6%) participants was progressed and that of 395 (12.9%) participants was improved from their baseline levels, respectively. Logistic regression showed that age ( OR=1.170,95% CI:1.147-1.194), marital status (married: OR=0.377,95% CI:0.292-0.486), physical exercise (never vs. every day: OR=18.610,95% CI:14.461-23.950; sometimes vs. every day: OR=4.210,95% CI:2.186-8.107), baseline frailty state (robust vs. frail: OR=20.464,95% CI:11.779-35.553;prefrail vs. frail: OR=2.147,95% CI:1.270-3.632), stroke ( OR=2.195,95% CI:1.454-3.313) and diabetes ( OR=1.811,95% CI:1.346-2.437) were identified as independent factors influencing frailty progression (all P<0.05). Conclusions:Frailty state progression is common among older adults, and its related factors include age, unmarried status, physical exercise, baseline frailty state, stroke and diabetes. It is necessary to identify elderly at high risk for frailty progression and implement medical interventions.

Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c.163G>C (p.Val55Leu) mutation in FKBP5 (encodes FK506-binding protein 51, FKBP51) associated with PDB using whole-exome sequencing. Mutant FKBP51 enhanced the Akt phosphorylation and kinase activity in cells. A study of osteoclast function using FKBP51V55L KI transgenic mice proved that osteoclast precursors from FKBP51V55L mice were hyperresponsive to RANKL, and osteoclasts derived from FKBP51V55L mice displayed more intensive bone resorbing activity than did FKBP51WT controls. The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. However, c-fos expression showed no significant difference in the wild-type and mutant groups. Akt phosphorylation in FKBP51V55L BMMs was elevated in response to RANKL. In contrast, IκB degradation, ERK phosphorylation and LC3II expression showed no difference in wild-type and mutant BMMs. Micro-CT analysis revealed an intensive trabecular bone resorption pattern in FKBP51V55L mice, and suspicious osteolytic bone lesions were noted in three-dimensional reconstruction of distal femurs from mutant mice. These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.
Acid Phosphatase ; Animals ; Asian Continental Ancestry Group ; Bone Diseases, Metabolic ; Bone Remodeling ; Bone Resorption ; Femur ; Humans ; Mice ; Mice, Transgenic ; Osteitis Deformans* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Phosphorylation ; Phosphotransferases ; Tacrolimus Binding Proteins ; Transcription Factors