Early-onset dementia and risk of hip fracture and major osteoporotic fractures.

INTRODUCTION: There is limited knowledge about early-onset dementia (EOD) on fracture risk. METHODS: Individuals ages 50 to 64 were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (2012 to 2019). The association between EOD and fractures and the association between cholinesterase inhibitors for EOD and fractures were evaluated using logistic regression analyses. RESULTS: We identified 13,614 EOD patients and 9,144,560 cognitively healthy individuals. The analysis revealed that EOD was associated with an increased risk of hip fractures (adjusted odds ratio, 95% confidence interval: 8.79, 7.37-10.48), vertebral fractures (1.73, 1.48-2.01), and major osteoporotic fractures (2.05, 1.83-2.30) over 3 years. The use of cholinesterase inhibitors was significantly associated with a reduction in hip fractures among EOD patients (0.28, 0.11-0.69). DISCUSSION: EOD patients have a higher risk of osteoporotic fractures than cognitively healthy individuals. The use of cholinesterase inhibitors may reduce the risk of hip fracture among EOD patients. HIGHLIGHTS: It is unknown whether early-onset dementia (EOD) increases the risk of fractures. We identified 13,614 individuals with EOD using a nationwide administrative database. Patients with EOD have a higher risk of hip, vertebral, and major osteoporotic fractures. The use of cholinesterase inhibitors may reduce hip fracture among patients with EOD.

Exercise-induced vitamin D receptor and androgen receptor mediate inhibition of IL-6 and STAT3 in muscle.

Background: Skeletal muscle produces interleukin-6 (IL-6) during exercise as a myokine. Although IL-6 is required for skeletal muscle regeneration, its action increases the expression of myostatin and other proteins involved in muscle atrophy, resulting in skeletal muscle atrophy. In this study, we clarified the effects exercise-induced vitamin D receptor (VDR) and androgen receptor (AR) expression on IL-6 and signal transducer and activator of transcription 3 (STAT3) in vivo and in vitro. Method: C2C12 myotubes were subjected to electric pulse stimulation (EPS) in vitro. To evaluate VDR and AR function, a VDR/AR agonist and antagonist were administered before EPS to C2C12 myotubes. C57BL6 mice underwent 4 weeks of exercise. The expression levels of proteolytic-associated genes, including CCAAT/enhancer-binding protein delta (C/EBPδ) and myostatin, were measured by quantitative real-time polymerase chain reaction, and phosphorylated and total STAT3 levels were measured by Western blot analysis. Result: The expression of VDR and AR mRNA was induced following EPS in C2C12 myotubes. IL-6 mRNA expression was also increased with a peak at 6 h after EPS and p-STAT3/STAT3 ratio reciprocally decreased. Although VDR/AR agonist administration decreased IL-6 mRNA expression and p-STAT3/STAT3 ratio, these two endpoints increased after treatment with VDR/AR antagonist, respectively. Exercise in mice also increased the expression of VDR/AR and IL-6 mRNA and decreased p-STAT3/STAT3 ratio. Conclusion: Exercise-induced VDR and AR expression results in the suppression of IL-6 mRNA and STAT3 phosphorylation in skeletal muscle.

Prescription of vitamin D was associated with a lower incidence of hip fractures.

Patients with osteoporosis are prone to fragility fractures. Evidence of the effects of active forms of vitamin D on hip fracture prevention is insufficient. We examined the association between vitamin D prescription and incidence of new fractures using the data of osteoporotic patients from the nationwide health insurance claims database of Japan. The follow-up period was 3 years after entry. The untreated patients were never prescribed vitamin D during follow-up (n = 422,454), and the treated patients had a vitamin D medication possession ratio of ≥ 0.5 at all time points (n = 169,774). Propensity score matching was implemented on these groups, yielding 105,041 pairs, and subsequently, the control and treatment groups were established and analyzed. The incidence of new fractures was significantly lower in the treatment group compared with the control group (6.25% vs. 5.69%, hazard ratio 0.936 [95% confidence interval 0.904-0.970], p < 0.001*). By site, hip fractures significantly decreased (0.89% vs. 0.42%, p < 0.001), but not vertebral and radial fractures. Subgroup analysis by vitamin D type showed a significantly lower incidence of total fractures only in alfacalcidol (hazard ratio 0.676 [95% confidence interval 0.628-0.728], p < 0.001*). The results suggest that vitamin D prescription was associated with a reduced incidence of hip fractures.

Association between the type of hypnotic drug and in-hospital fractures in older patients with neurocognitive disorders: A case-control study using a nationwide database.

AIM: Hypnotics might increase the risk of falls and fractures in older patients with neurocognitive disorders. Orexin receptor antagonists have recently been approved, but the relationship between the new drugs and fractures remains unclarified. This study aimed to evaluate the association between the type of hypnotic and in-hospital fractures in older patients with neurocognitive disorders using a nationwide inpatient database. METHODS: Using the Japanese Diagnosis Procedure Combination database, we collected information on inpatients aged ≥65 years with neurocognitive disorders between April 2014 and March 2021. We examined trends in the prescription patterns of benzodiazepine drugs, Z-drugs, orexin receptor antagonists and melatonin receptor agonists. We also carried out a 1:4 matched case-control analysis of in-hospital fractures. The odds ratio of each hypnotic drug was estimated using a generalized estimating equation with adjustment for walking ability, comorbidities, osteoporosis, dialysis, selective serotonin reuptake inhibitor use and anti-dementia drug use. RESULTS: The prescription of benzodiazepine hypnotics decreased and that of orexin receptor antagonists increased. This case-control analysis included 6832 patients with fractures and 23 463 controls. Ultrashort-acting benzodiazepines, short-acting benzodiazepines and Z-drugs were associated with an increased risk of bone fracture (odds ratio [95% confidence interval] 1.38 [1.08-1.77], 1.38 [1.27-1.50], 1.49 [1.37-1.61], respectively). Orexin receptor antagonists were not associated with an increased risk of bone fracture (1.07 [0.95-1.19]). CONCLUSIONS: In contrast to other types of hypnotics, orexin receptor antagonists were not associated with in-hospital fractures in older patients with neurocognitive disorders. Geriatr Gerontol Int 2023; 23: 500-505.

Relationship between antidementia medication and fracture prevention in patients with Alzheimer's dementia using a nationwide health insurance claims database.

This retrospective study aimed to evaluate the association between antidementia medication use and incidence of new vertebral, hip, and radial fractures in patients with Alzheimer's dementia (AD). We used the nationwide health insurance claims database of Japan from 2012 to 2019 and identified 12,167,938 patients aged ≥ 65 years who were newly registered from April 2012 to March 2016 and had verifiable data receipt from half-year before to 3 years after the registration. Among these patients, 304,658 were diagnosed with AD and we showed the prescription status of antidementia and osteoporosis medication among them. Propensity score matching was conducted for AD group with and without antidementia medication use, and 122,399 matched pairs were yielded. The incidence of hip fractures (4.0% vs. 1.9%, p < 0.001) and all clinical fractures (10.5% vs. 9.0%, p < 0.001) significantly decreased and that of radial fractures increased (0.6% vs. 1.0%, p < 0.001) in AD patients with antidementia medication use compared with AD patients without antidementia medication use. No significant difference was found in vertebral fractures (6.6% vs. 6.5%, p = 0.51). Overall, these results suggest a positive relationship between antidementia medication use and fracture prevention in patients with AD.

Validation of the questionnaire for medical checkup of old-old (QMCOO) score cutoff to diagnose frailty.

BACKGROUND: Frailty is a state of increased vulnerability to poor resolution of homeostasis following a stress. Early diagnosis and intervention of frailty are essential to prevent its adverse outcomes. However, simple diagnostic criteria have not been established. The Questionnaire for Medical Checkup of Old-Old (QMCOO) is widely used for medical checkups of older adults in Japan. In our previous report, we developed a method to score the QMCOO and showed that frailty can be diagnosed with the highest accuracy when the score cutoff was set at 3/4 points. We aimed to validate the criteria in a larger cohort. METHODS: Participants aged 65 years or over were recruited in the western region of Japan. They answered all the items of the Kihon Checklist (KCL) and the QMCOO. Based on the KCL score, they were diagnosed as robust (3 or lower), prefrail (4 to 7), or frail (8 or over). Then we tested the effectiveness to diagnose frailty using the QMCOO cutoff of 3/4 points. We also aimed to determine the score cutoff to separate robust and prefrail. RESULTS: 7,605 participants (3,458 males and 4,147 females, age 77.4 ± 6.9 years) were recruited. 3,665 participants were diagnosed as robust, 2,448 were prefrail, and 1,492 were frail based on the KCL score. The diagnosis of frailty had a sensitivity of 84.0%, specificity of 82.5%, and accuracy of 82.8% with a QMCOO score cutoff of 3/4 points, suggesting its validity. To separate robust and prefrail, both the accuracy and the Youden index were the highest with the QMCOO cutoff of 2/3 points (sensitivity, specificity, and accuracy were 63.9%, 83.4%, and 75.6%, respectively). All the questions of the QMCOO except Q12 (about smoking) were significantly related to prefrailty status after a logistic regression analysis. CONCLUSION: Diagnosis of frailty using the QMCOO score cutoff of 3/4 points was validated. Prefrailty could be diagnosed using the score cutoff of 2/3 points.

Effectiveness of the Questionnaire for Medical Checkup of Old-Old (QMCOO) to diagnose frailty in community-dwelling older adults.

AIM: Although frailty could be reversible by early diagnosis and interventions, it lacks definite diagnostic criteria. The Kihon Checklist is a 25-item questionnaire that diagnoses frailty with a cutoff score of 7/8. The Questionnaire for Medical Checkup of Old-Old (QMCOO) was recently established and used for medical checkups among Japanese older adults, but no method or cutoff score for diagnosing frailty has been established. Thus, we aimed to diagnose frailty using the QMCOO and to determine its cutoff score by comparing it with that of the Kihon Checklist. METHODS: We recruited 223 older adults in Yasugi City and Yonago City to answer all the questions in the Kihon Checklist and the QMCOO at the same time. Those scoring ≥8 for the Kihon Checklist (n = 38) were diagnosed as frail. We also determined the cutoff score for frailty for the QMCOO and examined which questionnaire items affected the frailty status. RESULTS: The QMCOO and the Kihon Checklist score showed a significant positive correlation (r = 0.670, P < 0.001). The area under the curve was 0.851. A cutoff score of 3/4 for the QMCOO represented the best results (sensitivity, 76.3%; specificity, 88.1%; and accuracy, 86.1%). Multiple linear regression analysis revealed that subjective health status, body weight loss, slowness, and forgetfulness still affected the frailty status. CONCLUSIONS: A cutoff score of 3/4 for the QMCOO might be effective in diagnosing frailty. Geriatr Gerontol Int 2022; 22: 127-131.

[A case of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in an elderly woman].

An 84-year-old woman who had diabetes mellitus and atrial fibrillation presented to our hospital with appetite loss and difficulty in standing up. Her cervical, axillary, and mediastinal lymph nodes were swollen. At first, malignant lymphoma was suspected, but positron emission tomography-computed tomography and cervical lymph node biopsy did not support this diagnosis. She was admitted to our hospital 41 days after the first consultation because of appetite loss and fever. We suspected a disorder related to Epstein-Barr virus infection because Epstein-Barr virus-encoded small RNAs were found in the lymph node. She was diagnosed with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) based on the diagnostic criteria of the Japanese Society for Pediatric Infectious Diseases. Her symptoms, including appetite loss and fever, were alleviated after the administration of prednisolone (20 mg per day). She was discharged 90 days after admission. At two weeks after discharge, she was readmitted for respiratory failure, and died five days after readmission.To the best of our knowledge there are no previous reports of EBV-HLH in patients over 80 years of age, and the optimal treatment strategy is unknown. This case suggested that prednisolone may alleviate the symptoms of EBV-HLH. When a patient presents with swollen lymph nodes, clinicians should keep the possibility of EBV-HLH in mind.