Objectives: In a mouse model, aldehyde dehydrogenase 2 (ALDH2) knockout resulted in lower bone mineral density; however, higher parathyroid hormone receptor expression than wild-type mice. This study aimed to investigate whether ALDH2 polymorphisms influence efficacy of intermittent parathyroid hormone therapy and bone mineral density changes in humans. Methods: Eighty-two patients with primary osteoporosis treated with parathyroid hormone for > 1 year were divided into wild-type ALDH2 (ALDH2*1) and variant (ALDH2*2) groups. Bone mineral densities were measured by dual-energy X-ray absorptiometry. Changes in bone mineral density, treatment response, bone turnover markers, and new fracture incidence were evaluated. Furthermore, bone mineral density was analyzed using a mixed-effects model. Results: Femoral neck bone mineral density increased by 1.0 ± 7.4% in the ALDH2*1 group and 4.3 ± 8.1% in the ALDH2*2 group (P < 0.05), whereas lumbar spine bone mineral density increased by 5.7 ± 8.2% and 9.4 ± 9.1% without significance. Treatment success rates were higher in ALDH2*2 group (femoral neck 38.7%, lumbar spine 68.8%) compared with ALDH2*1 (16.3%, 51.0%). Statistical significance was observed only at the femoral neck. Bone turnover markers and fracture incidence were comparable between groups. Mixed-effects analysis adjusting for confounders showed a significant ALDH2 genotype × duration interaction for femoral neck, indicating genotype-related differences in the rate of bone mineral density increase over time. For lumbar spine, the genotype main effect was significant, whereas the interaction was not. Conclusions These findings suggest that ALDH2 polymorphisms may influence the therapeutic response to PTH treatment and highlight the need for larger future studies.

The quantitation of serum tocilizumab using liquid chromatography tandem-mass spectrometry(LC-MS/MS)method has not been widely applied in clinical settings because of its time-consuming and costly sample pretreatments.The present study aimed to develop a validated LC-MS/MS method for detecting serum tocilizumab by utilizing immobilized trypsin without an immunoglobulin G purification step and evaluate its applicability in the treatment of rheumatoid arthritis(RA)patients administered intrave-nously or subcutaneously with tocilizumab.The tocilizumab-derived signature peptide was deciphered using a nano-LC system coupled to a hybrid quadrupole-orbitrap mass spectrometer.The serum tocili-zumab was rapidly digested by immobilized trypsin for 30 min.The chromatographic peak of the signature peptide and that of the internal standard were separated from the serum digests for a total run time of 15 min.The calibration curve of serum tocilizumab concentration was linear with a range of 2-200 μg/mL.The intra-and inter-day accuracy and relative standard deviation(RSD)were 90.7％-109.4％and＜10％,respectively.The serum tocilizumab concentrations in the RA patients receiving intravenous and subcutaneous injections were 5.8-28.9 and 2.4-63.5 pg/mL,respectively.The serum tocilizumab concentrations using the current method positively correlated with those using the enzyme-linked immunosorbent assay,although a systematic error was observed between these methods.In conclu-sion,a validated LC-MS/MS method with minimal sample pretreatments for monitoring serum tocili-zumab concentrations in RA patients was developed.

Background/Aims: Chronic constipation and lifestyle factors can affect sleep quality. We evaluated the relationship between chronic constipation and sleep in the Japanese population. Methods: This cross-sectional internet-based survey included 3000 subjects with constipation, classified according to sleep status (good/poor).Primary endpoints were Bristol stool form scale (BSFS) score and correlations between sleep disorder criteria of the Pittsburgh Sleep Quality Index (PSQI) and sleep status (good/poor sleep). Secondary endpoints included correlations between quality of life (QOL) and mood, medical, lifestyle, and sleep factors. Results: The proportion of participants with BSFS category 4 (normal stool) was significantly higher in the good sleep group (P < 0.001). Sleep disturbance (P < 0.05), sleep quality, and duration, use of hypnotic medication, and daytime dysfunction of PSQI (all P < 0.001) significantly correlated with poor sleep. In the poor sleep group, QOL was significantly worse and anxiety and depression levels were significantly higher (allP < 0.001) compared with the good sleep group. Anemia and smoking (both P < 0.05), recent body weight increases, and poor eating habits (all P < 0.001) were significantly higher in the poor sleep group. Male sex, onset associated with change in frequency of stools, sensation of incomplete evacuation for at least 25% of defecations, and manual maneuvers to facilitate at least 25% of defecations correlated with poor sleep. Conclusions Subjects with constipation and poor sleep experienced severe symptoms and had poor QOL. These data support the need for a multifocal treatment approach, including lifestyle advice and pharmacotherapy.

Background/Aims: Chronic constipation and lifestyle factors can affect sleep quality. We evaluated the relationship between chronic constipation and sleep in the Japanese population. Methods: This cross-sectional internet-based survey included 3000 subjects with constipation, classified according to sleep status (good/poor).Primary endpoints were Bristol stool form scale (BSFS) score and correlations between sleep disorder criteria of the Pittsburgh Sleep Quality Index (PSQI) and sleep status (good/poor sleep). Secondary endpoints included correlations between quality of life (QOL) and mood, medical, lifestyle, and sleep factors. Results: The proportion of participants with BSFS category 4 (normal stool) was significantly higher in the good sleep group (P < 0.001). Sleep disturbance (P < 0.05), sleep quality, and duration, use of hypnotic medication, and daytime dysfunction of PSQI (all P < 0.001) significantly correlated with poor sleep. In the poor sleep group, QOL was significantly worse and anxiety and depression levels were significantly higher (allP < 0.001) compared with the good sleep group. Anemia and smoking (both P < 0.05), recent body weight increases, and poor eating habits (all P < 0.001) were significantly higher in the poor sleep group. Male sex, onset associated with change in frequency of stools, sensation of incomplete evacuation for at least 25% of defecations, and manual maneuvers to facilitate at least 25% of defecations correlated with poor sleep. Conclusions Subjects with constipation and poor sleep experienced severe symptoms and had poor QOL. These data support the need for a multifocal treatment approach, including lifestyle advice and pharmacotherapy.