Hypocalcemia is the most common major adverse event in patients with osteoporosis receiving the bone resorption inhibitor denosumab; however, limited information is available regarding risk factors of hypocalcemia. Therefore, this study aimed to identify the risk factors of hypocalcemia induced by denosumab treatment for osteoporosis. We retrospectively reviewed the records of patients who had received initial denosumab supplemented with activated vitamin D for osteoporosis. Serum levels of the following bone turnover markers (BTMs) were measured at baseline: bone-specific alkaline phosphatase (BAP), total N-terminal propeptide of type 1 procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and urinary cross-linked N-telopeptide of type 1 collagen (NTX). Of the 85 denosumab-treated patients with osteoporosis studied, 22 (25.9%) developed hypocalcemia. Baseline serum total P1NP, TRACP-5b, and urinary NTX were significantly higher in patients with hypocalcemia than in those with normocalcemia following denosumab administration (all P<0.01). Multivariate logistic regression analysis revealed that patients with total P1NP >76.5 μg/L, TRACP-5b >474 mU/dL, or urinary NTX >49.5 nmol bone collagen equivalent/mmol creatinine had a higher risk of hypocalcemia (P<0.01). Our study suggests that denosumab may have a greater impact on serum calcium levels in patients with postmenopausal osteoporosis with higher baseline bone turnover than in patients with postmenopausal osteoporosis with normal baseline bone turnover, because maintenance of normal serum calcium in this subgroup is more dependent on bone resorption. Close monitoring of serum calcium levels is strongly recommended for denosumab-treated patients with high bone turnover, despite supplementation with activated vitamin D and oral calcium.
There is growing interest in “osteosarcopenia” as the coexistence of osteoporosis and sarcopenia exacerbates negative outcomes. However, limited information is available regarding the risk factors of osteosarcopenia development in patients with osteoporosis. Therefore, we retrospectively reviewed 276 consecutive patients with postmenopausal osteoporosis who regularly visited Showa University Hospital. Patients were eligible for the study if they were ≥65 years of age and underwent dual-energy X-ray absorptiometry, blood sampling, and physical performance assessment. Patients were divided into the osteosarcopenia and osteoporosis alone groups according to the diagnostic criteria of the Asian Working Group for Sarcopenia. Of the 276 patients with osteoporosis, 54 patients (19.6%) had osteosarcopenia. Patients in the osteosarcopenia group had a greater risk of frailty than did those in the osteoporosis alone group (odds ratio 2.33; 95% confidence interval, 1.13–4.80, P = 0.028). Low body mass index seemed to be the strongest factor related to the development of osteosarcopenia, and none of the patients in the osteosarcopenia group were obese (BMI ≥27.5 kg/m 2 ). Multiple logistic analyses revealed that patients aged 65–74 years who had comorbidities such as kidney dysfunction and high levels of HbA1c were at risk of developing osteosarcopenia. Thus, we strongly recommend the assessment of the key components of the diagnosis of osteosarcopenia in an osteoporosis clinic for patients with low body mass index. Furthermore, appropriate assessments, including comorbidities, will help in identifying patients at greater risk of developing osteosarcopenia.
Luteolin is a natural flavonoid with strong anti-oxidative properties that is reported to have an anti-cancer effect in several malignancies other than bladder cancer. In this study, we describe the effect of luteolin on a human bladder cancer cell line, T24, in the context of the regulation of p21, thioredoxin-1 (TRX1) and the mechanistic target of rapamycin (mTOR) pathway. Luteolin inhibited cell survival and induced G2/M cellcycle arrest, p21 upregulation and downregulation of phospho(p)-S6, which is downstream of mTOR signaling. Luteolin also upregulated TRX1 and reduced intracellular reactive oxygen species production. In a subcutaneous xenograft mouse model using the rat bladder cancer cell line, BC31, tumor volumes were significantly decreased in mice orally administered luteolin compared to control. Immunohistochemical analysis revealed that increased p21 and decreased p-S6 expression were induced in the luteolin treatment group. Moreover, in another in vivo N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer model, the oral administration of luteolin led to a trend of decreased bladder tumor dimension and significantly decreased the Ki67-labeling index and p-S6 expression. Furthermore, the major findings on the metabolism of luteolin suggest that both plasma and urine luteolin-3ʹ-O-glucuronide concentrations are strongly associated with the inhibition of cell proliferation and mTOR signaling. Moreover, a significant decrease in the squamous differentiation of bladder cancer is attributed to plasma luteolin-3ʹ-glucuronide concentration. In conclusion, luteolin, and in particular its metabolized product, may represent another natural product-derived therapeutic agent that acts against bladder cancer by upregulating p21 and inhibiting mTOR signaling. K E Y W O R D Sanimal model, bladder cancer, chemoprevention, mTOR, oxidative stress
The preoperative measurement of PS-vBMD was technically feasible and reliably predictive of screw insertional torque during transpedicular fixation in a clinical setting.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.