Hydroxychloroquine and a low activity bisphosphonate conjugate prevent and reverse ovariectomy-induced bone loss in mice through dual antiresorptive and anabolic effects.

Osteoporosis is incurable because there are no dual antiresorptive and anabolic therapeutic agents that can be administered long-term. The most widely used antiresorptive agents, bisphosphonates (BPs), also inhibit bone formation and thus have limited effect in preventing osteoporotic fracture. Hydroxychloroquine (HCQ), which is used to treat rheumatoid arthritis, prevents the lysosomal degradation of TNF receptor-associated factor 3 (TRAF3), an NF-κB adaptor protein that limits bone resorption and maintains bone formation. We attempted to covalently link HCQ to a hydroxyalklyl BP (HABP) with anticipated low antiresorptive activity, to target delivery of HCQ to bone to test if this targeting increases its efficacy to prevent TRAF3 degradation in the bone microenvironment and thus reduce bone resorption and increase bone formation, while reducing its systemic side effects. Unexpectedly, HABP-HCQ was found to exist as a salt in aqueous solution, composed of a protonated HCQ cation and a deprotonated HABP anion. Nevertheless, it inhibited osteoclastogenesis, stimulated osteoblast differentiation, and increased TRAF3 protein levels in vitro. HABP-HCQ significantly inhibited both osteoclast formation and bone marrow fibrosis in mice given multiple daily PTH injections. In contrast, HCQ inhibited fibrosis, but not osteoclast formation, while the HABP alone inhibited osteoclast formation, but not fibrosis, in the mice. HABP-HCQ, but not HCQ, prevented trabecular bone loss following ovariectomy in mice and, importantly, increased bone volume in ovariectomized mice with established bone loss because HABP-HCQ increased bone formation and decreased bone resorption parameters simultaneously. In contrast, HCQ increased bone formation, but did not decrease bone resorption parameters, while HABP also restored the bone lost in ovariectomized mice, but it inhibited parameters of both bone resorption and formation. Our findings suggest that the combination of HABP and HCQ could have dual antiresorptive and anabolic effects to prevent and treat osteoporosis.

An analysis of socioeconomic factors on multiple chronic conditions and its economic burden: evidence from the National Health Service Survey in Yunnan Province, China.

Background: The economic burden of multiple chronic conditions (MCCs) and its socio-economic influencing factors have widely raised public concerns. However, there are few large population-based studies on these problems in China. Our study aims at determining the economic burden of MCCs and associated factors specific to multimorbidity among middle-aged and older individuals. Methods: As our study population, we extracted all 11,304 participants over 35 years old from the 2018 National Health Service Survey (NHSS) in Yunnan. Economic burden and socio-demographic characteristics were analyzed with descriptive statistics. Chi-square test and generalized estimating equations (GEE) regression models were used to identify influencing factors. Results: The prevalence of chronic diseases was 35.93% in 11,304 participants and the prevalence of MCCs increased with age, was 10.12%. Residents who lived in rural areas were more likely to report MCCs than those who lived in urban areas (adjusted OR = 1.347, 97.5% CI: 1.116-1.626). Ethnic minority groups were less likely to report MCCs than those of Han (OR = 0.752, 97.5% CI: 0.601-0.942). Overweight or obese people were more likely to report MCCs than people with normal weight (OR = 1.317, 97.5% CI: 1.099-1.579). The per capita expenses of 2 weeks' illness, per capita hospitalization expenses, annual household income, annual household expenses, and annual household medical expenses of MCCs were ¥292.90 (±1427.80), ¥4804.22 (±11851.63), ¥51064.77 (±52158.76), ¥41933.50 (±39940.02) and ¥11724.94 (±11642.74), respectively. The per capita expenses of 2 weeks' illness, per capita hospitalization expenses, annual household income, annual household cost, and annual household medical expenses of hypertensive co-diabetic patients were more compared to those with other three comorbidity modes. Conclusion: The prevalence of MCCs was relatively high among middle-aged and older individuals in Yunnan, China, which bought a heavy economic burden. This encourages policy makers and health providers to pay more attention to the behavioral/lifestyle factors, that contribute to multimorbidity to a great extent. Furthermore, health promotion and education in terms of MCCs need to be prioritized in Yunnan.

Prevalence and influencing factors of chronic pain in middle-aged and older adults in China: results of a nationally representative survey.

Background: With China's rapidly aging population, chronic pain has become a major public health issue. This article aims at determining associations between chronic pain and multiple factors, including demographic characteristics, health status, and health service utilization of middle-aged and older adults in China. Methods: We selected all the 19,829 respondents who were over 45 years old from the China Health and Aging Tracking Survey 2018 (CHARLS) as our study population. The key information in terms of the body pain, demographic characteristics, health status, behaviors and health services use was extracted and analyzed. Logistic regression model was used to determine the influencing factors of chronic pain. Results: Analysis revealed that 60.02% (9,257) of the data from this survey reported physical pain, with pain sites concentrated at the head (40.9%), lower back (62.2%) and knees (47.2%). Pain was positively associated with influencing factors for pain: being a female (OR = 2.10, 95% CI 1.90-2.33, p < 0.001), living in a western region (OR = 1.28, 95% CI 1.16-1.41, p < 0.001), living in a rural area (OR = 1.14, 95% CI 1.06-1.23, p < 0.001), smoked (OR = 1.26, 95% CI 1.14-1.38, p < 0.001), drank alcohol (OR = 1.16, 95% CI 1.06-1.26, p = 0.001), and had poor self-rated health (OR = 6.84, 95% CI 5.41-8.65, p < 0.001), had hearing problems (OR = 1.23, 95% CI 1.11-3.37, p < 0.001), were depressed (OR = 1.56, 95% CI 1.03-1.29, p < 0.001), had arthritis (OR = 2.21, 95% CI 2.02-2.41, p < 0.001), stomach disorders (OR = 1.69, 95% CI 1.55-1.85, p < 0.001), visited a Western medicine hospital (OR = 1.28, 95% CI 1.10-1.50, p = 0.002), and visits to other medical institutions (OR = 1.42, 95%CI 1.22-1.64, p < 0.001). On the other side, as a protective factor for pain, having nighttime sleep ≥7 h (OR = 0.74, 95%CI 0.68-0.80, p < 0.001) was negatively associated with pain. Conclusion: Physical pain affects many older adults. Women, regional, rural residents, smokers, alcohol drinkers, people with poor self-rated health, those having <7 h of sleep at night, those with hearing problems, depression, arthritis, stomach disorders, and people who visits Western hospitals or other medical institutions are at greater risk for pain and deserve the attention of health care providers and policy makers to focus on pain prevention and management in middle-aged and older adults. Future research studies should also focus on the impact of health literacy on pain prevention and management outcomes.

Examining the impact of chronic diseases on activities of daily living of middle-aged and older adults aged 45 years and above in China: a nationally representative cohort study.

Background: China has by far one of the fastest-aging populations in the world. Increasing age is often accompanied by an increasing prevalence of chronic diseases and impaired Activities of Daily Living (ADL). The aim of this study was to analyze the effects of chronic diseases on ADL in Chinese middle-aged and older adults and to provide a scientific basis for delaying the impairment of ADL and prolonging the self-care life expectancy of middle-aged and older adults. Methods: This investigation utilized the survey information of 10,096 middle-aged and older adults from the China Health and Aging Tracking Survey (CHARLS) of 2011 as baseline data, then followed up this cohort until 2018, and performed multifactorial analyses using Cox proportional risk models to explore the strength of the associations between chronic diseases and the risk of impaired ADL in middle-aged and older adults. Results: Among the middle-aged and older adult population, the presence of hypertension was associated with a 38% higher risk of impaired ADL compared to those without the condition (HR = 1.38,95% CI:1.24-1.54); the involvement of heart disease was associated with a 27% higher risk of impaired ADL compared to those without the condition (HR = 1.27,95% CI:1.10- 1.46); the existence of arthritis was associated with a 38% higher risk of impaired ADL in middle-aged and older adults compared to those without arthritis (HR = 1.38,95% CI:1.25-2.08); additionally, the risk of impaired ADL with one or ≥ 2 chronic diseases was increased by 34% (HR = 1.34, 95% CI:1.18-1.52) and 84% (HR = 1.84, 95% CI:1.63-2.08) in middle-aged and older adult individuals, respectively. Conclusion: Hypertension is a risk factor for impaired ADL at any age in the subjects of this study. Examining the association between the number of chronic diseases and impairment in activities of daily living, it was revealed that the risk of ADL impairment increased with the number of chronic diseases in both the middle-aged (45-59 years) and older adult (60-74 years) groups.