Low Dose of Bisphosphonate Enhances Sclerostin Antibody‐Induced Trabecular Bone Mass Gains in Brtl/+ Osteogenesis Imperfecta Mouse Model

Osteogenesis imperfecta (OI) is a genetic disorder characterized by altered bone quality and imbalanced bone remodeling, leading to skeletal fractures that are most prominent during childhood. Treatments for OI have focused on restoring pediatric bone density and architecture to recover functional strength and consequently reduce fragility. Though antiresorptive agents like bisphosphonates (BPs) are currently the most common intervention for the treatment of OI, a number of studies have shown efficacy of sclerostin antibody (SclAb) in inducing gains in bone mass and reducing fragility in OI mouse models. In this study, the effects of the concurrent use of BP and SclAb were evaluated during bone growth in a mouse harboring an OI‐causing Gly→Cys mutation on col1a1. A single dose of antiresorptive BP facilitated the anabolic action of SclAb by increasing availability of surfaces for new bone formation via retention of primary trabeculae that would otherwise be remodeled. Chronic effects of concurrent administration of BP and SclAb revealed that accumulating cycles conferred synergistic gains in trabecular mass and vertebral stiffness, suggesting a distinct advantage of both therapies combined. Cortical gains in mass and strength occurred through SclAb alone, independent of presence of BP. In conclusion, these preclinical results support the scientific hypothesis that minimal antiresorptive treatment can amplify the effects of SclAb during early stages of skeletal growth to further improve bone structure and rigidity, a beneficial outcome for children with OI. © 2018 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144688/1/jbmr3421.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144688/2/jbmr3421_am.pd

Do People with Type 2 Diabetes Think They are Unhealthy? A Cross-Sectional Study in Celaya, Mexico

Background: Type 2 diabetes is a chronic disease that presents a significant burden on health care systems in many countries. With the rise of obesity, the incidence of Type 2 diabetes has also been steadily increasing. A healthy lifestyle and understanding of diabetes management are important factors for delaying the onset of comorbidities associated with Type 2 diabetes. The objective of this study was to evaluate the self-perception of health in individuals with Type 2 diabetes as it relates to BMI status, which has important implications for the implementation of preventive programs. Methods: A cross-sectional lifestyle survey was implemented in the region of Celaya, Guanajuato, Mexico, targeting 100 participants diagnosed with Type 2 diabetes. Anthropometric measurements and participant characteristics were also obtained. Fisher’s exact test was used to determine if the proportions of lifestyles perceptions differed by BMI status. Results:  Participants had a mean age of 56.12 ± 10.26, a mean BMI of 29.13 ± 5.48 kg/m2, were mostly married (67.0%), and female (70.0%). None of the normal weight participants perceived themselves as unhealthy. 95% of overweight/obese participants perceived themselves to be healthy, despite a diagnosis of diabetes and being overweight/obese, while only 5% perceived themselves to be unhealthy. However, these differences in the perceptions of health classified by BMI status were not statistically significant (p = 0.42).Conclusion: Our findings indicate that overweight and obese persons with Type 2 diabetes in Celaya, Mexico may have misperceptions about their own health, even though these findings were not statistically significant. These preliminary data highlight the importance of implementing prevention and educational programs among those with diabetes, in order to combat health misperceptions and raise awareness about the dangers of diabetes and obesity. Furthermore, more research with larger sample sizes is needed  in order to fully understand the effects of perception of health on actual health.

Racial Differences in Vascular Function in Response to Mental Stress

African Americans (AA) have a higher prevalence of hypertension and other cardiovascular (CV) complications compared to other populations. While the reasons for this elevated CV disease risk are multifactorial, vascular dysfunction is a key contributing factor. It has been previously shown that mental stress, induced by mental arithmetic, results in a significant increase in forearm blood flow (FBF). This response has been predominantly attributed to the release and vasodilatory effect of Nitric Oxide (NO). In this regard, a previous study has reported that AA have an attenuated increase in FBF as compared to Caucasians (CA) in response to mental stress, which may be related to impaired vascular function and thus elevated CV disease risk in AA. However, this study was conducted in a middle-age cohort (mid to late 40’s). Whether this attenuation is present in a young relatively healthy population is unknown. PURPOSE: The purpose of this study was to test the hypothesis that the vasodilatory response to mental stress is blunted in a relatively young and healthy AA population. METHODS: 6 relatively healthy young AA and 6 CA males (AA age: 22 + 2.6, CA age: 23 + 4.6) participated in this study. All measurements were obtained in the morning following an overnight fast. Brachial artery diameter and blood velocity were assessed using high resolution duplex ultrasound. Mental stress was induced by asking subjects to subtract 7 continuously from a 3-digit number while attempting to report answers at a pace set by a 60 bpm metronome. The 3-digit number was changed at 20 second intervals. FBF was measured during a two minute baseline followed by 3 minutes of mental stress. Vascular function was assessed as the absolute peak blood flow response (ml/min) as well as peak conductance (ml/min/mmHg) during the mental stress. RESULTS: The absolute peak flow (AA: 183 + 39 ml/min, CA: 307 + 127 ml/min; P = 0.05) were significantly greater in CA compared to AA. The maximum increase in conductance (AA: 2.03 + 0.32 ml/min/mmHg, CA: 3.69 + 1.39 ml/min/mmHg; P = .02) was also significantly higher in CA as compared to AA. CONCLUSION: This preliminary data supports our hypothesis that vascular function in response to mental stress is attenuated in young healthy AA as compared to their CA counterparts