RESUMEN
BACKGROUND: Hypertriglyceridaemia (HTG; defined as ≥1.7 mmol/L) has a prevalence of 18-33% with significant inter-regional variation. Despite meta-analysis demonstrating its association with increased risk of cardiovascular disease, only 40% of HTG is identified in the community resulting in underutilisation of lipid-lowering therapy and specialist clinics. An increase in awareness of its clinical risk factors is needed to improve the identification and management of HTG to prevent cardiovascular risk. AIMS: To evaluate the prevalence, distribution and clinical predictors of HTG ≥1.7 mmol/L in a representative community group. METHODS: Data were obtained from the Hunter Community Study (HCS), a longitudinal cohort of community-dwelling men and women aged 55-85 years residing in Newcastle, New South Wales. Fasting triglycerides were identified based on the availability of fasting blood glucose level and categorised according to normal (<1.7 mmol/L), mild (1.7 to <2.3 mmol/L) and moderate-severe HTG (≥2.3 mmol/L). Clinical predictors of HTG were assessed using linear and logistic regression models. RESULTS: Of 2536 triglyceride levels, 2216 (87%) were in a fasting state and included in the study. Three hundred and two (13.6%) participants had mild HTG and 221 (10.0%) participants had moderate-severe HTG. Significant clinical predictors of HTG included male gender, increasing body mass index, current smoking, decreasing daily step counts, increasing fasting glucose and higher thyroid-stimulating hormone. Alcohol intake and blood pressure were not significant in either adjusted regression model. CONCLUSIONS: HTG ≥1.7 mmol/L is common, affecting 24% of the HCS. Clinical predictors identify modifiable risk factors for cardiovascular risk management. Clinician education to promote awareness is required to improve patient outcomes.
Asunto(s)
Hiperlipidemias , Hipertrigliceridemia , Humanos , Masculino , Femenino , Prevalencia , Triglicéridos , Factores de RiesgoRESUMEN
Therapeutic enhancement of fracture healing would help to prevent the occurrence of orthopedic complications such as nonunion and revision surgery. Sclerostin is a negative regulator of bone formation, and treatment with a sclerostin monoclonal antibody (Scl-Ab) results in increased bone formation and bone mass in animal models. Our objective was to investigate the effects of systemic administration of Scl-Ab in two models of fracture healing. In both a closed femoral fracture model in rats and a fibular osteotomy model in cynomolgus monkeys, Scl-Ab significantly increased bone mass and bone strength at the site of fracture. After 10 weeks of healing in nonhuman primates, the fractures in the Scl-Ab group had less callus cartilage and smaller fracture gaps containing more bone and less fibrovascular tissue. These improvements at the fracture site corresponded with improvements in bone formation, bone mass, and bone strength at nonfractured cortical and trabecular sites in both studies. Thus the potent anabolic activity of Scl-Ab throughout the skeleton also was associated with an anabolic effect at the site of fracture. These results support the potential for systemic Scl-Ab administration to enhance fracture healing in patients.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/farmacología , Densidad Ósea/efectos de los fármacos , Fracturas del Fémur/fisiopatología , Curación de Fractura/efectos de los fármacos , Glicoproteínas/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales , Animales , Fenómenos Biomecánicos/efectos de los fármacos , Diáfisis/efectos de los fármacos , Diáfisis/patología , Diáfisis/fisiopatología , Modelos Animales de Enfermedad , Fémur/efectos de los fármacos , Fémur/patología , Fémur/fisiopatología , Peroné/efectos de los fármacos , Peroné/patología , Peroné/fisiopatología , Glicoproteínas/inmunología , Péptidos y Proteínas de Señalización Intercelular , Macaca fascicularis , Masculino , Tamaño de los Órganos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteotomía , Ratas , Ratas Sprague-DawleyRESUMEN
RANKL is an essential mediator of bone resorption, and its activity is inhibited by osteoprotegerin (OPG). Transgenic (Tg) rats were engineered to continuously overexpress OPG to study the effects of continuous long-term RANKL inhibition on bone volume, density, and strength. Lumbar vertebrae, femurs, and blood were obtained from 1-yr-old female OPG-Tg rats (n = 32) and from age-matched wildtype (WT) controls (n = 23). OPG-Tg rats had significantly greater serum OPG (up to 260-fold) and significantly lower serum TRACP5b and osteocalcin compared with WT controls. Vertebral histomorphometry showed significant reductions in osteoclasts and bone turnover parameters in OPG-Tg rats versus WT controls, and these reductions were associated with significantly greater peak load in vertebrae tested through compression. No apparent differences in bone material properties were observed in OPG-Tg rat vertebrae, based on their unchanged intrinsic strength parameters and their normal linear relationship between vertebral bone mass and strength. Femurs from OPG-Tg rats were of normal length but showed mild osteopetrotic changes, including reduced periosteal perimeter (-6%) and an associated reduction in bending strength. Serum OPG levels in WT rats showed no correlations with any measured parameter of bone turnover, mass, or strength, whereas the supraphysiological serum OPG levels in OPG-Tg rats correlated negatively with bone turnover parameters and positively with vertebral bone mass and strength parameters. In summary, low bone turnover after 1 yr of OPG overexpression in rats was associated with increased vertebral bone mass and proportional increases in bone strength, with no evidence for deleterious effects on vertebral material properties.