Data on the association of the metabolic syndrome (MetS) with bone mineral density (BMD) and fracture risk in men are inconsistent. We studied the association between MetS and bone status in 762 older men followed up for 10 years. After adjustment for age, body mass index, height, physical activity, smoking, alcohol intake, and serum 25-hydroxycholecalciferol D and 17b-estradiol levels, men with MetS had lower BMD at the hip, whole body, and distal forearm (2.2% to 3.2%, 0.24 to 0.27 SD, p < .05 to .005). This difference was related to abdominal obesity (assessed by waist circumference, waist-hip ratio, or central fat mass) but not other MetS components. Men with MetS had lower bone mineral content (3.1% to 4.5%, 0.22 to 0.29 SD, p < .05 to 0.001), whereas differences in bone size were milder. Men with MetS had a lower incidence of vertebral and peripheral fractures (6.7% versus 12.0%, p < .05). After adjustment for confounders, MetS was associated with a lower fracture incidence [odds ratio (OR) ¼ 0.33, 95% confidence interval (CI) 0.15-0.76, p < .01]. Among the MetS components, hypertriglyceridemia was most predictive of the lower fracture risk (OR ¼ 0.25, 95%CI 0.10-0.62, p < .005). Lower fracture risk in men with MetS cannot be explained by differences in bone size, rate of bone turnover rate and bone loss, or history of falls or fractures. Thus older men with MetS have a lower BMD related to the abdominal obesity and a lower risk of fracture related to hypertriglyceridemia. MetS probably is not a meaningful concept in the context of bone metabolism. Analysis of its association with bone-related variables may obscure the pathophysiologic links of its components with bone status. ß

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In healthy older men, circulating FGF23 is associated with parameters of mineral metabolism, including bone metabolism-regulating cytokines, and with severe AAC independent of traditional risk factors.

The performance of creatinine-based equations to obtain the estimated GFR in adolescents and young adults is poorly understood. We assessed creatinine-based GFR estimating equations in a cross-section of 751 adolescents and young adults (1054 measurements), using inulin clearance (measured GFR [mGFR]) as the reference method. We evaluated the following: Cockcroft-Gault, four-variable Modified Diet in Renal Disease, and the Chronic Kidney Disease Epidemiology Collaboration equations for adult participants, as well as the Schwartz 2009 and Schwartz-Lyon equations for pediatric age groups. Participants ranged in age from 10 to 26 years (mean 16.8 years); we divided the population into four groups according to age (10-12 years, 13-17 years, 18-21 years, and 21-25 years). Evaluation of the agreement between these formulas and mGFR (e.g., correlation, Bland-Altman plots, bias, and accuracy) showed that there was a good correlation between mGFR and both pediatric formulas in all age groups, whereas the adult formulas substantially overestimated mGFR. In conclusion, we recommend the use of pediatric equations to estimate GFR from childhood to early adulthood.

Higher baseline total osteocalcin concentrations were associated with lower AAC progression rate and lower mortality. These data suggest that osteocalcin level might be an independent indicator of cardiovascular risk and global health in elderly Caucasian men.

Objective: In the elderly, vitamin D deficit, low calcium intake, and impaired bone microarchitecture are associated with higher risk of hip fracture. We assessed the association of bone microarchitecture with calcium intake and serum concentrations of 25-hydroxycholecalciferol (25OHD) and parathyroid hormone (PTH) in men. Design: Cross-sectional analysis was performed in 1064 men aged 20-87 years not taking vitamin D or calcium supplements. Methods: Daily calcium intake was assessed using a food frequency questionnaire. Bone microarchitecture was assessed at distal radius and tibia by high-resolution peripheral quantitative computed tomography. We measured serum and urinary levels of biochemical bone turnover markers (BTMs). Statistical models were adjusted for age, weight, height, and glomerular filtration rate. Results: In 500 men aged !65 years, lower 25OHD levels and low calcium intake were associated with lower trabecular volumetric bone mineral density (Dtrab) at the distal tibia, due to lower trabecular number (Tb.N). Low calcium intake was associated with lower cortical thickness (Ct.Th). Higher PTH level was associated with higher BTM levels. In 563 men aged R65 years, the highest PTH quartile was associated with lower Ct.Th (tibia), lower Dtrab (both sites), and lower Tb.N (radius) compared with the lowest quartile. Low calcium intake was associated with lower Tb.N and more heterogenous trabecular distribution. BTM positively correlated with the PTH concentration. Conclusion: In older men, elevated PTH concentration is associated with high bone turnover, poor trabecular microarchitecture (radius and tibia), and, at the distal tibia, lower Ct.Th. Low calcium intake is associated with lower Tb.N and more heterogenous trabecular distribution.European Journal of Endocrinology 165 151-159

The opening of the mitochondrial permeability transition pore (PTP), which is regulated by the matrix protein cyclophilin D (CypD), plays a key role in the pathophysiology of post-cardiac arrest (CA) syndrome. We hypothesized that therapeutic hypothermia could prevent post-CA syndrome through a CypD-mediated PTP inhibition in both heart and brain. In addition, we investigated whether specific pharmacological PTP inhibition would confer additive protection to cooling. Adult male New Zealand White rabbits underwent 15 min of CA followed by 120 min of reperfusion. Five groups (n = 10-15/group) were studied: control group (CA only), hypothermia group (HT, hypothermia at 32-34 °C induced by external cooling at reperfusion), NIM group (injection at reperfusion of 2.5 mg/kg NIM811, a specific CypD inhibitor), HT + NIM, and sham group. The following measurements were taken: hemodynamics, echocardiography, and cellular damage markers (including S100β protein and troponin Ic). Oxidative phosphorylation and PTP opening were assessed on mitochondria isolated from both brain and heart. Acetylation of CypD was measured by immunoprecipitation in both the cerebral cortex and myocardium. Hypothermia and NIM811 significantly prevented cardiovascular dysfunction, pupillary areflexia, and early tissue damage. Hypothermia and NIM811 preserved oxidative phosphorylation, limited PTP opening in both brain and heart mitochondria and prevented increase in CypD acetylation in brain. There were no additive beneficial effects in the combination of NIM811 and therapeutic hypothermia. In conclusion, therapeutic hypothermia limited post-CA syndrome by preventing mitochondrial permeability transition mainly through a CypD-dependent mechanism.

Opening of the mitochondrial permeability transition pore (mPTP) appears to be a pivotal event in myocardial ischemia-reperfusion (I/R) injury. Resuscitated cardiac arrest (CA) leads to the post-CA syndrome that encompasses, not only myocardial dysfunction, but also brain injury, failure of other organs (kidney, liver, or lung), and systemic response to I/R. We aimed to determine whether cyclosporine A (CsA) might prevent multiple organ failure following CA through a ubiquitous mPTP inhibition in each distant vital organ. Anesthetized New Zealand White rabbits were subjected to 15 min of CA and 120 min of reperfusion. At the onset of resuscitation, the rabbits received CsA, its non-immunosuppressive derivative NIM811, or vehicle (controls). Survival, hemodynamics, brain damage, organ injuries, and systemic I/R response were analyzed. Fresh mitochondria were isolated from the brain, heart, kidney, liver, and lung to assess both oxidative phosphorylation and permeability transition. CsA analogs significantly improved short-term survival and prevented multiple organ failure, including brain damage and myocardial dysfunction (P < 0.05 vs. controls). Susceptibility of mPTP opening was significantly increased in heart, brain, kidney, and liver mitochondria isolated from controls, while mitochondrial respiration was impaired (P < 0.05 vs. sham). CsA analogs prevented these mitochondrial dysfunctions (P < 0.05 vs. controls). These results suggest that CsA and NIM811 can prevent the post-CA syndrome through a ubiquitous mitochondrial protective effect at the level of each major distant organ.