Long-term Bone Loss and Deterioration of Microarchitecture After Gastric Bypass in African American and Latina Women.

CONTEXT: The prevalence of obesity is burgeoning among African American and Latina women; however, few studies investigating the skeletal effects of bariatric surgery have focused on these groups. OBJECTIVE: To investigate long-term skeletal changes following Roux-en-Y gastric bypass (RYGB) in African American and Latina women. DESIGN: Four-year prospective cohort study. PATIENTS: African American and Latina women presenting for RYGB (n = 17, mean age 44, body mass index 44 kg/m2) were followed annually for 4 years postoperatively. MAIN OUTCOME MEASURES: Dual-energy x-ray absorptiometry (DXA) measured areal bone mineral density (aBMD) at the spine, hip, and forearm, and body composition. High-resolution peripheral quantitative computed tomography measured volumetric bone mineral density (vBMD) and microarchitecture. Individual trabecula segmentation-based morphological analysis assessed trabecular morphology and connectivity. RESULTS: Baseline DXA Z-Scores were normal. Weight decreased ~30% at Year 1, then stabilized. Parathyroid hormone (PTH) increased by 50% and 25-hydroxyvitamin D was stable. By Year 4, aBMD had declined at all sites, most substantially in the hip. There was significant, progressive loss of cortical and trabecular vBMD, deterioration of microarchitecture, and increased cortical porosity at both the radius and tibia over 4 years. There was loss of trabecular plates, loss of axially aligned trabeculae, and decreased trabecular connectivity. Whole bone stiffness and failure load declined. Risk factors for bone loss included greater weight loss, rise in PTH, and older age. CONCLUSIONS: African American and Latina women had substantial and progressive bone loss, deterioration of microarchitecture, and trabecular morphology following RYGB. Further studies are critical to understand the long-term skeletal consequences of bariatric surgery in this population.

Vitamin D Storage in Adipose Tissue of Obese and Normal Weight Women.

Although vitamin D deficiency is prevalent among obese individuals, its cause is poorly understood. Few studies have measured vitamin D concentrations in adipose of obese (OB) subjects, and none have included normal weight controls (C). The goal of this study was to investigate whether the relationship between body composition, serum 25-hydroxyvitamin D (25OHD), vitamin D in subcutaneous (SQ) and omental (OM) adipose, and total adipose stores of vitamin D differ among OB and C. Obese women undergoing bariatric surgery and normal-weight women undergoing abdominal surgery for benign gynecologic conditions were enrolled. Subjects had measurements of serum 25OHD by high-performance liquid chromatography (HPLC) and body composition by dual-energy X-ray absorptiometry (DXA). Vitamin D concentrations in SQ and OM adipose were measured by mass spectroscopy. Thirty-six women were enrolled. Serum 25OHD was similar between groups (OB 27 ± 2 versus C 26 ± 2 ng/mL; p = 0.71). Adipose vitamin D concentrations were not significantly different in either SQ (OB 34 ± 9 versus C 26 ± 12 ng/g; p = 0.63) or OM compartments (OB 51 ± 13 versus C 30 ± 18 ng/g; p = 0.37). The distribution of vitamin D between SQ and OM compartments was similar between groups. Serum 25OHD was directly related to adipose vitamin D in both groups. Total body vitamin D stores were significantly greater in OB than in C (2.3 ± 0.6 versus 0.4 ± 0.8 mg, respectively; p < 0.01). In summary, although OB had significantly greater total vitamin D stores than C, the relationship between serum 25OHD and fat vitamin D and the overall pattern of distribution of vitamin D between the OM and SQ fat compartments was similar. Our data demonstrate that obese subjects have greater adipose stores of vitamin D. They support the hypotheses that the enlarged adipose mass in obese individuals serves as a reservoir for vitamin D and that the increased amount of vitamin D required to saturate this depot may predispose obese individuals to inadequate serum 25OHD. © 2016 American Society for Bone and Mineral Research.

Effect of Parathyroidectomy Upon Left Ventricular Mass in Primary Hyperparathyroidism: A Meta-Analysis.

CONTEXT: Primary hyperparathyroidism (PHPT) has been associated with increased left ventricular mass (LVM) in many studies. Most studies have been inadequately powered to assess the effect of parathyroidectomy (PTX) on LVM. OBJECTIVE: The objective was to evaluate whether PTX has a benefit on LVM in patients with PHPT. DATA SOURCES: Sources included PubMed, Medline, Cochrane Library, clinicaltrials.gov, review articles, and abstracts from meetings. STUDY SELECTION: Eligible studies included prospective studies of PTX vs observation or PTX alone in patients with PHPT who had LVM measured by echocardiography. DATA EXTRACTION: Two investigators independently identified eligible studies and extracted data. Random-effects models were used to obtain final pooled estimates. DATA SYNTHESIS: Fifteen studies (four randomized controlled trials and 11 observational) of 457 participants undergoing PTX were included. PTX was associated with a reduction in LVM (crude Hedges gu -0.290 ± 0.070, 95% confidence interval [CI] -0.423 to -0.157) of 11.6 g/m(2) (12.5%) on average. Effect size estimates differed by study duration (P < .001), with improvements seen in shorter (≤ 6 mo) but not longer studies. There was a trend toward greater improvement in observational studies vs randomized controlled trials (P = .07), and both serum calcium and PTH were higher in the former. Using random-effects models, the estimated effect size remained significant (Hedges gu -0.250, 95% CI -0.450 to -0.050). Higher preoperative PTH but not calcium was associated with a greater decline in LVM (ß = -.039, 95% CI -0.075 to -0.004). CONCLUSION: PTX reduced LVM in PHPT, and higher preoperative PTH levels were associated with greater improvements. Because the benefit was limited to short-term studies and PHPT disease severity was not independent of study design, further work is needed to clarify the factors that influence the change in LVM and whether the benefit persists beyond 6 months after PTX. Although the clinical significance of the LVM improvement is unclear, these data indicate that PTH may underlie increased LVM in PHPT.

Bariatric surgery results in cortical bone loss.

BACKGROUND: Bariatric surgery results in bone loss at weight-bearing sites, the mechanism of which is unknown. METHODS: Twenty-two women (mean body mass index 44 kg/m(2); aged 45 years) who underwent Roux-en-Y gastric bypass (n = 14) and restrictive procedures (n = 8) had measurements of areal bone mineral density by dual-energy x-ray absorptiometry at the lumbar spine, total hip (TH), femoral neck (FN), and one third radius and trabecular and cortical volumetric bone mineral density and microstructure at the distal radius and tibia by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 12 months postoperatively. RESULTS: Mean weight loss was 28 ± 3 kg (P < .0001). PTH rose 23% (P < .02) and 25-hydroxyvitamin D was stable. C-telopeptide increased by 144% (P < .001). Bone-specific alkaline phosphatase did not change. Areal bone mineral density declined at TH (-5.2%; P < .005) and FN (-4.5%; P < .005). By HR-pQCT, trabecular parameters were stable, whereas cortical bone deteriorated, particularly at the tibia: cortical area (-2.7%; P < .01); cortical thickness (-2.1%; P < .01); total density (-1.3%; P = .059); cortical density (-1.7%; P < .01). In multivariate regression, bone loss at the TH and FN were predicted by weight loss. In contrast, only PTH increase predicted cortical deterioration at the tibia. Roux-en-Y gastric bypass patients lost more weight, had more bone loss by dual-energy x-ray absorptiometry and HR-pQCT than those with restrictive procedures, and had declines in cortical load share estimated by finite element analysis. CONCLUSIONS: After bariatric surgery, hip bone loss reflects skeletal unloading and cortical bone loss reflects secondary hyperparathyroidism. This study highlights deterioration of cortical bone loss as a novel mechanism for bone loss after bariatric surgery.

Vitamin D deficiency is associated with subclinical carotid atherosclerosis: the Northern Manhattan study.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the association of vitamin D deficiency and indices of mineral metabolism with subclinical carotid markers that predict cardiovascular events. METHODS: Two hundred three community-dwelling adults (Northern Manhattan Study; age, 68 ± 11; age range, 50 to 93 years) had serum measurements (calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, parathyroid hormone) and carotid ultrasound (plaque presence, number, maximal carotid plaque thickness, intima-media thickness). RESULTS: Adjusting for cardiovascular risk factors, plaque number was associated with phosphorus levels (ß=0.39 per 1-mg/dL increase; P=0.02) and calcium-phosphorus product (ß=0.36 per 10-U increase; P=0.03). In those with plaque (N=116 [57%]), the association of plaque number with phosphorus and calcium-phosphorus product persisted. In addition, 25-hydroxyvitamin D was inversely associated with both intima-media thickness (ß=-0.01 per 10-ng/mL increase; P=0.05) and maximal carotid plaque thickness (ß=-0.10 per 10-ng/mL increase; P=0.03). In a model containing traditional cardiac risk factors and indices of mineral metabolism, 25-hydroxyvitamin D accounted for 13% of the variance in both intima-media thickness and maximal carotid plaque thickness. Calcium, parathyroid hormone, and 1,25-dihydroxyvitamin D levels were not associated with carotid measures. CONCLUSIONS: After adjusting for cardiovascular risk factors and renal function, serum phosphorus and calcium-phosphorus product were associated with a greater burden of subclinical carotid atherosclerosis. Low 25-hydroxyvitamin D levels were associated with increased intima-media thickness and maximal carotid plaque thickness in those with plaque, and 25-hydroxyvitamin D contributed in a robust manner to the variance in both. These results confirm and extend data on the association of low vitamin D levels with subclinical carotid atherosclerosis. The precise nature of this association and the optimum levels of vitamin D for vascular health remain to be elucidated.

Postictal psychosis in partial epilepsy: a case-control study.

OBJECTIVE: Divergent findings among prior studies on correlates of risk for postictal psychosis (PIP) suggest the value of a controlled study involving a relatively large number of patients. METHODS: The study population consisted of a consecutive series of 59 patients with partial epilepsy and a history of PIP, and 94 control patients with partial epilepsy and no history of PIP evaluated as inpatients with video-electroencephalography. The groups did not differ significantly regarding demographic features. Exact tests yielded a subset of variables and a tentative interpretation that were evaluated further utilizing principal components analysis and logistic regression. RESULTS: PIP was associated with extratemporal versus temporal (p = 0.036) or undetermined (p = 0.001) localization of seizure onset, bilateral interictal epileptiform activity (p = 0.017), secondary generalization (p = 0.049), and history of encephalitis (p = 0.018). Interictal slow activity was more frequently absent in control patients (p = 0.045). PIP was associated with family histories of psychiatric disorders (p = 0.007) and epilepsy (p = 0.042), which themselves were significantly intercorrelated (r = 0.225; p = 0.006). Age of onset or duration of epilepsy and lateralized electroencephalographic or magnetic resonance imaging asymmetries did not differ significantly between control and PIP groups. The analysis indicated four underlying domains of risk for PIP: ambiguous/extratemporal localization, family neuropsychiatric history, abnormal interictal electroencephalographic activity, and encephalitis. Each unit increase on a simple additive scale composed of 9 dichotomous independent variables multiplied the odds ratio for PIP by 1.71 (95% confidence interval, 1.36-2.15; p < 0.0001). INTERPRETATION: PIP in partial epilepsy is associated with relatively broadly and bilaterally distributed epileptogenic networks, genetic determinants of psychiatric disorders and seizures, and encephalitis.

Effects of simvastatin on plasma lipoproteins and response to arterial injury in wild-type and apolipoprotein-E-deficient mice.

OBJECTIVE: To test the non-lipid-lowering effects of simvastatin on the response to injury in normolipidemic and hyperlipidemic mice. METHODS AND RESULTS: Wild-type (WT) mice (n = 40) and hyperlipidemic apolipoprotein-E-deficient (apoE(-/-)) mice (n = 40) received normal chow or chow containing simvastatin 100 mg/kg/day prior to bilateral femoral artery wire injury. Intimal hyperplasia and plasma cholesterol concentration were quantified after 4 weeks. Plasma cholesterol in WT mice treated or untreated with simvastatin was similar (100.9 +/- 6.6 vs. 94.3 +/- 17.5 mg/dl). Simvastatin did not affect intimal hyperplasia. In apoE(-/-) mice, intimal hyperplasia was increased 2.3-fold relative to WT mice (17090 +/- 4998 vs. 39490 +/- 16190; p < 0.001). In apoE(-/- )mice, simvastatin caused a paradoxical increase in plasma cholesterol (1094 +/- 60.3 vs. 658 +/- 66.8 mg/dl; p < 0.001), confirmed by FPLC. This was associated with a further increase in intimal area (39490 +/- 16190 vs. 55420 +/- 22590 mm(2); p < 0.01). CONCLUSIONS: (1). Simvastatin had no effect on plasma cholesterol or the response to arterial injury in normolipidemic WT mice; (2). hyperlipidemia was associated with markedly increased intimal hyperplasia, and (3). simvastatin treatment of apoE(-/-) mice caused paradoxical hyperlipidemia and increased intimal hyperplasia.