Daniel N. Nan

Metabolic syndrome and bone metabolism: the Camargo Cohort Study

Objectives: The aims of this study were to compare in participants with and without metabolic syndrome (1) bone mineral density (BMD), (2) prevalent vertebral and nonvertebral fractures, and (3) calciotropic hormones and bone turnover markers and to examine the association of each component of metabolic syndrome with bone parameters. Methods: A cross-sectional study (495 men and 1,013 women) from the Camargo Cohort Study was conducted. A multivariable regression approach was used to analyze the relationship between the components of metabolic syndrome and bone parameters. Results: Women with metabolic syndrome had higher age-adjusted BMD at all localizations (P < 0.0001) than did women without metabolic syndrome. Adjusting for body mass index canceled out this difference at the spine and femoral neck, although borderline significance persisted at the total hip. Moreover, in regression analyses, waist circumference (P < 0.0001) and hypertension (P between 0.002 and <0.0001) highly correlated with BMD at the three sites. However, no significant differences in BMD were found in men between those with and without metabolic syndrome. No differences in the prevalence of vertebral or nonvertebral fractures between participants with metabolic syndrome and controls were found for either sex. 25-Hydroxyvitamin D was significantly lower (P < 0.0001) and parathyroid hormone was significantly higher (P < 0.0001) in women with metabolic syndrome than in women without metabolic syndrome, whereas no differences were seen in men. Propeptide of type I collagen and C-terminal telopeptide of type I collagen were significantly lower in participants with metabolic syndrome than in controls in either sex. Conclusions: Women with metabolic syndrome show higher BMD than controls do, mainly driven by their higher body weight. Bone remodeling in these women is lower. Despite the greater bone mass and lower bone turnover, fracture prevalence is not reduced, suggesting worse bone quality and/or higher tendency to fall. No differences in BMD or fractures were seen in men, suggesting that the impact of metabolic syndrome on bone is sex dependent.

Wnt receptors, bone mass, and fractures: gene-wide association analysis of LRP5 and LRP6 polymorphisms with replication

OBJECTIVE Genes explaining the susceptibility to osteoporosis have not been fully elucidated. Our objective was to explore the association of polymorphisms capturing common variations of the lipoprotein receptor-related protein (LRP) 5 and 6 genes, encoding two Wnt receptors, with femoral neck bone mineral density (BMD) and osteoporotic fractures of the spine and the hip. DESIGN Cross-sectional, case-control, and replication genetic association study. METHODS Thirty-nine tagging and functional single nucleotide polymorphisms (SNPs) were analyzed in a group of 1043 postmenopausal women and 394 women with hip fractures. The results were replicated in a different group of 342 women. RESULTS Three SNPs of the LRP6 gene were associated with BMD (nominal uncorrected P values <0.05) in the discovery cohort. One showed a significant association after multiple test correction; two of them were also associated in the replication cohort, with a combined standardized mean difference of 0.51 (P=0.009) and 0.47 (P<0.003) across rs11054704 and rs2302685 genotypes. In the discovery cohort, several LRP5 SNPs were associated with vertebral fractures (odds ratio (OR) 0.67; P=0.01), with hip fractures (unadjusted ORs between 0.59 and 1.21; P=0.005-0.033, but not significant after multiple test adjustment or age adjustment), and with height and the projected femoral neck area, but not with BMD. Transcripts of LRP5 and LRP6 were similarly abundant in bone samples. CONCLUSIONS In this study, we found common polymorphisms of LRP5 associated with osteoporotic fractures, and polymorphisms of the LRP6 gene associated with BMD, thus suggesting them as likely candidates to contribute to the explaination of the hereditary influence on osteoporosis.

Bone turnover markers and bone mineral density in hypertensive postmenopausal women on treatment

OBJECTIVE To evaluate bone mineral density (BMD) and bone metabolism in hypertensive postmenopausal women, and to differentiate the effect of thiazides from that of other antihypertensive agents. SUBJECTS AND METHODS A community-based population of 636 postmenopausal women, 293 with hypertension (160 receiving thiazides, and 133 receiving other antihypertensive treatments), and 343 control women, were evaluated. Serum levels of aminoterminal propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (beta-CTX), 25-hydroxivitamin D, and intact parathyroid hormone were measured by electrochemiluminiscence. BMD was determined by DXA, and heel quantitative ultrasound measurements (QUS) with a gel-coupled device. RESULTS BMD expressed as Z-score was higher in both groups of hypertensive women at all locations. Expressed as g/cm(2), it was also higher in patients on thiazides at femoral neck and lumbar spine. Only in the latter site, differences remained significant after adjusting for potential confounding variables, including BMI. Bone turnover markers were lower in both groups of hypertensive women, although the difference was greater in those on thiazides. After adjusting for potential confounders, differences remained significant only in the thiazide group. CONCLUSIONS Our results add evidence to the idea that thiazides are beneficial to prevent bone loss.

Effects of 25-Hydroxyvitamin D3 Therapy on Bone Turnover Markers and PTH Levels in Postmenopausal Osteoporotic Women Treated with Alendronate

OBJECTIVE Our objective was to know the extent to which a fall in bone turnover markers is influenced by serum 25-hydroxyvitamin D (25OHD) levels in patients on alendronate (ALN) treatment. DESIGN, PARTICIPANTS, AND SETTING A total of 140 postmenopausal osteoporotic women were randomized to receive either ALN or ALN plus 25OHD(3) (ALN+VitD) over a 3-month period. Serum 25OHD, PTH, C-terminal telopeptide of type I collagen (CTX), and amino-terminal propeptide of type I collagen (P1NP) were measured at baseline and at the end of the 3 months. RESULTS 25OHD rose four times above baseline levels in the ALN+VitD group, whereas no changes were seen in the ALN group. Administering ALN resulted in a significant decline in both serum CTX (53 ± 24%) and P1NP (46 ± 19%). After ALN+VitD, the fall in CTX amounted to 61 ± 20% (P = 0.06 compared with ALN) and P1NP to 50 ± 23% (P = 0.35). When patients were divided into those below and above 20 ng/ml of baseline serum 25OHD, in those below, CTX decreased by 48 ± 26% in the ALN group and by 61 ± 17% in the ALN+VitD group (P = 0.015). For P1NP, the corresponding figures were 43 ± 20 and 50 ± 23% (P = 0.2). In patients above 20 ng/ml, no differences were seen regarding CTX (58 ± 21% decrease in the ALN group and 60 ± 23% in the ALN+VitD group; P = 0.7) or P1NP (49 ± 18 and 50 ± 20%; P = 0.9). CONCLUSIONS Administration of 25OHD(3) is not an indispensable requirement for bisphosphonates to develop their bone antiresorptive effect. In fact, in patients with vitamin D sufficiency, no benefit is observed when the vitamin is added. However, in patients with vitamin D deficiency, an approximately 25% greater fall in the bone resorption marker CTX is seen with its administration.

Influence of Vitamin D Status on Vertebral Fractures, Bone Mineral Density, and Bone Turnover Markers in Normocalcemic Postmenopausal Women With High Parathyroid Hormone Levels

OBJECTIVE The aims of the study were to analyze whether there is an association between serum PTH and the prevalence of vertebral fractures and its possible dependence on vitamin D status, and to assess the influence of serum 25-hydroxyvitamin D (25OHD) in the relationship between PTH and bone mineral density (BMD) or bone turnover markers (BTMs). DESIGN, PARTICIPANTS, AND SETTING A total of 820 postmenopausal women were recruited after excluding those with any known condition that could influence serum PTH levels, except for a possible low serum 25OHD. Serum PTH and 25OHD concentrations, as well as vertebral fracture prevalence, BMD, and BTM (CTX and PINP) values were recorded. Serum PTH levels were divided into tertiles, and women were grouped into those in the highest tertile (>58 pg/ml) and those below. Serum 25OHD levels were stratified in 3 categories (<20, 20-30, and >30 ng/ml). RESULTS Vertebral fracture prevalence was greater in women with PTH above 58 pg/ml (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.04-2.84). After stratifying by 25OHD, this difference was only significant in women below 20 ng/ml (OR, 2.00; 95% CI, 1.02-3.87), those with 25OHD between 20 and 30 ng/ml showing a trend toward this (OR, 1.99; 95% CI, 0.92-4.36). Differences in BMD or BTM between women above and below 58 pg/ml of PTH were also observed only in those below 20 ng/ml. CONCLUSION Elevated PTH levels are associated with increased prevalence of vertebral fractures, low bone mass, or higher BTM only in the presence of hypovitaminosis D. An adequate nutritional status in the vitamin appears to protect the bone from the deleterious effect of a high PTH.

Surgical Site Infection During Hospitalization and After Discharge in Patients Who Have Undergone Cardiac Surgery

During a 13-month period, 513 patients who were scheduled to undergo cardiac surgery were prospectively observed for surgical site infection during hospitalization after surgery and for 1 month after hospital discharge. Fifty-three patients showed evidence of surgical site infection (during hospitalization for 31 patients and after discharge for 22). Multivariate analysis identified that risk factors for surgical site infection differed between infections that occurred during hospitalization and those that occurred after discharge.

Henoch-Schönlein purpura after intravesical administration of bacillus Calmette-Guérin

The administration of intravesical bacille Calmette-Guérin (BCG) in early stages of bladder cancer is usually a safe therapy. Side-effects of BCG immunotherapy can be of both local and systemic nature. We report the first case of Henoch-Schönlein purpura following intravesical administration of BCG.

Diabetes mellitus following cisplatin treatment.

The association between cisplatin treatment and diabetes mellitus was analyzed retrospectively in 219 patients with locally advanced squamous cell head and neck cancer treated in two consecutive trials with cisplatin-based induction chemotherapy. It was found that 11 patients (5%) developed diabetes mellitus during the treatment period, two cases presenting as hyperosmolar coma. The literature contains only sporadic descriptions of cases of hyperosmolar coma related to cisplatin chemotherapy. The present study was initiated owing to a case of hyperosmolar coma observed by us. We suggest that glycemia levels in patients receiving chemotherapy with a cisplatin-based regimen should be monitored regularly.

Heel quantitative ultrasound parameters in subjects with the metabolic syndrome: the Camargo Cohort Study.

OBJECTIVES To compare bone parameters measured by calcaneous quantitative ultrasonography (BUS) in subjects with and without metabolic syndrome (MetS). In addition, we wanted to examine the association of each of the individual components of the syndrome with BUS measurements, to study the relationship between calciotropic hormones or bone turnover markers with BUS parameters in subjects with or without MetS, and to explore the possibility that the relationship between prevalent vertebral and non-vertebral fractures and BUS is influenced by MetS status. STUDY DESIGN Cross-sectional study. RESULTS We investigated 1209 (421 men and 788 women) participants from the Camargo Cohort Study. Prevalence of MetS was 27% in men and 31% in women. Women, but not men, with MetS had higher age-adjusted BUS parameters compared with those without (p<0.05), the difference disappearing after adjustment for BMI. Out of the five single components of MetS, only waist perimeter was significantly associated with BUS (p<0.01), the association being restricted to women. In men and women with MetS (but not without) a positive significant association was observed between BUS and 25OHD levels. BUS parameters were associated with serum P1NP or CTX in normal women, but not in those with MetS. Prevalent vertebral and non-vertebral fractures and BUS parameters (BUA and SOS, respectively) are inversely associated, but this relationship, however, is not influenced by MetS status. CONCLUSIONS BUS parameters are higher in women with MetS, and this difference disappears after adjusting for BMI. MetS status did not influence the relationship between BUS parameters and vertebral or non-vertebral fractures.

Postoperative Mediastinitis due to Salmonella

Mediastinitis remains one of the most serious and dreaded complications of median sternotomy. Salmonella is a rare cause of mediastinal infection. The case is reported of a patient who underwent heart valve surgery and developed a Salmonella enteritidis bacteraemia in the postoperative period, which caused aortic dissection and mediastinitis.