Depression and low bone mineral density: a meta-analysis of epidemiologic studies

Summary

The association between depression and loss of bone mineral density (BMD) has been reported inconsistently. This meta-analysis, which pooled results from 14 qualifying individual studies, found that depression was associated with a significantly decreased BMD, with a substantially greater BMD decrease in depressed women and in cases of clinical depression.

Introduction

The reported association between depression and loss of BMD has been controversial. This meta-analysis was conducted to determine whether depression and BMD are associated and to identify the variation in some subgroups.

Methods

English-language articles published before October 2008 were used as the data source. A total of six case-controlled and eight cross-sectional studies met prestated inclusion criteria (N?=?10,523). Information on study design, participant characteristics, measurements of BMD and depression, and control for potential confounders was abstracted independently by two investigators using a standardized protocol.

Results

Overall, depression was associated with a significant decrease in mean BMD of spine (?0.053 g/cm² [95% confidence interval {CI} ?0.087 to ?0.018 g/cm²]) and hip (?0.052 g/cm² [95% CI ?0.083 to ?0.022 g/cm²]). A substantially greater BMD decrease was observed in depressed women (?0.076 g/cm² in spine; ?0.059 g/cm² in hip) and in cases of clinical depression (?0.074 g/cm² in spine; ?0.080 g/cm² in hip).

Conclusion

Depression is associated with low BMD, with a substantially greater BMD decrease in depressed women and in cases of clinical depression. Depression should be considered as an important risk factor for osteoporosis.     

Metabolic syndrome does not always play a critical role in decreased GFR

Background There is a paucity of literature available as to the relationship between different levels of each metabolic syndrome (MetS) component and decreased GFR. In the present study, we aimed to demonstrate whether MetS always plays a critical role in decreased GFR. Methods A cross-sectional study was conducted between February 2010 and September 2012, with 75,468 adults enrolled undergoing measurements of blood pressure as well as tests of blood and urine samples. Univariate and multivariable logistic regression analyses were performed to estimate the odds ratio (OR) with 95% confidence intervals (CI), and the chi-square test was used for categorical variables and described as a percentage. Results Of the 75,468 participants, 350 (0.5%) subjects met criteria for the decreased GFR, with a mean age of 48.79?±?13.76?years. After adjustment for age, diastolic blood pressure and high-density lipoprotein were inversely related to decreased estimated glomerular filtration rate (eGFR) in multivariable analyses, with an OR (95% CI) of 0.57 (0.39–0.84) and 0.41 (0.24–0.72), respectively. The prevalence rate of CKD in critical group was 0.73% (154 of 21,127) and 0% (0 of 370) in noncritical group. In analysis stratified by the type of MetS components, the differences in noncritical group and the reference group were not statistically significant (χ^2?=^?1.349, p?>?0.05). Conclusions MetS does not always play a critical role in decreased GFR, with different levels of individual components of MetS exerting idiosyncratic effects in decreased eGFR. In fact, patients with abnormal body mass index, high triglycerides, and elevated fasting plasma glucose would not have impact on decreased GFR.     

Multi‐lineage differentiation and angiogenesis potentials of pigmented villonodular synovitis derived mesenchymal stem cells ‐ pathological implication

Pigmented villonodular synovitis (PVNS) is a benign tissue proliferation characterized by its hyper‐vascularity within the lesion. The true etiology and cell source of this disease entity still remain unclear. Mesenchymal stem cells (MSCs) exist in various tissues of human body. However, it has not been clarified whether MSCs could be isolated from tissue of PVNS. Here, we isolated MSCs from PVNS (PVNS‐SCs), and by comparing to the MSCs from normal synovium (Syn‐SCs) of the same individual, we investigated whether PVNS‐SCs differed in the capacity for multi‐differentiation and inducing angiogenesis. We first demonstrated that PVNS‐SCs existed in the lesion of PVNS of three individuals. Moreover, we showed PVNS‐SCs had better osteogenic differentiation potential than Syn‐SCs, whereas Syn‐SCs had better capacity for adipogenic and chondrogenic differentiation. By genome–wide analysis of gene expression profile using a complementary DNA microarray and comparing to Syn‐SCs, we identified in PVNS‐SCs a distinct gene expression profile characterized by up‐regulation of genes involved in angiogenesis. In vitro and in vivo studies further confirmed that PVNS‐SCs had better capacities for promoting angiogenesis. In summary, the identification of PVNS‐SCs in PVNS tissue and their distinct angiogenic potential may help elucidate the underlying etiology of this disease. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:395–403, 2016.     

Increased Expression of Aldehyde Dehydrogenase 2 Reduces Renal Cell Apoptosis During Ischemia/Reperfusion Injury After Hypothermic Machine Perfusion

Hypothermic machine perfusion (MP) can reduce graft's injury after kidney transplantation; however, the mechanism has not been elucidated. In the past decade, many studies showed that aldehyde dehydrogenase 2 (ALDH2) is a protease which can inhibit cell apoptosis. Therefore, this study aims to explore whether ALDH2 takes part in reducing organ damage after MP. Eighteen healthy male New Zealand rabbits (12 weeks old, weight 3.0 ± 0.3 kg) were randomly divided into three groups: normal group, MP group, and cold storage (CS) group (n = 6). The left kidney of rabbits underwent warm ischemia for 35 min through clamping the left renal pedicle and then reperfusion for 1 h. Left kidneys were preserved by MP or CS (4°C for 4 h) in vivo followed by the right nephrectomy and 24‐h reperfusion, and then the specimens and blood were collected. Finally, concentration of urine creatinine (Cr), blood urea nitrogen (BUN), and 4‐HNE were tested. Renal apoptosis was detected by TUNEL staining, and the expression of ALDH2, cleaved‐caspase 3, bcl‐2/ bax, MAPK in renal tissue was detected by immunohistochemistry or Western blot; 24 h after surgery, the concentration of Cr in MP group was 355 ± 71μmol/L, in CS group was 511 ± 44 μmol/L (P < 0.05), while the BUN was 15.02 ± 2.34 mmol/L in MP group, 22.64 ± 3.58 mmol/L in CS group (P < 0.05). The rate of apoptosis and expression of cleaved caspase‐3, p‐P38, p‐ERK, and p‐JNK in MP group was significantly lower than that in CS group (P < 0.05), while expression of ALDH2 and bcl‐2/bax in MP group was significantly higher than that in CS group (P < 0.05); expression of cleaved caspase‐3 in both MP and CS group significantly increased as compared with that in normal group (P < 0.05). In conclusion, increased expression of ALDH2 can reduce the renal cell apoptosis through inhibiting MAPK pathway during ischemia/reperfusion injury (IRI) after hypothermic MP.     

Impact of Temperature on Porcine Liver Machine Perfusion From Donors After Cardiac Death

Normothermic machine perfusion (NMP) has been introduced as a promising technology to preserve and possibly repair marginal liver grafts. The aim of this study was to compare the effect of temperature on the preservation of donation after cardiac death (DCD) liver grafts in an ex vivo perfusion model after NMP (38.5°C) and subnormothermic machine perfusion (SNMP, 21°C) with a control group preserved by cold storage (CS, 4°C). Fifteen porcine livers with 60 min of warm ischemia were preserved for 10 h by NMP, SNMP or CS (n = 5/group). After the preservation phase all livers were reperfused for 24 h in an isolated perfusion system with whole blood at 38.5°C to simulate transplantation. At the end of transplant simulation, the NMP group showed significantly lower hepatocellular enzyme level (AST: 277 ± 69 U/L; ALT: 22 ± 2 U/L; P < 0.03) compared to both SNMP (AST: 3243 ± 1048 U/L; ALT: 127 ± 70 U/L) and CS (AST: 3150 ± 1546 U/L; ALT: 185 ± 97 U/L). There was no significant difference between SNMP and CS. Bile production was significantly higher in the NMP group (219 ± 43 mL; P < 0.01) compared to both SNMP (49 ± 84 mL) and CS (12 ± 16 mL) with no significant difference between the latter two groups. Histologically, the NMP livers showed preserved cellular architecture compared to the SNMP and CS groups. NMP was able to recover DCD livers showing superior hepatocellular integrity, biliary function, and microcirculation compared to SNMP and CS. SNMP showed some significant benefit over CS, yet has not shown any advantage over NMP.     

Inhibition of Growth and Metastasis of Tumor in Nude Mice after Intraperitoneal Injection of Bevacizumab

Objective

To explore the inhibitory effect of bevacizumab, a vascular endothelial growth factor antibody, on angiogenesis in human osteosarcoma of nude mice.

Methods

Twenty‐one nude mice were inoculated with red fluorescent protein (RFP)‐labeled human osteosarcoma cell line 143B‐RFP, that is, clones that expressed RFP in the cytoplasm, and randomly assigned to one of three groups: G1 (Control group, injected with saline solution); G2 (intraperitoneal bevacizumab 2 mg/kg twice per week) and G3 (intraperitoneal bevacizumab 5 mg/kg, twice per week). The tumor‐bearing mice were examined in a fluorescence light box that was illuminated periodically. The primary tumors were measured by fluorescence imaging weekly and their volumes calculated.

Results

The mean tumor volumes were significantly smaller in the G3 (186.4 ± 100.8 mm³) than the control group (587.0 ± 406.8 mm³) (P < 0.05) on Day 31, and again significantly smaller in the G3 (677.3 ± 461.9 mm³) than the control group (3162.6 ± 1529.2 mm³) on Day 38 (P < 0.01). The average tumor volume in the G2 group was 493.5 ± 425.4 mm³ on Day 31 and 1870.1 ± 1524.8 mm³ on Day 38. The effect on tumor volume was greater in the G3 than the G2 group. Three mice in the G2 group, four in the G3 group and four in the control group developed lung metastases that were confirmed by pathological examination; these differences were not statistically significant (P < 0.05).

Conclusions

Bevacizumab exhibits strong antiangiogenesis activity in experimental osteosarcoma in a nude mouse model but does not influence the incidence of lung metastasis. Our findings may have considerable potential for the treatment of osteosarcoma.