Oral Calcitriol Use,Vertebral Fractures,and Vitamin K in Hemodialysis Patients: A Cross-Sectional Study

Fractures and vascular calcifications (VCs) are common in patients with chronic kidney disease (CKD). They are related to abnormalities in vitamin D metabolism, calcium, phosphorus, parathyroid hormone, and fibroblast growth factor 23 (FGF23)/Klotho that occur with CKD. Impaired vitamin D metabolism and abnormal levels of calcium, phosphate, parathyroid hormone (PTH), and FGF23/Klotho drive bone and vascular changes in CKD. It is unclear if oral calcitriol safely mitigates fracture risk without increasing the burden of calcifications. Therefore, we investigated whether treatment with calcitriol affected the prevalence of fractures and VC progression in hemodialysis (HD) patients. This report is a secondary analysis of the Vitamin K Italian (VIKI) study, a cross-sectional study involving 387 HD patients. We assessed vitamin 25(OH)D, alkaline phosphatase, PTH, calcium, phosphate, osteocalcin or bone Gla protein, matrix Gla protein, and vitamin K levels. Vertebral fractures (VFs) and VCs were determined by spine radiograph. A reduction of >20% of vertebral body height was considered a VF. VCs were quantified by the length of calcific lesions along the arteries. The patients treated with oral calcitriol were 177 of 387 patients (45.7%). The prevalence of VF was lower in patients receiving oral calcitriol than in those untreated (48.6% versus 61.0%, p  =  0.015), whereas the presence of aortic and iliac calcifications was similar (aortic: 81.9% versus 79.5%, respectively, p = 0.552; iliac: 52.0% and 59.5%, respectively, p = 0.167). In multivariable logistic regression analysis, oral calcitriol was associated with a 40.2% reduced odds of fracture (OR 0.598; 95% confidence interval [CI], 0.363–0.985; p = 0.043). In conclusion, we found a significant association between oral calcitriol and lower VF in HD patients without an increase in the burden of VC. Further prospective and interventional studies are needed to confirm these findings. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Skin Autofluorescence,a Noninvasive Biomarker for Advanced Glycation End-Products,Is Associated With Prevalent Vertebral and Major Osteoporotic Fractures: The Rotterdam Study

Advanced glycation end-products (AGEs), which bind to type 1 collagen in bone and skin, have been implicated in reduced bone quality. The AGE reader™ measures skin autofluorescence (SAF), which might be regarded as a marker of long-term accumulation of AGEs in tissues. We investigated the association of SAF with bone mineral density (BMD) and fractures in the general population. We studied 2853 individuals from the Rotterdam Study with available SAF measurements (median age, 74.1 years) and with data on prevalent major osteoporotic (MOFs: hip, humerus, wrist, clinical vertebral) and vertebral fractures (VFs: clinical + radiographic Genant’s grade 2 and 3). Radiographs were assessed 4 to 5 years before SAF. Multivariate regression models were performed adjusted for age, sex, BMI, creatinine, smoking status, and presence of diabetes and additionally for BMD with interaction terms to test for effect modification. Prevalence of MOFs was 8.5% and of VFs 7%. SAF had a curvilinear association with prevalent MOFs and VFs and therefore, age-adjusted, sex stratified SAF quartiles were used. The odds ratio (OR) (95% confidence interval [CI]) of the second, third and fourth quartiles of SAF for MOFs were as follows: OR 1.60 (95% CI, 1.08–2.35; p = .02); OR 1.30 (95% CI, 0.89–1.97; p = .20), and OR 1.40 (95% CI, 0.95–2.10; p = .09), respectively, with first (lowest) quartile as reference. For VFs the ORs were as follows: OR 1.69 (95% CI, 1.08–2.64; p = .02), OR 1.74(95% CI, 1.11–2.71; p = .01), and OR 1.73 (95% CI, 1.12–2.73; p = .02) for second, third, and fourth quartiles, respectively. When comparing the top three quartiles combined with the first quartile, the OR (95% CI) for MOFs was 1.43 (95% CI, 1.04–2.00; p = .03) and for VFs was 1.72 (95% CI, 1.18–2.53; p = .005). Additional adjustment for BMD did not change the associations. In conclusion, there is evidence of presence of a threshold of skin AGEs below which there is distinctly lower prevalence of fractures. Longitudinal analyses are needed to confirm our cross-sectional findings. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Vitamin K,vertebral fractures,vascular calcifications,and mortality: VItamin K Italian (VIKI) dialysis study

Vitamin K (vitamin K1 or phylloquinone and vitamin K2, a series of menaquinones [MKs]) is involved in the production of bone and matrix amino acid γ‐carboxy‐glutamic acid (Gla) proteins, regulating bone and vascular calcification. Low vitamin K concentrations are associated with increased risks of fractures and vascular calcification, and frequent complications in hemodialysis patients. We carried out an observational study to establish the prevalence of vitamin K deficiency and to assess the relationship between vitamin K status, vertebral fractures, vascular calcification, and survival in 387 patients on hemodialysis for ≥1 year. We determined plasma levels of vitamin K compound, bone‐Gla‐protein, matrix‐Gla‐protein, and routine biochemistry. Vertebral fractures (reduction in vertebral body height by ≥20%) and aortic and iliac calcifications were also investigated in a spine (D₅–L₄) radiograph. Three‐year patient survival was analyzed. Important proportions of patients had deficiency of MK7 (35.4%), vitamin K1 (23.5%), and MK4 (14.5%). A total of 55.3% of patients had vertebral fractures, 80.6% had abdominal aorta calcification, and 56.1% had iliac calcification. Vitamin K1 deficiency was the strongest predictor of vertebral fractures (odds ratio [OR], 2.94; 95% confidence interval [CI], 1.38–6.26). MK4 deficiency was a predictor of aortic calcification (OR, 2.82; 95% CI, 1.14–7.01), whereas MK5 deficiency actually protected against it (OR, 0.38; 95% CI, 0.15–0.95). MK7 deficiency was a predictor of iliac calcification (OR, 1.64; 95% CI, 1.03–2.60). The presence of vertebral fractures was also a predictor of vascular calcifications (OR, 1.76; 95% CI, 1.00–3.08). Increased alkaline phosphatase and C reactive protein (CRP), age, and cerebrovascular events were predictors of mortality. Our study suggests that the vitamin K system may be important for preserving bone mass and avoiding vascular calcification in hemodialysis patients, pointing out a possible role of vitamin K in bone and vascular health. Based on our results, we suggest that the general population should also be studied for vitamin K deficiency as a possible cause of both vertebral fractures and vascular calcification. © 2012 American Society for Bone and Mineral Research.     

High Prevalence of Vertebral Fractures Assessed by Quantitative Morphometry in Hemodialysis Patients, Strongly Associated with Vascular Calcifications

Few studies have provided information on the prevalence of vertebral fractures (VFs) and their risk factors in hemodialysis patients. A multicenter, cross-sectional, observational study was carried out to assess the prevalence of VFs and vascular calcifications (VCs) in 387 hemodialysis patients (mean age 64.2 ± 14.1 years, 63 % males) and in a control group of 51 osteoporotic subjects. Biochemical tests included 25(OH) vitamin D, bone Gla protein (total and undercarboxylated), and total matrix Gla protein. Vertebral quantitative morphometry was carried out centrally for the detection of VF, defined as reduction by ≥20 % of one of the vertebral body dimensions. In the same radiograph, aortic and iliac VC scores were calculated. Prevalence of VF was 55.3 % in hemodialysis patients and 51.0 % in the control group. Multivariate analysis disclosed that male gender (59.8 vs. 47.6 %, p = 0.02; OR = 1.78, 95 % CI 1.15–2.75) and age (mean ± SD 66.7 ± 13.1 vs. 61.0 ± 14.7 years, p < 0.001; OR = 1.03, 95 % CI 1.01–1.05) were significantly associated with VF. The prevalence of aortic VC was significantly higher in hemodialysis patients than in controls (80.6 vs. 68.4 %, p = 0.001). The factors with the strongest association with VC, apart from atrial fibrillation, were serum 25(OH)vitamin D levels below 29 ng/mL for aortic VC (OR = 1.85, 95 % CI 1.04–3.29) and VF both for aortic (OR = 1.77, 95 % CI 1.00–3.14) and iliac (OR = 1.96, 95 % CI 1.27–3.04) VC. In conclusion, the prevalence of VF, especially in males, and VC, in both genders, is high in hemodialysis patients. VF is associated with VC. Vitamin D deficiency is also associated with VC. Further longitudinal studies are warranted to investigate fractures in renal patients.     

Characterization of Osteocalcin (BGP) and Matrix Gla Protein (MGP) Fish Specific Antibodies: Validation for Immunodetection Studies in Lower Vertebrates

In fish species the basic mechanisms of bone development and bone remodeling are not fully understood. The classification of bone tissue in teleosts as cellular or acellular and the presence of transitional states between bone and cartilage and the finding of different types of cartilage in teleosts not previously recognized in higher vertebrates emphasizes the need for a study on the accumulation of the Gla-containing proteins MGP and BGP at the cellular level. In the present study, polyclonal antibodies developed against BGP and MGP from A. regius (a local marine teleost fish) and against MGP from G. galeus (a Pacific Ocean shark), were tested by Western blot for their specificity against BGP and MGP from several other species of teleost fish and shark. For this purpose we extracted and purified both proteins from various marine and freshwater teleosts, identified them by N-terminal amino acid sequence analysis and confirmed the presence of gamma-carboxylation in the proteins with the use of a stain specific for Gla residues. Each antibody recognized either BGP or MGP with no cross-reaction between proteins detected. All purified fish BGPs and MGPs tested were shown to be specifically recognized, thus validating the use of these antibodies for further studies.     

Association of matrix Gla protein gene functional polymorphisms with loss of bone mineral density and progression of aortic calcification

Summary

Two matrix Gla protein (MGP) polymorphisms were associated with progression of aortic calcification and femoral neck bone loss in men. All these findings were also functionally corroborated in two vascular and bone in vitro systems indicating that MGP genetic variations can be partly responsible of higher risk of bone loss and vascular calcification.

Introduction

MGP plays an important role in bone and vascular mineralization as confirmed by MGP-deficient murine model. We therefore aimed to find a genetic association among -138T>C, -7G>A, and Thr83Ala MGP single-nucleotide polymorphisms (SNPs), bone loss, and progression of aortic calcification in a randomly selected general population of 296 individuals who participated in the European Vertebral Osteoporosis Study.

Methods

To evaluate the rate of change in bone mineral density (BMD) and the progression of aortic calcification, dual X-ray absorptiometry and lateral spine X-rays were performed at baseline and after 4 years of follow-up. Genotyping for the three polymorphisms was carried out using polymerase chain reaction and restriction fragment length analysis. In addition, functional studies of MGP-7G>A and Thr83Ala SNPs were performed on transiently transfected osteoblast-like UMR-106 and vascular smooth muscle A7r5 cells.

Results

The proportion of men who had lost BMD in the femoral neck was higher among homozygous -7AA and 83Ala-Ala (p?=?0.039 and p?=?0.009, respectively), and also featured a higher risk of progression of aortic calcifications (OR?=?5.6, 95 % CI?=?1.2–27.8 and OR?=?6.8, 95 % CI?=?1.4–32.3, respectively). No effect was observed in women. The MGP-7A allele produced a reduction in luciferase activity compared to MGP-7G: 47 % less in vascular cells and 34 % less in bone cells (p?=?0.001 and 0.012, respectively). In vascular cells under calcifying conditions, the MGP 83Thr allele showed a slightly higher, although not significant, inhibition than the MGP 83 Ala allele in calcium content suggesting functional differences between both variants.

Conclusion

These results suggest that MGP genetic variations could predict a higher risk of bone loss and progression of vascular calcification in men.     

Induction of matrix gla protein synthesis during prolonged 1,25-Dihydroxyvitamin D3 treatment of osteosarcoma cells

Summary The synthesis of matrix Gla protein (MGP) and bone Gla protein (BGP) have been shown to be mutually exclusive in all osteosarcoma cell lines investigated. In the cell lines that produce the respective proteins, synthesis is stimulated by 1,25-dihydroxyvitamin D₃(1,25(OH)₂D₃) within the first several hours of hormone treatment. In the present studies we have investigated the effects of longer-term treatment with 1,25(OH)₂D₃ in the ROS 17/2 cell line, a cell line that synthesizes BGP constitutively but does not synthesize MGP. In agreement with earlier studies, the rate of BGP synthesis increases within 8 hours of hormone treatment, is maximal by 24 hours, and remains at the maximal rate through 48 hours of 1,25(OH)₂D₃ treatment. The present study is the first to report that the rate of BGP secretion at times beyond 48 hours declines to that of control cultures despite the continued administration of 1,25(OH)₂D₃, and that MGP synthesis is induced in ROS 17/2 cells by 48 hours of 1,25(OH)₂D₃ treatment. At this time, MGP mRNA could be detected by northern blot analysis and MGP secretion could be demonstrated by radioimmunoassay of culture medium. Both the level of MGP message per unit total RNA and the rate of MGP secretion into culture medium increased steadily between 2 and 6 days of 1,25(OH)₂D₃ treatment. The MGP synthesized by the 1,25(OH)₂D₃-treated ROS 17/2 cells was identical to that found in bone by northern blot analysis of message and by western blot analysis of the media antigen. Halfmaximal induction of MGP synthesis was obtained with 0.3 nM 1,25(OH)₂D₃, a 60-fold higher dosage than was required for the half maximal stimulation of BGP synthesis in these cells. Treatment of ROS 17/2 cells with 24,24-F₂1,25(OH)₂D₃ suggests that the observed difference in dose dependence is not due to an increased rate of hormone catabolism.     

Plasma Choline,Nicotine Exposure,and Risk of Low Bone Mineral Density and Hip Fracture: The Hordaland Health Study

Choline, obtained from diet and formed by biosynthesis, is the immediate precursor of betaine. Animal studies suggest an impact of choline on bone metabolism. We examined the associations of plasma choline and betaine with bone mineral density (BMD), the risk of hip fractures, and possible effect‐modification by nicotine exposure. The Hordaland Health Study (1998 to 2000) included 7074 women and men (ages 46 to 49 or 71 to 74 years). In 5315, BMD was measured. The oldest (n = 3311) were followed for hip fractures through 2009. Risk associations were studied by logistic and Cox regression by comparing the lowest and middle tertiles with the highest, as well as trends across tertiles of plasma choline and betaine. In analyses adjusted for sex and age, participants in the lowest (odds ratio [OR] = 2.00, 95% confidence interval [CI] 1.69–2.37) and middle (OR = 1.39, CI 1.17–1.66) tertiles of plasma choline had an increased risk of low BMD (lowest quintile) (p trend < 0.001). Separate analyses for sex and age groups revealed the strongest relations in elderly women (lowest tertile: OR = 2.84, CI 1.95–4.14; middle tertile: OR = 1.80, CI 1.22–2.67, p trend < 0.001), and highest OR among those in the lowest tertile who were exposed to nicotine (OR = 4.56, CI 1.87–11.11). Low plasma choline was also associated with an increased risk of hip fracture in elderly women and men (lowest tertile: hazard ratio [HR] = 1.45, CI 1.08–1.94; middle tertile: HR = 1.13, CI 0.83–1.54, p trend = 0.012). In elderly women, the HR for hip fracture was 1.90 (CI 1.32–2.73) and 1.36 (CI 0.92–1.99) (p trend < 0.001) for lowest and middle tertiles of choline, and the highest HR was found among women in the lowest tertile exposed to nicotine (HR = 2.68, CI 1.16–6.19). Plasma betaine was not related to BMD or hip fracture. Low plasma choline was associated with low BMD in both sexes and increased the risk of hip fracture in elderly women. These results should motivate further studies on choline, nicotine exposure, and bone metabolism. © 2014 American Society for Bone and Mineral Research.     

Vertebral Fracture Risk in Diabetic Elderly Men: The MrOS Study

Type 2 diabetes (T2DM) is associated with a significant increase in risk of nonvertebral fractures, but information on risk of vertebral fractures (VFs) in subjects with T2DM, particularly among men, is lacking. Furthermore, it is not known whether spine bone mineral density (BMD) can predict the risk of VF in T2DM. We sought to examine the effect of diabetes status on prevalent and incident vertebral fracture, and to estimate the effect of lumbar spine BMD (areal and volumetric) as a risk factor for prevalent and incident morphometric vertebral fracture in T2DM (n = 875) and nondiabetic men (n = 4679). We used data from the Osteoporotic Fractures in Men (MrOS) Study, which enrolled men aged ≥65 years. Lumbar spine areal BMD (aBMD) was measured with dual‐energy X‐ray absorptiometry (DXA), and volumetric BMD (vBMD) by quantitative computed tomography (QCT). Prevalence (7.0% versus 7.7%) and incidence (4.4% versus 4.5%) of VFs were not higher in T2DM versus nondiabetic men. The risk of prevalent (OR, 1.05; 95% CI, 0.78 to 1.40) or incident vertebral‐fracture (OR, 1.28; 95% CI, 0.81 to 2.00) was not higher in T2DM versus nondiabetic men in models adjusted for age, clinic site, race, BMI, and aBMD. Higher spine aBMD was associated with lower risk of prevalent VF in T2DM (OR, 0.55; 95% CI, 0.48 to 0.63) and nondiabetic men (OR, 0.66; 95% CI, 0.5 to 0.88) (p for interaction = 0.24) and of incident VF in T2DM (OR, 0.50; 95% CI, 0.41 to 0.60) and nondiabetic men (OR, 0.54; 95% CI, 0.33 to 0.88) (p for interaction = 0.77). Results were similar for vBMD. In conclusion, T2DM was not associated with higher prevalent or incident VF in older men, even after adjustment for BMI and BMD. Higher spine aBMD and vBMD are associated with lower prevalence and incidence of VF in T2DM as well as nondiabetic men. © 2017 American Society for Bone and Mineral Research.     

Comparative Analysis of the Radiology of Osteoporotic Vertebral Fractures in Women and Men: Cross‐Sectional and Longitudinal Observations from the Canadian Multicentre Osteoporosis Study (CaMos)

We compared two methods for osteoporotic vertebral fracture (VF) assessment on lateral spine radiographs, the Genant semiquantitative (GSQ) technique and a modified algorithm‐based qualitative (mABQ) approach. We evaluated 4465 women and 1771 men aged ≥50 years from the Canadian Multicentre Osteoporosis Study with available X‐ray images at baseline. Observer agreement was lowest for grade 1 VFs determined by GSQ. Among physician readers, agreement was greater for VFs diagnosed by mABQ (ranging from 0.62 [95% confidence interval (CI) 0.00–1.00] to 0.88 [0.76–1.00]) than by GSQ (ranging from 0.38 [0.17–0.60] to 0.69 [0.54–0.85]). GSQ VF prevalence (16.4% [95% CI 15.4–17.4]) and incidence (10.2/1000 person‐years [9.2; 11.2]) were higher than with the mABQ method (prevalence 6.7% [6.1–7.4] and incidence 6.3/1000 person‐years [5.5–7.1]). Women had more prevalent and incident VFs relative to men as defined by mABQ but not as defined by GSQ. Prevalent GSQ VFs were predominantly found in the mid‐thoracic spine, whereas prevalent mABQ and incident VFs by both methods co‐localized to the junction of the thoracic and lumbar spine. Prevalent mABQ VFs compared with GSQ VFs were more highly associated with reduced adjusted L₁ to L₄ bone mineral density (BMD) (–0.065 g/cm² [–0.087 to –0.042]), femoral neck BMD (–0.051 g/cm² [–0.065 to –0.036]), and total hip BMD (–0.059 g/cm² [–0.076 to –0.041]). Prevalent mABQ VFs compared with prevalent GSQ were also more highly associated with incident VF by GSQ (odds ratio [OR] = 3.3 [2.2–5.0]), incident VF by mABQ (9.0 [5.3–15.3]), and incident non‐vertebral major osteoporotic fractures (1.9 [1.2–3.0]). Grade 1 mABQ VFs, but not grade 1 GSQ VFs, were associated with incident non‐vertebral major osteoporotic fractures (OR = 3.0 [1.4–6.5]). We conclude that defining VF by mABQ is preferred to the use of GSQ for clinical assessments. © 2017 American Society for Bone and Mineral Research.     

Use of DXA‐based finite element analysis of the proximal femur in a longitudinal study of hip fracture

Bone mineral density (BMD) measured by dual‐energy X‐ray absorptiometry (DXA) is used for clinical assessment of fracture risk; however, measurements that incorporate bone strength could improve predictive ability. The aim of this study was to determine whether bone strength derived from finite element (FE) analysis was associated with hip fracture risk in a longitudinal study. We studied 728 women (mean age 82 years), 182 with subsequent hip fracture. FE models were generated from baseline DXA scans of the hip to determine femoral bone strength and load‐to‐strength ratio (LSR). The baseline LSR was significantly higher in fracture cases (median 1.1) compared with controls (0.7, p < 0.0001). Femoral strength and BMD were also significantly lower in cases (median 1820 N, 0.557 g/cm²) compared with controls (2614 N, 0.618 g/cm²) both p < 0.0001. Fracture risk increased per standard deviation decrease in femoral strength (odds ratio [OR] = 2.2, 95% confidence interval [CI] 1.8–2.8); femoral neck (FN) BMD (OR = 2.1, 95% CI 1.7–2.6); total hip BMD (OR = 1.8, 95% CI 1.5–2.1); and per SD increase in LSR (OR = 1.8, 95% CI 1.5–2.1). After adjusting for FN BMD, the odds ratio for femoral strength (OR = 1.7, 95% CI 1.2–2.4) and LSR (OR = 1.4, 95% CI 1.1–1.7) remained significantly greater than 1. The area under the curve (AUC) for LSR combined with FN BMD (AUC 0.69, 95% CI 0.64–0.73) was significantly greater than FN BMD alone (AUC 0.66, 95% CI 0.62–0.71, p = 0.004). Strength and LSR remained significant when adjusted for prevalent fragility fracture, VFA, and FRAX score. In conclusion, the DXA‐based FE model was able to discriminate incident hip fracture cases from controls in this longitudinal study independently from FN BMD, prior fracture, VFA, and FRAX score. Such an approach may provide a useful tool for better assessment of bone strength to identify patients at high risk of hip fracture who may benefit from treatment to reduce fracture risk. © 2013 American Society for Bone and Mineral Research.     

Preservation or Ligation of Splenic Vessels During Spleen-Preserving Distal Pancreatectomy: A Meta-Analysis

ABSTRACT

Purpose/aim: Spleen preservation distal pancreatectomy (SPDP) can be achieved by either splenic vessel preservation distal pancreatectomy (SVP-DP) or Warshaw technique (WT). Although studies comparing SVP-DP with WT have been reported, controversies exist. The aim of our study is to assess and compare the safety and feasibility of SVP-DP and WT. Materials and methods: Two authors searched the online database independently till April 30, 2017. Data extraction and quality assessment were performed independently by two authors. Short- and long-term outcomes of WT and SVP-DP were evaluated. Subgroup analysis was performed on laparoscopic surgery. Odds ratios (OR) with 95% confidence interval (CI) and mean difference (MD) with 95% CI were estimated. Results: A total of 664 patients from 11 retrospective cohort studies were included. Meta-analysis showed the WT group had a significantly higher incidence of splenic infarction (OR = 0.12; 95% CI: 0.07–0.20; p < 0.00001) and gastric/epigastric varices (OR = 0.11; 95% CI: 0.05–0.24; p < 0.00001). And more patients suffering from splenic infarction from WT group needed further splenectomy (OR = 0.13; 95% CI: 0.02–0.84; p = 0.03). While there was no difference between the two procedures in terms of pancreatic fistula (OR = 0.55; 95% CI: 0.25–1.19; p = 0.13), overall morbidity (OR = 0.87; 95% CI: 0.59–1.30; p = 0.50) and hospital stay (MD = ?0.45; 95% CI: ?1.73-0.82; p = 0.49). Conclusions: Due to relatively higher risk of postoperative splenic infarction, gastric/epigastric varices and Clavien–Dindo III–V complications, WT is not as safe as SVP-DP. However, well-conducted randomized clinical trials are still needed due to the limitations of current studies.     

Serum uric acid is associated with bone health in older men: A cross‐sectional population‐based study

Serum uric acid (UA) is a strong endogenous antioxidant. Since oxidative stress has been linked to osteoporosis, we examined the association between serum UA levels and bone mineral density (BMD), prevalent vertebral and nonvertebral fractures, and laboratory measures such as calcitropic hormones and bone turnover marker levels. This cross‐sectional analysis consisted of 1705 community‐dwelling men aged 70 years or over who participated in the baseline part of the Concord Health and Ageing in Men Project (CHAMP), a population‐based study of older men in Sydney, Australia. BMD at all sites was significantly higher among men with serum UA levels above the group median than among men with UA levels below the median. In multiple regression analyses adjusted for potential confounders, serum UA remained associated with BMD at all sites (β = 0.12 to 0.14, p < .001), serum calcium (β = 0.11, p = .001), parathyroid hormone (β = 0.09, p = .002), 25‐hydroxyvitamin D (β = 0.09, p = .005), and was negatively associated with urinary excretion amino‐terminal cross‐linked telopeptide of type 1 collagen (β = –0.09, p = .006). Overall, serum UA accounted for 1.0% to 1.44% of the variances in BMD (R² = 0.10 to 0.22). In multiple logistic regression analyses, above‐median serum UA levels were associated with a lower prevalence of osteoporosis at the femoral neck [odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.22–0.81, p = .010) and lumbar spine (OR = 0.44, 95% CI 0.23–0.86, p = .016) and a lower prevalence of vertebral (OR = 0.62, 95% CI 0.43–0.91, p = .015) and nonvertebral (OR = 0.51, 95% CI 0.29–0.89, p = .018) fractures. In conclusion, higher serum UA levels are associated with higher BMD at all skeletal sites and with a lower prevalence of vertebral and nonvertebral fractures in older men. © 2011 American Society for Bone and Mineral Research.     

Sex Differences in the Association Between Adiponectin and BMD,Bone Loss,and Fractures: The Rancho Bernardo Study

We evaluated sex differences in the prospective association between adiponectin with BMD, bone loss, and fractures. Adiponectin, an adipose‐derived protein with insulin‐sensitizing properties, is also expressed in bone‐forming cells. Conflicting results and sex differences in the adiponectin‐BMD association have been reported in cross‐sectional studies. Serum adiponectin was measured in fasting blood samples obtained in 1984–1987 in 447 postmenopausal women (mean age: 76 yr) and 484 men (mean age: 75 yr). Four years later, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA. In 1992–1996, axial BMD was remeasured in 261 women and 264 men. Multivariable analysis adjusted for age, weight, calcium intake, type 2 diabetes, alcohol intake, and exercise. Among women, adiponectin was inversely associated with BMD at the femoral neck (β = ?0.002, p = 0.007), total hip (β = ?0.002, p = 0.009), lumbar spine (β = ?0.003, p = 0.008), and midshaft radius (β = ?0.002, p = 0.01) after 4.4 yr and at the femoral neck and total hip 8.6 yr later. Among men, adiponectin was inversely associated with BMD at the femoral neck, (β = ?0.002, p = 0.03), total hip (β = ?0.004, p < 0.001), and midshaft radius (β = ?0.003, p < 0.001) after 4.4 yr and at the hip 8.6 yr later. Adiponectin was not associated with 4‐yr bone loss in either sex but was associated with vertebral fractures (adjusted OR: 1.13; 95% CI: 1.08–1.23; p = 0.009) among men only. Adiponectin was inversely associated with BMD; however, sex differences were observed by anatomical site and with regards to vertebral fractures.     

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70 µg/24 h (193.1 nmol/L); (2) cortisol after 1‐mg dexamethasone suppression test (1‐mg DST) >3.0 µg/dL (82.8 nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10 pg/mL (<2.2 pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X‐ray absorptiometry and TBS was assessed in the region of LS‐BMD; BMD and TBS data were reported as Z‐scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (n = 34) had lower LS‐BMD (?0.31 ± 1.17), FT‐BMD (?0.29 ± 0.91), and TBS (?3.18 ± 1.21) than patients without SH (n = 68, 0.31 ± 1.42, p = 0.03; 0.19 ± 0.97, p = 0.01; ?1.70 ± 1.54, p < 0.0001, respectively) and controls (0.42 ± 1.52, p = 0.02; 0.14 ± 0.76, p = 0.02; ?1.19 ± 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1‐mg DST (β = ?0.26, t = ?2.79, p = 0.006) regardless of age, LS‐BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85–12.42, p = 0.001) and with the cluster low TBS plus low LS‐BMD (OR, 4.37; 95% CI, 1.71–11.4, p = 0.002), after adjustment for age, BMI, and gender. Low TBS plus low LS‐BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie, > ?1.5) plus normal LS‐BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71–71.41, p = 0.012) regardless of LS‐BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures. © 2012 American Society for Bone and Mineral Research.     

Video-assisted thoracoscopic surgery thymectomy versus open thymectomy in patients with myasthenia gravis: a meta-analysis

Background: Video-assisted thoracoscopic surgery (VATS) thymectomy has become a feasible treatment for myasthenia gravis (MG) in recent years. The objective of the present meta-analysis was to evaluate the perioperative characteristics, safety, and completely stable remission rate in patients with MG who received VATS or open thymectomy (OT).

Methods: We searched PubMed, Embase, ScienceDirect, Web of Science, and CNKI for related articles using combinations of the search terms video-assisted thoracoscopic thymectomy, transsternal thymectomy, and MG. The inter-study heterogeneity was assessed by χ²-based Q statistics, and the extent of inconsistency was generated by I² statistics.

Results: A total of 12 studies with 1173 patients were included, and there was no difference in the operation time (p?=?0.08) and ICU time (p?=?0.14) between the two groups, but VATS thymectomy was associated with less intra-operation blood loss and hospital time (p?p?=?0.03) and myasthenic crisis (OR = 0.51; 95% CI, 0.28–0.92; p?=?0.03), but the rates of pneumonia (OR = 0.59; 95% CI, 0.29–1.32; p?=?0.21) and complete remission rate (CSR) (OR = 0.64; 95% CI, 0.38–1.09; p?=?0.10) had no obvious differences between the VATS and OT groups.

Conclusion: Patients with MG undergoing VATS thymectomy achieved better surgical outcomes and fewer complications than those who received OT.     

A polymorphism of matrix Gla protein gene is associated with kidney stones

PURPOSE: Matrix Gla protein, a potent calcification inhibitor in arterial vessels, is also expressed in the kidney and is up-regulated following the administration of ethylene glycol, a precursor of oxalate. Considering the analogous characteristics between arterial calcification and kidney stones, we identified variants of the human matrix Gla protein gene and investigated whether there is an association between MGP genetic polymorphisms and kidney stones. MATERIALS AND METHODS: We studied single nucleotide polymorphisms in matrix Gla protein in 122 kidney stone cases and 125 controls. We resequenced the human genomic MGP gene, including the 1,000 bp promoter 5'-untranslated region, 4 exons and 3'-untranslated regions, and we performed systematic genetic analysis. A single nucleotide polymorphism was genotyped using a fluorescent 5'endonuclease assay and its association with kidney stones was analyzed. RESULTS: We observed 19 polymorphisms. A single nucleotide polymorphism was associated with kidney stones (OR 0.51, 95% CI 0.30-0.87; p = 0.012). The G allele carrier had a 2-fold decreased kidney stone risk compared with A allele carriers in single nucleotide polymorphism 11 (OR 0.55, 95% CI 0.31-1.00, p = 0.047). We found no association between the polymorphism and kidney stone clinical characteristics. CONCLUSIONS: Our findings show that an MGP gene polymorphism is associated with kidney stones and influences genetic susceptibility to kidney stones. In the future functional assays of the polymorphism should permit better understanding of the role of matrix Gla protein genetic variants and kidney stones.     

Examining the Relationships Between Bone Tissue Composition,Compositional Heterogeneity,and Fragility Fracture: A Matched Case‐Controlled FTIRI Study

Fourier transform infrared imaging (FTIRI) provides information on spatial distribution of the chemical composition of thin tissue specimens at ～7 µm spatial resolution. This study of 120 age‐ and bone mineral density (BMD)‐matched patients was designed to investigate the association of FTIRI variables, measured in iliac crest biopsies, with fragility fractures at any site. An earlier study of 54 women found hip BMD to be a significant explanatory variable of fracture risk for cortical bone but not for cancellous bone. In the current study, where age and BMD were controlled through matching, no such association was observed, validating the pairing scheme. Our first study of unmatched iliac crest biopsies found increases in collagen maturity (cancellous and cortical bone) and mineral crystal size (cortical bone only) to be a significant explanatory variable of fracture when combined with other covariates. The ratio for collagen maturity has been correlated to the amount of enzymatic collagen cross‐links. To assess the impact of other FTIRI variables (acid phosphate substitution, carbonate‐to‐phosphate ratio, and the pixel distribution [heterogeneity] of all relevant FTIRI variables), we examined biopsies from a matched case‐controlled study, in which 60 women with fractures were each paired with an age‐ and BMD‐matched female control. With the matched data set of 120 women, conditional logistic regression analyses revealed that significant explanatory variables of fracture were decreased carbonate‐to‐phosphate ratio in both cancellous (odds ratio [OR] = 0.580, 95% confidence interval [CI] 0.37–0.909, p = 0.0176) and cortical bone (OR = 0.519, 95% CI 0.325–0.829, p = 0.0061), and increased heterogeneity (broadened pixel distribution) of collagen maturity for cancellous bone (OR = 1.549, 95% CI 1.002–2.396, p = 0.0491). The observation that collagen maturity was no longer linked to fracture in age‐ and BMD‐matched samples suggests that age‐dependent variation in collagen maturity may be a more important contributory factor to fragility fractures than previously thought. © 2015 American Society for Bone and Mineral Research.     

Therapeutic Efficacy and Safety of Percutaneous Curved Vertebroplasty in Osteoporotic Vertebral Compression Fractures: A Systematic Review and Meta‐Analysis

This systematic review and meta-analysis is aimed to provide higher quality evidence regarding the efficacy and safety between PCVP and PVP/KP in OVCFs. We searched the Cochrane Library, PubMed, Web of Science, and Embase databases for all randomized controlled trials (RCTs) and observational studies (cohort or case–control studies) that compare PCVP to PVP/KP for OVCFs. The Cochrane Collaboration's Risk of Bias Tool and Newcastle–Ottawa Scale (NOS) were used to evaluate the quality of the RCTs and non-RCTs, respectively. Meta-analysis was performed using RevMan 5.4 software. A total of seven articles consisting of 562 patients with 593 diseased vertebral bodies were included. Statistically significant differences were found in the postoperative visual analog scale (VAS) at 1 day (MD = −0.11; 95% CI: [−0.21 to −0.01], p = 0.03), but not at 3 months (MD = −0.21; 95% CI: [−0.41–0.00], p = 0.05) or 6 months (MD = 0.03; 95% CI: [−0.13–0.20], p = 0.70). There was no statistically significant difference in postoperative Oswestry disability index (ODI) at 1 day (MD = −0.28; 95% CI: [−0.62–0.05], p = 0.10), 3 months (MD = −1.52; 95% CI: [−3.11–0.07], p = 0.06), or 6 months (MD = 0.18; 95% CI: [−0.13–0.48], p = 0.25). Additionally, there were no statistically significant differences in Cobb angle (MD = 0.30; 95% CI: [−1.69–2.30], p = 0.77) or anterior vertebral body height (SMD = −0.01; 95% CI: [−0.26–0.23], p = 0.92) after surgery. Statistically significant differences were found in surgical time (MD = −8.60; 95% CI: [−13.75 to −3.45], p = 0.001), cement infusion volume (MD = −0.82; 95% CI: [−1.50 to −0.14], P = 0.02), and dose of fluoroscopy (SMD = −1.22; 95% CI: [−1.84 to −0.60], p = 0.0001) between curved and noncurved techniques, especially compared to bilateral PVP. Moreover, cement leakage showed statistically significant difference (OR = 0.40; 95% CI: [0.27–0.60], p < 0.0001). Compared with PVP/KP, PCVP is superior for pain relief at short-term follow-up. Additionally, PCVP has the advantages of significantly lower surgical time, radiation exposure, bone cement infusion volume, and cement leakage incidence compared to bilateral PVP, while no statistically significant difference is found when compared with unilateral PVP or PKP. In terms of quality of life and radiologic outcomes, the effects of PCVP and PVP/KP are not significantly different. Overall, this meta-analysis reveals that PCVP was an effective and safe therapy for patients with OVCFs.     

Relationship between GSTM1/GSTT1 Null Genotypes and Renal Cell Carcinoma Risk: A Meta-Analysis

The results from the published studies on the relationship between GSTM1/GSTT1 null genotypes and renal cell carcinoma (RCC) risk are still conflicting. This meta-analysis was performed to evaluate the relationship between GSTM1/GSTT1 null genotypes and RCC susceptibility. Association studies were identified from the databases of PubMed, Embase, Cochrane Library, and CBM-disc (China Biological Medicine Database) on 1 February 2012, and eligible investigations from 1950 to 2012 were synthesized using meta-analysis method. Results were expressed as odds ratios (ORs) for dichotomous data, and 95% confidence intervals (CIs) were also calculated. Six studies were identified for the analysis of association between polymorphic deletion of GSTM1/GSTT1 and RCC risk. There was no association between GSTM1/GSTT1 null genotype and RCC susceptibility (GSTM1: N = 6, p-heterogeneity = 0.07, OR = 1.07, 95% CI: 0.85–1.35, p = 0.57; GSTT1: N = 6, p-heterogeneity < 0.00001, OR = 0.98, 95% CI: 0.58–1.65, p = 0.94). Interestingly, null genotype of GSTT1 was associated with RCC risk in Caucasians and Asians (Caucasians: N = 4, p-heterogeneity = 0.38, OR = 0.76, 95% CI: 0.61–0.95, p = 0.01; Asians: N = 1, OR = 2.39, 95% CI: 1.63–3.51, p < 0.00001). For the GSTM1–GSTT1 interaction analysis, the dual null genotype of GSTM1/GSTT1 was not significantly associated with RCC susceptibility (N = 4, p-heterogeneity = 0.006, OR = 1.17, 95% CI: 0.98–1.39, p = 0.09). However, the dual null genotype of GSTM1–GSTT1 was associated with RCC risk in Asians (N = 1, OR = 2.06, 95% CI: 1.36–3.13, p = 0.007). In conclusion, our study results suggest that GSTT1 null genotype is associated with the RCC susceptibility in Caucasians and Asians, and the dual null genotype of GSTM1–GSTT1 is associated with RCC risk in Asians. However, more genetic epidemiological investigations are required to further explore this relationship.