Search Results

You are looking at 61 - 70 of 118 items for :

  • Abstract: Calcium x
  • Abstract: Hypoparathyroidism x
  • Abstract: Osteo* x
  • Abstract: Skeleton x
Clear All Modify Search
Jane Fletcher Nutrition Nurses, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, UK
School of Nursing, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, UK

Search for other papers by Jane Fletcher in
Google Scholar
PubMed
Close
,
Emma L Bishop Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

Search for other papers by Emma L Bishop in
Google Scholar
PubMed
Close
,
Stephanie R Harrison Leeds Institute of Rheumatic and Musculoskeletal Medicine, Chapel Allerton Hospital, Leeds, UK

Search for other papers by Stephanie R Harrison in
Google Scholar
PubMed
Close
,
Amelia Swift School of Nursing, Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham, UK

Search for other papers by Amelia Swift in
Google Scholar
PubMed
Close
,
Sheldon C Cooper Gastroenterology Department, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, UK

Search for other papers by Sheldon C Cooper in
Google Scholar
PubMed
Close
,
Sarah K Dimeloe Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK

Search for other papers by Sarah K Dimeloe in
Google Scholar
PubMed
Close
,
Karim Raza Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK

Search for other papers by Karim Raza in
Google Scholar
PubMed
Close
, and
Martin Hewison Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

Search for other papers by Martin Hewison in
Google Scholar
PubMed
Close

Vitamin D has well-documented effects on calcium homeostasis and bone metabolism but recent studies suggest a much broader role for this secosteroid in human health. Key components of the vitamin D system, notably the vitamin D receptor (VDR) and the vitamin D-activating enzyme (1α-hydroxylase), are present in a wide array of tissues, notably macrophages, dendritic cells and T lymphocytes (T cells) from the immune system. Thus, serum 25-hydroxyvitamin D (25D) can be converted to hormonal 1,25-dihydroxyvitamin D (1,25D) within immune cells, and then interact with VDR and promote transcriptional and epigenomic responses in the same or neighbouring cells. These intracrine and paracrine effects of 1,25D have been shown to drive antibacterial or antiviral innate responses, as well as to attenuate inflammatory T cell adaptive immunity. Beyond these mechanistic observations, association studies have reported the correlation between low serum 25D levels and the risk and severity of human immune disorders including autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, type 1 diabetes and rheumatoid arthritis. The proposed explanation for this is that decreased availability of 25D compromises immune cell synthesis of 1,25D leading to impaired innate immunity and over-exuberant inflammatory adaptive immunity. The aim of the current review is to explore the mechanistic basis for immunomodulatory effects of 25D and 1,25D in greater detail with specific emphasis on how vitamin D-deficiency (low serum levels of 25D) may lead to dysregulation of macrophage, dendritic cell and T cell function and increase the risk of inflammatory autoimmune disease.

Open access
Johanna Öberg Tromso Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway

Search for other papers by Johanna Öberg in
Google Scholar
PubMed
Close
,
Rolf Jorde Tromso Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway

Search for other papers by Rolf Jorde in
Google Scholar
PubMed
Close
,
Yngve Figenschau Tromso Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway
Diagnostic Clinic, University Hospital of North Norway, Tromso, Norway

Search for other papers by Yngve Figenschau in
Google Scholar
PubMed
Close
,
Per Medbøe Thorsby Hormone Laboratory, Department of Medical Biochemistry and Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway

Search for other papers by Per Medbøe Thorsby in
Google Scholar
PubMed
Close
,
Sandra Rinne Dahl Hormone Laboratory, Department of Medical Biochemistry and Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway

Search for other papers by Sandra Rinne Dahl in
Google Scholar
PubMed
Close
,
Anne Winther Division of Neurosciences, Orthopedics and Rehabilitation Services, University Hospital of North Norway, Tromso, Norway

Search for other papers by Anne Winther in
Google Scholar
PubMed
Close
, and
Guri Grimnes Tromso Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway
Division of Internal Medicine, University Hospital of North Norway, Tromso, Norway

Search for other papers by Guri Grimnes in
Google Scholar
PubMed
Close

Objective

Combined hormonal contraceptive (CHC) use has been associated with higher total 25-hydroxyvitamin D (25(OH)D) levels. Here, we investigate the relation between CHC use and vitamin D metabolism to elucidate its clinical interpretation.

Methods

The cross-sectional Fit Futures 1 included 1038 adolescents. Here, a subgroup of 182 girls with available 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D (24,25(OH)2D), vitamin D-binding protein (DBP) and measured free 25(OH)D levels, in addition to parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23), was investigated. Vitamin D metabolites were compared between girls using (CHC+) and not using CHC (CHC−). Further, the predictability of CHC on 25(OH)D levels was assessed in a multiple regression model including lifestyle factors. The ratios 1,25(OH)2D/25(OH)D and 24,25(OH)2D/25(OH)D (vitamin D metabolite ratio (VMR)) in relation to 25(OH)D were presented in scatterplots.

Results

CHC+ (n  = 64; 35% of the girls) had higher 25(OH)D levels (mean ± s.d., 60.3 ± 22.2) nmol/L) than CHC- (n  = 118; 41.8 ± 19.3 nmol/L), P -values <0.01. The differences in 25(OH)D levels between CHC+ and CHC− were attenuated but remained significant after the adjustment of lifestyle factors. CHC+ also had higher levels of 1,25(OH)2D, 24,25(OH)2D, DBP and calcium than CHC−, whereas 1,25(OH)2D/25(OH)D, PTH, FGF23 and albumin were significantly lower. Free 25(OH)D and VMR did not statistically differ, and both ratios appeared similar in relation to 25(OH)D, irrespective of CHC status.

Conclusion

This confirms a clinical impact of CHC on vitamin D levels in adolescents. Our observations are likely due to an increased DBP-concentration, whereas the free 25(OH)D appears unaltered.

Open access
Matteo Scopel Medical Clinic III, Department of Medicine (DIMED), University Hospital of Padua, Padua, Italy

Search for other papers by Matteo Scopel in
Google Scholar
PubMed
Close
,
Eugenio De Carlo Medical Clinic III, Department of Medicine (DIMED), University Hospital of Padua, Padua, Italy

Search for other papers by Eugenio De Carlo in
Google Scholar
PubMed
Close
,
Francesca Bergamo Unit of Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy

Search for other papers by Francesca Bergamo in
Google Scholar
PubMed
Close
,
Sabina Murgioni Unit of Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy

Search for other papers by Sabina Murgioni in
Google Scholar
PubMed
Close
,
Riccardo Carandina Radiodiagnostic Unit, University Hospital of Padua, Padua, Italy

Search for other papers by Riccardo Carandina in
Google Scholar
PubMed
Close
,
Anna Rita Cervino Radiotherapy and Nuclear Medicine Unit, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy

Search for other papers by Anna Rita Cervino in
Google Scholar
PubMed
Close
,
Marta Burei Radiotherapy and Nuclear Medicine Unit, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy

Search for other papers by Marta Burei in
Google Scholar
PubMed
Close
,
Federica Vianello Radiotherapy and Nuclear Medicine Unit, Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy

Search for other papers by Federica Vianello in
Google Scholar
PubMed
Close
,
Vittorina Zagonel Unit of Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy

Search for other papers by Vittorina Zagonel in
Google Scholar
PubMed
Close
,
Matteo Fassan Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy

Search for other papers by Matteo Fassan in
Google Scholar
PubMed
Close
, and
Roberto Vettor Medical Clinic III, Department of Medicine (DIMED), University Hospital of Padua, Padua, Italy

Search for other papers by Roberto Vettor in
Google Scholar
PubMed
Close

We considered 351 patients affected by neuroendocrine tumors (NETs), followed at the University Hospital of Padua and at the Veneto Oncological Institute. Of these, 72 (20.5%) suffered from bone metastases. The sample was divided according to the timing of presentation of bone metastases into synchronous (within 6 months of diagnosis of primary tumor) and metachronous (after 6 months). We collected data on the type and grading of the primary tumor and on the features of bone metastases. Our analysis shows that the group of synchronous metastases generally presents primary tumors with a higher degree of malignancy rather than the ones of the metachronous group. This is supported by the finding of a Ki-67 level in GEP-NETs, at the diagnosis of bone metastases, significantly higher in the synchronous group. Moreover, in low-grade NETs, chromogranin A values are higher in the patients with synchronous metastases, indicating a more burden of disease. The parameters of phospho-calcium metabolism are within the normal range, and we do not find significant differences between the groups. Serious bone complications are not frequent and are not correlated with the site of origin of the primary tumor. From the analysis of the survival curves of the total sample, a cumulative survival rate of 33% at 10 years emerges. The average survival is 80 months, higher than what is reported in the literature, while the median is 84 months. In our observation period, synchronous patients tend to have a worse prognosis than metachronous ones with 52-months survival rates of 58 and 86%.

Open access
Keiko Ohkuwa Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Keiko Ohkuwa in
Google Scholar
PubMed
Close
,
Kiminori Sugino Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Kiminori Sugino in
Google Scholar
PubMed
Close
,
Ryohei Katoh Department of Pathology, Ito Hospital, Tokyo, Japan

Search for other papers by Ryohei Katoh in
Google Scholar
PubMed
Close
,
Mitsuji Nagahama Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Mitsuji Nagahama in
Google Scholar
PubMed
Close
,
Wataru Kitagawa Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Wataru Kitagawa in
Google Scholar
PubMed
Close
,
Kenichi Matsuzu Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Kenichi Matsuzu in
Google Scholar
PubMed
Close
,
Akifumi Suzuki Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Akifumi Suzuki in
Google Scholar
PubMed
Close
,
Chisato Tomoda Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Chisato Tomoda in
Google Scholar
PubMed
Close
,
Kiyomi Hames Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Kiyomi Hames in
Google Scholar
PubMed
Close
,
Junko Akaishi Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Junko Akaishi in
Google Scholar
PubMed
Close
,
Chie Masaki Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Chie Masaki in
Google Scholar
PubMed
Close
,
Kana Yoshioka Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Kana Yoshioka in
Google Scholar
PubMed
Close
, and
Koichi Ito Department of Surgery, Ito Hospital, Tokyo, Japan

Search for other papers by Koichi Ito in
Google Scholar
PubMed
Close

Objective

Parathyroid carcinoma is a rare tumor among parathyroid tumors. Aspiration cytology and needle biopsy are generally not recommended for diagnostic purposes because they cause dissemination. Therefore, it is commonly diagnosed by postoperative histopathological examination. In this study, we investigated whether preoperative inflammatory markers can be used as predictors of cancer in patients with primary hyperparathyroidism.

Design

This was a retrospective study.

Methods

Thirty-six cases of parathyroid carcinoma and 50 cases of parathyroid adenoma (PA) operated with the diagnosis of primary hyperparathyroidism and confirmed histopathologically at Ito Hospital were included in this study. Preoperative clinical characteristics and inflammatory markers (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (LMR)) were compared and their values in preoperative prediction were evaluated and analyzed.

Results

Preoperative intact-parathyroid hormone (P  = 0.0003), serum calcium (P  = 0.0048), and tumor diameter (P  = 0.0002) were significantly higher in parathyroid carcinoma than in PA. LMR showed a significant decrease in parathyroid carcinoma (P  = 0.0062). In multivariate analysis, LMR and tumor length diameter were independent predictors. In the receiver operating characteristics analysis, the cut-off values for LMR and tumor length diameter were 4.85 and 28.0 mm, respectively, for parathyroid cancer prediction. When the two extracted factors were stratified by the number of factors held, the predictive ability improved as the number of factors increased.

Conclusion

In the preoperative evaluation, a combination of tumor length diameter of more than 28 mm and LMR of less than 4.85 was considered to have a high probability of cancer.

Open access
Sharon A Huish University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK
The University of Warwick, Coventry, UK
Royal Devon and Exeter NHS Foundation Trust, Exeter, UK

Search for other papers by Sharon A Huish in
Google Scholar
PubMed
Close
,
Carl Jenkinson The University of Birmingham, Birmingham, UK

Search for other papers by Carl Jenkinson in
Google Scholar
PubMed
Close
,
Janet A Dunn The University of Warwick, Coventry, UK

Search for other papers by Janet A Dunn in
Google Scholar
PubMed
Close
,
David J Meredith Royal Devon and Exeter NHS Foundation Trust, Exeter, UK

Search for other papers by David J Meredith in
Google Scholar
PubMed
Close
,
Rosemary Bland The University of Warwick, Coventry, UK

Search for other papers by Rosemary Bland in
Google Scholar
PubMed
Close
, and
Martin Hewison The University of Birmingham, Birmingham, UK

Search for other papers by Martin Hewison in
Google Scholar
PubMed
Close

Low serum 1,25-dihydroxyvitamin D (1,25(OH)2D) in end-stage renal disease (ESRD) is considered a consequence of elevated fibroblast growth factor 23 (FGF23) and concomitant reduced activity of renal 1α-hydroxylase (CYP27B1). Current ESRD treatment strategies to increase serum calcium and suppress secondary hyperparathyroidism involve supplementation with vitamin D analogues that circumvent 1α-hydroxylase. This overlooks the potential importance of 25-hydroxyvitamin D (25(OH)D) deficiency as a contributor to low serum 1,25(OH)2D. We investigated the effects of vitamin D (cholecalciferol) supplementation (40,000 IU for 12 weeks and maintenance dose of 20,000 IU fortnightly), on multiple serum vitamin D metabolites (25(OH)D, 1,25(OH)2D3 and 24,25(OH)2D3) in 55 haemodialysis patients. Baseline and 12 month data were compared using related-samples Wilcoxon signed rank test. All patients remained on active vitamin D analogues as part of routine ESRD care. 1,25(OH)2D3 levels were low at baseline (normal range: 60–120 pmol/L). Cholecalciferol supplementation normalised both serum 25(OH)D and 1,25(OH)2D3. Median serum 25(OH)D increased from 35.1 nmol/L (IQR: 23.0–47.5 nmol/L) to 119.9 nmol/L (IQR: 99.5–143.3 nmol/L) (P < 0.001). Median serum 1,25(OH)2D3 and 24,25(OH)2D3 increased from 48.3 pmol/L (IQR: 35.9–57.9 pmol/L) and 3.8 nmol/L (IQR: 2.3–6.0 nmol/L) to 96.2 pmol/L (IQR: 77.1–130.6 pmol/L) and 12.3 nmol/L (IQR: 9–16.4 nmol/L), respectively (P < 0.001). A non-significant reduction in daily active vitamin D analogue dose occurred, 0.94 µmcg at baseline to 0.77 µmcg at 12 months (P = 0.73). The ability to synthesise 1,25(OH)2D3 in ESRD is maintained but is substrate dependent, and serum 25(OH)D was a limiting factor at baseline. Therefore, 1,25(OH)2D3 deficiency in ESRD is partly a consequence of 25(OH)D deficiency, rather than solely due to reduced 1α-hydroxylase activity as suggested by current treatment strategies.

Open access
Anouar Aznou Department of Internal Medicine, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

Search for other papers by Anouar Aznou in
Google Scholar
PubMed
Close
,
Rick Meijer Department of Internal Medicine, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

Search for other papers by Rick Meijer in
Google Scholar
PubMed
Close
,
Daniel van Raalte Department of Internal Medicine, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

Search for other papers by Daniel van Raalte in
Google Scholar
PubMed
Close
,
Martin den Heijer Department of Internal Medicine, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

Search for other papers by Martin den Heijer in
Google Scholar
PubMed
Close
,
Annemieke Heijboer Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

Search for other papers by Annemieke Heijboer in
Google Scholar
PubMed
Close
, and
Renate de Jongh Department of Internal Medicine, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

Search for other papers by Renate de Jongh in
Google Scholar
PubMed
Close

Objective

The mechanisms underlying the development of peripheral insulin resistance are complex. Several studies have linked sclerostin, an osteocyte-derived inhibitor of the Wnt/β-catenin pathway, to obesity and insulin resistance. The aim of this study was to investigate (1) whether serum sclerostin is associated with insulin sensitivity in lean and/or obese women; and (2) whether hyperinsulinaemia affects serum sclerostin concentrations.

Design

A cross-sectional study.

Methods

Insulin sensitivity was measured in lean (BMI < 25 kg/m2) and obese (BMI > 30 kg/m2) women using a hyperinsulinaemic–euglycaemic clamp. Serum sclerostin was measured at baseline and during the clamp procedure.

Results

We studied 21 lean and 22 obese women with a median age of 40 and 43 years and a median BMI of 22.4 and 33.5 kg/m2, respectively. Obese women had higher serum sclerostin than lean women (122 ± 33 vs 93 ± 33 nmol/L, P < 0.01). Higher serum sclerostin was associated with lower insulin sensitivity in obese, but not in lean individuals (difference in M-value between highest and lowest quartile: −7.02 mg/kg/min, P = 0.03 and 1.59 mg/kg/min, P = 0.50, respectively). Hyperinsulinaemia did not affect serum sclerostin in lean nor obese women (P > 0.5).

Conclusion

Serum sclerostin is negatively associated with insulin sensitivity as measured with the hyperinsulinaemic–euglycaemic clamp in obese, but not lean women. This indicates a potential role of the Wnt/β-catenin pathway in regulating insulin sensitivity particularly in obese individuals. Our findings remain hypothesis-generating and should be confirmed by additional studies.

Open access
Franca Genest Clinical Trial Unit, Orthopedic Department, University of Wuerzburg, Wuerzburg, Germany

Search for other papers by Franca Genest in
Google Scholar
PubMed
Close
,
Michael Schneider Clinical Trial Unit, Orthopedic Department, University of Wuerzburg, Wuerzburg, Germany

Search for other papers by Michael Schneider in
Google Scholar
PubMed
Close
,
Andreas Zehnder Clinical Trial Unit, Orthopedic Department, University of Wuerzburg, Wuerzburg, Germany

Search for other papers by Andreas Zehnder in
Google Scholar
PubMed
Close
,
Dominik Lieberoth-Leden Clinical Trial Unit, Orthopedic Department, University of Wuerzburg, Wuerzburg, Germany

Search for other papers by Dominik Lieberoth-Leden in
Google Scholar
PubMed
Close
, and
Lothar Seefried Clinical Trial Unit, Orthopedic Department, University of Wuerzburg, Wuerzburg, Germany

Search for other papers by Lothar Seefried in
Google Scholar
PubMed
Close

Purpose

Aging and concurrent constitutional changes as sarcopenia, osteoporosis and obesity are associated with progressive functional decline. Coincidence and mutual interference of this risk factors require further evaluation.

Methods

Cross-sectional evaluation of musculoskeletal health in a community-dwelling cohort of men aged 65–90 years. Objectives included descriptive analysis of age-related decline in physical performance, prevalence of osteoporosis (FRAX-Score), sarcopenia (EWGSOP criteria) and obesity (BMI > 30 kg/m2) and their coincidence/interference.

Results

Based on 507 participants assessed, aging was associated with progressive functional deterioration, regarding power (chair rise test −1.54% per year), performance (usual gait speed −1.38% per year) and muscle force (grip strength −1.52% per year) while muscle mass declined only marginally (skeletal muscle index −0.29% per year). Prevalence of osteoporosis was 41.8% (n = 212) while only 22.9% (n = 116) of the participants met the criteria for sarcopenia and 23.7% (n = 120) were obese. Osteosarcopenia was found in n = 79 (15.6%), sarcopenic obesity was present in 14 men (2.8%). A combination of all three conditions could be confirmed in n = 8 (1.6%). There was an inverse correlation of BMI with physical performance whereas osteoporosis and sarcopenia did not interfere with functional outcomes.

Conclusion

Based on current definitions, there is considerable overlap in the prevalence of osteoporosis and sarcopenia, while obesity appears to be a distinct problem. Functional decline appears to be associated with obesity rather than osteoporosis or sarcopenia. It remains to be determined to what extend obesity itself causes performance deficits or if obesity is merely an indicator of insufficient activity eventually predisposing to functional decline.

Open access
Haojie Zhang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

Search for other papers by Haojie Zhang in
Google Scholar
PubMed
Close
,
Yuke Cui Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

Search for other papers by Yuke Cui in
Google Scholar
PubMed
Close
,
Ruihua Dong Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, School of Public Health, Fudan University, Shanghai, China

Search for other papers by Ruihua Dong in
Google Scholar
PubMed
Close
,
Wen Zhang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

Search for other papers by Wen Zhang in
Google Scholar
PubMed
Close
,
Shihan Chen Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

Search for other papers by Shihan Chen in
Google Scholar
PubMed
Close
,
Heng Wan Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

Search for other papers by Heng Wan in
Google Scholar
PubMed
Close
,
Chi Chen Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

Search for other papers by Chi Chen in
Google Scholar
PubMed
Close
,
Yi Chen Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

Search for other papers by Yi Chen in
Google Scholar
PubMed
Close
,
Yuying Wang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

Search for other papers by Yuying Wang in
Google Scholar
PubMed
Close
,
Chunfang Zhu Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

Search for other papers by Chunfang Zhu in
Google Scholar
PubMed
Close
,
Bo Chen Key Laboratory of Public Health Safety of Ministry of Education, Collaborative Innovation Center of Social Risks Governance in Health, School of Public Health, Fudan University, Shanghai, China

Search for other papers by Bo Chen in
Google Scholar
PubMed
Close
,
Ningjian Wang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

Search for other papers by Ningjian Wang in
Google Scholar
PubMed
Close
, and
Yingli Lu Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

Search for other papers by Yingli Lu in
Google Scholar
PubMed
Close

Background

Bone is thought to be the reservoir of the human lead burden, and vitamin D is associated with bone turnover. We aimed to explore whether exposure to lower 25-hydroxy vitamin D (25(OH)D) levels was associated with higher blood lead levels (BLLs) by increasing the bone turnover rate in individuals with type 2 diabetes.

Methods

A total of 4103 type 2 diabetic men and postmenopausal women in Shanghai, China, were enrolled in 2018. Their 25(OH)D, β-C-terminal telopeptide (β-CTX), N-MID osteocalcin and procollagen type 1 N-peptide (P1NP) levels were detected. Their BLLs were determined by atomic absorption spectrometry. Mediation analyses were performed to identify the possible role that bone turnover played in the underlying mechanisms.

Results

In both the men and postmenopausal women, all three bone turnover markers were inversely associated with 25(OH)D and positively associated with the BLL (all P < 0.01) after adjusting for age, current smoking habits, metabolic parameters, duration of diabetes, vitamin D intake, and use of anti-osteoporosis medication. In the mediation analyses, none of the direct associations between 25(OH)D and BLL was significant for the three bone turnover markers, but all three bone turnover markers were found to be significant mediators of the indirect associations between 25(OH)D and BLL.

Conclusion

The association between vitamin D and BLL was fully mediated by bone turnover markers in type 2 diabetic patients (mediation effect). This finding suggested that vitamin D may protect against blood lead exposure from the bone reservoir by decreasing bone turnover in individuals with type 2 diabetes.

Open access
Tingting Jia Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

Search for other papers by Tingting Jia in
Google Scholar
PubMed
Close
,
Ya-nan Wang Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

Search for other papers by Ya-nan Wang in
Google Scholar
PubMed
Close
,
Dongjiao Zhang Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

Search for other papers by Dongjiao Zhang in
Google Scholar
PubMed
Close
, and
Xin Xu Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

Search for other papers by Xin Xu in
Google Scholar
PubMed
Close

Diabetes-induced advanced glycation end products (AGEs) overproduction would result in compromised osseointegration of titanium implant and high rate of implantation failure. 1α,25-dihydroxyvitamin D3 (1,25VD3) plays a vital role in osteogenesis, whereas its effects on the osseointegration and the underlying mechanism are unclear. The purpose of this study was to investigate that 1,25VD3 might promote the defensive ability of osseointegration through suppressing AGEs/RAGE in type 2 diabetes mellitus. In animal study, streptozotocin-induced diabetic rats accepted implant surgery, with or without 1,25VD3 intervention for 12 weeks. After killing, the serum AGEs level, bone microarchitecture and biomechanical index of rats were measured systematically. In vitro study, osteoblasts differentiation capacity was analyzed by alizarin red staining, alkaline phosphatase assay and Western blotting, after treatment with BSA, AGEs, AGEs with RAGE inhibitor and AGEs with 1,25VD3. And the expression of RAGE protein was detected to explore the mechanism. Results showed that 1,25VD3 could reverse the impaired osseointegration and mechanical strength, which possibly resulted from the increased AGEs. Moreover, 1,25VD3 could ameliorate AGEs-induced damage of cell osteogenic differentiation, as well as downregulating the RAGE expression. These data may provide a theoretical basis that 1,25VD3 could work as an adjuvant treatment against poor osseointegration in patients with type 2 diabetes mellitus.

Open access
Lijuan Yuan Department of Biochemistry and Molecular Biology, Center for DNA Typing, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China
Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China

Search for other papers by Lijuan Yuan in
Google Scholar
PubMed
Close
,
Xihui Chen Department of Biochemistry and Molecular Biology, Center for DNA Typing, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China

Search for other papers by Xihui Chen in
Google Scholar
PubMed
Close
,
Ziyu Liu Department of Microbiology, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China

Search for other papers by Ziyu Liu in
Google Scholar
PubMed
Close
,
Dan Wu Department of Biochemistry and Molecular Biology, Center for DNA Typing, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China

Search for other papers by Dan Wu in
Google Scholar
PubMed
Close
,
Jianguo Lu Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China

Search for other papers by Jianguo Lu in
Google Scholar
PubMed
Close
,
Guoqiang Bao Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China

Search for other papers by Guoqiang Bao in
Google Scholar
PubMed
Close
,
Sijia Zhang Department of Biochemistry and Molecular Biology, Center for DNA Typing, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China

Search for other papers by Sijia Zhang in
Google Scholar
PubMed
Close
,
Lifeng Wang Department of Biochemistry and Molecular Biology, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China

Search for other papers by Lifeng Wang in
Google Scholar
PubMed
Close
, and
Yuanming Wu Department of Biochemistry and Molecular Biology, Center for DNA Typing, Air Force Medical University, Xi’an, Shaanxi, People’s Republic of China

Search for other papers by Yuanming Wu in
Google Scholar
PubMed
Close

Primary hypertrophic osteoarthropathy (PHO) is a rare familial disorder with reduced penetrance for females. The genetic mutations associated with PHO have been identified in HPGD and SLCO2A1, which involved in prostaglandin E2 metabolism. Here, we report 5 PHO patients from four non-consanguineous families. Two heterozygous mutations in solute carrier organic anion transporter family member 2A1 (SLCO2A1) were identified in two brothers by whole-exome sequencing. Three heterozygous mutations and one homozygous mutation were identified in other three PHO families by Sanger sequencing. However, there was no mutation in HPGD. These findings confirmed that homozygous or compound heterozygous mutations of SLCO2A1 were the pathogenic cause of PHO. A female individual shared the same mutations in SLCO2A1 with her PHO brother but did not have any typical PHO symptoms. The influence of sex hormones on the pathogenesis of PHO and its implication were discussed.

Open access