scholarly journals Low sclerostin levels after long-term remission of acromegaly

Endocrine ◽  
2021 ◽  
Author(s):  
Kim M. J. A. Claessen ◽  
Iris C. M. Pelsma ◽  
Herman M. Kroon ◽  
Antoon H. van Lierop ◽  
Alberto M. Pereira ◽  
...  
Keyword(s):  
Bone Health ◽  
Serum Levels ◽  
Elisa Assay ◽  
Healthy Controls ◽  
Mineral Density ◽  
Lower Plasma ◽  
X Ray ◽  
Current Growth ◽  
Biochemical Remission

Abstract Purpose Bone health is compromised in acromegaly resulting in vertebral fractures (VFs), regardless of biochemical remission. Sclerostin is a negative inhibitor of bone formation and is associated with increased fracture risk in the general population. Therefore, we compared sclerostin concentrations between well-controlled acromegaly patients and healthy controls, and assessed its relationship with bone mineral density (BMD), and VFs in acromegaly. Methods Seventy-nine patients (mean age 58.9 ± 11.4 years, 49% women) with controlled acromegaly, and 91 healthy controls (mean age 51.1 ± 16.9 years, 59% women) were included. Plasma sclerostin levels (pg/mL) in patients were measured with an ELISA assay, whereas in controls, serum levels were converted to plasma levels by multiplication with 3.6. In patients, VFs were radiographically assessed, and BMD was assessed using dual X-ray absorptiometry. Results Median sclerostin concentration in controlled acromegaly patients was significantly lower than in healthy controls (104.5 pg/mL (range 45.7–234.7 pg/mL) vs 140.0 pg/mL (range 44.8–401.6 pg/mL), p < 0.001). Plasma sclerostin levels were not related to age, current growth hormone (GH) or insulin-like factor-1 (IGF-1) levels, gonadal state, treatment modality, remission duration, or BMD, VF presence, severity or progression. Conclusion Patients with long-term controlled acromegaly have lower plasma sclerostin levels than healthy controls, as a reflection of decreased osteocyte activity. Further longitudinal studies are needed to establish the course of sclerostin during different phases of disease and its exact effects in acromegalic osteopathy.

scholarly journals Glucocorticoid-induced osteoporosis in systemic lupus erythematosus

2018 ◽  
Vol 3 ◽  
pp. 205990211880251
Author(s):  
Kee Fong Phang ◽  
Jiacai Cho ◽  
Weixian Lee ◽  
Anselm Mak
Keyword(s):  
Bone Mineral Density ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Bone Health ◽  
Mineral Density ◽  
Systemic Lupus ◽  
Treatment Of Osteoporosis ◽  
Improvement In Survival ◽  
Prevalence Of Osteoporosis

Improvement in survival of systemic lupus erythematosus has been brought about with new advancement in treatment. However, glucocorticoids remain the sole cornerstone and as patients live longer, there is a need to address long-term complications brought by long-term glucocorticoid use such as osteoporosis. In this review, glucocorticoid-induced osteoporosis in systemic lupus erythematosus will be extensively discussed. This would include prevalence of osteoporosis in systemic lupus erythematosus patients, the difficulties in measuring fracture risk and pitfalls in using conventional methods such as bone mineral density. In addition, the mechanism of actions of glucocorticoids and evidence for glucocorticoids in the treatment of specific systemic lupus erythematosus manifestations would be explored and we also discussed specific pathophysiological mechanisms in the development of glucocorticoid-induced osteoporosis in systemic lupus erythematosus. We also reviewed the latest guidelines in the treatment of glucocorticoid-induced osteoporosis and the evidence for various osteoporosis medications. Finally, we recommend an approach in monitoring bone health and the treatment of osteoporosis specifically in systemic lupus erythematosus patients.

scholarly journals Genotoxicity in Patients on Long-term Proton Pump Inhibitor Therapy in Korea: A Nested Case-control, Prospective, Pilot Study

2020 ◽  
Vol 20 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Youn I Choi ◽  
Jun-Won Chung ◽  
Dong Kyun Park ◽  
Kyoung Oh Kim ◽  
Kwang An Kwon ◽  
...  
Keyword(s):  
Pilot Study ◽  
Medical History ◽  
Proton Pump ◽  
Serum Levels ◽  
Self Report ◽  
Healthy Controls ◽  
Control Subjects ◽  
Increased Risk ◽  
Healthy Control

Background/Aims: Although proton pump inhibitors (PPIs) remain a mainstay for the suppression of gastric acid secretion, long-term PPI use is associated with side effects. However, the genotoxicity associated with long-term PPI use is unclear.Materials and Methods: This prospective observational pilot study enrolled patients who had been on PPIs for >1 year and healthy controls from July 2015 to August 2016. The subjects completed self-report questionnaires pertaining to their drug and medical history, and only those with no medical history and a ≥2-year wash-out period (for drugs other than PPIs) were included. We collected peripheral-blood lymphocytes from long-term PPI users and healthy controls and analyzed the genotoxicity by using the cytokinesis-block micronucleus cytome assay; we also determined the fasting serum levels of pyridoxine, folate, cobalamin, and homocysteine.Results: Ten long-term PPI users and 40 healthy control subjects were enrolled. The median serum pyridoxine, folate, cobalamin, and homocysteine levels were not significantly different between the groups. The median frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (Nbuds) per 1,000 binucleated cells, in long-term PPI users and healthy controls, were 30.3 and 16.3 (<i>P</i><0.005), 2.5 and 1.8 (<i>P</i><0.005), and 9.3 and 5.0 (<i>P</i><0.005), respectively. Even after adjustment for confounding factors, the OR of the MNi, NPBs, and Nbuds for long-term PPI users compared with healthy control subjects were 14.1 (<i>P</i><0.001), 2.0 (<i>P</i>=0.001), and 1.3 (<i>P</i>=0.3), respectively.Conclusions: Long-term PPI use was significantly associated with an increased risk of genotoxicity after adjustment for age, sex, body mass index, medical history, drug history, and the serum levels of vitamins.

CTRP3 is Significantly Decreased in Patients with Primary Hyperparathyroidism and Closely Related with Osteoporosis

2019 ◽  
Vol 128 (03) ◽  
pp. 152-157
Author(s):  
Derya Demirtas ◽  
Fettah Acıbucu ◽  
Filiz Alkan Baylan ◽  
Erdinc Gulumsek ◽  
Tayyibe Saler
Keyword(s):  
Primary Hyperparathyroidism ◽  
Serum Levels ◽  
Dual Energy ◽  
Control Group ◽  
Mineral Density ◽  
Urine Calcium ◽  
X Ray ◽  
Complement C1q ◽  
Necrosis Factor

Abstract Background Adipokines derived from adipocytes are one of the important factors that act as circulating regulators of bone metabolism. Complement C1q/tumor necrosis factor-related protein-3 (CTRP3), a paralog of adiponectin, is are member of the CTRP superfamily. The aim of this study was to investigate the role of serum CTRP3 in the development of osteoporosis in patients with primary hyperparathyroidism. Methods This study included 53 patients with diagnosed primary hyperparathyroidism and 30 healthy controls. Laboratory tests for the diagnosis of primary hyperparathyroidism and serum levels of CTRP3 measured for all patients. Bone mineral density was obtained on lumbar spine 1 and 4 by dual energy X-ray absorptiometry. Results Serum CTRP3 levels were lower in patients with primary hyperparathyroidism than in the control group (p<0.001). In addition, primary hyperparathyroidism patients are were divided into two groups as, with and without osteoporosis; the levels of CTRP3 were lower in patients with osteoporosis than in patients without osteoporosis (p=0.004). In logistic regression analysis, only CTRP3 levels independently determined the patients to be osteoporosis (p<0.05). According to this analysis, decreased CTRP3 (per 1 ng/mL) levels were found to increase the risk of patients for osteoporosis by 6.9%. When the CTRP3 cut-off values were taken as 30 ng/mL, it determined osteoporosis with 76.4% sensitivity and 73.2% specificity. CTRP3 and urine calcium levels were independently associated with T score in dual energy X-ray absorptiometry. Conclusions CTRP3 levels were significantly decreased in patients with primary hyperparathyroidism, and it is also related to osteoporosis.

Reduced Bone Mineral Density in Factor VIII Deficient Mice and the Role of Inflammatory Cytokines

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 21-21 ◽  
Author(s):  
Meghan S. Liel ◽  
Robert Klein ◽  
Michael Recht ◽  
Daniel L. Greenberg ◽  
Jason Taylor
Keyword(s):  
Bone Mineral Density ◽  
Bone Turnover ◽  
Inflammatory Cytokines ◽  
Bone Health ◽  
Inflammatory Cytokine ◽  
Serum Levels ◽  
Mineral Density ◽  
Markers Of Bone Turnover ◽  
Skeletal Phenotype ◽  
Deficient Mice

Abstract Abstract 21 Background: Low bone mineral density (BMD) and increased risk of fracture are increasingly being identified in patients with hemophilia. Multiple clinical studies have shown that both children and adults with hemophilia have significantly decreased BMD, with up to 70% of adult patients affected. Decreased BMD in this population has previously been attributed to inactivity due to hemophilic arthropathy and comorbid conditions including infection with HIV and hepatitis C. The factor VIII (FVIII) knockout (KO) mouse model has been extensively characterized with respect to bleeding and the development of inhibitors. However, the skeletal status of these animals has not been described. Therefore, the purpose of this study is to examine the skeletal phenotype of FVIII deficient mice and measure serum markers of bone turnover and regulation. Methods: We compared the skeletal phenotype of 11 male FVIII KO mice and 8 matched wild-type (WT) controls at 20 weeks of age. BMD was measured using dual energy x-ray absorptiometry (DXA), bone geometry was examined by μCT and, after sacrifice, femoral breaking strength was measured by three-point bending until failure (ultimate force). In a second group of 24 mice (12 KO and 12 WT), serum was obtained under uniform conditions at 20 weeks of age via cardiac puncture. Serum levels of receptor activator of nuclear factor kappa-B ligand (RANK-L), osteoprotegerin (OPG), interleukin 1α (IL-1α) and osteocalcin were measured using commercially available ELISAs. Alkaline phosphatase (alk phos) activity was measured using a colorimetric assay. The RANK-L/OPG system regulates bone turnover, osteocalcin and alk phos are markers of bone turnover and IL-1α is an inflammatory cytokine. Results: No differences in body weight, length, percent fat, or femoral length were observed between FVIII KO and WT mice (data not shown). No spontaneous bleeding was observed in any animal. As shown in Table I, KO mice had significantly decreased BMD, cortical thickness and stiffness compared to WT mice. This resulted in decreased resistance to fracture as measured via ultimate force. The data presented here demonstrate that adult FVIII KO male mice exhibit lower cortical bone mass resulting in femora less resistant to fracture compared with WT controls. Because FVIII KO mice do not have spontaneous joint hemorrhages and exhibit normal behavior and activity levels, these data suggest that there is an underlying connection between the coagulation system and bone metabolism that results in lower BMD and bone strength. To understand why KO mice have decreased BMD, we measured serum levels of regulators of bone metabolism, markers of bone turnover and inflammatory cytokines. There was no difference in RANK-L, OPG or the RANK-L/OPG ratio between the KO and WT mice. In addition, there was no observed difference in osteocalcin and alk phos. However, WT animals had significantly higher levels of IL-1α expression (P = 0.008). All of the KO animals had undetectable IL-1α levels under physiologic conditions whereas the mean IL-1α level in WT mice was 32.2 pg/ml. Thrombin production is reduced in hemophilia and thrombin has previously been shown to stimulate inflammatory cytokine production. Therefore, these data suggest that thrombin may be necessary for IL-1α production under non-stress conditions and that lower levels of IL-1α may be detrimental to bone health. Although increased inflammatory cytokines are typically associated with decreased BMD, prior research has shown that physiologic levels of cytokines are necessary to maintain bone health. Conclusions: These data provide compelling evidence that the link between FVIII deficiency and impaired skeletal health is real and independent of differences in physical activity and other medical co-morbidities. In addition, the decreased levels of IL-1α observed in KO mice suggest that inflammatory cytokines are involved in this pathophysiology. Ongoing work in our laboratory is aimed at further exploring these connections. Disclosures: No relevant conflicts of interest to declare.

Bone loss and vitamin D deficiency post gastrectomy for gastro-esophageal malignancy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 165-165 ◽  
Author(s):  
Kiran Virik ◽  
Robert Wilson
Keyword(s):  
Risk Factors ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Bone Disease ◽  
Bone Health ◽  
Nutritional Supplementation ◽  
Type I ◽  
Mineral Density ◽  
Post Surgery

165 Background: Metabolic bone disease is a known but incompletely understood consequence of gastrectomy. Post gastrectomy osteoporosis (OP) is multifactorial. Evidence suggests that patients who undergo this surgery require long term bone health assessment and nutritional support. Methods: 30 post gastrectomy patients (2000-2008) from a single centre in Australia were evaluated re bone health post surgery and post nutritional supplementation. Exploratory analysis included: age, gender, pathology, type of surgery, 25 OH-vitamin D, calcium, parathyroid hormone (PTH), bone mineral density (BMD), vertebral XRs, urinary calcium and N telopeptides of type I collagen. Other risk factors evaluated were: smoking, corticosteroid use, alcohol intake, hyperthyroidism, menopausal status, hyperparathyroidism (hPTH), pre-existing bone disease. Results: The median age of the cohort was 67.5 (range 53-83) of whom 22 (73%) were male. Histology showed 16 (53%) gastric adenocarcinoma, 6 (20%) esophageal adenocarcinoma, 2 (7%) GISTs, 5 (17%) gastric/duodenal lymphoma and 1 other category. Similar numbers of patients underwent total (12) and partial/distal gastrectomy (12), with 6 having a subtotal gastrectomy. 22 (73%) had a Roux-en-Y or BR II reconstruction and 8 had a BRI/other. Median time from surgery to first BMD was 54.5 months (range 12-360) with median correlative calcium level 2.24 (range 1.97-2.49), median vitamin D level 43 (range 11-82) and median PTH 6.4 (range 1.8-13.8). Osteoporosis was diagnosed in 14 (47%) of patients, osteopenia in 14 and 2 (7%) patients had a normal BMD. Low vitamin D was seen in 23 (77%) patients, low calcium levels in 5 (17%) and secondary hPTH in 12 (41%). Post nutritional supplementation preliminary results showed 2/23 (9%) had a low vitamin D level, 3/11 (27%) had secondary hPTH, 5/19 (26%) had osteoporosis, 12/19 (63%) had osteopenia and 2/19 had a normal BMD. Analysis of other risk factors is to follow. Conclusions: Poor bone health and vitamin D deficiency is a clinically significant problem post gastrectomy. Patients should undergo long term nutritional and bone health surveillance in addition to their oncological follow up post resection.

scholarly journals PO-046 Gene expression profiling of peripheral blood mononuclear cells in young male trampoline athletes

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Li Gao ◽  
Yong Jie Yang ◽  
En Qi Li ◽  
Jia Ning Mao
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Bone Health ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Healthy Controls ◽  
Mineral Density

Objective Evidence indicates that physical activity influence bone health. However, the molecular mechanisms mediating the beneficial adaptations to exercise are not well understood. The purpose of this study was to examine the differentially expressed genes in PBMC between athletes and healthy controls, and to analyze the important functional genes and signal pathways that cause increased bone mineral density in athletes, in order to further reveal the molecular mechanisms of exercise promoting bone health. Methods Five professional trampoline athletes and five age-matched untrained college students participated in this study. Used the human expression Microarray V4.0 expression profiling chip to detect differentially expressed genes in the two groups, and performed KEGG Pathway analysis and application of STRING database to construct protein interaction Network; Real-Time PCR technology was used to verify the expression of some differential genes.  Results Compared with healthy controls, there were significant improvement in lumbar spine bone mineral density, and 236 up-regulated as well as 265 down-regulated in serum samples of athletes. The differentially expressed genes involved 28 signal pathways, such as cell adhesion molecules. Protein interaction network showed that MYC was at the core node position. Real-time PCR results showed that the expression levels of CD40 and ITGα6 genes in the athletes were up-regulated compared with the healthy controls, the detection results were consistent with that of the gene chip. Conclusions The findings highlight that long-term high-intensity trampoline training could induce transcriptional changes in PBMC of the athletes. These data suggest that gene expression fingerprints can serve as a powerful research tool to design novel strategies for monitoring exercise. The findings of the study also provide support for the notion that PBMC could be used as a substitute to study exercise training that affects bone health.

scholarly journals Severity of reduced bone mineral density and risk of fractures in long‐term survivors of childhood leukemia and lymphoma undergoing guideline‐recommended surveillance for bone health

Cancer ◽  
2019 ◽  
Vol 126 (1) ◽  
pp. 202-210
Author(s):  
Hadley M. Bloomhardt ◽  
Kyaw Sint ◽  
Wilhelmenia L. Ross ◽  
Jaime Rotatori ◽  
Kathryn Ness ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Bone Health ◽  
Childhood Leukemia ◽  
Mineral Density ◽  
Long Term Survivors

Serum CTRP3 Level is Associated with Osteoporosis in Postmenopausal Women

2018 ◽  
Vol 126 (09) ◽  
pp. 559-563 ◽  
Author(s):  
Zhong-Hua Xu ◽  
Xing Zhang ◽  
Hua Xie ◽  
Jin He ◽  
Wen-Chao Zhang ◽  
...  
Keyword(s):  
Postmenopausal Women ◽  
Case Control Study ◽  
Serum Levels ◽  
Case Control ◽  
Dual Energy ◽  
Complex Interaction ◽  
Mineral Density ◽  
X Ray ◽  
Control Study

Abstract Background As a novel adipokine, CTRP3 involves in various functions of energy metabolism. Recent advance reveals a complex interaction between bone and adipose tissue via the secretion of adipokines. Aims A hospital-based case-control study was conducted to investigate the role of serum CTRP3 in osteoporosis among postmenopausal women. Methods Serum levels of CTRP3 and osteocalcin were measured. Bone mineral density (BMD) was obtained on femoral neck and lumbar spines by dual energy X-ray absorptiometry. Results Serum CTRP3 level was lower in subjects with osteoporosis (76.7±22.1 ng/ml) than it in controls (89.4±22.5 ng/ml) (P<0.001). Meanwhile, the frequency of osteoporosis presented a significant decrease (66.4%, 53.9% and 35.9%, P<0.001), in the tertiles of serum CTRP3. Furthermore, serum CTRP3 witnessed an association with a lower risk of osteoporosis (adjusted odds ratio=0.973, 95% confidence interval [0.963–0.983], P<0.001). Lastly, serum CTRP3 level was positively correlated with femoral BMD (r=0.403, P<0.001), lumbar BMD (r=0.368, P<0.001), and HDL-C (r=0.118, P=0.022), among all participants after adjustment. Meanwhile, CTRP3 presented negative correlations with HOMA-IR (r=−0.136, P=0.008) and insulin (r=−0.192, P <0.001). Conclusions It shows that a decreased serum level of CTRP3 was independently associated with osteoporosis.

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