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https://www.readbyqxmd.com/read/27925287/treatment-sequence-matters-anabolic-and-antiresorptive-therapy-for-osteoporosis
#1
Felicia Cosman, Jeri W Nieves, David Dempster
The majority of osteoporosis medications are antiresorptive agents, which reduce the rate of bone remodeling. Within this group are the bisphosphonates, which inhibit protein prenylation in the mature osteoclast, reducing osteoclast capacity to resorb bone(1) and denosumab, a monoclonal antibody to rank ligand that inhibits osteoclast formation, function and survival(2) . Although several new anabolic agents are in development(3-5) , teriparatide is currently the only available anabolic therapy for osteoporosis in the United States, with the addition of only PTH(1-84) in the EU [referred to as PTH)...
December 7, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27923758/evidence-for-use-of-teriparatide-in-spinal-fusion-surgery-in-osteoporotic-patients
#2
REVIEW
Navjot Chaudhary, Jennifer S Lee, Joy Y Wu, Suzanne Tharin
Osteoporosis is defined as a bone mineral density (BMD) less than 2.5 standard deviations below the mean BMD at peak bone mass, or the presence of a fragility fracture. In the setting of osteoporosis, early hardware loosening is thought to cause decreased spinal fusion rates. The two mainstays of osteoporosis treatment are bisphosphonates and Teriparatide. Teriparatide, a form of synthetic parathyroid hormone (PTH), is an anabolic agent that increases osteoblast activity and, thereby, bone mass. Preclinical studies in animal models show that Teriparatide increases spinal fusion rates...
December 3, 2016: World Neurosurgery
https://www.readbyqxmd.com/read/27922245/a-novel-mutation-in-a-case-of-pseudohypoparathyroidism-type-ia
#3
Birgül Kırel, Meliha Demiral, Özkan Bozdağ, Kadri Karaer
Pseudohypoparathyroidism (PHP) type Ia is characterized by multiple hormone resistance; primarily parathyroid hormone (PTH) resistance and Albright's hereditary osteodystrophy (AHO) which involves skeletal and developmental defects. The AHO phenotype alone without hormone resistance is defined as pseudoPHP. A boy was first diagnosed as having both rickets and primary hypothyroidism at 2.5 months of age. His calcium level remained within normal levels after vitamin D treatment, but, elevated PTH and ALP levels and normal-high phosphate levels persisted during his follow-up by age of 2...
2016: Turkish Journal of Pediatrics
https://www.readbyqxmd.com/read/27919752/bioavailable-25-oh-d-but-not-total-25-oh-d-is-an-independent-determinant-for-bone-mineral-density-in-chinese-postmenopausal-women
#4
Chenguang Li, Peizhan Chen, Xiaohua Duan, Jing Wang, Bing Shu, Xiaoguang Li, Qian Ba, Jingquan Li, Yongjun Wang, Hui Wang
Total 25(OH)D levels were determined to assess bone health in elderly populations; however, the bioavailability of 25(OH)D is regulated by the albumin and vitamin D binding protein (DBP) levels and DBP variations. Whether bioavailable 25(OH)D level is a superior biomarker for vitamin D than total 25(OH)D level regarding the BMD and the bone metabolism were not yet fully understood. With a community based cross-sectional study of 967 postmenopausal women, we found that the variant rs7041, but not rs4588, of DBP was significantly associated with the blood DBP level, which was positively correlated with the total 25(OH)D level but negatively associated with bioavailable 25(OH)D levels...
November 28, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27917278/the-preventive-and-therapeutic-roles-of-phytoestrogen-%C3%AE-zearalanol-on-osteoporetic-rats-due-to-ovariectomization
#5
Shaochun Li, Weiwei Zhang, Fei Duan, Weihua Liu, Xiaofang Sun, Xuefeng Pan
OBJECTIVES: The aim of this study was to observe the influence of phytoestrogen α-Zearalanol on ovariectomy-induced postmenopausal osteoporosis in rats. MATERIALS AND METHODS: 40 SD female rats were randomly divided into four groups: Sham group, OVX group (ovariectomized and fed estrogen), α-Zearalanol group (ovariectomized and fed α-Zearalanol) and untreated group (ovariectomized). Three weeks later after surgery, α-Zearalanol and estradiol valerate were administered by oral gavage for 12 weeks to the α-Zearalanol group and the OVX group, respectively...
November 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27908835/modulation-of-signaling-through-gpcr-camp-pka-pathways-by-pde4-depends-on-stimulus-intensity-possible-implications-for-the-pathogenesis-of-acrodysostosis-without-hormone-resistance
#6
Emmanuelle Motte, Catherine Le Stunff, Claire Briet, Nicolas Dumaz, Caroline Silve
In acrodysostosis without hormone resistance, a disease caused by phosphodiesterase (PDE)-4D mutations, increased PDE activity leads to bone developmental defects but with normal renal responses to PTH. To identify potential mechanisms for these disparate responses, we compared the effect of PDE activity on hormone signaling through the GPCR-Gsα-cAMP-PKA pathway in cells from two lineages, HEK-293 cells stably overexpressing PTH1R (HEKpthr) and human dermal fibroblasts, including studies evaluating cAMP levels using an Epac-based BRET-sensor for cAMP (CAMYEL)...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27908723/oxidation-inhibits-pth-receptor-signaling-and-trafficking
#7
Juan A Ardura, Verónica Alonso, Pedro Esbrit, Peter A Friedman
Reactive Oxygen Species (ROS) increase during aging, potentially affecting many tissues including brain, heart, and bone. ROS alter signaling pathways and constitute potential therapeutic targets to limit oxidative damaging effects in aging-associated diseases. Parathyroid hormone receptors (PTHR) are widely expressed and PTH is the only anabolic therapy for osteoporosis. The effects of oxidative stress on PTHR signaling and trafficking have not been elucidated. Here, we used Fluorescence Resonance Energy Transfer (FRET)-based cAMP, ERK, and calcium fluorescent biosensors to analyze the effects of ROS on PTHR signaling and trafficking by live-cell imaging...
November 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27905210/erythrocyte-fatty-acid-composition-does-not-influence-levels-of-free-bioavailable-and-total-25-hydroxy-vitamin-d
#8
Martin Carlsson, Ingela Nilsson, Lars Brudin, Siv-Ping Von, Pär Wanby
In vitro, mono- and polyunsaturated fatty acids (FAs) may decrease the binding affinity of vitamin D metabolites for vitamin D-binding protein, which in turn may influence their bioavailability. FAs incorporated as phospholipids in erythrocyte (ery-) cell membranes reflect dietary intake. The purpose of this study was to investigate ery-FA composition in relation to markers for vitamin D. In healthy females (age 22.6 ± 2.0 years) total 25(OH)D was measured by LC-MS/MS (n = 78), free 25(OH)D with ELISA (n = 64 of 78), and bioavailable 25(OH)D was calculated...
December 1, 2016: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/27905067/mathematical-model-of-bone-remodeling-captures-the-antiresorptive-and-anabolic-actions-of-various-therapies
#9
David S Ross, Khamir Mehta, Antonio Cabal
A better understanding of the molecular pathways regulating the bone remodeling process should help in the development of new antiresorptive regulators and anabolic regulators, that is, regulators of bone resorption and of bone formation. Understanding the mechanisms by which parathyroid hormone (PTH) influences bone formation and how it switches from anabolic to catabolic action is important for treating osteoporosis (Poole and Reeve in Curr Opin Pharmacol 5:612-617, 2005). In this paper we describe a mathematical model of bone remodeling that incorporates, extends, and integrates several models of particular aspects of this biochemical system (Cabal et al...
November 30, 2016: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/27904108/denosumab-is-effective-for-controlling-serum-calcium-levels-in-patients-with-humoral-hypercalcemia-of-malignancy-syndrome-a-case-report-on-parathyroid-hormone-related-protein-producing-cholangiocarcinoma
#10
Norihiro Ashihara, Koji Nakajima, Yoshiyuki Nakamura, Mutsuhiro Kobayashi, Kumiko Shirahata, Chika Maeda, Takeshi Uehara, Daisuke Gomi, Nobuo Ito
Hypercalcemia resulting in the elevation of serum parathyroid hormone-related protein (PTHrP) and suppression of serum PTH was observed in a patient with advanced cholangiocarcinoma (CCC) and multiple lymph node metastases. We confirmed humoral hypercalcemia of malignancy based on PTHrP-producing CCC. Chemotherapy with gemcitabine and cisplatin could not control the patient's serum PTHrP levels and the patient was affected with bisphosphonate-refractory hypercalcemia. We administered a single dose of denosumab, an anti-receptor activator of nuclear factor-kappaB ligand monoclonal antibody, and the patient's serum calcium levels remained close to the normal range for approximately 3 weeks without additional treatment...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27901181/evaluation-of-preoperative-ultrasonographic-and-biochemical-features-of-patients-with-aggressive-parathyroid-disease-is-there-a-reliable-predictive-marker
#11
Bekir Cakir, Sefika Burcak Polat, Mehmet Kilic, Didem Ozdemir, Cevdet Aydin, Nuran Süngü, Reyhan Ersoy
Objective: Parathyroid cancer (PC) represents < 1% of cases of PHPT. Tumors demonstrating atypical histopathologic features and don't fulfill criteria for carcinoma are classified as atypical adenomas (APA). The purpose of this study was to determine a biochemical or ultrasonographic feature that can predict aggressive disease requiring more extensive surgery and closer follow-up. Subjects and methods: Twenty eight patients operated for PHPT and diagnosed with atypical adenoma (23 patients) or carcinoma (5 patients) were enrolled in this study...
November 24, 2016: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27899434/development-of-cgrp-dependent-pain-and-headache-related-behaviours-in-a-rat-model-of-concussion-implications-for-mechanisms-of-post-traumatic-headache
#12
Dara Bree, Dan Levy
BACKGROUND AND OBJECTIVE: Posttraumatic headache (PTH) is one of the most common, debilitating and difficult symptoms to manage after a mild traumatic brain injury, or concussion. However, the mechanisms underlying PTH remain elusive, in part due to the lack of a clinically relevant animal model. Here, we characterized for the first time, headache and pain-related behaviours in a rat model of concussion evoked by a mild closed head injury (mCHI) - the major type of military and civilian related trauma associated with PTH - and tested responses to current and novel headache therapies...
November 29, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27899269/pixe-study-on-the-effects-of-parathyroid-hormone-on-elemental-content-in-rat-bones
#13
M H Eisa, H Shen, W Jin, Abdulaziz S Alaamer, M A Al-Rajhi, Hajo Idriss
Parathyroid hormone (PTH) has attracted considerable interest as a bone anabolic agent. PTH plays a central role in regulating calcium phosphate metabolism and its increases in production in response to low serum calcium levels. A continuous hypersecretion of PTH, as occurs in primary hyperparathyroidism, leads to bone resorption. In this study, the effect of different doses of parathyroid hormone (PTH) on bone mineral content (BMC) in rats was investigated by particle-induced X-ray emission (PIXE). This study will help in investigating further the toxicity of extremely high doses of PTH on BMC...
November 26, 2016: Physica Medica: PM
https://www.readbyqxmd.com/read/27898723/pth1r-mutants-found-in-patients-with-primary-failure-of-tooth-eruption-disrupt-g-protein-signaling
#14
Hariharan Subramanian, Frank Döring, Sina Kollert, Natalia Rukoyatkina, Julia Sturm, Stepan Gambaryan, Angelika Stellzig-Eisenhauer, Philipp Meyer-Marcotty, Martin Eigenthaler, Erhard Wischmeyer
AIM: Primary failure of tooth eruption (PFE) is causally linked to heterozygous mutations of the parathyroid hormone receptor (PTH1R) gene. The mutants described so far lead to exchange of amino acids or truncation of the protein that may result in structural changes of the expressed PTH1R. However, functional effects of these mutations have not been investigated yet. MATERIALS AND METHODS: In HEK293 cells, PTH1R wild type was co-transfected with selected PTH1R mutants identified in patients with PFE...
2016: PloS One
https://www.readbyqxmd.com/read/27895088/hormonal-alterations-in-pcos-and-its-influence-on-bone-metabolism
#15
Abhaya Krishnan, Sridhar Muthusami
According to the World Health Organization (WHO) polycystic ovary syndrome (PCOS) occurs in 4-8% of women worldwide. The prevalence of PCOS in Indian adolescents is 12.2% according to ICMR (Indian Council of Medical Research) report. National Institute of Health documented that it affects approximately 5 million women of reproductive age in the United States . Hormonal imbalance is the characteristic of many women with polycystic ovarian syndrome. The impact of various endocrine changes in PCOS women and their relevance to bone remains to be documented...
November 28, 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27882224/correlation-between-serum-parathyroid-hormone-levels-and-coronary-artery-calcification-in-patients-without-renal-failure
#16
Gang-Yong Wu, Bai-Da Xu, Ting Wu, Xiao-Ying Wang, Tian-Xiao Wang, Xiao Zhang, Xiao Wang, Yang Xia, Gang-Jun Zong
The aim of the present study was to investigate the correlation between serum parathyroid hormone (PTH) levels and coronary artery calcification (CAC) in patients without renal failure, as well as to determine independent risk factors of CAC score (CACS). A total of 157 patients who underwent coronary computed tomography angiographic examination at the 101th Hospital of the People's Liberation Army between December 2013 and February 2015 were retrospectively evaluated. The correlation between PTH levels and CACS was determined using a Pearson correlation analysis...
November 2016: Biomedical Reports
https://www.readbyqxmd.com/read/27880946/2md-dp001-a-single-agent-in-the-management-of-hemodialysis-patients-a-randomized-trial
#17
Ravi Thadhani, Julia B Zella, Danielle C Knutson, William J Blaser, Lori A Plum, Margaret Clagett-Dame, Raymond D Buck, Hector F DeLuca
BACKGROUND: Vitamin D analogs and calcimimetics are used to manage secondary hyperparathyroidism (SHPT) in dialysis patients. DP001 is an oral vitamin D analog that suppresses parathyroid hormone (PTH) in uremic rats, osteopenic women, and hemodialysis patients. The safety and effectiveness of DP001 suppressing PTH in dialysis patients previously managed with active vitamin D with or without a calcimimetic are presented. METHODS: A multicenter, randomized, double-blind study compared DP001 to placebo in hemodialysis patients with serum-intact PTH (iPTH) ≥300 pg/ml...
November 24, 2016: American Journal of Nephrology
https://www.readbyqxmd.com/read/27876426/pin1-and-secondary-hyperparathyroidism-of-chronic-kidney-disease-gene-polymorphisms-and-protein-levels
#18
Yu Zhao, Li-Li Zhang, Fa-Xian Ding, Ping Cao, Yuan-Yuan Qi, Jing Wang
BACKGROUND: Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a key regulator of PTH mRNA stability. Secondary hyperparathyroidism (SHPT), which is characterized by elevated serum PTH levels, is a common complication of CKD. We investigated the possible associations between CKD with SHPT (CKD SHPT) and single-nucleotide polymorphisms of the Pin1 gene and compared the levels of the Pin1 protein in the CKD SHPT patients with those of the controls. METHODS: The study group included 251 CKD SHPT patients and 61 controls...
November 23, 2016: Renal Failure
https://www.readbyqxmd.com/read/27871893/clinical-effects-of-pre-transplant-serum-25-hydroxyvitamin-d-level-on-post-transplant-immunologic-and-non-immunologic-outcomes-in-kidney-transplant-recipients
#19
Tae Hyun Ban, Jeong Ho Kim, Han Beol Jang, Yoon Seo Lee, Bum Soon Choi, Cheol Whee Park, Chul Woo Yang, Yong-Soo Kim, Byung Ha Chung
BACKGROUND: The aim of this study was to investigate the effects of pre-transplant serum 25-hydroxyvitamin D (25(OH)D) level on non-immunologic and immunologic aspects of post-transplant clinical outcomes in kidney transplant recipients (KTRs). METHODS: We investigated 174 KTRs with low immunologic risk at baseline. We divided the patients into three groups according to baseline serum 25(OH)D level and compared the post-transplant clinical outcomes of acute rejection, infectious complications, and osteoporosis among the groups...
November 18, 2016: Transplant Immunology
https://www.readbyqxmd.com/read/27871812/effects-of-roux-en-y-gastric-bypass-and-sleeve-gastrectomy-on-bone-mineral-density-and-marrow-adipose-tissue
#20
Miriam A Bredella, Logan B Greenblatt, Alireza Eajazi, Martin Torriani, Elaine W Yu
Bariatric surgery is associated with bone loss but skeletal consequences may differ between Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the two most commonly performed bariatric procedures. Furthermore, severe weight loss is associated with high marrow adipose tissue (MAT); however, MAT is also increased in visceral adiposity. The purpose of our study was to determine the effects of RYGB and SG on BMD and MAT. We hypothesized that both bariatric procedures would lead to a decrease in BMD and MAT...
November 15, 2016: Bone
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