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https://www.readbyqxmd.com/read/28436937/efficacy-of-anti-sclerostin-monoclonal-antibody-bps804-in-adult-patients-with-hypophosphatasia
#1
Lothar Seefried, Jasmin Baumann, Sarah Hemsley, Christine Hofmann, Erdmute Kunstmann, Beate Kiese, Yue Huang, Simon Chivers, Marie-Anne Valentin, Babul Borah, Ronenn Roubenoff, Uwe Junker, Franz Jakob
BACKGROUND: Hypophosphatasia (HPP) is a rare genetic disorder resulting in variable alterations of bone formation and mineralization that are caused by mutations in the ALPL gene, encoding the tissue-nonspecific alkaline phosphatase (ALP) enzyme. METHODS: In this phase IIA open-label, single-center, intra-patient, dose-escalating study, adult patients with HPP received 3 ascending intravenous doses of 5, 10, and 20 mg/kg BPS804, a fully human anti-sclerostin monoclonal antibody, on days 1, 15, and 29, respectively...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28429560/is-there-a-role-for-newer-biomarkers-in-chronic-kidney-disease-mineral-and-bone-disorder-management
#2
Sven-Jean Tan, Michael Mx Cai
The current management of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) relies largely on clinical judgement and assessment of biochemical parameters including serum calcium, phosphate and intact parathyroid hormone concentrations. In the past two decades, there has been a leap in the understanding of the pathophysiology of CKD-MBD, leading to the discovery of novel biomarkers. The potential utility of these markers in this clinical setting is an area of intense investigation. In the absence of any guidelines aiding the clinician's understanding and application of these markers, we summarise the current available literature surrounding fibroblast growth factor-23, α-Klotho, sclerostin and serum calcification propensity testing and their respective assays in the context of CKD-MBD management...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28421193/molecular-abnormalities-underlying-bone-fragility-in-chronic-kidney-disease
#3
REVIEW
Yoshiko Iwasaki, Junichiro James Kazama, Masafumi Fukagawa
Prevention of bone fractures is one goal of therapy for patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney Disease: Improving Global Outcomes guidelines. CKD patients, including those on hemodialysis, are at higher risk for fractures and fracture-related death compared to people with normal kidney function. However, few clinicians focus on this issue as it is very difficult to estimate bone fragility. Additionally, uremia-related bone fragility has a more complicated pathological process compared to osteoporosis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28420716/a-men1-pancreatic-neuroendocrine-tumour-mouse-model-under-temporal-control
#4
Kate E Lines, Roeland P Vas Nunes, Morten Frost, Christopher J Yates, Mark Stevenson, Rajesh Thakker
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by occurrence of parathyroid tumours, and neuroendocrine tumours (NETs) of the pancreatic islets and anterior pituitary. The MEN1 gene, encoding menin, is a tumour suppressor, but its precise role in initiating in vivo tumourigenesis remains to be elucidated. The availability of a temporally controlled conditional MEN1 mouse model would greatly facilitate the study of such early tumourigenic events, and overcome the limitations of other MEN1 knockout models, in which menin is lost from conception, or tumour development occurs asynchronously...
April 18, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28419560/fibroblast-growth-factor-23-concentration-in-dogs-with-chronic-kidney-disease
#5
L M Harjes, V J Parker, K Dembek, G S Young, L H Giovaninni, M M Kogika, D J Chew, R E Toribio
BACKGROUND: Chronic kidney disease (CKD) is associated with hyperphosphatemia, decreased vitamin D metabolite concentrations, and hyperparathyroidism. This syndrome is known as CKD-mineral bone disorder (CKD-MBD). Recently, it has been shown that an increase in fibroblast growth factor-23 (FGF-23) concentration is an early biomarker of CKD in people. It is an independent risk factor for both progression of renal disease and survival time in humans and cats with CKD. Information about FGF-23 in healthy dogs and those with CKD is lacking...
April 17, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28414058/assessment-of-bone-turnover-markers-to-predict-mineral-and-bone-disorder-in-men-with-pre-dialysis-non-diabetic-chronic-kidney-disease
#6
Joseph Jessy Davina, M Priyadarssini, Medha Rajappa, Sreejith Parameswaran, Jayaprakash Sahoo, P S Mohan Raj, G Revathy, C Palanivel, Marie Gilbert Marella
BACKGROUND: Chronic kidney disease (CKD) is commonly associated with disturbances in mineral metabolism and bone disease. Bone biopsy is the gold standard in diagnosing mineral bone disorder. Hence the search for non-invasive assessment of bone health gains importance. We undertook to assess the bone health in men with stage 4 and 5 chronic kidney Disease. METHODS: We recruited 32 male subjects with Stage 4 and 5 chronic kidney disease and 32 age-matched healthy male controls...
April 14, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28412266/hyperparathyroidism-diagnosed-due-to-brown-tumors-of-the-jaw-a-case-report-and-literature-review
#7
Philip Brabyn, Ana Capote, Marko Belloti, Ian Zylberberg
This report describes the case of a 42-year-old woman who consulted with a maxillofacial specialist for pain and an exophytic lesion in the maxilla. Biopsy examination disclosed a bone cyst with abundant giant cells, and head and neck computed tomography was performed. A diagnosis of brown tumor in the maxilla and mandible was made, and primary hyperparathyroidism (parathyroid adenoma) was determined as the origin of the bone lesions. The patient underwent a left superior parathyroidectomy, which resolved the hormonal disorder (as determined by normal calcium and parathyroid hormone levels) and the brown tumors, which appeared to have mineralized at 1-year follow-up computed tomography...
March 20, 2017: Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28398918/histological-features-of-methylene-blue-induced-phototoxicity-administered-in-the-context-of-parathyroid-surgery
#8
Ciara A Maguire, Anup Sharma, Lida Alarcon, Lorrette Ffolkes, Malgorzata Kurzepa, Lucy Ostlere, Venura Samarasinghe, Manuraj Singh
Methylene blue is a chromophore dye known for its photosensitizing properties. It is also administered intravenously as a tracer in parathyroid surgery to identify abnormal glands. We describe 2 cases of acute methylene blue-induced phototoxicity in patients who underwent parathyroidectomy. Both patients developed an acute vesiculopustular inflammatory rash on the anterior neck corresponding to the site exposed intraoperatively to overhanging surgical lights. One of the patients also developed a bulla on her finger at the site of attachment of the oxygen probe...
March 16, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28397663/-a-rare-type-of-severe-obesity-in-children-and-adolescents
#9
Sara Østergaard Christensen, Kirsten Holm, Hanne Buciek Hove
A four-year-old girl was referred to a paediatric department with low height, obesity and hypothyroidism. Her paraclinical tests were characteristic with elevated P-parathyroid hormone concentration, hypothyroidism, growth hormone deficiency, abnormal phenotype with brachydactyly, tooth problems and mental retardation, which led to a suspicion of Albright's hereditary osteodystrophy (AHO). The diagnosis was verified by molecular genetic testing. Less than 1% of children with obesity have an endocrine disorder, and AHO is one of them...
February 20, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28394292/gender-specific-impact-of-cadmium-exposure-on-bone-metabolism-in-older-people-living-in-a-cadmium-polluted-area-in-thailand
#10
Muneko Nishijo, Kowit Nambunmee, Dhitiwass Suvagandha, Witaya Swaddiwudhipong, Werawan Ruangyuttikarn, Yoshikazu Nishino
To elucidate the influence of cadmium exposure on bone metabolism, associations between urinary/blood cadmium and bone resorption/formation markers were investigated in older cadmium exposed men and women. Increased urinary cross-linked N-telopeptide of type I collagen (NTx), a bone resorption marker, was found to be associated with increased levels of parathyroid hormone, fractional excretion of calcium, and urinary/blood cadmium after adjusting for confounding factors in men. In women, urinary NTx was significantly associated with only urinary cadmium and a strong relationship with increased fractional excretion of calcium...
April 10, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28386879/evaluation-of-fracture-risk-in-chronic-kidney-disease
#11
REVIEW
Pablo Antonio Ureña Torres, Martine Cohen-Solal
Chronic kidney disease (CKD) is associated with mineral and bone disorders (MBD) that are now considered as a syndrome. Bone fragility and a four to tenfold increased rate of skeletal fractures are often reported in CKD patients. The evaluation of the risk of these fractures in CKD patients should explore the same risk factors identified for the general population including low body weight, menopause, personal and familial history of osteoporosis, chronic inflammatory diseases, and corticosteroid therapy. The aim of this article is to provide a critical review of the tools used for the evaluation of bone loss and the risk of fracture in CKD patients, ranging from the measurement of bone mineral density (BMD), fracture risk assessment (Frax™), quantitative computed tomography (QCT), high-resolution peripheral quantitative computed tomography (HRpQTC), to circulating biomarkers of bone metabolism including vitamin D, parathyroid hormone (PTH), bone-specific alkaline phosphatase, osteocalcin, and some collagen type 1-related molecules indicators of bone remodeling...
April 6, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28378123/secondary-hyperparthyroidism-pathogenesis-diagnosis-preventive-and-therapeutic-strategies
#12
REVIEW
Mariano Rodríguez Portillo, María E Rodríguez-Ortiz
Uremic secondary hyperparathyroidism is a multifactorial and complex disease often present in advanced stages of chronic kidney disease. The accumulation of phosphate, the increased FGF23 levels, the reduction in active vitamin D production, and the tendency to hypocalcemia are persistent stimuli for the development and progression of parathyroid hyperplasia with increased secretion of PTH. Parathyroid proliferation may become nodular mainly in cases of advanced hyperparathyroidism. The alterations in the regulation of mineral metabolism, the development of bone disease and extraosseous calcifications are essential components of chronic kidney disease-mineral and bone disorder and have been associated with negative outcomes...
March 2017: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/28363951/heterotrimeric-g-proteins-in-the-control-of-parathyroid-hormone-actions
#13
REVIEW
Murat Bastepe, Serap Turan, Qing He
Parathyroid hormone (PTH) is a key regulator of skeletal physiology and calcium and phosphate homeostasis. It acts on bone and kidney to stimulate bone turnover, increase the circulating levels of 1,25 dihydroxyvitamin D and calcium and inhibit the reabsorption of phosphate from the glomerular filtrate. Dysregulated PTH actions contribute to or are the cause of several endocrine disorders. This calciotropic hormone exerts its actions via binding to the PTH/PTH-related peptide receptor (PTH1R), which couples to multiple heterotrimeric G proteins, including Gs and Gq/11 Genetic mutations affecting the activity or expression of the alpha-subunit of Gs, encoded by the GNAS complex locus, are responsible for several human diseases for which the clinical findings result, at least partly, from aberrant PTH signaling...
May 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28362393/two-techniques-to-create-hypoparathyroid-mice-parathyroidectomy-using-gfp-glands-and-diphtheria-toxin-mediated-parathyroid-ablation
#14
Ruiye Bi, Yi Fan, En Luo, Quan Yuan, Michael Mannstadt
Hypoparathyroidism (HP) is a disorder characterized by low levels of PTH which lead to hypocalcemia, hyperphosphatemia, and low bone turnover. The most common cause of the disease is accidental removal of the parathyroid glands during thyroid surgery. Novel therapies for HP are needed, but testing them requires reliable animal models of acquired HP. Here, we demonstrate the generation of two mouse models of acquired HP. In the GFP-PTX model, mice with green fluorescent protein (GFP) expressed specifically in the parathyroids (PTHcre-mTmG) were created by crossing PTHcre(+) mice with Rosa-mTmG(fl/fl) mice...
March 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28341898/functional-block-of-il-17-cytokine-promotes-bone-healing-by-augmenting-foxo1-and-atf4-activity-in-cortical-bone-defect-model
#15
M Dixit, K B Singh, R Prakash, D Singh
We determine the effect of interleukin (IL)-17 neutralizing antibody on new bone regeneration. Anti-IL-17 antibody promoted new bone regeneration in cortical bone defect model by augmenting FOXO1 and ATF4 activity thereby decreasing oxidative stress. Our study demonstrates the bone healing and regeneration potential of neutralizing IL-17antibody in osteoporotic fractures. INTRODUCTION: The immune system plays important role in the fracture healing process. However, fracture healing is prolonged in disorders associated with systemic inflammation...
March 24, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28336831/-calcilytic-drugs-feature-and-future
#16
Itsuro Endo
Calcium-sensing receptor(CaSR)is highly expressed in parathyroid, kidney, bone, and small and large intestines to regulate Ca homeostasis. Calcilytics are allosteric antagonists of CaSR, and stimulate endogenous PTH release. Several calcilytics have been evaluated as anabolic therapies for postmenopausal osteoporosis but clinical development of all of them has been abandoned because the lacked clinical efficacy. Calcilytics might be repurposed for new indications like autosomal dominant hypocalcemia or other disorders...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336830/-the-discovery-research-and-development-of-etelcalcetide-hydrochloride-the-world-1st-intravenous-calcimimetics
#17
Atsuto Inoue, Kazutsune Harada
Etelcalcetide hydrochloride is the first intravenous calcimimetics agent for secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is to be administered through dialysis circuit by physician or medical staff upon completion of dialysis and such administration is expected to reduce the burden of medication in patients. From the nonclinical study results, etelcalcetide functions as an allosteric activator of calcium-sensing receptor(CaSR). Etelcalcetide suppressed PTH secretion both in vitro and in vivo...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336823/-regulatory-mechanism-of-calcium-metabolism
#18
Keiichi Ozono
It is often difficult for terrestrial animals to take enough calcium. To maintain serum or extracellular calcium levels is very important for muscle and nerve function. Two major regulators to increase the serum calcium levels are parathyroid hormone(PTH)and vitamin D. PTH binds to the G protein coupling receptor, PTH1R, and increases intracellular cAMP levels. Impirement in the PTH signalling causes many diseases such as pseudohypoparathyroidism and acrodysostosis with hormone resistance. Vitamin D is activated to 1,25-dihydroxyvitamin D[1,25(OH)2D]by two steps of hydroxylation which occurs in the Liver and Kidney...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28332412/drug-safety-evaluation-of-parathyroid-hormone-for-hypocalcemia-in-patients-with-hypoparathyroidism
#19
Gemma Marcucci, Giuseppe Della Pepa, Maria Luisa Brandi
Hypoparathyroidism is a rare disorder characterized by low serum calcium levels and high serum phosphate levels. This disease is commonly treated with calcium supplements and active vitamin D metabolites or analogues, but large doses of these supplements are often utilized to relieve the symptoms caused by hypocalcemia, without guarantee of a physiological normalization of calcium-phosphate homeostasis. Areas covered: Several studies have investigated replacement therapy with recombinant human PTH [rhPTH (1-84) and rhPTH (1-34)] for subjects with hypoparathyroidism...
March 23, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28328802/curative-effect-of-neutral-macroporous-resin-hemoperfusion-on-treating-hemodialysis-patients-with-refractory-uremic-pruritus
#20
RANDOMIZED CONTROLLED TRIAL
Wen-Hong Li, Yu-Min Yin, Hao Chen, Xiao-Dan Wang, He Yun, Hui Li, Jie Luo, Jin-Wen Wang
This study aims to investigate the efficacy and safety of neutral macroporous resin hemoperfusion in treating maintenance hemodialysis (MHD) patients with refractory uremic pruritus (RUP).Ninety patients were enrolled and were randomly divided into 3 groups: control group, experiment 1 group, and experiment 2 group. Clinical symptom scores of skin itching were recorded before and at 4 and 8 weeks after the treatment. In addition, serum parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and C-reactive protein (CRP) were detected; and the calcium-phosphorus product ([Ca] × [P]) was calculated to compare the curative effect...
March 2017: Medicine (Baltimore)
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