DOCSLIB.ORG

THE INFLUENCE of DIET and NUTRITION on BONE METABOLISM in ENDURANCE ATHLETES By

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
THE INFLUENCE of DIET and NUTRITION on BONE METABOLISM in ENDURANCE ATHLETES By THE INFLUENCE OF DIET AND NUTRITION ON BONE METABOLISM IN ENDURANCE ATHLETES By REBECCA TOWNSEND A thesis submitted in partial fulfilment of the requirements of Nottingham Trent University for the degree of: Doctor of Philosophy This research programme was carried out in collaboration with the English Institute of Sport December 2016 This work is the intellectual property of the author. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if more substantial copy is required, should be directed in the owner of the Intellectual Property Rights. i ABSTRACT Both accelerated and suppressed bone remodelling can lead to the development of a stress fracture injury. A stress fracture injury can threaten an athlete’s performance by causing months of missed training time if a stress fracture is sustained during a crucial phase of the season. This thesis presents a series of studies that investigated bone metabolism in endurance athletes and potential ways to improve bone health and reduce the risk of stress fracture injury. Triathletes are endurance athletes that anecdotally have a high incidence of stress fracture injury, but there is limited research into bone health in these athletes. Therefore, the first two studies in this thesis investigated bone metabolism in a group of elite British triathletes during off-season and pre- competition training. The results showed that elite triathletes had elevated bone turnover at both phases of the season, although this was highest during off-season training. The high bone turnover may be related to large training volumes, low energy intakes and high dermal calcium losses in the sweat. Given the potential contribution of high dermal calcium losses to the disruption of calcium homeostasis and the different rates of losses in different types of training sessions, the timing of calcium ingestion around training sessions may be more important than total calcium intakes throughout the day. As such, the third study in this thesis investigated the mechanism and timeframe of Parathyroid hormone (PTH) and calcium regulation during exercise and recovery. The results showed that PTH secretion was controlled by a combination of changes in ionised calcium (Ca2+) and phosphate (PO4) and that the mechanism might be different during exercise and recovery. Taken together these results advocate the use of pre-exercise calcium supplementation, which may prevent the disruption of calcium homeostasis and attenuate the PTH and bone resorption response to intense exercise, although further research is required before this can be implemented in elite triathletes. ii The large training volumes performed by elite triathletes, meant that daily energy expenditures and energy requirements were high, although consuming almost 6,000 kcal.d-1 was difficult when three or four training sessions were regularly performed each day. Therefore, a practical nutritional intervention was needed to help triathletes ingest some of the required nutrients. The fourth study in this thesis investigated the effect of a post-exercise carbohydrate and protein (CHO+PRO) recovery solution on the bone metabolism response to an intense running bout. The results showed that consuming a CHO+PRO recovery solution immediately after exercise created a more positive bone turnover balance in the acute recovery period from exercise, by suppressing bone resorption and increasing bone formation. Further research is required to explore the long-term effects of post- exercise suppression of bone resorption. This thesis had direct impact on elite British triathletes, by influencing athlete behaviour and nutritional practices in the daily training environment. The research has also influenced British Triathlon coaches and sports science and medicine staff by increasing the importance placed on bone health and by providing information that will allow training and nutritional practices to be improved or altered to promote a more anabolic environment for bone. Key words: Bone, Bone Turnover, Bone metabolism, Bone Injury, Stress Fracture Injury, Endurance, Athlete, Triathlete, Training, Nutrition, Parathyroid Hormone, Calcium, Carbohydrate, Protein. iii TABLE OF CONTENTS TABLE OF CONTENTS IV ACKNOWLEDGEMENTS IX PUBLICATIONS AND CONFERENCE PROCEEDINGS XI LIST OF TABLES XII LIST OF FIGURES XIII DEFINITIONS OF TERMS XIV LIST OF ABBREVIATIONS XV CHAPTER 1: INTRODUCTION 1 AIMS AND OBJECTIVES 7 1.2 Aims 8 1.3 Objectives 8 CHAPTER 2: REVIEW OF LITERATURE 9 2.1 Introduction to the review of literature 10 2.2 Bone mass 11 2.2.1 Bone mass and mechanical loading 12 2.2.2 Bone mass measurements in athletes 15 2.3 Stress fracture injuries 17 2.3.1 Risk factors for the development of stress fracture injury 19 2.3.2 Stress fractures in athletes 23 2.4 Triathlon 25 2.5 The Female Athlete Triad 27 2.6 Relative Energy Deficit in Sport (RED-S) 30 2.7 Methods of measuring energy expenditure 32 2.8 The skeletal system and bone remodelling 35 2. 9 Biochemical markers of bone turnover 39 2.9.1 Bone formation markers 41 2.9.2 Bone resorption markers 43 iv 2.9.3 Variability of bone turnover markers 44 2.9.4 Circadian rhythms of bone turnover markers 46 2.10 Effects of exercise on bone turnover markers 49 2.10.1 Bone turnover markers and acute exercise 49 2.10.2 Bone turnover and repeated bouts of exercise 54 2.10.3 Bone turnover throughout a competitive season 57 2.11 Calcium 59 2.12 Parathyroid hormone 63 2.12.1 Parathyroid hormone in response to exercise 66 2.13 Nutrient ingestion and bone 68 2.13.1 Mixed nutrient ingestion 68 2.13.2 Endocrine mediators 69 2.14 Exercise related feeding practices 71 2.15 Summary 73 CHAPTER 3: GENERAL METHODS 75 3.1 Participants 76 3.2 Experimental protocols 76 3.2.1 Speed lactate and maximal oxygen uptake (VO2max) test 76 3.3 Measurements 77 3.3.1 Height and body mass 77 3.3.2 Blood sampling 77 3.3.3 Sweat collection 78 3.4 Blood analysis 79 3.4.1 Blood lactate 79 3.4.2 Ca2+ and pH 79 3.4.3 β-CTX, P1NP and PTH 81 3.4.4 Albumin, total calcium and PO4 82 3.4.5 Vitamin D 83 3.5 Sweat analysis 83 3.6 Dietary analysis 84 3.7 Urine osmolality 84 3.8 Statistical analysis 84 CHAPTER 4: INVESTIGATING BONE METABOLISM IN ELITE TRIATHLETES DURING OFF-SEASON TRAINING 86 4.1 Introduction 87 v 4.2 Methodology 90 4.2.1 Participants 90 4.2.2 Experimental design 90 4.2.3 Testing procedures 91 4.2.3.1 Morning blood and urine collection 91 4.2.3.2 Sweat collection 91 4.2.3.4 Stress fracture history 91 4.2.3.5 Dietary information 91 4.2.4 Energy expenditure by Doubly Labelled Water 92 4.2.5 Blood sample analysis 93 4.2.6 Sweat analysis 93 4.2.7 Bone turnover markers and metabolites 93 4.3 Results 95 4.3.1 Stress fracture history 95 4.3.2 Menstrual status 96 4.3.3 Bone turnover markers 97 4.3.4 Calcium metabolism 100 4.3.5 Vitamin D 102 4.3.6 Total energy expenditure 103 4.3.7 Energy intakes and hydration status 104 4.3.8 Supplementation 105 4.3.9 Training loads 106 4.3.10 Sweat losses and dermal calcium losses 107 4.4 Discussion 108 CHAPTER 5: INVESTIGATING BONE METABOLISM IN A SUBSET OF ELITE TRIATHLETES DURING PRE-COMPETITION TRAINING 119 5.1 Introduction 120 5.2 Methodology 122 5.2.1 Participants 122 5.2.2 Experimental design 122 5.2.3 Testing procedures 122 5.2.4 Bone turnover markers and metabolites 123 5.2.5 Statistical analysis 123 5.3 Results 124 5.3.1 Bone turnover markers 124 5.3.2 Calcium metabolism 127 5.3.3 Vitamin D 130 5.3.4 Energy intakes 131 5.3.5 Supplementation 132 5.3.6 Training loads 133 5.3.7 Sweat losses and dermal calcium losses 134 5.2.8 Menstrual status 135 5.4 Discussion 136 vi CHAPTER 6: EXPLORING THE MECHANISM OF PARATHYROID REGULATION DURING EXERCISE AND RECOVERY IN RECREATIONAL RUNNERS 142 6.1 Introduction 143 6.2 Methodology 147 6.2.1 Participants 147 6.2.2 Experimental design 147 6.2.3 Trial procedures 147 6.2.3.1 Assessment of VO2max 147 6.2.4 Main trials 147 6.2.5 Biochemical analysis 148 6.2.6 Statistical analysis 148 6.3 Results 150 6.3.1 Baseline biochemistry 150 6.3.2 PTH 150 6.3.3 PO4 151 6.3.4 ACa 151 6.3.5 Albumin 152 6.3.6 Ca2+ 154 6.3.7 pH 156 6.3.8 Correlation analyses 156 6.4 Discussion 158 CHAPTER 7: INVESTIGATING THE EFFECT OF POST-EXERCISE CARBOHYDRATE AND PROTEIN INGESTION ON BONE METABOLSIM IN TRAINED ENDURANCE ATHLETES 164 7.1 Introduction 165 7.2 Methodology 168 7.2.1 Participants 168 7.2.2 Experimental design 168 7.2.3 Assessment of VO2max 169 7.2.4 Experimental dietary provision 170 7.2.5 Experimental trial procedure 170 7.2.6 Recovery solutions and evening meal composition 171 7.2.7 Treatment and storage of blood samples 172 7.2.8 Biochemical analysis 172 7.2.9 Statistical analysis 172 7.3 Results 173 7.3.1 Baseline biochemistry 173 7.3.2 Habitual diet and experimental dietary provision 173 7.3.3 Hydration status 174 7.3.4 Exercise variables 174 7.3.5 Bone turnover markers 174 7.3.6 Calcium metabolism 177 vii 7.4 Discussion 182 CHAPTER 8: GENERAL DISCUSSION 188 8.1 Research impact on British Triathlon 199 8.2 Conclusions 202 REFERENCES 204 APPENDICES 248 Appendix A Resting bone turnover marker concentrations 248 Appendix B Health screening questionnaire 249 Appendix C ARTD Lifestyle Questionnaire (includes stress fracture injury questions*) 251 Appendix D Ambient conditions during sweat collection 254 Appendix E Menstrual questionnaire 255 Appendix F Example training log 258 Appendix G Example diet log 259 Appendix H Example Nutritics analysis 262 Appendix I Example 48 h lead in diet 263 Appendix J Supplement screening certificate 265 Appendix K Supplement disclaimer 266 Appendix L Standard operating procedure for the production of the CHO+PRO recovery solutions 267 Appendix M Example experimental diet 269 Appendix N Parathyroid Hormone Secretion is Controlled by Both Ionised Calcium and Phosphate During Exercise and Recovery in Men 270 viii ACKNOWLEDGEMENTS First and foremost I would like to thank my supervisors, Professor Craig Sale, Dr Kirsty Elliott-Sale and Dr Kevin Currell, for their continued support and guidance.
Load more

Recommended publications
  • WHO Manual of Diagnostic Imaging Radiographic Anatomy and Interpretation of the Musculoskeletal System
    The WHO manual of diagnostic imaging Radiographic Anatomy and Interpretation of the Musculoskeletal System Editors Harald Ostensen M.D. Holger Pettersson M.D. Authors A. Mark Davies M.D. Holger Pettersson M.D. In collaboration with F. Arredondo M.D., M.R. El Meligi M.D., R. Guenther M.D., G.K. Ikundu M.D., L. Leong M.D., P. Palmer M.D., P. Scally M.D. Published by the World Health Organization in collaboration with the International Society of Radiology WHO Library Cataloguing-in-Publication Data Davies, A. Mark Radiography of the musculoskeletal system / authors : A. Mark Davies, Holger Pettersson; in collaboration with F. Arredondo . [et al.] WHO manuals of diagnostic imaging / editors : Harald Ostensen, Holger Pettersson; vol. 2 Published by the World Health Organization in collaboration with the International Society of Radiology 1.Musculoskeletal system – radiography 2.Musculoskeletal diseases – radiography 3.Musculoskeletal abnormalities – radiography 4.Manuals I.Pettersson, Holger II.Arredondo, F. III.Series editor: Ostensen, Harald ISBN 92 4 154555 0 (NLM Classification: WE 141) The World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in full. Applications and enquiries should be addressed to the Office of Publications, World Health Organization, CH-1211 Geneva 27, Switzerland, which will be glad to provide the latest information on any changes made to the text, plans for new editions, and reprints and translations already available. © World Health Organization 2002 Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved.
    [Show full text]
  • Rheumatology-TP 1..2
    Rheumatology 2015 The British Society for Rheumatology and British Health Professionals in Rheumatology Annual Meeting 2015 28 April – 30 April 2015 Manchester Central, Manchester, UK The abstracts are freely available online to all visitors to the Rheumatology website (http://www.rheumatology.oxfordjournals.org). RheumatologyDOI is incorrect10.1093/rheumatology/ker000ker000ContentsRheumatologyContents- Contents2012000000002012Volume 51 Supplement 3 May 2012 Volume 54 Supplement 1 April 2015 CONTENTS Rheumatology 2015 Abstracts INVITED SPEAKER ABSTRACTS (TUESDAY 28 APRIL 2015) I01–I03 Imaging in rheumatology: a practical perspective i1 I04–I06 Biologics in SLE: getting close to lift off (at last!) i1 I07–I09 Shared decision making and self-management support: why they matter in i1 rheumatology I10–I11 Challenges of remote and rural rheumatology i2 I12–I15 A step in the right direction: addressing foot health in rheumatoid arthritis i2 I16–I18 Musculoskeletal health and vocational rehabilitation i3 I19–I21 Making it happen: optimizing the service to RA patients i4 I22–I24 Community-based physical activity for osteoarthritis: the emerging role of i4 non-healthcare professionals I25–I26 Post-doctoral, PhD and postgraduate student network i5 I27–I32 Jewels in the Crown and top scoring abstracts (including Michael Mason and Garrod i5 prize winners and young investigator award) I33 Heberden Round i6 INVITED SPEAKER ABSTRACTS (WEDNESDAY 29 APRIL 2015) I34–I36 Pain in the 21st century: sensory–immune interactions, biologic agents and i8 bisphosphonates
    [Show full text]
  • Multiple Repetitive Fragility Fractures in Young Patients
    Rom J Leg Med [22] 217-220 [2014] DOI: 10.4323/rjlm.2014.217 © 2014 Romanian Society of Legal Medicine Multiple repetitive fragility fractures in young patients- differentiation between osteogenesis imperfecta, osteomalacia (secondary to vitamin D deficiency) and domestic abuse Cristina Capatina1,*, Mara Carsote1, Corneliu Capatina2, C. Poiana1, M. Berteanu3 _________________________________________________________________________________________ Abstract: Fragility fractures (i.e. fractures occuring in abnormal bones, caused by minimal or no trauma) during childhood are infrequent and secondary to rare metabolic or bone diseases. The presence of multiple fractures should also raise the suspicion of inflicted injury (abuse), which is much more frequent, thus it is extremely important to distinguish between genuine fragility fractures and traumatic fractures. We report the case of a 20 years old male with a history of multiple unexplained fractures of the long bones during the entire childhood and adolescence. In this patient a diagnosis of both osteogenesis imperfecta and severe vitamin D deficiency was made on the basis of the clinical picture, biological data and radiographic findings. We provide a brief overview of the most important elements to be sought for in the differential diagnosis between fractures caused by induced trauma and fragility fractures secondary to either osteogenesis imperfecta or defective bone mineralisation due to vitamin D deficiency. Key Words: fragility fractures, osteogenesis imperfecta, vitamin D deficiency, domestic abuse. athological (fragility) fractures (i.e. fractures fractures and bone loss [2]. Multiple fractures in children, occuring in abnormal bones, caused by minimal adolescents and young adults should therefore prompt a P or no trauma) are infrequent in young patients and they thorough investigation aiming at the detection of such rare are caused by the abnormal bone structure secondary to etiologies.
    [Show full text]
  • Surgical Treatment of Cervical Cord Compression in Rheumatoid Arthritis
    Ann Rheum Dis: first published as 10.1136/ard.44.12.809 on 1 December 1985. Downloaded from Annals of the Rheumatic Diseases, 1985, 44, 809-816 Surgical treatment of cervical cord compression in rheumatoid arthritis H A CROCKARD,' W K ESSIGMAN,2 J M STEVENS,' J L POZO,1 A 0 RANSFORD,1 B E KENDALL' From 'the National Hospitals for Nervous Diseases and University College Hospital, London WCJ; and the 2Lister Hospital, Stevenage, Herts SUMMARY Cervical myelopathy is a rare but potentially dangerous complication of rheumatoid arthritis and presents considerable therapeutic problems. A conservative approach carries high mortality and surgical intervention is not without serious risks. Reduction of subluxation and posterior fusion is widely practised but may require prolonged bed rest and continuous skull traction, sometimes for many weeks. When anterior decompression has been attempted prolonged immobilisation and external fixation have created problems. In this series 23 rheumatoid patients with cervical myelopathy were investigated over a four-year period. Seventeen underwent anterior decompression of the cervical cord, of whom 14 had a transoral removal of the odontoid peg and pannus and posterior occipitocervical fusion during the same by copyright. anaesthetic without mortality or serious postoperative complications; all but one have improved. The authors believe that early mobilisation after a combined cord decompression and internal fixation has reduced the mortality and morbidity. Management of cervical myelopathy in rheumatoid arthritis and indications for operation are discussed. Key words: atlantoaxial subluxation, rheumatoid pannus, cervical myelopathy, transoral surgery, surgery - rheumatoid arthritis. http://ard.bmj.com/ The involvement of the cervical spine in rheumatoid dangerous complication of trauma (1824) and arthritis has become recognised increasingly over syphilitic ulceration of the pharynx (1830) by Sir the last decade.
    [Show full text]
  • Anti-HMGB1 Monoclonal Antibody Ameliorates Immunosuppression
    Hindawi Publishing Corporation Mediators of Inflammation Volume 2015, Article ID 458626, 10 pages http://dx.doi.org/10.1155/2015/458626 Research Article Anti-HMGB1 Monoclonal Antibody Ameliorates Immunosuppression after Peripheral Tissue Trauma: Attenuated T-Lymphocyte Response and Increased Splenic CD11b+Gr-1+ Myeloid-Derived Suppressor Cells Require HMGB1 Xiangcai Ruan,1,2 Sophie S. Darwiche,2 Changchun Cai,2 Melanie J. Scott,2 Hans-Christoph Pape,3 and Timothy R. Billiar2 1 Department of Anesthesiology, First Municipal People’s Hospital of Guangzhou, Affiliated Hospital of Guangzhou Medical College, Guangzhou, China 2 Department of Surgery, University of Pittsburgh, University of Pittsburgh Medical Center, Suite F1281, 200 Lothrop Street, Pittsburgh, PA 15213, USA 3 Department of Orthopaedic and Trauma Surgery, Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany Correspondence should be addressed to Sophie S. Darwiche; [email protected] and Timothy R. Billiar; [email protected] Received 9 May 2014; Accepted 10 September 2014 Academic Editor: Philip Stahel Copyright © 2015 Xiangcai Ruan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Although tissue-derived high mobility group box 1 (HMGB1) is involved in many aspects of inflammation and tissue injury after trauma, its role in trauma-induced immune suppression remains elusive. Using an established mouse model of peripheral tissue trauma, which includes soft tissue and fracture components, we report here that treatment with anti-HMGB1 monoclonal antibody + + ameliorated the trauma-induced attenuated T-cell responses and accumulation of CD11b Gr-1 myeloid-derived suppressor cells in the spleens seen two days after injury.
    [Show full text]
  • Osteomalacia and Vitamin D Status: a Clinical Update 2020
    Henry Ford Health System Henry Ford Health System Scholarly Commons Endocrinology Articles Endocrinology and Metabolism 1-1-2021 Osteomalacia and Vitamin D Status: A Clinical Update 2020 Salvatore Minisola Luciano Colangelo Jessica Pepe Daniele Diacinti Cristiana Cipriani See next page for additional authors Follow this and additional works at: https://scholarlycommons.henryford.com/endocrinology_articles Authors Salvatore Minisola, Luciano Colangelo, Jessica Pepe, Daniele Diacinti, Cristiana Cipriani, and Sudhaker D. Rao SPECIAL ISSUE Osteomalacia and Vitamin D Status: A Clinical Update 2020 Salvatore Minisola,1 Luciano Colangelo,1 Jessica Pepe,1 Daniele Diacinti,1 Cristiana Cipriani,1 and Sudhaker D Rao2 1Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy 2Bone and Mineral Research Laboratory, Division of Endocrinology, Diabetes & Bore and Mineral Disorders, Henry Ford Hospital, Detroit, MI, USA ABSTRACT Historically, rickets and osteomalacia have been synonymous with vitamin D deficiency dating back to the 17th century. The term osteomalacia, which literally means soft bone, was traditionally applied to characteristic radiologically or histologically documented skeletal disease and not just to clinical or biochemical abnormalities. Osteomalacia results from impaired mineralization of bone that can manifest in several types, which differ from one another by the relationships of osteoid (ie, unmineralized bone matrix) thickness both with osteoid surface and mineral apposition rate. Osteomalacia related to vitamin D deficiency evolves in three stages. The initial stage is characterized by normal serum levels of calcium and phosphate and elevated alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D [1,25(OH)2D]—the latter a consequence of increased PTH. In the second stage, serum calcium and often phosphate levels usually decline, and both serum PTH and alkaline phosphatase values increase further.
    [Show full text]
  • 143 Osteomalacia Due to Vitamin D Deficiency: a Case Report
    Case Report / Olgu Sunumu 143 DOI: 10.4274/tod.galenos.2020.26056 Turk J Osteoporos 2020;26:143-5 Osteomalacia due to Vitamin D Deficiency: A Case Report D Vitamini Eksikliğine Bağlı Osteomalazi: Olgu Sunumu Banu Ordahan, Kaan Uslu, Hatice Uğurlu Necmettin Erbakan University Meram Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Konya, Turkey Abstract Osteomalacia is a metabolic bone disease characterized by demineralization of the newly formed osteoid in adults. Vitamin D deficiency due to insufficient vitamin D intake, inadequate exposure to sunlight, and malabsorption of vitamin D are the most widespread cause of osteomalacia. Here,we present the case of 18 year old female patient who presented to our hospital with complaints of low back pain. Sacral bone pseudofracture was detected by magnetic resonance imaging due to osteomalacia. Patient was treated with vitamin D. Keywords: Osteomalacia, vitamin D deficiency, pseudofracture Öz Osteomalazi, yetişkinlerde yeni oluşan osteoidin mineralleşmesinde azalma ile karakterize metabolik bir kemik hastalığıdır. Yetersiz D vitamini alımı, güneş ışığına yetersiz maruz kalma ve D vitamini malabsorpsiyonu nedeniyle D vitamini eksikliği, osteomalazinin en sık nedenidir. Bu yazıda, bel ağrısı şikayeti ile hastaneye başvuran 18 yaşında kadın hastayı sunduk. Osteomalazi nedeniyle manyetik rezonans görüntüleme ile sakral kemik psödofraktürü saptandı. Hasta D vitamini ile tedavi edildi. Anahtar kelimeler: Osteomalazi, D vitamini eksikliği, psödofraktür Introduction who was seen by the neurosurgery department because of low back pain, was diagnosed as having spondylolisthesis at Osteomalacia is a metabolic bone disease identify by a decrease the L5-S1 level and was given a lumbosacral steel corset. There in the mineralization of the newly formed osteoid in adults.
    [Show full text]
  • 761068Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 761068Orig1s000 MULTI-DISCIPLINE REVIEW Summary Review Office Director Cross Discipline Team Leader Review Clinical Review Non-Clinical Review Statistical Review Clinical Pharmacology Review MultiͲDisciplinary Review BLA 761068 (burosumab Ͳ twza) MULTIͲDISCIPLINARY REVIEW Application Type BLA Application Number(s) 761068 Priority or Standard Priority Submit Date(s) 8/17/2017 Received Date(s) 8/17/2017 PDUFA Goal Date 4/17/2018 Division/Office Division of Bone, Reproductive and Urologic Products/ Office of Drug Evaluation III Review Completion Date 4/5/2018 Established/Proper Name Burosumab (Proposed) Trade Name Crysvita Applicant Ultragenyx Pharmaceutical Inc. Dosage Form(s) 10, 20 and 30 mg/mL solution for injection in singleͲdose vial Applicant Proposed Dosing Pediatric: 0.8 mg/kg SC Q2 weeks (starting dose; titration to Regimen(s) max 2.0 mg/kg Q2weeks based on serum phosphorus; minimum dose 10 mg, maximum dose 90 mg) Adult: 1 mg/kg SC Q4 weeks, maximum dose 90 mg Applicant Proposed Treatment of XͲlinked hypophosphatemia (XLH) in adult and Indication(s)/Population(s) pediatric patients 1 year of age and older Recommendation on Approval for both adult and pediatric patients Regulatory Action Recommended Treatment of XͲlinked hypophosphatemia (XLH) in adult and Indication(s)/Population(s) pediatric patients 1 year of age and older (if applicable) 1 Reference ID: 4247337 MultiͲDisciplinary Review BLA 761068 (burosumab Ͳ twza) Table of Contents Reviewers of MultiͲDisciplinary Review
    [Show full text]
  • 37-Year-Old Female with Xlh Study*
    CASE 37-YEAR-OLD FEMALE WITH XLH STUDY* No known abnormalities XLH confirmed by CRYSVITA therapy reported genetic testing initiated BIRTH 2 YEARS 13 YEARS 35 YEARS 36 YEARS 37 YEARS XLH Joint stiffness Symptoms diagnosis in hips, knees, improved and ankles MEDICAL HISTORY X-RAY 1: FEET During childhood • Age 2: diagnosed with X-linked hypophosphatemia L L (XLH) as a toddler – Initiated oral phosphate and calcitriol and was compliant XLH diagnosis was confirmed by • Age 13: Enthesophyte genetic testing R Family history • Mother and maternal grandmother had XLH XLH symptoms and associated complications in adulthood • Chiari malformation requiring two corrective surgeries Enthesophyte • Chronic ankle pain and swelling in joints At 35 years old: prominent bilateral calcaneal enthesophytes; • Gait abnormalities severe bilateral tibiotalar osteoarthritis; slight bilateral bowing in • Sustained pelvic fracture during childbirth tibias and fibulas. • Age 33: discontinued oral phosphate and calcitriol Evaluation prior to CRYSVITA • Age 35: presented to adult endocrinology with – Hypertrophic bone formation occurring at the bowing of upper and lower extremities and joint hip articulation and trochanters; sclerosis at stiffness in hips, knees, and ankles the sacroiliac joints; slight bilateral bowing of • Physical exam femurs (X-ray 2, page 2) – Height, 5'2" – Bowing deformity at each femur and – Required the use of assistive walking device degenerative changes of the knees including (cane) for long distances and handicap tags bilateral articular
    [Show full text]
  • The Prevalence of Micronutrient Deficiencies and Inadequacies In
    nutrients Review The Prevalence of Micronutrient Deficiencies and Inadequacies in the Middle East and Approaches to Interventions Nahla Hwalla 1, Ayesha Salem Al Dhaheri 2, Hadia Radwan 3, Hanan Abdullah Alfawaz 4, Mona A. Fouda 5, Nasser Mohammed Al-Daghri 6, Sahar Zaghloul 7 and Jeffrey B. Blumberg 8,* 1 Faculty of Agricultural and Food Sciences, American University of Beirut, Beirut 1107 2020, Lebanon; [email protected] 2 Nutrition and Health Department, College of Food and Agriculture, United Arab Emirates University, Al Ain, UAE; [email protected] 3 College of Health Sciences, Clinical Nutrition and Dietetics Department, University of Sharjah, Sharjah, UAE; [email protected] 4 Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh, Saudi Arabia; [email protected] 5 Department of Medicine, Division of Endocrinology, College of medicine and KSUMC, King Saud University, Riyadh, Saudi Arabia; [email protected] 6 Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia; [email protected] 7 Department of Nutrition Requirements and Growth, National Nutrition Institute, Cairo, Egypt; [email protected] 8 Friedman School of Nutrition Science and Policy, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 20111, USA * Correspondence: [email protected]; Tel./Fax: +1-617-556-3334 Received: 29 December 2016; Accepted: 28 February 2017; Published: 3 March 2017 Abstract: Micronutrient deficiencies and inadequacies constitute a global health issue, particularly among countries in the Middle East. The objective of this review is to identify micronutrient deficits in the Middle East and to consider current and new approaches to address this problem.
    [Show full text]
  • Clinical Pediatric Endocrinology
    Clinical Pediatric Vol.29 / No.1 January 2020 Endocrinology pp 9–24 Special Report Clinical Practice Guidelines for Hypophosphatasia* Toshimi Michigami1, 9, Yasuhisa Ohata2, 9, Makoto Fujiwara2, 9, Hiroshi Mochizuki3, 9, Masanori Adachi4, 9, Taichi Kitaoka2, 9, Takuo Kubota2, 9, Hideaki Sawai5, 9, Noriyuki Namba6, 9, Kosei Hasegawa7, 9, Ikuma Fujiwara8, 9, and Keiichi Ozono2, 9 1 Department of Bone and Mineral Research, Research Institute, Osaka Women’s and Children’s Hospital, Osaka Prefectural Hospital Organization, Osaka, Japan 2 Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan 3 Division of Endocrinology and Metabolism, Saitama Children’s Medical Center, Saitama, Japan 4 Department of Endocrinology and Metabolism, Kanagawa Children’s Medical Center, Kanagawa, Japan 5 Department of Obstetrics and Gynecology, Hyogo College of Medicine, Hyogo, Japan 6 Division of Pediatrics and Perinatology, Tottori University Faculty of Medicine, Tottori, Japan 7 Department of Pediatrics, Okayama University Hospital, Okayama, Japan 8 Department of Pediatrics, Sendai City Hospital, Miyagi, Japan 9 Task Force for Hypophosphatasia Guidelines Abstract. Hypophosphatasia (HPP) is a rare bone disease caused by inactivating mutations in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). Patients with HPP have varied clinical manifestations and are classified based on the age of onset and severity. Recently, enzyme replacement therapy using bone-targeted recombinant alkaline phosphatase (ALP) has been developed, leading to improvement in the prognosis of patients with life-threatening HPP. Considering these recent advances, clinical practice guidelines have been generated to provide physicians with guides for standard medical care for HPP and to support their clinical decisions. A task force was convened for this purpose, and twenty-one clinical questions (CQs) were formulated, addressing the issues of clinical manifestations and diagnosis (7 CQs) and those of management and treatment (14 CQs).
    [Show full text]
  • 74Th Annual Meeting of the American Association for the Surgery of Trauma and Clinical Congress of Acute Care Surgery
    74th Annual Meeting of the American Association for the Surgery of Trauma and Clinical Congress of Acute Care Surgery September 9 — September 12, 2015 WYNN LAS VEGAS LAS VEGAS, NV HISTORICAL BACKGROUND AAST The American Association for the Surgery of Trauma started with conversations at the meetings of the Western Surgical Association and Southern Surgical Association in December, 1937. The 14 founders, who were present at one or both of these meetings, sub- sequently invited another 68 surgeons to a Founding Members meeting in San Francisco on June 14, 1938. The first meeting of the AAST was held in Hot Springs, Virginia, in May, 1939, and Dr. Kellogg Speed’s first Presidential Address was published in The American Journal of Surgery 47:261-264, 1940. Today, the Association holds an annual scientific meeting, owns and publish- es The Journal of Trauma and Acute Care Surgery, initiated in 1961, and has approximately 1,300 members from 30 countries. American Association for the Surgery of Trauma (AAST) Annual Meeting of AAST and Clinical Congress of Acute Care Surgery Learning Objectives and Outcomes Exchange knowledge pertaining to current research practices and training in the surgery of trauma. Design research studies to investigate new methods of preventing, correcting, and treating acute care surgery (trauma, surgical critical care and emergency surgery) injuries. CONTINUING MEDICAL EDUCATION CREDIT INFORMATION Accreditation This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the American College of Surgeons and the American Association for the Surgery of Trauma.
    [Show full text]