Clinical Focus Seris: Bone and Mineral Disorders Romesh K Khardori, Subhash C Kukreja, Sanjay K Bhadada
INDEX
Page numbers followed by b refer to box, f refer to figure, and t refer to table.
A
Abaloparatide 117, 119, 120, 135, 138
treatment 119
Acetazolamide 44, 55
Acid secretion 55
Acidosis, type of 55
Adaptor protein 2 sigma subunit 80
Addison's disease 63, 81, 91
Adefovir 44
Adenomas, atypical 75
Adenosine triphosphate 35
Albumin 12, 95
adjustment 10
Alcoholism 44
Alendronate 114, 115, 129
Alkaline phosphatase 54, 56
Amino acids arginine 39f
Aminoglycoside 44
Ammonium loading test 55
Amphotericin B 55
Amyloidosis 55
Anabolic 124
agent 121
Antacids containing calcium 44
Antiepileptic drugs 101
Antiresorptive agent 118, 142
Antiresorptive therapy 137
Antiresorptive treatment, duration of 131
Antiretroviral inhibitor therapy 101
Antisclerostin antibody 139
Apoptosis 3
Aromatase inhibitors 101
Atrial fibrillation 125
Autoimmune 91
hypoparathyroidism 91
polyglandular syndrome 89, 90
regulator gene 91
Autosomal dominant 90
hypophosphatemic rickets 41, 53
manner 80
Autosomal recessive 90
hypophosphatemic rickets 41, 53
B
Berylliosis 66
Bisphosphonate 71, 113, 124, 135
chemical structure 124
efficacy of 126t
mechanism of action 124
pharmacokinetics 124
therapy, indications for 129t
treatment 130b, 131, 133
use 117
Blood
25-hydroxyvitamin D 16
bone exchange 10
calcium analyses 61
Body mass index, high 104
Bone
anabolic agents 119
architecture, tools for measurement of 103
balance 143
steady-state 142
cell function 3, 5f
cellular activity 8
densitometry 144
disease
absence of 76
adynamic 121
distribution 1
formation 124
gain 108
health 7
histology 7
histomorphometry 7, 56
loss, process of 108
markers 81, 105
mass 103, 105
tools for measurement of 101
matrix 6
metastases 64
mineral
content 29
density 29, 77, 83, 101, 110, 131, 137, 143
density measurements 108
mineralization 30
properties 100
remodeling 7, 11, 12
conceptual optimal 8f
sequence 2f
transient 142
unit 2
resorption 5, 6, 112, 124
specific alkaline phosphatase 45
structure 1
ultrasound, quantitative 103
vitality of 7
Bradycardia 18
Breast cancer 72
infiltrative 64
C
Cadmium toxicity 52
Café-au-lait spots 42
Calcitonin 8, 71, 112
inhibits bone resorption 71
Calcitriol dose 47
Calcium 8, 9, 17, 28, 32, 80, 110
absorption 53
amounts of 9
balance 143
positive 144
whole-body 11
daily administration of 29
deficiency rickets 52
for bone health 28, 29
in kidney 10
intake, low 30
intestinal absorption of 30
ion 118
maintenance of 12
phosphate
homeostasis 51
product 97
proximal tubular reabsorption of 10
renal handling of 10
sensing receptor 77, 90
supplement 20, 30, 143
supplementation
daily 30
effects of 30
Canalicular system connecting 4f
Cancer 21
diagnosis of 70
mortality, randomized trials of 21
prevention, randomized trials of 21
Carbohydrate 28
meals, high 44
Carcinogenesis 17
Cardiac arrhythmias 88
Cardiomyopathy, dilated 88
Cardiovascular disease 20, 21
observational studies 21
randomized trials 21
Catecholamines 44
Cathepsin K inhibitor 118
Cell
lung cancer 65
types of 7
Cellular life, vital for 35
Cement cells 2
Central nervous system symptoms 72
Childhood and adolescence, presentation in 80
Chloride channel, mutations in 42
Chloride-phosphate ratio, elevated 81
Cholecalciferol 16, 51
Cisplatin 44
Coccidioidomycosis 66
Collagen fibers 6
Columnar cells 3
Cortical bone, structure of 2
Creatinine 118
C-terminal telopeptide 143
Cushing's syndrome 101
Cystinosis 42
D
Deformity, areas of 45
Denosumab 71, 117, 131, 133
efficacy of 132t
treatment 133
side effects of 132
Dent's disease 42, 52
Dental involvement 56
Dentin matrix
acidic phosphoprotein 1 40
protein 1 53
Depo-provera 101
Diabetes mellitus 22, 101
type 1 22
type 2 22
Diabetic ketoacidosis 44
Dialysis 72
Dietary allowance 30
Dietary calcium 30
Divalent ion
absorption, components of 10
distribution of 9t
Drug
interaction 23
rash 118
Dual-energy X-ray absorptiometry 83, 101, 102
bone mineral density results, interpretation of 102
E
Eczema 132
Elemental phosphorus ranging, doses of 47
Enamel hypoplasia 56
Endocrine
disorders 81
neoplasia, part of multiple 75
Endogenous secretion 10
Enzymatic hydroxylation 16
Enzyme-linked immunosorbent assay 47
Eosinophilia 118
Ergocalciferol 16
Estrogen 106, 112
deficiency 11
receptor modulators, selective 113
Extracellular fluid 9
F
Familial hypocalciuric hypercalcemia 80
Familial tumoral calcinosis 43
Fanconi syndrome 42, 45, 52, 55
Fat
malabsorption 90
soluble vitamin 111
Fecal excretion 10
Femur fractures, atypical 115, 130
Fibroblast growth factor 23 4, 5, 17, 37, 38, 38f, 39, 43, 53
Fibroblast growth factor 23
independent hypophosphatemic syndromes 42
structure of 39f
Fibrous dysplasia 3, 42, 45
Follicle stimulating hormone 93
Foreign body granulomas 66
Fracture
high risk of 131
low risk of 131
mild risk of 131
moderate risk of 131
risk 105
factors for 106
Furosemide 10, 71
G
Gallium nitrate 72
Gallstone disease, high prevalence of 79
Gammopathies 10
Gastrointestinal discomfort 118
Gastrointestinal distress 47
Gastrointestinal manifestations 79
Gastrointestinal tract disorder 97
Glomerular filtration rate 43
Glucocorticoid 72, 101
induced osteoporosis 120, 140
inhibit bone resorption 72
use 106, 108
Glucose infusion 44
Glycosylation 39
Gonadotropin 93
releasing hormone agents 101
G-protein alpha-11 subunit 80
Granulomatous disease 66
diagnosis of 70
Granulomatous disorders 63, 81
Granulomatous leprosy 66
Growth hormone-releasing hormone 93
Gut absorption 43
H
Haversian system 1, 2f
Headache 118
Hematopoietic progenitors 3
Hemodilution 11
Hemolysis 44
Heparin 101
Hereditary hypophosphatemic rickets 42
Heritable rickets 41
Hip fracture 140
prevention of 31
Histiocytosis X 66
Histoplasmosis 66
Homeostatic systems 9
Hormone resistance 93
Human immunodeficiency virus 101
Human magnesium deficiency 12
Human parathyroid hormone 97
Human T-lymphotropic virus 65
Humoral hypercalcemia, syndrome of 63
Hungry bone syndrome 90, 94
Hyperbilirubinemia 44
Hypercalcemia 11, 47, 61, 62, 64, 6870, 76, 136
absence of 47
acute
management of 70
treatment of 70
causes of 63, 63b, 65, 68, 70
childhood causes of 68
clinical manifestations of 61, 62t
combination of 65
diagnosis of 60
epidemiology of 61
family history of 80
immobilization-induced 67
lithium, medications-induced 67
malignancy
associated 72, 61, 81
induced 63
management of 71
manifestations of 61
medications-induced 67
mild 136
nonmalignant causes of 81
prevalence of 61
reduces 62
tamoxifen, medications-induced 67
treatment of 70
unusual causes of 69
Hypercalcemic states 10
Hypercalciuria 18, 42, 47, 55
Hyperglobulinemia 44
Hyperlipidemia 44
Hypermagnesemia 12
Hyperostosis-hyperphosphatemia syndrome 43
Hyperparathyroidism 101
Hyperparathyroidism
asymptomatic primary 83t
causes of primary 76t
diagnosis of 45
in pregnancy, primary 80
pathogenesis of primary 75
primary 3, 11, 60, 63, 75, 76, 77t
secondary 3, 89
tertiary 47
Hyperphosphatemia 43, 44, 48, 97
risk of 43
Hyperphosphatemic disorders 43
Hyperthyroidism 63, 66, 81, 101
Hypoalbuminemia 10
Hypocalcemia 92, 95, 132
causes of 89, 90t, 94, 97
clinical manifestations of 88b
diagnosis of true 95
duration of 95
long-term management of 96
prevalence of 87
with critical illness 94
with high serum parathyroid hormone 91
with hypomagnesemia 94
with low serum parathyroid hormone 89
Hypocalcemic disorders 87
Hypocalcemic rickets, types of 54t
Hypogonadism 101
Hypokalemia 55
Hypoparathyroidism 43, 89, 97b
postsurgical 89
X-linked 91
Hypophosphatemia 37, 47, 63
acute 45, 48
severe 35
chronic 36, 45, 47
drugs with 44t
evaluation of 44
mild 35
pretreatment phase of 46t
Hypophosphatemic disorders 41
Hypophosphatemic osteomalacia 56
Hypophosphatemic rickets 56t
types of 54t
X-linked 40, 53
Hypovitaminosis D 18, 25
I
Ibandronate 114, 129
Ifosfamide 44
Imatinib 44
Immobilization 81, 101
Immune system disorders 17
Inadequate sun exposure 90
Indian Primary Hyperparathyroidism Registry 82
Infantile hypercalcemia, idiopathic 68
Infantile idiopathic hypercalcemia 63
Inflammatory bowel disease 66
Inherited hyperphosphatemic disorders 43
Inorganic free phosphorus 35
Inorganic phosphorus 35
Inorganic pyrophosphatem, generating 41
Insulin
infusion 44
like growth factor 5
Intact parathyroid hormone 77
International Society for Clinical Densitometry 103
Intestinal absorption, impaired 44
Intestinal calcium absorption 12
Intestinal disease 12
Intracellular
cleavage 39
pH 44
phosphate level 35
protein, multifunctional scaffolding 37
Intrauterine growth retardation 80
Ionized calcium
changes 60
measurement of 60
Iron polymaltose infusions 44
Isoforms 40
J
Jaw, osteonecrosis of 71, 116, 125, 132
K
Kidney
disease 92
chronic 43
failure 92
ureter-urinary bladder complex 78
L
Leucocytosis, severe 44
Leukemias 65
Life-threatening hypercalcemia 72
Linear nevus sebaceous syndrome 42
Lining cells 2
Lipid parameters 113
Liposomal amphotericin B 44
Lithium 55
therapy 81
Liver disease 66, 92
Lumbar spine 139
Luteinizing hormone 93
Lymphomas 65
M
Macrophage colony-stimulating factor 64
Macrophage inflammatory protein 64
Magnesium 8, 9
deficiency 90
distribution of 11
homeostasis 12
Malabsorption 101
Malnutrition 101
McCune-Albright syndrome 42
Medullary thyroid cancer 8
Memory loss 118
MEN syndromes 82
Metabolic disorders 3
Metastatic bone disease 3
Micronutrient 12
Milk-alkali syndrome 63, 66, 81
Mineral 28
disorders 12
homeostasis 1, 8, 12
homeostatic system 8
Monoclonal gammopathy 44
Mucocutaneous candidiasis, development of 91
Musculoskeletal pain 131
Myeloma, multiple 44, 55, 61, 70, 101
Myocardial infarction 118
N
Nephrocalcinosis 55, 78
frequency of 78
Nephropathic cystinosis 42
Nephrotoxins, use of 55
Nervous system, signs and symptoms of 118
Neuroendocrine tumors 8
Neuromuscular irritability 88
Neuromuscular symptoms 79
Nonbiologic materials 7
Noninherited hyperphosphatemic disorders 43
Nonosseous tissue 35
Nonskeletal effects 19
Nonvertebral fracture 31
prevention of 31
Nutritional deficiency 90
O
Oily fish 51
Oncogenic osteomalacia 53
Organ system 62
Organism, phosphate for 1
Osseous 35
Osteitis fibrosa cystica, multiple 78f
Osteoblasts 1
Osteocalcin 143
Osteoclasts 1
Osteocyte 3, 4
function 120
Osteogenesis imperfecta 101
Osteoglophonic dysplasia 43
Osteoid 2
Osteolytic factors, local 65
Osteomalacia 11, 30, 5153, 54t, 56t
tumor-induced 42, 53
types of 54t
Osteoporosis 102, 124, 135, 142
anabolic agents for treatment of 135
causes of 100, 101t
diagnosis of 100, 107
management of 110, 120
prevention of 28
treatment threshold for 108
Osteoporotic fracture prevention 19
Osteopotegerin 5
P
Paget's disease 68
of bone 3
Pamidronate 71
Pancreatic pseudocyst 79
Pancreatitis, alcoholic acute 12
Parathyroid adenoma 75
Parathyroid glands, abnormal 81
Parathyroid hormone 5, 8, 17, 37, 38, 56, 63, 69, 90, 135, 137, 143
analogs 97, 135
combined 137
effects of 87
independent hypercalcemia 60
causes of 62
induced bone anabolic effects, duration of 136
interaction of 38f
production, authentic 65
receptor 38
related protein 63
analog 138
resistance 92
Pediatric syndromes 63
Peptic ulcer disease 79
Peptide receptor radionuclide therapy 48
Peripheral skeleton 103
PHEX gene 40, 41, 53
Phosphate
absorption 37
binders 44
deficiency rickets 53, 54
distribution 11
in gut, regulation of 36
in kidney
absorption of 37
regulation of 37
intake of 36
maintenance 11
metabolism, regulators of 40
regulation 4
therapy 47
side effects of 47
transport of 36f, 37
tubular
reabsorption of 45
resorption of 45
Phosphaturic hormone 39
Phospholipids 11
Phosphorus 8, 9, 17, 35
metabolism
disorders of 4, 11, 35
imaging 45
Pigment-epithelium derived factor 5
Plasma
phosphate 35
phosphorus 44
concentration 44
Plicamycin 72
Pluripotential mesenchymal stem cells 4f
Polydipsia 72
Polyuria 72
Postmenopausal
skeleton 143
women 120, 144
Potential therapies 140
Premenopausal women 107
Proprotein convertase enzyme 39
Protease inhibitor therapy 101
Protein 111
bound 35
nucleophosmin 76
Proton pump inhibitors 101
Proximal tubular disorder 45
Proximal tubule, apical membrane of 37
Pseudofractures 45
detect 45
Pseudohypoparathyroidism 89, 90, 9294
subtypes 93t
Pseudopseudohypoparathyroidism 93
Pyrophosphate, mineralization inhibitor 53
R
Raloxifene 113
Reaction, acute phase 130
Red blood cell 9
Renal cell carcinoma 63
Renal complications 130
Renal disease 66
Renal excretion 10, 44
Renal failure 12
Renal insufficiency 120
severe 121
Renal manifestations 76, 78
Renal phosphate
loss 52
transport, hormonal regulators of 37
Renal proximal tubular cells 37
Renal stone disease, delayed diagnosis of 78
Renal tubular acidosis 55, 55t
proximal 53
Renal tubular damage 12
Renal tubule sensitivity 62
Respiratory alkalosis 44
Rheumatoid arthritis 101
Rickets 30, 36, 51
detect signs of 45
features of 80
Risedronate 114, 129
Romosozumab 120, 135, 139
S
Salicylate poisoning 44
Salt and pepper appearance 78f
Sarcoidosis 66, 81
Sclerostin neutralizing antibodies 119
Secretory process 39
Seizure 118
Serotonin reuptake inhibitors, selective 101
Serum
alkaline phosphatase, level of 81
calcium 8, 56, 60
concentration, inadequate control of 97
restoration of normal 72
creatinine 47
parathyroid hormone 60
related protein, causes of elevated 65
suppressed 75
pH turns alkaline 60
phosphate 11, 44, 56
measurement of 43
nocturnal peaking of 44
phosphorus 81
Sjögren's syndrome 55
Skeletal deformities 76
Skeletal effects 19
Skeletal events, prevention of 61
Skeletal homeostasis 7
Skeletal integrity, maintenance of 7
Skeletal loss 100
Skeletal manifestations 77
Skeletal metastatic bone disease, evidence of 64
Skeletal tissue 1
Sodium fluoride 135
Sodium-dependent phosphate
cotransporter 52
transporter 37
Sodium-hydrogen exchanger regulatory factor 38, 38f
Solid tumors 61, 70
Stomach 10
Strontium 118
ranelate 118
Subapical endocytic vesicles 37
Systemic hormonal influences 3
T
T-cell leukemia 65
Tenofovir 44
Teriparatide 119, 136, 137
Terminal ileum 10
Tetracycline 44, 55
Thiazide 10, 44, 81
diuretics 96
Thiazolidinediones 101
Thyroid
hormone 101
stimulating hormone 93
Trabecular bone 6, 77
score 104
Trabecular plates 6
Transcellular shift 44
Transmembrane receptors, cytoplasmic domains of 37
Trimethoprim 55
Tuberculosis 81
Tumor 65
lysis syndrome 95
U
Urinary calcium excretion 68
Urinary cyclic adenosine monophosphate 92
Urinary phosphate excretion 39
Urine
calcium 47
cyclic adenosine monophosphate 63
V
Valproate 55
Venous thromboembolism 118
Vertebral fracture treatment 137
Vitamin 16, 28
A 63, 67, 70
D 8, 16, 23, 24, 24t, 28, 51, 90, 110, 111
activation, abnormal 92
active metabolite of 37
analogs, active 96
binding protein 17, 51
deficiency of 30
dependent rickets 53, 90
discovery and physiology 16
excess and toxicity 18
for bone health 30
health effects of 19
insufficiency, prevalence of 18
levels 111
metabolism 51
nutrition, borderline 29
nutritional status 76
receptor 16, 76, 77, 92
severe deficiency of 30
sources of 23
states, abnormal 91
status 17, 17t
supplementation with 31
D deficiency 18, 31, 44, 45, 52, 56t, 81, 92
hallmark of 60
rickets 56
severe 91
treating 57
D supplementation 22, 32
dose of 32
efficacy of 31
D toxicity 43
long-standing 18
D2 16, 23, 51
D3 16, 23, 51
food sources of 24t
W
Waldenström's macroglobulinemia 44
Watery diarrhea, syndrome of 68
Williams’ syndrome 63
Wilson's disease 55
X
X-chromosome 40
Z
Zoledronic acid 71, 114, 115, 129
×
Chapter Notes

Save Clear


fm1CLINICAL FOCUS SERIES: BONE AND MINERAL DISORDERS
fm2
fm3CLINICAL FOCUS SERIES: BONE AND MINERAL DISORDERS
Series Editor Romesh K Khardori MD PhD FACP FRCP(C) Professor Division of Endocrinology, Diabetes and Metabolism Department of Internal Medicine Eastern Virginia Medical School Consultant EVMS Strelitz Center for Diabetes Endocrine and Metabolic Disorders Norfolk, Virginia, USA Editor Subhash C Kukreja MD Professor of Medicine and Chief of Endocrinology, Diabetes and Metabolism University of Illinois College of Medicine Chicago, Illinois, USA Associate Editor Sanjay K Bhadada MD DM MNAMS FICP FRCPI FNAMS Professor Department of Endocrinology Postgraduate Institute of Medical Education and Research Chandigarh, India
fm4
Jaypee Brothers Medical Publishers (P) Ltd
Headquarters
Jaypee Brothers Medical Publishers (P) Ltd
4838/24, Ansari Road, Daryaganj
New Delhi 110 002, India
Phone: +91-11-43574357
Fax: +91-11-43574314
Overseas Offices
J.P. Medical Ltd
83 Victoria Street, London
SW1H 0HW (UK)
Phone: +44 20 3170 8910
Fax: +44 (0)20 3008 6180
Jaypee-Highlights Medical Publishers Inc
City of Knowledge, Bld. 235, 2nd floor, Clayton
Panama City, Panama
Phone: +1 507-301-0496
Fax: +1 507-301-0499
Jaypee Brothers Medical Publishers (P) Ltd
Bhotahity, Kathmandu, Nepal
Phone: +977-9741283608
© 2020, Jaypee Brothers Medical Publishers
The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book.
All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers.
All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book.
Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book.
This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought.
Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity. The CD/DVD-ROM (if any) provided in the sealed envelope with this book is complimentary and free of cost. Not meant for sale.
Inquiries for bulk sales may be solicited at: jaypee@jaypeebrothers.com
Clinical Focus Series
Bone and Mineral Disorders / Romesh K Khardori, Subhash C Kukreja
Cover images: Vitamin D deficiency osteomalacia. Before (left) and after (right) treatment with vitamin D. Courtesy: Dr Sudhaker Rao.
First Edition: 2020
9789352704781
Printed at
fm5Dedication
Dedicated to our students who teach
us more than we teach themfm6
fm7Contributors
SERIES EDITOR
EDITOR
ASSOCIATE EDITOR
CONTRIBUTING AUTHORS
fm9PREFACE
The new knowledge in the field of bone and mineral metabolism and bone disorders has expanded vastly in the past 25 years. Discovery of novel mechanisms involved in bone resorption through osteoclasts and bone formation through osteoblasts, has allowed the development of effective therapeutic agents for osteoporosis, resulting in reduction of fracture risk and reduced mortality. We now understand the critical role played by the osteocytes (previously thought to be inactive resting cells) in regulating calcium and phosphorus metabolism and in the regulation of bone cell functions through autocrine, paracrine and endocrine mechanisms. These observations have led to the discovery of potential anabolic therapeutic agents for osteoporosis and novel compounds for treating disorders of phosphorus metabolism. Adequate levels of various nutrients (calcium, phosphorus, vitamin D and others) are important for optimal bone health and health in general. It has been clear that deficiency of these nutrients leads to disease states. We now have a better understanding of the optimal levels of these nutrients for normal individuals or on the potential risks of excessive intake.
We are grateful to various authors for taking time out of their busy lives to assemble this monograph on current state of knowledge in the field. We know that this information could become outdated as new discoveries are made. However, we are confident that the information in this book will provide a strong basis for basic understanding of bone and mineral physiology and treatment for disease states.
Subhash C Kukreja
Sanjay K Bhadadafm10