Bisphosphonates in Bone Disease : From the Laboratory to the Patient

by Fleisch

• ISBN13: 9780122603709
• ISBN10: 0122603702
• Edition: 4th
• Format: Paperback
• Copyright: 2000-03-24
• Publisher: Elsevier Science & Technology

Summary

This book is an essential handbook on bisphosphonates, the most widely used new class of drugs for osteoporosis therapy. It reviews basic physiology in addition to the indications and adverse reactions of these drugs. Bisphosphonates in Bone Disease, 4E, discusses the compounds' chemistry, mechanisms of action, and animal toxicology before presenting a clinical picture of the diseases treated by bisphosphonates. The book provides a table listing the trade names of the commercially available bisphosphonates, registered indications, and the available forms for various countries. The revised Fourth Edition contains approximately 50% new material, including information on all of the latest drugs.

Table of Contents

Preface	xi
Bone and mineral metabolism	1	(26)
Bone physiology	1	(26)
Morphology	1	(2)
Composition of bone	3	(1)
Mineral	3	(1)
Organic matrix	4	(1)
Bone cells	5	(1)
Osteoblasts	5	(2)
Lining cells	7	(1)
Osteocytes	7	(1)
Osteoclasts	8	(4)
Other cells	12	(1)
Modeling and remodeling	12	(4)
Calcium homeostasis	16	(3)
Bone as an organ	19	(2)
Assessment of bone turnover	21	(1)
Recommended selected reading	21	(6)
Bisphosphonates---preclinical	27	(40)
Background to the pharmacological development	27	(3)
Recommended selected reading	29	(1)
Chemistry	30	(4)
Recommended selected reading	33	(1)
Actions	34	(22)
Physicochemical effects	34	(1)
Biological effects	34	(1)
Inhibition of bone resorption	34	(1)
In vitro	34	(2)
Intact animals	36	(3)
Animals with experimentally increased bone resorption	39	(1)
Relative activity of bisphosphonates	40	(1)
Mechanisms of action	41	(2)
Direct effect	43	(2)
Indirect effect through other cells	45	(3)
Inhibition of mineralization	48	(1)
Ectopic mineralization	48	(1)
Normal mineralization	49	(1)
Mechanisms of action in the inhibition of calcification	50	(1)
Other effects	50	(1)
Recommended selected reading	51	(5)
Pharmacokinetics	56	(7)
Intestinal absorption	56	(1)
Distribution	57	(2)
Renal clearance	59	(1)
Other modes of application	60	(1)
Recommended selected reading	60	(3)
Animal toxicology	63	(4)
Acute toxicity	63	(1)
Nonacute toxicity	63	(1)
Alendronate	64	(1)
Clodronate	64	(1)
Etidronate	65	(1)
Pamidronate	65	(1)
Other bisphosphonates	65	(1)
Recommended selected reading	66	(1)
Bisphosphonates---clinical	67	(115)
Introduction	67	(1)
Paget's disease	68	(20)
Definition	68	(1)
Epidemiology	68	(1)
Pathophysiology	68	(1)
Clinical manifestations	69	(1)
Signs and symptoms	69	(1)
Laboratory	70	(1)
Diagnosis	71	(1)
Follow-up of progression of the disease	71	(1)
Treatment with drugs other than bisphosphonates	72	(1)
Treatment with bisphosphonates	72	(1)
Preclinical studies	72	(1)
Clinical studies	73	(1)
Effects	73	(3)
Treatment regimens	76	(2)
Alendronate	78	(1)
Clodronate	79	(1)
Etidronate	79	(1)
Olpadronate	80	(1)
Pamidronate	80	(1)
Risedronate	81	(1)
Tiludronate	82	(1)
Other bisphosphonates	83	(1)
Conclusion	83	(1)
Recommended selected reading	84	(4)
Osteolytic tumor-induced bone disease	88	(30)
Definition	88	(1)
Pathophysiology	88	(1)
Local bone destruction	88	(2)
Generalized bone destruction	90	(1)
Mechanisms of hypercalcemia	90	(2)
Clinical manifestations	92	(1)
Signs and symptoms	92	(1)
Laboratory	93	(1)
Follow-up of progression of the disease	94	(1)
Treatment with drugs other than bisphosphonates	94	(1)
Treatment with bisphosphonates	95	(1)
Preclinical studies	95	(3)
Clinical studies	98	(1)
Effects	98	(1)
Hypercalcemia	98	(1)
Urinary parameters	99	(2)
Other effects	101	(3)
Treatment regimens	104	(1)
Clodronate	104	(1)
Etidronate	105	(1)
Ibandronate	106	(1)
Pamidronate	106	(2)
Other bisphosphonates	108	(1)
Comparison of the various bisphosphonates	109	(1)
Conclusion	110	(1)
Recommended selected reading	111	(7)
Non-tumor-induced hypercalcemia	118	(5)
Definition	118	(1)
Pathophysiology	118	(1)
Clinical manifestations	118	(1)
Treatment with drugs other than bisphosphonates	119	(1)
Treatment with bisphosphonates	119	(1)
Preclinical studies	119	(1)
Clinical studies	119	(1)
Effects	120	(1)
Treatment regimens	120	(1)
Conclusion	121	(1)
Recommended selected reading	121	(2)
Osteoporosis	123	(37)
Definition	123	(1)
Epidemiology	123	(1)
Pathophysiology	124	(4)
Clinical manifestations	128	(1)
Signs and symptoms	128	(1)
Laboratory	128	(1)
Diagnosis	129	(1)
Follow-up of progression of the disease	129	(1)
Treatment with drugs other than bisphosphonates	130	(3)
Treatment with bisphosphonates	133	(1)
Preclinical studies	133	(3)
Clinical studies	136	(1)
Effects	136	(1)
Effect on bone mineral density	137	(6)
Effect on bone turnover	143	(1)
Effect on fractures	144	(4)
Effects after discontinuation of the drug	148	(1)
Various other effects	148	(1)
Treatment regimens	149	(1)
Alendronate	149	(1)
Clodronate	150	(1)
Etidronate	150	(1)
Ibandronate	151	(1)
Pamidronate	151	(1)
Risedronate	151	(1)
Tiludronate	152	(1)
Conclusion	152	(1)
Recommended selected reading	152	(8)
Heterotopic calcification and ossification	160	(6)
Definition	160	(1)
Pathophysiology	160	(1)
Clinical manifestations	160	(1)
Treatment with drugs other than bisphosphonates	161	(1)
Treatment with bisphosphonates	161	(1)
Preclinical studies	161	(1)
Clinical studies	161	(1)
Heterotopic calcification	161	(1)
Soft tissue calcification	161	(1)
Urolithiasis	162	(1)
Dental calculus	162	(1)
Heterotopic ossification	162	(1)
Fibrodysplasia (previously myositis) ossificans progressiva	162	(1)
Other heterotopic ossifications	163	(1)
Conclusion	164	(1)
Recommended selected reading	164	(2)
Other diseases	166	(2)
Diseases with enhanced resorption	166	(1)
Osteogenesis imperfecta	166	(1)
Other diseases	166	(1)
Recommended selected reading	167	(1)
Adverse events	168	(10)
Bisphosphonates in general	168	(1)
Individual bisphosphonates	169	(1)
Alendronate	169	(1)
Clodronate	170	(1)
Etidronate	171	(2)
Pamidronate	173	(1)
Risedronate	174	(1)
Tilidronate	175	(1)
Other bisphosphonates	175	(1)
Recommended selected reading	175	(3)
Contraindications	178	(3)
Recommended selected reading	180	(1)
Future prospects	181	(1)
Commercially available bisphosphonates	182	(25)
Index	207