Genetics of Bone Biology and Skeletal Disease, Second Edition, is aimed at students of bone biology and genetics and includes general introductory chapters on bone biology and genetics. More specific disease orientated chapters comprehensively summarize the clinical, genetic, molecular, animal model, molecular pathology, diagnostic, counseling, and treatment aspects of each disorder. The book is organized into five sections that each emphasize a particular theme, general background to bone biology, general background to genetics and epigenetics, disorders of bone and joint, parathyroid and related disorders, and vitamin D and renal disorders.
The first section is specifically devoted to providing an overview of bone biology and structure, joint and cartilage biology, principles of endocrine regulation of bone, and the role of neuronal regulation and energy homeostasis. The second section reviews the principles and progress of medical genetics and epigenetics related to bone disease, including genome-wide association studies (GWAS), genomic profiling, copy number variation, prospects of gene therapy, pharmacogenomics, genetic testing and counseling, as well as the generation and utilizing of mouse models.
The third section details advances in the genetics and molecular biology of bone and joint diseases, both monogenic and polygenic, as well as skeletal dysplasias, and rarer bone disorders. The fourth section highlights the central role of the parathyroids in calcium and skeletal homeostasis by reviewing the molecular genetics of: hyperparathyroidism, hypoparathyrodism, endocrine neoplasias, and disorders of the PTH and calcium-sensing receptors. The fifth section details molecular and cellular advances across associated renal disorders such as vitamin D and rickets.
1. Chapter 1: Introduction to Genetics of Skeletal and Mineral Metabolic Diseases - p. xviii 2. Chapter 2: Epigenetics - p. 23 3. Chapter 3: Genome-Wide Association Studies - p. 32 4. Chapter 4: Copy Number Variation - p. 41 5. Chapter 5: Genomic Profiling in Bone - p. 54 6. Chapter 6: Functional Genomics - p. 75 7. Chapter 7: Mouse Models: Approaches to Generate In Vivo Models for Hereditary Disorders of Mineral and Skeletal Homeostasis - p. 88 8. Chapter 8: Prospects of Gene Therapy for Skeletal Diseases - p. 118 9. Chapter 9: Pharmacogenetics and Pharmacogenomics of Osteoporosis: Personalized Medicine Outlook - p. 137 10. Chapter 10: Genetic Testing and Counseling - p. 157 11. Section 2: General Background to Bone Biology - p. 169 12. Chapter 11: Biology of Bone and Cartilage - p. 169 13. Chapter 12: Overview of Bone Structure and Strength - p. 195 14. Chapter 13: Overview of Joint and Cartilage Biology - p. 208 15. Chapter 14: Osteocyte Biology - p. 225 16. Chapter 15: Skeletal Stem Cells/Bone Marrow Stromal Cells - p. 240 17. Chapter 16: Osteoimmunology - p. 260 18. Chapter 17: Integrating Endocrine and Paracrine Influences on Bone; Lessons From Parathyroid Hormone and Parathyroid Hormone-Related Protein - p. 282 19. Chapter 18: Genetics of Bone Fat and Energy Regulation - p. 299 20. Chapter 19: The Cross Talk Between the Central Nervous System, Bone, and Energy Metabolism - p. 315 21. Chapter 20: Fetal Control of Calcium and Phosphate Homeostasis - p. 328 22. Chapter 21: Control of Mineral and Skeletal Homeostasis During Pregnancy and Lactation - p. 347 23. Section 3: Disorders of Bone and Joint - p. 373 24. Chapter 22: Osteoporosis Genes Identified by Genome-Wide Association Studies - p. 373 25. Chapter 23: Osteogenesis Imperfecta - p. 395 26. Chapter 24: Osteoarthritis: Genetic Studies of Monogenic and Complex Forms - p. 420 27. Chapter 25: Genetics of Paget’s Disease of Bone - p. 438 28. Chapter 26: Mendelian Disorders of RANKL/OPG/RANK/NF-κB Signaling - p. 452 29. Chapter 27: Skeletal Dysplasias - p. 468 30. Chapter 28: Hypophosphatasia and How Alkaline Phosphatase Promotes Mineralization - p. 480 31. Chapter 29: Sclerosing Bone Disorders - p. 505 32. Chapter 30: Fibrodysplasia (Myositis) Ossificans Progressiva - p. 521 33. Chapter 31: Thyroid Hormone in Bone and Joint Disorders - p. 545 34. Chapter 32: Disorders and Mechanisms of Ectopic Calcification - p. 569 35. Section 4: Parathyroid and Related Disorders - p. 595 36. Chapter 33: Hyperparathyroidism - p. 595 37. Chapter 34: Hypoparathyroidism - p. 615 38. Chapter 35: Gsα, Pseudohypoparathyroidism, Fibrous Dysplasia, and McCune–Albright Syndrome - p. 636 39. Chapter 36: Genetic Disorders Caused by Mutations in the PTH/PTHrP Receptor, its Ligands, and Downstream Effector Molecules - p. 653 40. Chapter 37: Genetically Determined Disorders of Extracellular Calcium (Ca2+o) Sensing and Ca2+o Homeostasis - p. 674 41. Chapter 38: Multiple Endocrine Neoplasia Syndromes - p. 697 42. Section 5: Vitamin D and Renal Disorders - p. 732 43. Chapter 39: Genetic Disorders Of Vitamin D Synthesis and Action - p. 732 44. Chapter 40: Heritable Renal Phosphate Wasting Disorders - p. 759 45. Chapter 41: Renal Fanconi Syndrome, Dent Disease, and Bartter Syndrome - p. 782 46. Chapter 42: Inherited Magnesium Disorders - p. 799 47. Chapter 43: Genetic Hypercalciuria: A Major Risk Factor in Kidney Stones - p. 817 48. Index - p. 839
Genetics of Bone Biology and Skeletal Disease, Second Edition, is aimed at students of bone biology and genetics and includes general introductory chapters on bone biology and genetics. More specific disease orientated chapters comprehensively summarize the clinical, genetic, molecular, animal model, molecular pathology, diagnostic, counseling, and treatment aspects of each disorder. The book is organized into five sections that each emphasize a particular theme, general background to bone biology, general background to genetics and epigenetics, disorders of bone and joint, parathyroid and related disorders, and vitamin D and renal disorders.
The first section is specifically devoted to providing an overview of bone biology and structure, joint and cartilage biology, principles of endocrine regulation of bone, and the role of neuronal regulation and energy homeostasis. The second section reviews the principles and progress of medical genetics and epigenetics related to bone disease, including genome-wide association studies (GWAS), genomic profiling, copy number variation, prospects of gene therapy, pharmacogenomics, genetic testing and counseling, as well as the generation and utilizing of mouse models.
The third section details advances in the genetics and molecular biology of bone and joint diseases, both monogenic and polygenic, as well as skeletal dysplasias, and rarer bone disorders. The fourth section highlights the central role of the parathyroids in calcium and skeletal homeostasis by reviewing the molecular genetics of: hyperparathyroidism, hypoparathyrodism, endocrine neoplasias, and disorders of the PTH and calcium-sensing receptors. The fifth section details molecular and cellular advances across associated renal disorders such as vitamin D and rickets.
1. Chapter 1: Introduction to Genetics of Skeletal and Mineral Metabolic Diseases - p. xviii 2. Chapter 2: Epigenetics - p. 23 3. Chapter 3: Genome-Wide Association Studies - p. 32 4. Chapter 4: Copy Number Variation - p. 41 5. Chapter 5: Genomic Profiling in Bone - p. 54 6. Chapter 6: Functional Genomics - p. 75 7. Chapter 7: Mouse Models: Approaches to Generate In Vivo Models for Hereditary Disorders of Mineral and Skeletal Homeostasis - p. 88 8. Chapter 8: Prospects of Gene Therapy for Skeletal Diseases - p. 118 9. Chapter 9: Pharmacogenetics and Pharmacogenomics of Osteoporosis: Personalized Medicine Outlook - p. 137 10. Chapter 10: Genetic Testing and Counseling - p. 157 11. Section 2: General Background to Bone Biology - p. 169 12. Chapter 11: Biology of Bone and Cartilage - p. 169 13. Chapter 12: Overview of Bone Structure and Strength - p. 195 14. Chapter 13: Overview of Joint and Cartilage Biology - p. 208 15. Chapter 14: Osteocyte Biology - p. 225 16. Chapter 15: Skeletal Stem Cells/Bone Marrow Stromal Cells - p. 240 17. Chapter 16: Osteoimmunology - p. 260 18. Chapter 17: Integrating Endocrine and Paracrine Influences on Bone; Lessons From Parathyroid Hormone and Parathyroid Hormone-Related Protein - p. 282 19. Chapter 18: Genetics of Bone Fat and Energy Regulation - p. 299 20. Chapter 19: The Cross Talk Between the Central Nervous System, Bone, and Energy Metabolism - p. 315 21. Chapter 20: Fetal Control of Calcium and Phosphate Homeostasis - p. 328 22. Chapter 21: Control of Mineral and Skeletal Homeostasis During Pregnancy and Lactation - p. 347 23. Section 3: Disorders of Bone and Joint - p. 373 24. Chapter 22: Osteoporosis Genes Identified by Genome-Wide Association Studies - p. 373 25. Chapter 23: Osteogenesis Imperfecta - p. 395 26. Chapter 24: Osteoarthritis: Genetic Studies of Monogenic and Complex Forms - p. 420 27. Chapter 25: Genetics of Paget’s Disease of Bone - p. 438 28. Chapter 26: Mendelian Disorders of RANKL/OPG/RANK/NF-κB Signaling - p. 452 29. Chapter 27: Skeletal Dysplasias - p. 468 30. Chapter 28: Hypophosphatasia and How Alkaline Phosphatase Promotes Mineralization - p. 480 31. Chapter 29: Sclerosing Bone Disorders - p. 505 32. Chapter 30: Fibrodysplasia (Myositis) Ossificans Progressiva - p. 521 33. Chapter 31: Thyroid Hormone in Bone and Joint Disorders - p. 545 34. Chapter 32: Disorders and Mechanisms of Ectopic Calcification - p. 569 35. Section 4: Parathyroid and Related Disorders - p. 595 36. Chapter 33: Hyperparathyroidism - p. 595 37. Chapter 34: Hypoparathyroidism - p. 615 38. Chapter 35: Gsα, Pseudohypoparathyroidism, Fibrous Dysplasia, and McCune–Albright Syndrome - p. 636 39. Chapter 36: Genetic Disorders Caused by Mutations in the PTH/PTHrP Receptor, its Ligands, and Downstream Effector Molecules - p. 653 40. Chapter 37: Genetically Determined Disorders of Extracellular Calcium (Ca2+o) Sensing and Ca2+o Homeostasis - p. 674 41. Chapter 38: Multiple Endocrine Neoplasia Syndromes - p. 697 42. Section 5: Vitamin D and Renal Disorders - p. 732 43. Chapter 39: Genetic Disorders Of Vitamin D Synthesis and Action - p. 732 44. Chapter 40: Heritable Renal Phosphate Wasting Disorders - p. 759 45. Chapter 41: Renal Fanconi Syndrome, Dent Disease, and Bartter Syndrome - p. 782 46. Chapter 42: Inherited Magnesium Disorders - p. 799 47. Chapter 43: Genetic Hypercalciuria: A Major Risk Factor in Kidney Stones - p. 817 48. Index - p. 839
