The Aging Skeleton

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ISBN: 9780120986552 | 0120986558
Cover: Hardcover
Copyright: 7/21/1999

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The Aging Skeleton is a comprehensive and timely book on all aspects of the skeleton as it ages, including basic mechanisms and pathways as well as pathobiology. Chapters cover general aspects and models of aging, determinants and maintenance of peak bone mass, mechanisms of age-related bone loss, quantifiable manifestations of age-related bone loss, fractures, and therapeutics. Key Features * Covers all aspects of the aging skeleton in one comprehensive volume * Looks at the influence of genetics, nutrition, environment, hormones, and other factors on bone mass * Provides a thorough discussion of fractures, one of the major consequences of the aging skeleton * Reviews current therapeutic approaches and methods * Written by internationally renowned authors and edited by leaders in the field * Is the only book available on this subject

Contributors	p. xiii
Foreword	p. xvii
Preface	p. xix
General Aspects and Models of Aging
Aging through the Ages	p. 3
Evolutionary Forces and Aging	p. 4
Genetics and Longevity	p. 5
Primates	p. 6
Changing Demographics through the Ages	p. 6
Low Bone Mass in Past Populations	p. 7
Altering the Human Life Span	p. 8
Human Aging at the Millennium	p. 11
Aging Is Highly Variable	p. 11
Aging and Body Composition	p. 12
Physiological and Functional Changes	p. 12
Preventing Frailty and Promoting Successful Aging	p. 15
Population Aging	p. 15
Aging and Calcium Balance	p. 19
The Calcium Requirement	p. 20
The Calcium Economy	p. 22
Constraints of Experimental Paradigms Used to Model the Aging Skeleton	p. 27
Introduction: Bone as a Complex System	p. 27
The Aging Human: Bone Mineral Density Is Only Part of Fracture Risk	p. 28
The Aging Rat: Using Animal Models to Study Aging in Humans	p. 29
What Is an Aging Cell?	p. 31
An Alternative Approach to Cellular Aging	p. 32
Animal Models of the Aging Skeleton	p. 37
Characteristics of Human Skeletal Aging	p. 37
The Animal Model Paradox	p. 38
Characteristics of a Good Animal Model	p. 38
Why Animal Models of the Aging Skeleton Are Required	p. 39
Candidate Animal Models of Aging Bone Loss	p. 39
Other Animal Models of Bone Loss	p. 45
Large Nonrodent Animal Models of Aging Bone Loss	p. 46
Human Diseases as Models of Accelerated Aging	p. 51
The Aging Imperative	p. 51
The Mechanism of Aging	p. 51
Diseases That Can Accelerate the Aging Process	p. 53
Cellular Models of Human Aging	p. 59
Replicative Senescence	p. 59
Telomere Length	p. 62
Gene Expression	p. 64
Functional Senescence in Vitro	p. 66
Cellular Aging in Progeria and Werner Syndromes	p. 68
Determinants of Peak Bone Mass; Maintenance of Peak Bone Mass
Genetic Determinants of the Population Variance in Bone Mineral Density	p. 77
The Question	p. 77
Is "BMD" a Suitable Phenotypic End Point?	p. 78
Relative Growth in Bone Mass and Size Determines Volumetric BMD	p. 78
Polymorphisms and Growth	p. 80
Hip Axis Length and Genotypes	p. 82
Issues in Study Design That May Partly Account for Discrepant Associations between BMD and Genotypes	p. 83
Bone Loss and Genotypes	p. 84
Vagaries of the Notion of Bone "Loss"	p. 85
Calcium Absorption and Genotypes	p. 85
Biochemical Measurements of Bone Turnover and Genotypes	p. 86
BMD Responses to Intervention and Genotypes	p. 86
Fracture Rates and Genotypes	p. 86
Confounding	p. 87
The Misleading Notion of Heritability	p. 87
Genetic and Environmental Components of Variance in Areal BMD	p. 88
Nutritional Determinants of Peak Bone Mass	p. 95
Timing of Adolescent Bone Gain	p. 95
Secular Trends in Diets of Young Women	p. 95
Candidate Nutrient-Bone Relationships	p. 96
Nutrient Intake Assessments	p. 96
Relationships among Adolescent Bone Gain and Specific Nutrients	p. 96
Total Body Bone Gain and Calcium Intake by Adolescent Females during Ages 12-18	p. 97
Total Body Bone Gain and Hip Density as a Function of Sodium Intake	p. 97
Total Body Bone Gain and Hip Density as a Function of the Calcium/Protein Ratio	p. 98
Total Calories per Kilogram during Ages 12-18 and Bone Gain	p. 98
Discussion	p. 99
Other Nutrients and Adolescent Bone Gain	p. 100
Calcium Intakes, Absorbability, Retention, and Bone Accretion	p. 100
Mechanical Determinants of Peak Bone Mass	p. 105
Mechanical Mechanisms of Bone Mass Acquisition	p. 106
Clinical Studies of Accretion of Bone Mass	p. 110
Hormonal Influences on the Establishment of Peak Bone Mass	p. 115
Formation of Bone Mass	p. 115
Models Where Peak Bone Mass Is Altered	p. 116
Racial Determinants of Peak Bone Mass	p. 127
African Americans	p. 127
Asian Indians and Pakistanis	p. 131
Other Races	p. 131
Determinants of Maintenance of Bone Mass	p. 137
Premenopausal Bone Loss	p. 137
Dietary Calcium and Premenopausal Bone Loss	p. 138
Exercise, Menstrual Status, and Premenopausal Bone Mass	p. 139
Mechanisms of Age-Related Bone Loss
Cellular Mechanisms of Age-Related Bone Loss	p. 145
Bone Turnover and Aging	p. 145
Osteoblastic Cells	p. 146
Osteoclasts	p. 152
Sex Steroids, Bone, and Aging	p. 159
Menopause	p. 159
Andropause	p. 163
Adrenopause	p. 167
Parathyroid Hormone	p. 175
Parathyroid Hormone and Normal Aging	p. 175
Parathyroid Hormone and Osteoporosis	p. 177
Parathyroid Hormone and Estrogen	p. 180
Vitamin D	p. 185
Consequences of Vitamin D Deficiency	p. 186
Vitamin D Requirements in the Elderly	p. 189
Cytokines and Prostaglanding in the Aging Skeleton	p. 195
Cytokines and the Aging Skeleton	p. 195
Prostaglandins and the Aging Skeleton	p. 200
Role of Growth Hormone/Insulin-like Growth Factor Axis	p. 209
Role of GH/IGF Axis in the Regulation of Bone Formation	p. 209
Age Changes in GH Secretion: Potential Mechanisms	p. 212
Age Changes in IGF System Components: Potential Mechanisms	p. 213
Model of Age Changes in the GH/IGF Axis and the Age-Related Impairment in Bone Formation	p. 215
Other Pharmacologic Agents Influencing Bone Loss	p. 221
General Pharmacokinetic Issues	p. 221
Pharmacologic Agents	p. 222
Nutritional Mechanisms of Age-Related Bone Loss	p. 229
Introduction to Nutrient-Induced Osteopenia	p. 229
Excessive Animal Protein Intake	p. 229
Excessive Sodium Intake and Inadequate Potassium Intake	p. 230
Inadequacies of Other Nutrients	p. 230
Excessive Fluoride Ingestion	p. 231
Bone-Related Food Issues of the Elderly in Technologically Advanced Nations	p. 231
Intake Recommendations for Bone Health	p. 232
Quantifiable Manifestations of Age-Related Bone Loss
Racial/Ethnic Influences on Risk of Osteoporosis	p. 237
Factors Affecting Bone Mass	p. 238
Bone Geometry	p. 243
Ethnic Differences in Rates of Hip Fracture	p. 243
Histomorphometric Manifestations of Age-Related Bone Loss	p. 251
Bone Remodeling and Turnover	p. 251
Mechanisms of Bone Loss	p. 252
Effects of Bone Loss on Bone Structure	p. 252
Histomorphometric Assessment of Age-Related Bone Loss in Humans	p. 253
Techniques and Limitations of Bone Histomorphometry	p. 253
Histomorphometric Assessment of Bone Turnover	p. 254
Histomorphometric Assessment of Remodeling Balance	p. 254
Histomorphometric Assessment of Mineralization	p. 255
Assessment of Cancellous Bone Structure	p. 255
Age-Related Changes in Cancellous and Cortical Bone	p. 255
Age-Related Changes in Bone Turnover	p. 255
Age-Related Changes in Mineralization	p. 256
Age-Related Changes in Remodeling Balance	p. 256
Age-Related Changes in Cancellous Bone Structure	p. 257
Microfractures	p. 259
Relationship of Primary Osteoporosis to Age-Related Bone Loss	p. 259
Densitometric Manifestations in Age-Related Bone Loss	p. 263
Effect of Aging on the Vertebral Skeleton	p. 265
Effect of Aging on the Proximal Femur	p. 266
Effect of Aging on Total Skeleton Bone Mineral Density	p. 269
Effect of Age on Ultrasound Values	p. 270
Effect of Aging on Bone Mineral Density by QCT	p. 272
Biochemical Dynamics	p. 277
Biochemical Markers of Bone Formation	p. 278
Biochemical Markers of Bone Resorption	p. 281
Effects of Normal Aging on Bone Turnover	p. 284
Biochemical Dynamics of Bone Turnover in Postmenopausal and Age-Related Osteoporosis	p. 285
Biomechanical Measurements in Age-Related Bone Loss	p. 301
Biomechanical Measurements and Concepts	p. 301
Mechanical Strength of Bone Declines with Age	p. 302
Quality of Bone Tissue Deteriorates with Age	p. 304
Fracture Toughness of Human Bone Declines with Age	p. 306
Fatigue Properties of Bone Decrease with Age	p. 307
Age-Related Structural Compensations for Reduced Mechanical Strength	p. 307
Fractures: A Consequence of the Aging Skeleton
Application of Biomechanics to the Aging Human Skeleton	p. 315
Age-Related Changes in the Mechanical Properties of Bone as a Material	p. 316
Age-Related Changes in Bone Geometry	p. 318
Biomechanics of Hip Fractures	p. 320
Biomechanics of Vertebral Fractures	p. 324
What Is a Fragility Fracture?	p. 333
Trauma Categorization	p. 333
Bone Density Categorization	p. 333
Fracture Classification	p. 334
Prognostic Implications of a Fragility Fracture	p. 336
Epidemiology and Consequences of Osteoporotic Fractures	p. 339
Health Care Costs of Osteoporotic Fractures	p. 339
How Common Is Osteoporosis?	p. 339
Mortality and Morbidity	p. 341
Risk Factors for Bone Loss and Fractures	p. 342
Osteoporosis and Fragility Fractures in the Elderly	p. 349
Frequency of Osteoporosis and Low Bone Mass	p. 349
Frequency and Economic Cost of Osteoporotic Fractures	p. 351
Lifetime Risk of Fracture	p. 352
Heterogeneity in the Relationship of Different Types of Fractures to Gender, Age, and Bone Density	p. 353
Possible Causes of Heterogeneity in Age-Related Fractures	p. 354
The Aging Maxillofacial Skeleton	p. 359
Skeletal Changes from Birth to Maturity	p. 359
Skeletal Changes after Maturity Associated with Tooth Loss	p. 361
Skeletal Changes after Maturity without Tooth Loss	p. 362
Changes in the Temporomandibular Joint Associated with Aging	p. 363
Changes in Bite Force and Chewing Efficiency with Age	p. 364
Osteoporosis and Metabolic Bone Disease: Effects on the Maxilla and Mandible	p. 365
Changes in Dentition with Aging	p. 368
Fractures: Effects on Quality of Life	p. 373
Osteoporotic Fractures	p. 373
Quality of Life: A Definition	p. 374
Dimensions of Quality of Life	p. 374
Future Directions	p. 380
General Orthopedic Principles	p. 383
Fractures in the Aging Skeleton	p. 383
Guidelines for the Management of Osteoporotic Fractures	p. 384
Lower Extremity Fractures	p. 384
Upper Extremity Fractures	p. 392
Spine and Pelvis Fractures	p. 395
Future Directions in the Treatment of Osteoporotic Fractures	p. 396
Nutritional Approaches to Healing Fractures in the Elderly	p. 399
Protein and Bone Mineral Mass Acquisition	p. 399
Protein Malnutrition	p. 400
Nutritional Control of Insulin-like Growth Factor-I and Bone Homeostasis	p. 401
Outcome of Fracture of the Proximal Femur	p. 403
Analgesic Management	p. 411
Fractures and Pain Assessment	p. 411
Treatment Modalities	p. 412
Therapeutics
Complications of Joint Replacement in the Elderly	p. 421
Results of Joint Replacement	p. 421
Patient Considerations	p. 422
Surgical Considerations	p. 425
Shape and Size of an Osteoporotic Woman	p. 441
Musculoskeletal Consequences of Osteoporosis	p. 441
Hyperkyphosis and Falls	p. 445
Camouflaging Postural Disfiguration	p. 447
Exercise and the Osteoporotic Spine	p. 449
Prevention of Falls	p. 453
Epidemiology of Falls	p. 453
Etiology of Falls	p. 454
Clinical Approach	p. 457
Treatment and Prevention	p. 459
Clinical Guidelines	p. 463
The Impact of Physical Activity on Age-Related Bone Loss	p. 467
The Nature of Age-Related Bone Loss	p. 467
Skeletal Effects of Mechanical Loading	p. 468
Effects of Physical Activity on Aging Bone	p. 469
Impact of Physical Activity on Falling and Fracture	p. 474
Therapeutic Recommendations	p. 474
The Rationale for Calcium Supplementation in the Therapeutics of Age-Related Osteoporosis	p. 479
Calcium and the Aging Skeleton: Rationale for Increasing Dietary Calcium Intake	p. 479
Calcium Balance: Extracellular Space versus Whole Body	p. 479
Determinants of Gut Calcium Absorption	p. 482
Role of the Kidney in Extracellular Calcium Balance	p. 487
Clinical Data on the Effectiveness of Calcium Supplementation	p. 489
Estrogen	p. 495
Estrogen and Growth	p. 495
Premenopausal Women	p. 496
Postmenopausal Women	p. 496
Estrogen Replacement	p. 498
Fracture Outcomes	p. 499
Estrogens in Older Age	p. 501
Selective Estrogen Receptor Modulators	p. 507
Concept of a SERM	p. 507
Mechanism of Action of SERMs	p. 508
Tamoxifen	p. 512
Raloxifene	p. 514
Androgens	p. 521
Mechanisms of Androgen Action in Bone: The Androgen Receptor	p. 521
Metabolism of Androgens in Bone: Aromatase and 5[alpha]-Reductase Activities	p. 522
Effects of Androgens on the Cellular Biology of Bone	p. 522
Androgen Effects on Bone: Animal Studies	p. 523
Effects of Androgens on the Skeleton in Men	p. 525
Influence of Androgens on Bone in Women	p. 528
Androgen Therapy: Potentially Useful Androgen Effects	p. 529
Androgen Replacement in Hypogonadal Adult Men	p. 530
Androgen Therapy in Eugonadal Men	p. 532
Androgen Replacement in Adolescence	p. 532
Androgen Replacement in Aging Men	p. 533
Androgen Therapy in Secondary Forms of Metabolic Bone Disease	p. 533
Androgen Therapy in Women	p. 534
Therapy with Other Androgens	p. 535
Research Directions	p. 535
Bisphosphonates	p. 541
Chemistry and Pharmacology	p. 541
Bisphosphonates in Osteoporosis	p. 544
Antifracture Efficacy of Bisphosphonate Treatment	p. 544
Glucocorticoid-Induced Osteoporosis	p. 545
Safety and Tolerability	p. 546
Calcitonin	p. 551
Effects of Aging and Hormonal Status on Calcitonin	p. 552
Efficacy of Calcitonin in the Prevention and Treatment of Postmenopausal Osteoporosis	p. 553
Parathyroid Hormone	p. 563
Advantages of Anabolic Agents for Reversal of Osteoporosis	p. 563
Potential Mechanisms of Anabolic Action	p. 564
Animal Models of PTH Effects on Bone Metabolism	p. 565
Clinical Experience of PTH Therapy in Osteoporotic Subjects	p. 566
Analysis of Concurrent Therapies Used with PTH Protocols	p. 572
Pharmacokinetics of PTH Administration	p. 573
Immunological Responses to Exogenous PTH	p. 574
Side Effects during PTH Therapy	p. 574
Growth Hormone and Insulin-like Growth Factor I as Therapeutic Modalities for Age-Related Osteoporosis	p. 579
IGF-I and Its Regulatory Components	p. 580
IGF-I and Age-Related Osteoporosis	p. 580
GH or IGF-I as Therapeutic Options for Osteoporosis	p. 582
GH/IGF-I as Short-Term Treatment of Catabolic States Associated with Osteoporosis	p. 583
Disadvantages of rhGH or rhIGF-I Treatment for Age-Related Osteoporosis	p. 584
Fluoride Therapy of Established Osteoporosis	p. 587
Anabolic Actions of Fluoride	p. 587
Fluoride Pharmacokinetics	p. 591
Therapeutic Serum Level of Fluoride	p. 593
Skeletal Response to Fluoride Therapy	p. 595
Side Effects of Fluoride Therapy	p. 599
Efficacy of Fluoride Therapy	p. 601
Strategies to Improve Fluoride Therapy	p. 604
Vitamin D	p. 613
Evidence for Altered Vitamin D Metabolism in Aging	p. 613
Vitamin D Efficacy in the Treatment of Osteoporosis	p. 617
Index	p. 623
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The Aging Skeleton

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