The Aging Skeleton

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  • Edition: 1st
  • Format: Hardcover
  • Copyright: 1999-07-21
  • Publisher: Elsevier Science
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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

Table of Contents

Contributorsp. xiii
Forewordp. xvii
Prefacep. xix
General Aspects and Models of Aging
Aging through the Agesp. 3
Evolutionary Forces and Agingp. 4
Genetics and Longevityp. 5
Primatesp. 6
Changing Demographics through the Agesp. 6
Low Bone Mass in Past Populationsp. 7
Altering the Human Life Spanp. 8
Human Aging at the Millenniump. 11
Aging Is Highly Variablep. 11
Aging and Body Compositionp. 12
Physiological and Functional Changesp. 12
Preventing Frailty and Promoting Successful Agingp. 15
Population Agingp. 15
Aging and Calcium Balancep. 19
The Calcium Requirementp. 20
The Calcium Economyp. 22
Constraints of Experimental Paradigms Used to Model the Aging Skeletonp. 27
Introduction: Bone as a Complex Systemp. 27
The Aging Human: Bone Mineral Density Is Only Part of Fracture Riskp. 28
The Aging Rat: Using Animal Models to Study Aging in Humansp. 29
What Is an Aging Cell?p. 31
An Alternative Approach to Cellular Agingp. 32
Animal Models of the Aging Skeletonp. 37
Characteristics of Human Skeletal Agingp. 37
The Animal Model Paradoxp. 38
Characteristics of a Good Animal Modelp. 38
Why Animal Models of the Aging Skeleton Are Requiredp. 39
Candidate Animal Models of Aging Bone Lossp. 39
Other Animal Models of Bone Lossp. 45
Large Nonrodent Animal Models of Aging Bone Lossp. 46
Human Diseases as Models of Accelerated Agingp. 51
The Aging Imperativep. 51
The Mechanism of Agingp. 51
Diseases That Can Accelerate the Aging Processp. 53
Cellular Models of Human Agingp. 59
Replicative Senescencep. 59
Telomere Lengthp. 62
Gene Expressionp. 64
Functional Senescence in Vitrop. 66
Cellular Aging in Progeria and Werner Syndromesp. 68
Determinants of Peak Bone Mass; Maintenance of Peak Bone Mass
Genetic Determinants of the Population Variance in Bone Mineral Densityp. 77
The Questionp. 77
Is "BMD" a Suitable Phenotypic End Point?p. 78
Relative Growth in Bone Mass and Size Determines Volumetric BMDp. 78
Polymorphisms and Growthp. 80
Hip Axis Length and Genotypesp. 82
Issues in Study Design That May Partly Account for Discrepant Associations between BMD and Genotypesp. 83
Bone Loss and Genotypesp. 84
Vagaries of the Notion of Bone "Loss"p. 85
Calcium Absorption and Genotypesp. 85
Biochemical Measurements of Bone Turnover and Genotypesp. 86
BMD Responses to Intervention and Genotypesp. 86
Fracture Rates and Genotypesp. 86
Confoundingp. 87
The Misleading Notion of Heritabilityp. 87
Genetic and Environmental Components of Variance in Areal BMDp. 88
Nutritional Determinants of Peak Bone Massp. 95
Timing of Adolescent Bone Gainp. 95
Secular Trends in Diets of Young Womenp. 95
Candidate Nutrient-Bone Relationshipsp. 96
Nutrient Intake Assessmentsp. 96
Relationships among Adolescent Bone Gain and Specific Nutrientsp. 96
Total Body Bone Gain and Calcium Intake by Adolescent Females during Ages 12-18p. 97
Total Body Bone Gain and Hip Density as a Function of Sodium Intakep. 97
Total Body Bone Gain and Hip Density as a Function of the Calcium/Protein Ratiop. 98
Total Calories per Kilogram during Ages 12-18 and Bone Gainp. 98
Discussionp. 99
Other Nutrients and Adolescent Bone Gainp. 100
Calcium Intakes, Absorbability, Retention, and Bone Accretionp. 100
Mechanical Determinants of Peak Bone Massp. 105
Mechanical Mechanisms of Bone Mass Acquisitionp. 106
Clinical Studies of Accretion of Bone Massp. 110
Hormonal Influences on the Establishment of Peak Bone Massp. 115
Formation of Bone Massp. 115
Models Where Peak Bone Mass Is Alteredp. 116
Racial Determinants of Peak Bone Massp. 127
African Americansp. 127
Asian Indians and Pakistanisp. 131
Other Racesp. 131
Determinants of Maintenance of Bone Massp. 137
Premenopausal Bone Lossp. 137
Dietary Calcium and Premenopausal Bone Lossp. 138
Exercise, Menstrual Status, and Premenopausal Bone Massp. 139
Mechanisms of Age-Related Bone Loss
Cellular Mechanisms of Age-Related Bone Lossp. 145
Bone Turnover and Agingp. 145
Osteoblastic Cellsp. 146
Osteoclastsp. 152
Sex Steroids, Bone, and Agingp. 159
Menopausep. 159
Andropausep. 163
Adrenopausep. 167
Parathyroid Hormonep. 175
Parathyroid Hormone and Normal Agingp. 175
Parathyroid Hormone and Osteoporosisp. 177
Parathyroid Hormone and Estrogenp. 180
Vitamin Dp. 185
Consequences of Vitamin D Deficiencyp. 186
Vitamin D Requirements in the Elderlyp. 189
Cytokines and Prostaglanding in the Aging Skeletonp. 195
Cytokines and the Aging Skeletonp. 195
Prostaglandins and the Aging Skeletonp. 200
Role of Growth Hormone/Insulin-like Growth Factor Axisp. 209
Role of GH/IGF Axis in the Regulation of Bone Formationp. 209
Age Changes in GH Secretion: Potential Mechanismsp. 212
Age Changes in IGF System Components: Potential Mechanismsp. 213
Model of Age Changes in the GH/IGF Axis and the Age-Related Impairment in Bone Formationp. 215
Other Pharmacologic Agents Influencing Bone Lossp. 221
General Pharmacokinetic Issuesp. 221
Pharmacologic Agentsp. 222
Nutritional Mechanisms of Age-Related Bone Lossp. 229
Introduction to Nutrient-Induced Osteopeniap. 229
Excessive Animal Protein Intakep. 229
Excessive Sodium Intake and Inadequate Potassium Intakep. 230
Inadequacies of Other Nutrientsp. 230
Excessive Fluoride Ingestionp. 231
Bone-Related Food Issues of the Elderly in Technologically Advanced Nationsp. 231
Intake Recommendations for Bone Healthp. 232
Quantifiable Manifestations of Age-Related Bone Loss
Racial/Ethnic Influences on Risk of Osteoporosisp. 237
Factors Affecting Bone Massp. 238
Bone Geometryp. 243
Ethnic Differences in Rates of Hip Fracturep. 243
Histomorphometric Manifestations of Age-Related Bone Lossp. 251
Bone Remodeling and Turnoverp. 251
Mechanisms of Bone Lossp. 252
Effects of Bone Loss on Bone Structurep. 252
Histomorphometric Assessment of Age-Related Bone Loss in Humansp. 253
Techniques and Limitations of Bone Histomorphometryp. 253
Histomorphometric Assessment of Bone Turnoverp. 254
Histomorphometric Assessment of Remodeling Balancep. 254
Histomorphometric Assessment of Mineralizationp. 255
Assessment of Cancellous Bone Structurep. 255
Age-Related Changes in Cancellous and Cortical Bonep. 255
Age-Related Changes in Bone Turnoverp. 255
Age-Related Changes in Mineralizationp. 256
Age-Related Changes in Remodeling Balancep. 256
Age-Related Changes in Cancellous Bone Structurep. 257
Microfracturesp. 259
Relationship of Primary Osteoporosis to Age-Related Bone Lossp. 259
Densitometric Manifestations in Age-Related Bone Lossp. 263
Effect of Aging on the Vertebral Skeletonp. 265
Effect of Aging on the Proximal Femurp. 266
Effect of Aging on Total Skeleton Bone Mineral Densityp. 269
Effect of Age on Ultrasound Valuesp. 270
Effect of Aging on Bone Mineral Density by QCTp. 272
Biochemical Dynamicsp. 277
Biochemical Markers of Bone Formationp. 278
Biochemical Markers of Bone Resorptionp. 281
Effects of Normal Aging on Bone Turnoverp. 284
Biochemical Dynamics of Bone Turnover in Postmenopausal and Age-Related Osteoporosisp. 285
Biomechanical Measurements in Age-Related Bone Lossp. 301
Biomechanical Measurements and Conceptsp. 301
Mechanical Strength of Bone Declines with Agep. 302
Quality of Bone Tissue Deteriorates with Agep. 304
Fracture Toughness of Human Bone Declines with Agep. 306
Fatigue Properties of Bone Decrease with Agep. 307
Age-Related Structural Compensations for Reduced Mechanical Strengthp. 307
Fractures: A Consequence of the Aging Skeleton
Application of Biomechanics to the Aging Human Skeletonp. 315
Age-Related Changes in the Mechanical Properties of Bone as a Materialp. 316
Age-Related Changes in Bone Geometryp. 318
Biomechanics of Hip Fracturesp. 320
Biomechanics of Vertebral Fracturesp. 324
What Is a Fragility Fracture?p. 333
Trauma Categorizationp. 333
Bone Density Categorizationp. 333
Fracture Classificationp. 334
Prognostic Implications of a Fragility Fracturep. 336
Epidemiology and Consequences of Osteoporotic Fracturesp. 339
Health Care Costs of Osteoporotic Fracturesp. 339
How Common Is Osteoporosis?p. 339
Mortality and Morbidityp. 341
Risk Factors for Bone Loss and Fracturesp. 342
Osteoporosis and Fragility Fractures in the Elderlyp. 349
Frequency of Osteoporosis and Low Bone Massp. 349
Frequency and Economic Cost of Osteoporotic Fracturesp. 351
Lifetime Risk of Fracturep. 352
Heterogeneity in the Relationship of Different Types of Fractures to Gender, Age, and Bone Densityp. 353
Possible Causes of Heterogeneity in Age-Related Fracturesp. 354
The Aging Maxillofacial Skeletonp. 359
Skeletal Changes from Birth to Maturityp. 359
Skeletal Changes after Maturity Associated with Tooth Lossp. 361
Skeletal Changes after Maturity without Tooth Lossp. 362
Changes in the Temporomandibular Joint Associated with Agingp. 363
Changes in Bite Force and Chewing Efficiency with Agep. 364
Osteoporosis and Metabolic Bone Disease: Effects on the Maxilla and Mandiblep. 365
Changes in Dentition with Agingp. 368
Fractures: Effects on Quality of Lifep. 373
Osteoporotic Fracturesp. 373
Quality of Life: A Definitionp. 374
Dimensions of Quality of Lifep. 374
Future Directionsp. 380
General Orthopedic Principlesp. 383
Fractures in the Aging Skeletonp. 383
Guidelines for the Management of Osteoporotic Fracturesp. 384
Lower Extremity Fracturesp. 384
Upper Extremity Fracturesp. 392
Spine and Pelvis Fracturesp. 395
Future Directions in the Treatment of Osteoporotic Fracturesp. 396
Nutritional Approaches to Healing Fractures in the Elderlyp. 399
Protein and Bone Mineral Mass Acquisitionp. 399
Protein Malnutritionp. 400
Nutritional Control of Insulin-like Growth Factor-I and Bone Homeostasisp. 401
Outcome of Fracture of the Proximal Femurp. 403
Analgesic Managementp. 411
Fractures and Pain Assessmentp. 411
Treatment Modalitiesp. 412
Complications of Joint Replacement in the Elderlyp. 421
Results of Joint Replacementp. 421
Patient Considerationsp. 422
Surgical Considerationsp. 425
Shape and Size of an Osteoporotic Womanp. 441
Musculoskeletal Consequences of Osteoporosisp. 441
Hyperkyphosis and Fallsp. 445
Camouflaging Postural Disfigurationp. 447
Exercise and the Osteoporotic Spinep. 449
Prevention of Fallsp. 453
Epidemiology of Fallsp. 453
Etiology of Fallsp. 454
Clinical Approachp. 457
Treatment and Preventionp. 459
Clinical Guidelinesp. 463
The Impact of Physical Activity on Age-Related Bone Lossp. 467
The Nature of Age-Related Bone Lossp. 467
Skeletal Effects of Mechanical Loadingp. 468
Effects of Physical Activity on Aging Bonep. 469
Impact of Physical Activity on Falling and Fracturep. 474
Therapeutic Recommendationsp. 474
The Rationale for Calcium Supplementation in the Therapeutics of Age-Related Osteoporosisp. 479
Calcium and the Aging Skeleton: Rationale for Increasing Dietary Calcium Intakep. 479
Calcium Balance: Extracellular Space versus Whole Bodyp. 479
Determinants of Gut Calcium Absorptionp. 482
Role of the Kidney in Extracellular Calcium Balancep. 487
Clinical Data on the Effectiveness of Calcium Supplementationp. 489
Estrogenp. 495
Estrogen and Growthp. 495
Premenopausal Womenp. 496
Postmenopausal Womenp. 496
Estrogen Replacementp. 498
Fracture Outcomesp. 499
Estrogens in Older Agep. 501
Selective Estrogen Receptor Modulatorsp. 507
Concept of a SERMp. 507
Mechanism of Action of SERMsp. 508
Tamoxifenp. 512
Raloxifenep. 514
Androgensp. 521
Mechanisms of Androgen Action in Bone: The Androgen Receptorp. 521
Metabolism of Androgens in Bone: Aromatase and 5[alpha]-Reductase Activitiesp. 522
Effects of Androgens on the Cellular Biology of Bonep. 522
Androgen Effects on Bone: Animal Studiesp. 523
Effects of Androgens on the Skeleton in Menp. 525
Influence of Androgens on Bone in Womenp. 528
Androgen Therapy: Potentially Useful Androgen Effectsp. 529
Androgen Replacement in Hypogonadal Adult Menp. 530
Androgen Therapy in Eugonadal Menp. 532
Androgen Replacement in Adolescencep. 532
Androgen Replacement in Aging Menp. 533
Androgen Therapy in Secondary Forms of Metabolic Bone Diseasep. 533
Androgen Therapy in Womenp. 534
Therapy with Other Androgensp. 535
Research Directionsp. 535
Bisphosphonatesp. 541
Chemistry and Pharmacologyp. 541
Bisphosphonates in Osteoporosisp. 544
Antifracture Efficacy of Bisphosphonate Treatmentp. 544
Glucocorticoid-Induced Osteoporosisp. 545
Safety and Tolerabilityp. 546
Calcitoninp. 551
Effects of Aging and Hormonal Status on Calcitoninp. 552
Efficacy of Calcitonin in the Prevention and Treatment of Postmenopausal Osteoporosisp. 553
Parathyroid Hormonep. 563
Advantages of Anabolic Agents for Reversal of Osteoporosisp. 563
Potential Mechanisms of Anabolic Actionp. 564
Animal Models of PTH Effects on Bone Metabolismp. 565
Clinical Experience of PTH Therapy in Osteoporotic Subjectsp. 566
Analysis of Concurrent Therapies Used with PTH Protocolsp. 572
Pharmacokinetics of PTH Administrationp. 573
Immunological Responses to Exogenous PTHp. 574
Side Effects during PTH Therapyp. 574
Growth Hormone and Insulin-like Growth Factor I as Therapeutic Modalities for Age-Related Osteoporosisp. 579
IGF-I and Its Regulatory Componentsp. 580
IGF-I and Age-Related Osteoporosisp. 580
GH or IGF-I as Therapeutic Options for Osteoporosisp. 582
GH/IGF-I as Short-Term Treatment of Catabolic States Associated with Osteoporosisp. 583
Disadvantages of rhGH or rhIGF-I Treatment for Age-Related Osteoporosisp. 584
Fluoride Therapy of Established Osteoporosisp. 587
Anabolic Actions of Fluoridep. 587
Fluoride Pharmacokineticsp. 591
Therapeutic Serum Level of Fluoridep. 593
Skeletal Response to Fluoride Therapyp. 595
Side Effects of Fluoride Therapyp. 599
Efficacy of Fluoride Therapyp. 601
Strategies to Improve Fluoride Therapyp. 604
Vitamin Dp. 613
Evidence for Altered Vitamin D Metabolism in Agingp. 613
Vitamin D Efficacy in the Treatment of Osteoporosisp. 617
Indexp. 623
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