New Horizons in Osteoporosis Management

Preface
Contents
Contributors
Part I: Bone Health: Towards Better Bones
1: Bone Health: Basic and Applied Bone Biology
Introduction
Basic Bone Biology
Cellular Composition
Osteoblasts
Bone Lining Cells
Osteocytes
Osteoclasts
Bone Structure
Cells Gaps
Gap Junctions and Skeletal Development
Bone Remodeling
The Bone Remodeling Compartment
The Remodeling Cycle – Cellular and Molecular Mechanisms
Activation
Resorption (Approximately Two Weeks in Duration)
Reversal (Approximately Four to Five Weeks in Duration)
Formation (Approximately Four Months in Duration)
Termination
The Remodeling Cycle – Major Signaling Pathways
Receptor Activator of Nuclear Factor Kappa-B Ligand Signaling Pathway (RANKL/RANK/OPG Signaling)
Wnt Signaling
Hormonal Impact on Bone Remodeling
Parathyroid Hormone (PTH)
Estrogen
Calcitonin
Growth Hormone
Glucocorticoids
Thyroid Hormone
Bone Modelling Vs. Remodeling
Bone Modeling
Bone Remodeling
Applied Bone Biology
Abnormalities of the Bone Remodeling Cycle
Bone Modeling/Remodeling as Therapeutic Targets
Antiresorptives
Anabolic Agents
Bone Formation-Sparing Antiresorptive Treatment
Combined Anabolic and Antiresorptive Treatment
Drugs that Act on the Bone Mineral/Matrix Composite
Bone Turnover and Fracture Risk
Building Better Bones: Sequential and Combination therapy for Osteoporosis
Challenges in Developing Treatments for Osteoporosis
References
2: Muscle Health
Introduction
Muscles in Health
Muscle Mass
Muscle Bone Interaction
Bone and Body Composition
Relationships Between Muscle and Bone in Clinical Studies
Bone and Muscle Interactions During Development
Genetic Factors
Endocrine Factors
Vitamin D
GH/IGF- I Axis
Sex Hormones
Glucocorticoid Excess
Diabetes Mellitus
Mechanical Factors
Muscle and Bone Coupling
Links from Muscle to Bone
Data from Diseases and Gene Mutations
Local Factors Affecting Muscle Ossification
Myostatin
Links from Bone to Muscle
Techniques of Muscle Imaging: Measurement of Lean Body Mass and Muscle Mass
Dual Energy X-Ray Absorptiometry
Computed Tomography
Magnetic Resonance Imaging
Bioimpedance Analysis
Emerging Techniques for the Assessment of Muscle Mass
Towards a Reference Standard
Different Indices to Express Lean Body Mass
Nutrition and Muscle Health
Proteins
Dietary Protein Requirements for Optimal Muscle Mass and Strength
Vitamin D
Homocysteine Levels, Vitamin B12, and Folic Acid
Acid-Producing Diets
Muscle in Aging Adults and in Disease
Muscle Health in Aging
Measurement of Muscle Health in Aging
Age-Related Change in Muscle or Lean Tissue Mass
Age-Related Change in Muscle Quality
Functional Capability
Muscle and Inactivity/Bed Rest
Muscle Health in Disease
Muscles and the Acute Response to Critical Illness
Muscles Role in Chronic Diseases
Obesity and Muscle
Muscle in Insulin Resistance and Diabetes
Muscle and Osteoporosis
Muscle and Kidney Diseases
Approaches to Management of Muscle Loss?
Hormonal Therapy
Exercise
Nutrition
References
3: Osteosarcopenia
Introduction
Aging Human Body
Potential Mechanisms of Age-Related Sarcopenia
Mitochondrial Reactive Oxygen Species and Mitochondrial Dysfunction
Mitochondrial Apoptosis
Mitochondrial Dynamics
Mitochondrial Autophagy
Myostatin
Inflammatory Cytokines
Bone–Muscle Crosstalks
Biomechanical: The Mechanostat Theory and Biomechanical Coupling in the Musculoskeletal Unit
Biochemical Communication between Muscle and Bone: Muscle and Bone as Endocrine Organs
Indirect Links
Nervous System
Macrophages
The Molecular Clock
Sarcopenia Operational Definition
Osteosarcopenia Clinic: Case Finding Practical Algorithm
Validated Tests and tools for Current Use
Finding Sarcopenia Cases
Measuring Sarcopenia Parameters
Muscle Strength
Muscle Quantity
Physical Performance
Alternative or New Tests and Tools
Lumbar Third Vertebra Imaging By Computed Tomography
Mid-Thigh Muscle Measurement
Psoas Muscle Measurement with Computed Tomography
Muscle Quality Measurement
Creatine Dilution Test
Ultrasound Assessment of Muscle
Specific Biomarkers or Panels of Biomarkers
SarQoL Questionnaire
How to Diagnose Osteosarcopenia?
Osteosarcopenia in Standard Clinical Practice
Categories of Sarcopenia and Sarcopenia-like Conditions
Primary and Secondary Sarcopenia
Acute and Chronic Sarcopenia
Sarcopenic Obesity
Frailty
Malnutrition-Associated Sarcopenia
Therapeutic Intervention
Exercise
Nutrition
Drug Therapy
Vitamin D
Sex Hormones
Estrogens
Insulin and Insulin-Like Growth Factor-1
Growth Hormone
Myostatin Inactivation
Urocortins
Angiotensin 1–7 and Angiotensin-Converting Enzyme Inhibitors
Selective Androgen Receptor Modulators (SARMs)
Future Therapies
Patient-Centered Approach for Sarcopenia Management
References
4: Bone Health in Women
Introduction
Young and Adulthood
Pregnancy and Lactation
Premenopausal Women
Postmenopausal Osteoporosis (Type I Osteoporosis)
Osteoporosis in Elderly Females
Definition of Osteoporosis
Physiologic Changes in the Bone Mass in Association with Pregnancy and Lactation
Clinical Approach to Patient Identification and Diagnosis
Young/Premenopausal Females
Postmenopausal Females
Approach 1: Quantitative Assessment
Approach 2: Probability-Based Assessment
Specific Clinical Situations
Idiopathic Osteoporosis in the Young
References
5: Bone Health in Men
Introduction
Why Bone Health in Men Is Important?
Epidemiology
Bone Development and Loss in Men
Childhood through to Young Adulthood
Ages: 20–60 Years
Age 70 Years and Onwards
Pathogenesis: The Role of Hormones
Causes of Osteoporosis in Men
Hypogonadism
Steroids
Alcohol Consumption
Smoking
Diabetes-Related Osteoporosis
Hypercalciuria
Immobilization
Gastrointestinal Disorders
Idiopathic Osteoporosis
Diagnosis
Clinical Approach
DXA Scan Interpretation
Laboratory Tests
Vertebral Fracture Assessment
References
6: Bone Health in the Transgenders
Introduction
Sex Hormones and Bone Health
Bone Mass Effects of Cross-Sex Hormone Therapy in Transgender People
Practical Guidelines for Transgender Hormone Treatment
Osteoporosis Risk in Transgender Individuals
Screening for Osteoporosis in Transgender Individuals
Implications for Standard Clinical Practice
References
Part II: Diagnosis: Clinician’s Guide
7: Osteoporosis Risk Assessment Tools
Introduction
The Evidence
Benefits and Harms of Early Detection of Osteoporosis
Risk Assessment Tools
FRAX
FRAX in Patients’ Management
QFracture
Garvan
Comparative Features
Comparison of Input
Comparison of Output
Osteoporosis Self-Assessment Tool
Osteoporosis Self-Assessment Tool (OST)
Index of Risk (OSIRIS)
Performance of Fracture Risk Model
The Concept of Very High Fracture Risk
Thresholds for Intervention
Closing the Gap: Intervention Thresholds of Very High vs High Fracture Risk
National Osteoporosis Guideline Group (NOGG)
European Society of Endocrinology
Fracture Risk Assessment Tools: Room for Improvement
Genetic Profiling
Trabecular Bone Score
Bone Turnover Markers
Fracture Type-Specific Prediction
Artificial Intelligence
Time-Variant Predictions
Ethnic-Specific Models
References
8: Current Imaging Techniques
Introduction
Importance of Osteoporosis Imaging
Dual X-ray Absorptiometry (DXA) Scan
DXA Technology
Nomenclature
Clinical Applications of DXA
Vertebral Fracture Assessment
DXA Additional Parameters
Quantitative Computed Tomography (QCT)
Clinical Applications of QCT
Standard QCT
Single-Slice QCT
Volumetric QCT
High-Resolution Peripheral Quantitative CT (HR-)pQCT)
Projectional QCT: Hip
Discordance in Diagnosis of Osteoporosis by QCT and DXA
Ultrasound Scanning
MRI
Bone Marrow Fat Imaging
Positron Emission Tomography (PET)
Bioengineering: Using an Electronic Stethoscope and Machine Learning to Detect Osteoporosis from Percussion Responses
References
9: The Challenges and Limitations of Osteoporosis Diagnosis
Introduction
Challenge 1: Underdiagnosis of Osteoporosis (Even after Fractures)
Challenges 2: From T-Score to Bone Strength and Quality
Changes in Density Account Partially for the Decrease in Fractures
Challenge 3: The Scanning Process
Challenge 4: Patient Awareness
Challenge 5: The Missed Falls Risk Assessment
References
10: Best Practice Recommendations for DXA Scans and Reports
Introduction
Basic Principles of DXA Scanning
Best Practice of DXA
How to Collect Local Reference Data
Role of Healthcare Professionals in the DXA Scanning Service
Radiographers
Falls Service
DXA Scanning in Standard Clinical Practice
Referring for DXA Scanning
Pre-scan Assessment
Reporting DXA Scans
Report Targets
Demographics
Medical History Used for Risk Determination
Test Results
Technical Notes
Diagnostic Category
Fracture Risk
Interpretation
Follow-Up Recommendation
Limitations
Follow-Up Adult BMD Report
Follow-Up Referral Form
Demographics
Fracture Risk Category
Changes in Density
Interpretation
Pediatric DXA Scanning
Diagnostic Category
Technical Comments
Follow-Up Pediatric DXA Scanning
Changes in Density
References
11: Pitfalls in DXA Scanning
Principle of DXA Scanning
Contraindications
Who Should Have a DXA Measurement?
Sites of Measurement of BMD
Interpreting a DXA Scan
Positioning
DXA Scan Analysis
Concordance Between Measurement Sites
Prevalence and Risk Factors of T-Score Discordance
Consequences of T-Score Discordance on Osteoporosis Management
Monitoring of DXA
Methods of Bone Mineral Density Reproducibility Measurement
Clinical Implications of Bone Mineral Density Reproducibility Measurement
Other Factors Influencing DXA Monitoring
Vertebral Fracture Assessment (VFA)
Trabecular Bone Score (TBS)
Body Composition
Conclusions
References
12: Osteopenia: Mind the Gap
Introduction
From T-score to Bone Health
Bone Loss Is a Continuum, Not a T score
The Burden of Fragility Fractures
The Problem of Osteopenia
The Challenge of Case Finding: Mind the Gap
Case Finding Strategies
Identification of Osteopenic Patients with High Fracture Risk
Identification of Patients with Prevalent Fractures
Identification of High-Risk Individuals Without History of Fracture
Thresholds for Intervention
Treatment Decisions
Lifestyle Changes General
Calcium and Vitamin Supplement Therapy
Prevention of Falls and Protection Against Fall Trauma
Pharmacotherapy
Androgen Replacement Therapy in Males
Management of Osteoporosis and Osteopenia in the Very Elderly
Treatment Algorithm for Osteopenia
References
Part III: Prevention: Recent Advances
13: Imminent Fracture Risk
Introduction
Imminent Fracture Risk
The Challenge of Identifying the Long-Term Risks of Fractures
Imminent Risk and the Location of the Previous Fracture
Central Versus Peripheral Sited Fractures
Predicting Imminent Risk for Fracture
Imminent Fracture Risk: Patient Perception
Medication Adherence
Imminent Fracture Risk Assessments and Fracture Liaison Service (FLS) Setting
Gaps in Treatment
Therapeutic Window of Opportunity
References
14: Fracture Liaison Service
Introduction
Fracture Liaison Service: The Concept
Fracture Liaison Service Models
Components of Fracture Liaison Service
Identify
Inpatient Fractures
Outpatient Fractures
Silent Vertebral Fractures
Referrals
Out of the Hospital FLS Setup
Investigate
Fracture Risk Assessment
DXA Scans
Vertebral Fracture Assessment (VFA)
Trabecular Bone Score (TBS)
Falls Risk Assessment
Other Investigations
Inform
Intervention
Osteoporosis Therapy
Falls Management
Improving Adherence
Integrate
Management Plan
Quality
FLS Outcomes
Future Fracture Risk Reduction
Vertebral Fragility Fractures
Mortality
Bone Health and Bone Mineral Density Assessment
Osteoporosis Treatment Initiation and Adherence
Cost-Effectiveness of an FLS
Best Practice Framework for Fracture Liaison Services
References
15: Unmet Needs and Challenges in Osteoporosis
Introduction
Challenge 1: Fracture Risk Score and Absolute Risk of Fracture
Challenge 2: Implementation of Health Economics into Clinical Guidelines
Challenge 3: Treatment Thresholds
Challenge 4: DXA
Diagnosis of Osteoporosis: More Than Dual-Energy X-Ray Absorptiometry Alone
Challenge 5: Measuring Bone Strength
Challenge 6: Osteoporosis Treatment
Challenge 6: Patient Education
How to Improve Peak Bone Mass?
Proactive Non-pharmacological Measures to Prevent Fractures
Multifaceted Osteoporosis Group Education
References
16: Osteoporosis Update for Primary Care Physicians
Introduction
Primary Care Perception About Osteoporosis
Gaps in Care in the Primary Care Setting
Gap 1: Failure to Implement and Follow Osteoporosis Screening Guidelines
Gap 2: Failure to Address the Imminent Fracture Risk in the Primary Care Setting
Gap 3: Insufficient Physician-Patient Communication/Poor Patient Education
Gap 4: Poor Monitoring After Prescribing Osteoporosis Therapy
Gap 5: Pitfalls in the Healthcare System
Improving Osteoporosis Service in the Primary Care: Breaking Barriers Not Bones
The Bone Health Team
The Role of the Osteoporosis Nurse Specialist
The Role of the Fracture Liaison Service (FLS) Nurse
Components of Screening Interventions
Rationale for Screening
Assessment of Fracture Risk
Treatment Thresholds and Decisions
Osteoporosis Management Guidelines for the Primary Care
References
Part IV: New Treatment Concepts
17: Bone Modulation
Introduction
The Dynamic Skeleton
Bone Modeling
Bone Remodeling
Coupling of Bone Remodeling
Principles of Bone Modulation
Implications from Research Studies and Clinical Practice
Inhibitors of Bone Resorption
Cathepsin K Inhibitors
Stimulators of Bone Formation
New Aspects of the Bone-Protecting Effects of Vitamin D
Further Nontraditional Molecules with Anti-osteoporotic Potential
Implications of Remodeling and Modeling on the Long-Term Effects of Osteoporosis Drugs on Bone Mass and Strength
References
18: Treat-to-Target in Osteoporosis
Introduction
Treat-to-Target as a Strategy in Osteoporosis
Establishing Treatment Goals
Bone Mineral Density/T-Score as a Goal
Fracture Probability as a Goal
Indices of Bone Strength as a Goal
Bone Turnover Markers (BTM) as a Goal
Comparison Between the Standard Treatment and Goal-Directed Treatment
Goal-Directed Selection of Initial Therapy
Goal-Directed Assessments and Treatment Decisions During Treatment
Assessing Adherence to Treatment
Monitoring Response to Therapy
Drug Holiday
Proposed Algorithm to Monitoring Osteoporosis Therapy
Limitation and Expectations of Treat-to-Target Approach
References
19: Geroscience and Management of Osteoporosis in Older Adults
Introduction
Geroscience: The Intersection of Basic Aging Biology, Chronic Disease, and Health
Aging and Bone Loss
Mechanisms of Age-Related Bone Loss
Role of Menopause in Women
Role of Sex Steroid Deficiency in Men
Bone Marrow Fat
Secondary Hyperparathyroidism
Other Contributing Factors
Bone Changes with Aging
Mechanical and Morphological Changes with Age
Bone Protein Changes with Age
Mineral Changes with Age
Changes in BMD with Aging
Approach to Management of Osteoporosis in the Older Adults
Medications
Calcium and Vitamin D
Antiresorptive Osteoporosis Therapy
Osteoanabolic Agents
Osteoporosis by Aiming at Bone Marrow Stromal Cells (BMSCs)
When to Repeat the BMD Testing
The Onset of Anti-fracture Efficacy
Safety of Anti-osteoporotic Drugs
Gastrointestinal Effects
Vascular Effects
Musculoskeletal Pain
Immune Reactions
Nervous System Effects
Cancer
Cardiac Effects
Impaired Fracture Healing and Induced Bone Weakening
Renal Safety
Optimizing Therapeutic Adherence in Osteoporosis
Predictors of Nonadherence
References
20: Bone Healing and Osteoporosis
Introduction
Pathophysiology of Fractured Bone Healing
The Inflammatory Phase
Osteoimmunology in Older Adults
The Repair Phase
Bone Formation Phase
Effects of Aging on Fracture Healing
Implications of Osteoporosis Treatment for Fracture Healing
Anti-catabolic Medications
Bisphosphonates
Local Application of Bisphosphonates and Its Effect on Bone Repair
Denosumab
Selective Estrogen Receptor Modulators: Raloxifene
Anabolic Medications
Parathyroid Hormone
Romosozumab
Management of Atypical Femoral Fractures
References
Part V: Towards Optimized Practice
21: Osteoporosis Management: Gaps in Patients’ Care and Treatment
Introduction
Osteoporosis: The Need to Treat
Osteoporosis: Gaps in Care
Gap 1: Failure to Follow Guidelines for Screening for Osteoporosis
Gap 2: Failure of Secondary Fracture Prevention
Gap 3: Patient-Physician Communication Failure
Osteoporosis: Mind the Treatment Gap
Fear of Rare Side Effects
Concerns Regarding Long-Term Efficacy
Osteoporosis: Closing the Gaps
Closing Gap 1: Secondary Fracture Prevention
Models of Care: Orthogeriatrics Services and Fracture Liaison Services
Closing Gap 2: Medication-Induced Osteoporosis
Steroids-Induced Osteoporosis
Androgen Deprivation Therapy-Induced Osteoporosis
Aromatase Inhibitor-Induced Osteoporosis
Closing Gap 3: Diseases Associated with Osteoporosis
Closing Gap 4: Primary Fracture Prevention
Closing Gap 5: Adherence to Therapy
Closing Gap 6: Public Awareness of Osteoporosis and Fracture Risk
Closing Gap 7: Public Awareness of Benefits Versus Risks of Osteoporosis Treatment
Closing the Gap 8: Access and Reimbursement for Osteoporosis Assessment and Treatment
Closing the Gap 9: Prioritization of Fragility Fracture Prevention in National Policy
Closing the Gap 10: The Burden of Osteoporosis in the Developing World
Guidelines
References
22: Precision Medicine: Pharmacogenetics and Pharmacogenomics of Osteoporosis
Introduction
Terminology
Elucidating Pharmacogenomic Mechanisms
Bone Mass Pharmacogenetics
Osteoporosis Pharmacogenomics and Fracture Prediction
Pharmacogenomics of Osteoporosis Therapy
Osteoporosis Pharmacogenomics: Recent Insights and Future Perspectives
Pharmacogenomics of Adverse Drug Reactions
Towards Personalized Medicine
References
23: Romosozumab: Optimizing the Anabolic Window
Introduction
Bone-Forming and Antiresorptive Effects of Romosozumab
Bone Morphological Changes
Time-Dependent Effects of Romosozumab
Pharmacokinetics
Clinical Trials
Profile of Romosozumab and its Potential in the Management of Osteoporosis
Phase II Trials: Efficacy and Safety of Romosozumab
Phase III Trials: Efficacy, Effectiveness, and Safety of Romosozumab
Antifracture Efficacy
Adverse Events
Sustainability
The Clinical Potential of Romosozumab
Guidelines
Technical Remarks
The Potential of Romosozumab Retreatment
Treatment in Male Osteoporosis
Sclerostin Antibody for Potential Healing Enhancement of Osteoporotic Fracture
Romosozumab and Cardiovascular Events
Romosozumab/Alendronate and Atherosclerosis
ROMO and Renal/Vascular Disease
References
24: New Frontiers in Osteoporosis Management: Optimizing Sequential and Combination Therapy
Introduction
Unmet Needs in the Management of Bone Fragility
Clinical Vs Radiologic Osteoporosis
Pathophysiology: What Is and Is Not Achievable Using Different Osteoporosis Therapies?
Therapeutic Implications
Anti-resorptive Therapy
Anabolic Therapy
Does the Sequence Matter?
Optimizing Osteoporosis Therapy: Combination and Sequential Therapies
Sequential Therapy
Anti-resorptives After Anabolic Agents for the Treatment of Osteoporosis
Anabolics After Anti-resorptive Agents for the Treatment of Osteoporosis
Anti-resorptives Sequential to Anti-resorptives for the Treatment of Osteoporosis (Anastasia)
Combination Therapy
Combination Therapies with Anabolics and Anti-resorptive Agents
Combination Treatment with Hormone Replacement Therapy
Challenges with the Outcomes of Sequential and Combined Osteoporosis Therapy
The Way Forward
References
Part VI: Disparities in Bone Health
25: Osteoporosis in Men
Introduction
Bone Changes Across the Men’s Life Span
Epidemiology of Osteoporosis in Men
Pathophysiology
Secondary Osteoporosis
Differences Between Men and Women
Male Osteoporosis in the Elderly
Risk Factors: Identifying Men at High Risk of Fracture
The Journey Toward Making of the Diagnosis of Osteoporosis in Men
Case Finding
Screening
Making the Diagnosis
Absolute Risk Assessment
BMD Vs FRAX in Men
Management
Gaps in Access to Osteoporosis Therapy
Who to Treat
Treatment Plan
General Nonpharmacologic Treatment
Pharmacological Agents
Selection of Therapeutic Agent
Bisphosphonates
Alendronate
Risedronate
Zoledronic Acid
Other Bisphosphonates
Contraindications or Intolerance to Oral Bisphosphonates
Teriparatide
Denosumab
Romosozumab
Combination/Sequential Therapy
Monitoring the Response to Therapy
Duration of Therapy
References
26: Pediatric Osteoporosis and Optimizing Bone Health in Children
Introduction
Bone Acquisition During Childhood and Adolescence
Definition of Pediatric Osteoporosis
Etiology of Pediatric Osteoporosis
Primary Bone Loss in Children
Secondary Osteoporosis in Children
Clinical Signs and Risk Factors for Osteoporosis in Children
Predictors of Fractures in Children at High Risk
Predictors of Vertebral Fractures
Predictors of Nonvertebral Fractures
Assessment of Bone Mass and Structure
Mobility, Muscle, and Functional Tests
DXA Scan Technical Aspects
DXA Technicalities, Interpretation, and Reporting in Children and Adolescents
Vertebral Fracture Assessment (VFA) in Pediatric Patients
Densitometry in Infants and Young Children
When Osteoporosis Should Be Suspected?
Laboratory Tests
Making the Diagnosis of Osteoporosis in Children
Bone Health Monitoring in at-Risk Children
Monitoring of Vertebral Fractures
Spontaneous Recovery from Osteoporosis in the Absence of Osteoporosis Therapy
The Management of Osteoporosis in Children
Goals of Treatment
General Measures for Optimization of Bone Health
Calcium and Vitamin D Supplementation
Bisphosphonates
What About Nonosteogenesis Imperfecta Primary and Secondary Osteoporosis?
Is There a Room for Individualized Treatment Approach?
Novel Therapies
Treatment Considerations in Specific Conditions
Osteogenesis Imperfecta
Glucocorticoids-Induced Osteoporosis
Anorexia Nervosa
Epilepsy and Antiepileptic Drug Therapy
Consider Puberty and Nutrition
Improving Muscle Strength, Mobility, and Rehabilitation
Osteoporosis Diagnosis and Treatment Algorithm
Initial Assessment
Treatment: Stabilization Phase
Maintenance Phase and Discontinuation of Osteoporosis Therapy
References
27: Atypical Femur Fractures
Introduction
Definition
Terminology
Epidemiology
AFFs in Osteoporosis Patients Treated with Denosumab
AFFs in Osteoporosis Patients Treated with Romosozumab
AFF in Autoimmune Disease and Steroid Therapy
AFFs in Cancer Patients Treated with Bisphosphonates and/or Denosumab
Periprosthetic AFFs
Pathogenesis of AFF
Stress or Insufficiency Fracture
Hip Geometry and AFF
Genetic Predisposition
Other Medications: Glucocorticoids, Proton Pump Inhibitors
Bone Material Properties in Patients with AFFs
Mechanisms of Impaired Fracture Healing in AFF
Atypical Fractures in Other Bones
Clinical Features and Diagnosis of Atypical Femur Fractures
Management of Atypical Femoral Fractures
Early Detection of AFFs
Prophylactic Treatment
Management of Patients After Atypical Femur Fractures
Medical Management of AFF
Time for a New Treatment Paradigm
References
28: Pregnancy, Lactation, and Bone Health
Introduction
The Calcium Demand During Pregnancy and Lactation
Body Adaptation During Pregnancy and Lactation
Mineral Ions During Pregnancy
Intestinal and Renal Handling of Calcium
Vitamin D
Parathyroid Hormone
IGF1 and Pituitary Growth Hormone (PGH)
Other Regulators
Pathophysiology and Lactation-Associated Osteocytic Osteolysis
BMD Changes During Pregnancy and Lactation
Methodological Problems for Evaluating BMD in Pregnant and Lactating Women
Variation of the Confounding Factors That Can Influence BMD
So, Are There Any Changes in BMD During a Pregnancy?
Variation of the Confounding Factors That Can Influence BMD During Lactation
So, Are There Any Changes in BMD During Lactation?
Parity and Bone Long-Term Effects of Pregnancy and Lactation on the BMD
Pregnancy-Related Transient Osteoporosis of the Hip
Pregnancy, Lactation, and Risk of Fracture
Pregnancy, Lactation, and Bone Biomarkers
Osteoporosis During Pregnancy
Clinical Presentation
Diagnosis
Treatment
Recovery of the Bone Health After Lactation
Long-Term Effect of Pregnancy and Lactation on Bone Health
References
Part VII: Bone Health as a Comorbidity
29: Bone Health and Cancer Therapy
Introduction
Unique Aspects of Cancer Therapy-Associated Bone Loss
Cancer, Hormones, and Bones
Sex Steroids and Bone
The Interaction Between Cancer, Sex Hormones, and Bones
Prostate and Bone
Pathophysiology of Cancer Treatment-Induced Bone Loss
Pathophysiology of Bone Loss in Breast Cancer Patients
Endocrine Therapy
Ovarian-Ablative Therapies
Effects of Breast Cancer and Its Therapies on Bone in Men
Effects of Prostate Cancer Therapies on Bone
Bone Metastases and Skeletal-Related Events (SRE)
Cancer Treatment-Induced Fractures
Screening for Bone Loss in Cancer Patients
Diagnosis of Cancer Therapy-Induced Bone Loss
Monitoring Bone Mineral Density
Clinical Sequelae of Cancer Therapy-Induced Bone Loss
Management
Diet and Lifestyle Changes
Specific Lifestyle Measures for CTIBL in Prostate Cancer
Specific Lifestyle Measures for CTIBL in Breast Cancer
Bone-Targeted Agents (BTAs)
Prevention of Skeletal Morbidity in Metastatic Bone Disease
Breast Cancer
Prostate Cancer
Prevention of Bone Loss in Prostate Cancer
Prevention of Bone Loss in Breast Cancer
Oophorectomy, GnRH Agonist (ASCO)
Cessation of Ovarian Function (CIOF)
Patients with Chronic (> 6 Months) Glucocorticoid Use
Management of Bone Metastases
Palliative Radiotherapy
Multidisciplinary Management Approach of Bone Metastases
Clinical Implications
Age Considerations: Older Adults
Safety Considerations
Algorithm for Identifying and Managing Cancer Treatment-Induced Bone Loss
References
30: Bone Health in Chronic Kidney Disease
Introduction
Mechanisms Underlying the Development of Osteoporosis
Dysregulation of RANK/RANKL/OPG System (Fig. 30.1)
Excessive Wnt/β-Catenin Signaling Inhibitors
Inflammatory Cytokine-Related Osteolysis
Disturbed Bone Remodeling: High or Low Bone Turnover-Related Osteoporosis
High Bone Turnover Disorder
Secondary Hyperparathyroidism
Chronic Inflammation
Low Bone Turnover Disorders
Adynamic Bone Disease and Osteomalacia in CKD
Glucocorticoid-Induced Osteoporosis (GIO) (Fig. 30.2)
Bone Quality Loss
Bone Mineral Density in Patient with CKD
Relationship Between BMD and Renal Osteodystrophy
CKD Progression and BMD Changes
Low BMD in CKD Not Yet Receiving Dialysis
Influence of Comorbidities
Influence of Treatments (Medications) on CKD-Related Osteodystrophy
Influence of Age and Gender
Dialysis Modalities on BMD
BMD in Hemodialysis Patients
BMD in Peritoneal Dialysis Patients
Secondary Hyperparathyroidism and Renal Osteodystrophy
The Pathophysiology of Secondary Hyperparathyroidism (SHPT)
Impact of SHPT on BMD
Vitamin D Deficiency in Bone Loss
The Alteration of Vitamin D Metabolism in CKD
Decrease Vitamin D Synthesis and Increase Vitamin-D Catabolism in CKD
Nutritional Vitamin D Hunger in the Parathyroid Gland
Vitamin D Deficiency: Effect on Bone Quantity and Quality Loss
Vitamin D Deficiency and Bone Quantity Loss
Vitamin D Deficiency and Bone Quality Loss
Role of Vitamin D Supplementation in High and Low Bone Turnover Disorders
Treatment of High Bone Turnover Disorder
Effect of Vitamin D Supplementation on Bone Quantity Loss (Fig. 30.4)
Effect of Vitamin D Supplementation on Bone Loss: Bone Quality
Extraskeletal Effect of Vitamin D in Treating Osteoporosis: Alleviating Inflammation and Oxidative End Products
Vitamin D for Treating Low Bone Turnover Disorder: Combination with Anabolic Agents
Treatment of Osteoporosis: According to Bone Turnover (Fig. 30.7)
High Bone Turnover Disorder: Enhance Osteoclastogenesis Couple With More Increased in Osteoblast Viability
Antiresorptive Agents
Bisphosphonates
Anti-RANKL Antibody
Calcimimetics
Low Bone Turnover Disorder: Rescute the Osteoblast Viability: Anabolic Agents: PTH Analogs, Monoclonal Antibodies Against Wnt Pathway Inhibitors
Parathyroid Hormone
Monoclonal Antibodies Against Wnt Pathway Inhibitors
Effect of Nutritional Vitamin D on Osteoporosis
Conclusions
References
31: Glucocorticoids and Musculoskeletal Health
Introduction
Epidemiology
Pathophysiology
Mechanism of Action of Glucocorticoids
Role of Underlying Inflammation
Effect on the Bone
Direct Effect on the Bone
Indirect Effects on Bone
Effect on the Muscles
Clinical Correlations of Glucocorticoid-Induced Osteoporosis
Glucocorticoids Pharmacologic Preparation
Risk Stratification, Screening, and Assessment
Glucocorticoid-Induced Changes in BMD and Bone Microarchitecture
Monitoring BMD Changes/Response to Therapy
Fracture Risk Assessment in Individuals Treated with Steroids
Glucocorticoid-Induced Osteoporosis in Children and Adolescents
Management of Glucocorticoid-Induced Osteoporosis
General Measures
Nutrition/Calcium and Vitamin D Supplementation
Pharmacologic
Antiresorptive Agents
Bisphosphonates
Denosumab
Anabolic in the Management of Glucocorticoid-Induced Osteoporosis
Romosozumab
Third-Line Agents
Follow-Up
Algorithm for Assessment and Management of GIO
High Fracture Risk
Moderate Fracture Risk
Low Fracture Risk
References
32: Osteonecrosis of the Jaw
Introduction
Osteonecrosis of the Jaws: A Review and Update in Etiology and Treatment
Definition
Incidence of MRONJ
Characteristics of the Jawbone
Pathophysiology
Hypothesis 1: Bone Remodeling Inhibition
Hypothesis 2: Inflammation, Infection, and the Biofilm
Hypothesis 3: Angiogenesis Inhibition
Hypothesis 4: Soft Tissue Toxicity
Hypothesis 5: Innate or Acquired Immunity Dysfunction
Diagnosis and Stages of MRONJ
Risk Factors for MRONJ
Differences in Antiresorptive Functions Between Bisphosphonates and Denosumab
Duration of Medication Therapy as a Risk Factor for MRONJ
Imaging and Diagnosis
Imaging in Patients with Bisphosphonate-Associated Osteonecrosis of the Jaws (MRONJ)
Anatomical Imaging
Panoramic Radiographs
Cone-Beam Computed Tomography (CBCT)
Computed Tomography
Magnetic Resonance Imaging
Functional Imaging
Bone Scan (Skeletal Scintigraphy)
18F-FDG Positron Emission Tomography/Computed Tomography (PET/CT)
Fluorescence-Guided Bone Resection/Visually Enhanced Lesion Scope (VELscope®)
Clinical Application of MRONJ Imaging
Defining the Area of Inflammation
Monitoring of the Disease Course
Providing Useful Imaging Findings for Surgery
Predicting Disease Prognosis
Lab Investigation: Bone Markers in MRONJ
Bone Markers as Predictors of MRONJ
Association Between Periodontitis and ONJ
Prevention, Management, and Treatment of MRONJ
Preventive Measures Taken Before Antiresorptive Therapy
Discussing Medication-Related Osteonecrosis of the Jaw with  Patients
Oral Assessments and Other Preventive Measures
Preventive Measures Taken During Antiresorptive Therapy
Managing Oral Infections Before and During Antiresorptive Therapy
Treatment
Asymptomatic Patients
Asymptomatic Patients Receiving IV BP or Antiangiogenic Drugs for Cancer
Asymptomatic Patients Receiving Antiresorptive Therapy for Osteoporosis
Patients with Established MRONJ
Stage-Specific Management Approach
Teriparatide as a Treatment Modality of MRONJ (PTH in OJN)
Drug Holiday and Treatment
MRONJ and the Need for Multiprofessional Teamwork
References
Index