Foreword...v Preface...vii Acknowledgments... xi Dedication... xiii Continuing Medical Education... xxv. Chapter 1: Densitometry Techniques...

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CONTENTS Foreword...v Preface...vii Acknowledgments... xi Dedication... xiii Continuing Medical Education... xxv Chapter 1: Densitometry Techniques... 1 Plain Radiography in the Assessment of Bone Density... 1 Qualitative Morphometry... 2 Qualitative Spinal Morphometry... 2 The Singh Index... 2 Quantitative Morphometric Techniques... 3 Calcar Femorale Thickness... 3 Radiogrammetry... 4 The Radiologic Osteoporosis Score... 5 Radiographic Photodensitometry... 5 Radiographic Absorptiometry... 6 Photon Absorptiometry Techniques... 9 Single-Photon Absorptiometry... 9 Dual-Photon Absorptiometry... 11 Dual-Energy X-Ray Absorptiometry... 13 Peripheral DXA... 18 Single-Energy X-Ray Absorptiometry... 18 Quantitative Computed Tomography... 19 Peripheral QCT... 22 Quantitative Ultrasound Bone Densitometry... 22 References... 24 Chapter 2: Skeletal Anatomy in Densitometry... 29 Characterizing the Skeleton in Densitometry... 29 The Axial and Appendicular Skeleton... 29 The Weight-Bearing and Nonweight-Bearing Skeleton... 30 The Central and Peripheral Skeleton... 30 The Trabecular/Cortical Composition of the Skeleton... 32 Forearm Composition... 32 Vertebral Composition... 32 Femoral Composition... 33 All Sites... 33 The Spine in Densitometry... 33 xv

xvi Contents Vertebral Anatomy... 34 Artifacts in PA or AP Spine Densitometry... 39 Vertebral Fractures... 39 Degenerative Changes and Dystrophic Calcification... 40 Effect of Osteophytes on BMD... 40 Effect of Aortic Calcification on BMD... 44 Effect of Facet Sclerosis on BMD... 45 The Vertebral Rotation and PA Lumbar Spine Bone Density... 46 Other Causes of Artifacts in PA and AP Lumbar Spine Studies... 48 The Spine in the Lateral Projection... 48 The Proximal Femur in Densitometry... 50 Proximal Femur Anatomy... 50 Effect of Rotation on BMD in the Proximal Femur... 52 Effect of Leg Dominance on BMD in the Proximal Femur... 54 Effect of Scoliosis, Osteoarthritis, Osteophytes, Surgery, and Fracture on BMD in the Proximal Femur... 54 The Forearm in Densitometry... 54 Nomenclature... 54 Effect of Arm Dominance on Forearm BMD... 57 Effect of Artifacts on BMD in the Forearm... 58 The Metacarpals, Phalanges, and Calcaneus... 58 Bone Physiology... 60 Bone Growth, Modeling, and Remodeling... 61 Bone Modeling... 62 Bone Remodeling... 62 The Basic Multicellular Unit in Bone Remodeling... 63 References... 65 Chapter 3: Statistics in Densitometry... 69 The Mean, Variance, and Standard Deviation... 69 The Mean... 69 The Variance and Standard Deviation... 70 Coefficient of Variation... 71 Standard Scores... 71 Z-Scores... 72 T-Scores... 72 Standard Scores on Bone Density Reports... 73 Measures of Risk... 76 Prevalence and Incidence... 76 Prevalence... 76 Incidence... 77 Absolute, Relative, and Attributable Risk... 77 Absolute Risk... 77 Relative Risk... 77 Attributable Risk... 78 Odds Ratios... 79

Contents xvii Confidence Intervals... 79 Accuracy and Precision... 81 Accuracy... 82 Precision... 82 Types of Data... 83 Quantitative Data... 83 Qualitative or Categorical Data... 83 Data and Variables... 83 Correlation... 84 Statistical Significance and the P Value... 85 Regression Analysis... 85 Statistical Evaluations of Diagnostic Tests... 86 Sensitivity and Specificity... 86 Likelihood Ratios... 88 Receiver Operating Characteristic Curves... 89 Regression to the Mean... 90 References... 91 Chapter 4: Quality Control... 93 Phantoms... 94 The European Spine Phantom... 95 The Bona Fide Spine Phantom... 95 The Hologic Spine and Hip Phantoms... 95 The Lunar Spine Phantom... 95 Using the Phantom to Create Control Tables and Charts... 96 Shewhart Rules and CUSUM Charts... 99 Shewhart Rules... 100 CUSUM Charts... 102 Automated Quality Control Procedures... 104 Replacing a Densitometer... 107 References... 108 Chapter 5: Bone Density Data: From DPA to DXA and Manufacturer to Manufacturer...111 From DPA to DXA... 111 Hologic DXA and Lunar DPA... 112 Lunar DXA and Lunar DPA... 113 Hologic DXA, Lunar DXA, and Lunar DPA... 113 DXA: From Lunar to Hologic to Norland... 114 Hologic DXA and Norland DXA... 114 Lunar DXA and Hologic DXA... 114 Standardization of Absolute BMD Results... 115 Standardization of Central DXA Absolute BMD Values... 115 Standardization of DXA BMD Results for the Femoral Neck, Trochanter, and Ward s Area... 117 Standardization of Forearm DXA Results... 119

xviii Contents The Utility of the sbmd... 120 From DXA Machine to DXA Machine Within Manufacturers... 120 From Pencil-Beam to Fan-Array DXA Data... 121 Reference Databases... 122 References... 125 Chapter 6: The Effects of Age, Disease, Procedures, and Drugs on Bone Density...127 Age-Related Changes in Bone Density... 127 Bone Density in Children... 128 Bone Density in Premenopausal Women... 129 Dissimilar BMDs Between Skeletal Sites at Peak and Prior to Menopause... 129 Bone Density in Perimenopausal Women... 130 Dissimilar Spine and Femoral BMDs in Perimenopausal Women... 131 Changes in Bone Density in Postmenopausal Women... 131 Changes in Bone Density in Men... 132 The Effect of Diseases and Procedures on Bone Density... 132 Acromegaly... 132 Ankylosing Spondylitis... 133 Alcoholism... 133 Amenorrhea... 134 Hyperandrogenic Amenorrhea... 134 Exercise-Induced Amenorrhea... 134 Anorexia Nervosa... 134 Cirrhosis... 135 Cushing s Syndrome... 135 Cystic Fibrosis... 136 Diabetes... 136 Insulin-Dependent Diabetes Mellitus... 136 Noninsulin-Dependent Diabetes Mellitus (NIDDM)... 136 Ehlers-Danlos Syndrome... 136 Estrogen Deficiency (Postmenopausal)... 137 Familial Dysautonomia... 137 Gastrectomy... 138 Type 1 Gaucher Disease... 138 Gluten-Sensitive Enteropathy... 138 Human Immunodeficiency Virus Infection... 139 Hypercalciuria... 139 Hyperparathyroidism... 140 Hyperprolactinemia... 141 Hyperthyroidism... 141 Inflammatory Bowel Disease... 142 Intravenous Drug Abuse... 142 Klinefelter s Syndrome... 143 Marfan s Syndrome... 143 Mastocytosis... 143

Contents xix Multiple Myeloma... 144 Multiple Sclerosis... 144 Neurofibromatosis... 144 Osteoarthritis... 144 Paralysis... 145 Hemiplegia... 145 Paraplegia... 146 Parkinson s Disease... 146 Pregnancy and Lactation... 146 Radiotherapy... 148 Regional Migratory Osteoporosis... 148 Renal Failure... 149 Rheumatoid Arthritis... 149 Thalassemia Major... 150 Transient Osteoporosis of the Hip... 151 Transplantation... 151 Cardiac Transplantation... 151 Liver Transplantation... 151 Marrow Transplantation... 152 Renal Transplantation... 152 Weight Loss... 152 Wilson Disease... 153 The Effect of Drugs on Bone Density... 153 Alendronate Sodium... 153 Calcitriol... 155 Calcium and Vitamin D... 156 Corticosteroids... 156 Oral Corticosteroids... 156 Inhaled Corticosteroids... 157 Estrogen/Hormone Replacement... 158 Etidronate... 160 GnRH Agonists... 160 Heparin... 161 Ipriflavone... 161 Medroxyprogesterone Acetate... 162 Nandrolone Decanoate... 162 Raloxifene... 162 Risedronate... 163 Salmon Calcitonin... 165 Sodium Fluoride... 166 Tamoxifen... 167 Teriparatide... 167 Thyroid Hormone... 168 Tibolone... 169 Zoledronic Acid... 170 References... 171

xx Contents Chapter 7: Selecting Patients for Bone Mass Measurements: Clinical Guidelines...179 Clinical Guidelines... 179 1988 National Osteoporosis Foundation Guidelines... 179 1998 NOF Guidelines... 181 1996 Guidelines of the International Society for Clinical Densitometry... 182 1996 American Association of Clinical Endocrinologists Guidelines... 184 2001 AACE Guidelines... 185 Guidelines from the European Foundation for Osteoporosis and Bone Disease... 186 2002 ACOG Recommendations for Bone Density Screening for Osteoporosis... 187 2002 North American Menopause Society Recommendations... 188 2002 US Preventive Services Task Force Recommendations... 189 Guidelines for Bone Density Testing in Men... 191 1999 World Health Organization Task Force Recommendations for Men and Women... 193 How Do the Guidelines Compare?... 193 References... 194 Chapter 8: Selecting Patients for Bone Mass Measurements: Self-Assessment Indices... 197 Simple Calculated Osteoporosis Risk Estimation... 198 Osteoporosis Risk Assessment Instrument... 201 The Study of Osteoporotic Fractures Simple Useful Risk Factor System... 203 ABONE... 203 The Osteoporosis Self-Assessment Tool... 205 Weight Selection Criteria... 208 The FRACTURE Index... 208 Comparing the Performance of Self-Assessment Questionnaires... 211 Summary... 214 References... 215 Chapter 9: Diagnosing Osteoporosis... 217 Guidelines of the Study Group of the WHO for the Diagnosis of Osteoporosis... 218 The 1999 WHO and 2000 IOF Recommendations... 219 The Clinical Dilemma... 220 Peripheral Site T-Score Equivalents for the Diagnosis of Osteopenia and Osteoporosis... 221 Changing the Definition of Osteoporosis... 226 Diagnosing Osteoporosis in Men... 226 Additional Considerations in Site Selection for Diagnosis... 229 References... 231

Contents xxi Chapter 10: Predicting Fracture Risk... 233 The Prevalence of Fracture at Different Levels of BMD... 233 Fracture Risk Prediction... 234 Site-Specific and Global Fracture Risk Prediction... 234 Relative Risk Fracture Data... 234 Global Fracture Relative Risk Data... 235 Site-Specific Spine Fracture Relative Risk Data... 236 Site-Specific Hip Fracture Relative Risk Data... 237 Applying Relative Risk Data in Clinical Practice... 237 Lifetime Risk of Fracture... 240 10-Year Fracture Probability... 240 Remaining Lifetime Fracture Probability... 244 The Fracture Threshold... 245 Qualitative Risk Assessments... 247 Predicting Fracture Risk in Men... 249 Using Skeletal Morphometry from Densitometry to Predict Fracture Risk... 250 Vertebral Morphometry and Fractures... 250 The Relationship Between Prevalent Spine Fractures and Future Fracture Risk... 250 Diagnosing Vertebral Fractures... 252 Vertebral Fracture Assessment with Genant s Semiquantitative Technique... 252 Quantitative Techniques... 252 Performance Comparisons of Semiquantitative and Quantitative Techniques... 254 Fan-Array Spine Imaging with DXA... 254 Proximal Femur Morphometry... 257 Hip Axis Length... 257 The Femoral Neck-Shaft Angle... 260 Femoral Neck Width... 260 The Upper Femoral Neck... 260 Hip Strength Analysis... 261 Combining Clinical Risk Factors with BMD to Predict Fracture Risk... 262 References... 263 Chapter 11: Monitoring Changes in Bone Density...267 The Concept of Precision... 267 Performing a Precision Study... 268 Short-Term Precision Studies... 270 Mathematical Procedures Used to Calculate Precision... 271 Step 1... 271 Step 2... 272 Long-Term Precision Studies... 273 Applying the Precision Value to Serial Measurements... 273 The Determination of LSC... 274 A Case in Point... 277

xxii Contents More Sophisticated Issues of Statistical Confidence for the Measured Change... 278 Determining the Level of Confidence for Any Change and Precision... 278 The Confidence Interval (CI) for the Change in BMD Between Two Measurements... 279 The Importance of Precision... 280 Which Skeletal Sites Should Be Used for Monitoring?... 281 How Frequently Should Measurements Be Repeated?... 283 Regression to the Mean and Monitoring... 283 A Final Consideration... 284 References... 285 Chapter 12: Reporting Densitometry...287 Elements of Densitometry Reports Requested by Primary Care Physicians... 287 US Densitometry Center Reporting Practices... 288 Recommendations from the Canadian Panel of the ISCD for Bone Density Reporting... 289 Reporting the Diagnosis... 289 Reporting Fracture Risk... 289 Recommending Evaluations for Secondary Causes of Bone Loss... 291 Treatment Recommendations... 294 Recommending a Follow-Up Densitometry Study... 295 Assessment of Risk Factors... 296 Reporting Serial Studies... 297 The Challenge in Reporting Densitometry Results... 297 References... 300 Chapter 13: FDA-Approved Densitometry Devices...301 Computer-Enhanced Radiogrammetry... 301 Sectra Osteoporosis Package IDS5 Workstation Clinical Application... 301 Computer-Enhanced Radiographic Absorptiometry... 303 Automated OsteoGram... 303 MetriScan... 303 Central X-Ray Densitometers... 304 Delphi... 304 Discovery... 306 DPX-IQ... 308 DPX MD... 309 DPX MD+... 310 DPX-NT... 312 Excell... 313 Excell plus... 313 EXPERT -XL... 315 Prodigy... 317 QDR 4500 A... 318

Contents xxiii QDR 4500 C... 320 QDR 4500 SL... 321 QDR 4500 W... 322 XR-46... 323 Peripheral X-Ray Densitometers... 325 accudexa... 325 Apollo... 326 DexaCare G4... 327 DTX-200 DexaCare... 328 pdexa... 329 PIXI (Peripheral Instantaneous X-Ray Imager)... 331 XCT 2000... 332 Ultrasound Bone Densitometers... 333 Achilles+... 333 Achilles Express... 334 Achilles InSight... 335 DTU-one UltraSure... 337 McCue C.U.B.A.Clinical (Contact Ultrasound Bone Analyzer)... 338 Omnisense 7000S Ultrasound Bone Sonometer... 339 QUS-2 Calcaneal Ultrasonometer... 341 Sahara Clinical Bone Sonometer... 342 Appendix I: Contacts for Bone Densitometry Manufacturers and Organizations of Interest... 345 Appendix II: Conversion Formulas... 349 Appendix III: Formulas and Tables Used in Serial Bone Density Measurements... 353 Appendix IV: World Health Organization Criteria for the Diagnosis of Osteoporosis Based on the Measurement of Bone Density... 359 Appendix V: Recent Guidelines for Bone Density Testing... 361 Appendix VI: Bone Mass Measurement Act of 1997... 363 Appendix VII: CPT Codes for Bone Densitometry... 365 Appendix VIII: 2002 Medicare Reimbursement Rates... 367 Appendix IX: NHANES III Proximal Femur Reference Data... 371 Appendix X: Norland DXA Reference Data... 379 Appendix XI: Hologic DXA Reference Data... 383 Appendix XII: Lunar DXA Reference Data... 393

xxiv Contents Appendix XIII: Densitometry Patient Questionnaire... 397 Appendix XIV: The CD-ROM Companion... 399 Index... 403

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