f sBISCD i Isrenygriow Soctery Fon Curnicat Disstromere International Society for Bone Densitometry Clinician Course Syllabus ISCD Bone Densitometry Course for Clinician Syllabus Editors Neil Binkley, MD, CCD Chair, Bone Density Course Committee, Past President Susan Broy, MD, CCD ISCD Board member, Chair VFA committee Ed Lieb, MD, CCD Chair, Cducation Council Steven Petak, MD, JD, CCD Past President Bobo Tanner, MD, CCD ISCD Executive Committee Special Acknowledgement ISCD would like to express gratitude to the many people who over the last 15 years have contributed their vision, expertise, time, and insight into the develuprneril of the ISCD course curriculum. Version 10.0 - Copyright © 2010 by the Intemational Society far Clinical Nensitametry 1Clinician Course Objectives Recognize the clinical utility of bone densitometry and other modalities to assess and monitor the fracture risk of your patients with low bone mass. Implement recommendations of the 2007 Official Positions to reduce DXA acquisition and interpretation errors. Recognize the utility and limitations of the WHO classification to diagnose osteoporosis. Conduct a precision assessment to ensure the accuracy and precision of the BMD testing done on your patients. Apply the recommendations of the ISCD Official Positions for interpreting and reporting DXA scan results to improve patient management for your patients with low bone mass. Accreditation Statement The International Society for Clinical Densitometry is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to offer continuing medical education for physicians. Version 10.0 - Copyright 9 2010 by the International Society for Clinical Densitometry « « 4 < ‘ « é ‘ ‘ ‘ ‘ ‘ ‘ « ‘ 5 ‘ « ‘ ‘ « ‘ . ‘ ‘ ‘ ‘ ‘ aDisclosures + ISCD — Policy on Commercial Support and Conflict of Interest: The ISCD maintains a policy on the use of commercial support, which ensures that all educational activities sponsored by the ISCD provide in-depth presentations that are fair, balanced, independent and scientifically rigorous. All faculty and planners are required to complete a Conflict of Interest form. This information will be made available through syllabus materials. Registration fees are not industry supported. + Course The course presents principles and concepts of bone density testing, diagnosis and treatment of osteoporosis. Course materials are periodically reviewed, updated and approved by the ISCD Scientific Advisory Committee. The course is not a substitute for the manufacturer's instruction manual. + Neutrality The ISCD and its faculty do not endorse any product or company. Disclaimer The material presented in the ISCD Bone Densitometry Course is educational and does not constitute a medical or professional service. Great effort has been made to assure that the course material is timely and accurate. However, due to the rapidly changing nature of the field, some information provided may be outdated or invalidated by subsequent developments. The lecturers and authors shall not be held liable or responsible to any person or entity with respect to any loss or damage alleged to be caused directly or indirectly by the information presented at this program. Version 10.0 - Copyright © 2010 by the international Society for Clinical Densitometry 3TABLE OF CONTENTS |. Overview of Osteoporosis (General Session)... I. Basic Science of Bone Densitometry and Device Operating Principles (General Session) ll X-Ray Science, Radiation Safety and Quality Assurance (General Session) IV. Clinical Evaluation of Bone Health V. Use of Bone Densitometry for the Diagnosis of Osteoporosis VI. Assessment of Fracture Risk VI. Monitoring with Bone Densitometry Vl. Clinical Management of Osteoporosis IX. Principles of DXA Scan Interpretation. X. Principles of Reporting of DXA Scans Appendix A: Official Positions of the ISCD Appendix B: Patient Questionnaire. Appendix C: Precision Assessment and Radiation Safety for Dual-energy X-ray Absorptiometry. Version 10.0 - Copyright © 2010 by the Intemational Society for Cl 5 ical Densitometry 8 20 34 45 64 7 90 100 114 129 133 149 151OVERVIEW OF OSTEOPOROSIS A Learning objectives 1) 2) 3) 4) 5) 6) 7) Slate definitions of osteoporosis Summarize the pathophysiology of osteoporosis Explain the prevalence and incidence of osteoporosis and fractures Describe types of fractures and the morbidity and mortality related to osteoporotic fractures List the economic costs of osteoporosis Compare the incidence, prevalence, morbidity, mortality, and cost of osteoporosis with other chronic diseases Explain the value of bone densitometry for diagnosis, fracture risk estimation and monitoring Definitions of osteoporosis 1) 2) 3) Old definition: a reduced amount of bone that is qualitatively normal (Albright F. Ann intern Med. 1947; 27:861) Modern definition: “A systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture.” (Consensus Development Conference. (Am J Med. 1991;90:107-110.) Newest definition: “Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture Bone strength reflects the integration of two main features: bone density and bone quality.” (NIH Consensus Development Panel. JAMA. 2001;285:785-795.) Osteoporosis can also be defined based on the presence or history of a low-trauma or fragility fracture. The definition of an osteoporotic fracture is not straightforward. Fragility and low trauma fracture is defined as a fracture resulting from the force of a fall from a standing height or less or a bone that breaks under conditions that would not cause a normal bone to break The composition of bone 1) 2) 3) Bone matrix is 90% collagen (Type-1 collagen containing crosslinks of N- telopeptides, C-telopeptides and deoxypyridinolines) and 10% other proteins (osteocalcin, osteonectin, osteopontin). They are the basis for the commercial assays for bone turnover markers. Bone mineral is hydroxyapatite (calcium and phosphorus). Bone cells are osteoclasts, osteoblasts, osteocytes, and lining cells. Bone modeling and remodeling 1) 2) 3) Bone growth occurs as a result of modeling: renewal of bone substance and alteration in the size and shape of bone. Bone health is maintained by remodeling: replacement of old bone with new bone. The bone remodeling cycle is a coordinated sequence of activation, resorption, and formation. Bone remodeling is done by osteoclasts (cells derived from bone marrow Version 10.0 - Copyright © 2010 by the Intemational Saciety for Clinical Densitamatry 6 SBHASSOHH HHO OHODH A OHS HSHVHSHOHOHKH OH HDHOPDOOHHKOHRSHBkSSBSkEBEE4eprecursors) that remove old bone (resorption) and osteoblasts (cells derived from mesenchymal precursors) that produce new bone matrix, which then becomes mineralized mature bone (formation). 4) Bone loss occurs when resorption exceeds formation F. Peak bone mass 1) Peak bone mass is the maximum bone mass or density achieved during allfetime. It is reached when the growth in the size of bones and accumulation of bone mineral has stabilized (consolidation). 2) Different skeletal sites reach maturity at different times: trochanter, mid- teens; femoral neck, late teens; spine, early 20s (Li Y-C, et al. Bone. 2003;32:546-555.) 3) Determinants of peak bone mass include heredity (70%-80%) [sex and race] and lifestyle factors (20%-30%) [calcium, vitamin D, exercise, smoking, etc] G. Changes in bone density with age 1) There is a dramatic increase in BMD during adolescence. 2) Peak bone mass is achieved in the teens or early twenties. 3) Aplateau is maintained for a time. 4) Age-related bone loss occurs at a rate of ~0.5%-1,0% per year. 5) Bone loss accelerates with menopause (1.0%-2.0% per year); this accelerated phase lasts 5-10 years. 6) Age-related bone loss continues, with bone loss eventually going back down to pre-adolescent levels ete MTL y ee) ee ee Tt) Pee SA resumes Ca) oo H. Influence of sex and race on BMD 1) Onaverage, BMD is higher in men than in women, and higher in blacks than in whites. Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry Te2) The variability around the average is such that above-average white women have higher BMD than below-average black men DXA Terminology: The skeleton is divided into different regions 1) The central skeleton (axial skeleton plus hips and shoulders) consists of the spine, ribs, pelvis, and shoulders, and hips. 2) The peripheral skeleton (appendicular skeleton minus hips and shoulders) consists of the extremities (arms and legs). J. Different skeletal regions have different types of bone 1) Cortical or compact bone makes up the shafts of the long bones and the outer envelope of all bones (appendicular skeleton) 2) Cancellous or trabecular bone makes up the inner parts of the bones of the axial skeleton. 3) Cortical bone makes up about 80% of the skeleton, but is only about 20% of the surface area. About 3% of cortical bone is renewed each year. 4) Cancellous bone accounts for about 20% of the skeléton but 80% of the surface area, About 25% of cancellous bone is renewed each year. 5) About 10% of the skeleton is being remodeled at any one time. K. Cancellous and cortical bone loss occurs at different times and rates ) Gancellous bone loss is rapid in the early menopause. Wrist fractures increase in frequency as cancellous bone loss begins. 2) As cancellous bone loss continues the risk of vertebral fractures increases. 3) Cortical bone loss is more gradual, but also more persistent. The risk of hip fractures increases as a result of the loss of both cancellous and cortical bone. Cancellous and Cortical Bone Loss Occurs EME eMac) eed “i bone Sores) | fractures | Py oy ISCD Ren nN en Version 10.0 - Copyriaht © 2010 by the International 8 Society for Clinical Densitometry ¢ ‘ 4 « ‘ « ‘ ‘ i ‘ ‘ ‘M Summary: Bone Mass and Bone Loss 1) Women have lower peak bone mass than men. 2) Whites have lower peak bone mass than blacks. 3) Bone loss ocours with advancing age, because resorption is greater than formation 4) As bone loss ocours, there is loss of quality as well as quantity. 5) There are no symptoms from low bone mass or from bone loss. Definitions of prevalence and incidence 1) Prevalence (i) Frequeney of disease at a specific point in time = (number with disease risk) (ii) Often expressed as percent, or as number per 1,000 people (iii) Example: 30% of women over age 50 have osteoporosis 2) Incidence (i) New cases of disease over a specific period of time = (new cases within the period of time/number at risk) (ii) Often expressed as number of cases per person-years (iii) Example: the incidence of hip fractures in an elderly population is 12 per 1000 person-years Osteoporosis Prevalence and Incidence Worldwide 1) Prevalence: Estimated 200 million people have osteoporosis worldwide 2) Incidence: Hip fracture projected to increase 240% in women and 320% in men by 2050 3) Even if there is no increase in age-adjusted hip fracture risk, the number of hip fractures will increase 1.7 million in 1990 to to 6.3 milliun in 2050 ww. iofbonehealth.ora). WHO classification for postmenopausal osteoporosis (World Health Organization (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. WHO Technical Report Series. No 843; WHO, Geneva and Kanie JA, et al. J Bone Miner Res. 199. 1137-1141.) 1) The T-score compares an individual's BMD with the mean value for young normals, and expresses the difference as a standard deviation score ) Normal, T-score -1.0 and above ) Low bone mass (‘osteopenia (low bone density)"), between ~1.0 and -25 4) Osteoporosis, -2.5 and below 5) Severe or established osteoporosis, -2.5 and below with fragility fractures Rochester Osteoporosis Project: Prevalence 1) Definition: WHO classification Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 92) Technique: DXA 3) Skeletal sites: PA spine, proximal femur (hip) 4) Reference population: local young normal women 5) Study population: older white women in Rochester MIN 6) The prevalence of osteoporosis increases with age; in white women over age 50, itis found in approximately 16% at spine and approximately 16% at the femoral neck 7) Atyounger ages, the prevalence of osteoporosis at the spine is higher than the prevalence at the hip 8) In older age, the prevalence of osteoporosis at the hip is higher than the prevalence at the spine 9) Overall, the prevalence at the spine and hip are similar NHANES Il 1) Definition: WHO classification 2) Technique: DXA 3) Skeletal sites: only proximal femur (hip) 4) Reference population: white women and men, 20-29 years of age, from multiple geographic regions of the US 5) Study population: women and men age 250 years, different races, multiple regions of the US 6) The prevalence of osteoporosis based on femoral neck measurements is 22% of white women age 50 and older, approximately 10% of Hispanic women, approximately 5% of black women, and approximately 6% of men 7) The prevalence of osteoporosis increases with age. About 40% of women aged 50-59 have low bone mass (less than 10% have osteoporosis); over 90% age 80+ have low bone mass, and over 60% have osteoporosis. National Osteoporosis Foundation (NOF) 1) 2) 3) 4) 5) 40 million people in the US have osteoporosis (T-score ~2.5 or below) 8 million women 2 million men 34 snillion US men and women have low bone mass (T-score between — 1.0 and ~2.5) Projections for the future: by 2020, there will be almost 14 million Americans with osteoporosis. There are different types of fractures 1) 2) 3) 4) Traumatic fracture Pathological fracture — a fracture that occurs in an area of bone previously weakened by another process i.e. tumor, infection, inherited bone disorder Stress fracture — a hairline fracture of bone resulting from repeated stress Osteoporotic fracture (fragllty fracture or low-trauma fracture occurring Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 10 SHPPPPEHRPLCKKLHKECTLERSeELKHLLLLLPRKLCRPKP LCR PRERePPResR 2a &w. with minimal trauma, such as force equal to or less than falling from standing height) Epidemiology and incidence of osteoporotic fractures 1) Fracture incidence is bimodal, with peaks in youth (15-25 years) and again over age 45 2) Inyoung people, fractures of long bones predominate, often occur following substantial trauma, and the incidence is greater in men than women 3) Above the age of 45, fracture incidence in women increases so that the rate in women becomes twice that of men, and fractures are of the fragility type (Garraway WM, et al. Mayo Clin Proc. 1979;54:701.) 4) Fracture incidence in the United States: Approximately 1.5 million osteoporotic fractures per year. This includes 700,000 spine fractures, 300,000 hip fractures, 250,000 wrist fractures, and 300,000 other fractures (Wwww.NOF.org). Incidence of Osteoporotic fractures Increase with Advancing Age (Modified from Cooper et al. Trends Endocrinol Metab. 1992:3:224-229.) 1) Inwomen, the incidence of forearm fractures begins to rise about age 45 or 60 and levels off around age 65. There is no increase in the rate of forearm fractures in men. 2) Inwomen, the incidence of clinival verlebral (ravtures begins to increase around age 55 or 60 and rises linearly thereafter. In men, the risk of vertebral fractures begins to rise about 5 to 10 years later. 3) Inwomen, the incidence of hip fractures begins to rise about age 65 and increases exponentially; in men, the incidence of hip fractures begins to rise about 5 to 10 years later. Dircction of a fall makes a difference 1) Forward fall (younger women) leads to wrist fracture 2) Sideways fall (older women) leads to hip fracture Distal forearm fractures 1) Third most common osteoporotic fracture (Approximately 250,000 per eat) 2) Marker for future fracture; RR for forearm fracture = 3.3, vertebral fracture RR = 1.7, hip fracture RR = 1.9 (Klotzbuecher CM, et al JBMR 2000; 15:721-739) 3) _ Risk increases early in women (age 45-50) but levels off at age 60-65 4) No increase in men 5) Most are caused by fall on outstretched hand 6) More likely to occur outdoors, in winter (icy weather) 7) Most are diagnosed clinically and confirmed with x-rays 8) Complications of distal forearm fractures: (i) Pain (i) Temporary disability; difficulty dressing, toileting, meal preparation (iii) Degenerative arthritis (iv) Reflex sympathetic dystraphy Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 14() Six months after fracture, 23% report fair/poor recovery in functional outcome (Kaukonen JP et al Ann Chir Gyn 1988; 77:27) Response to Intervention after Wrist Fracture (i) Six months following ER presentation of wrist fracture in untreated patients, only 18% had DXA and 7% were given bisphosphonates in control group. (Majumdar CAMJ 2008; 178:569-575) © Vertebral fracture 1) Vertebral fracture may be wedge, biconcave, or crush. (i) Inwomen, the incidence of clinical vertebral fractures begins to increase around age 55 or 60 and rises linearly thereafter. (i) In men, the risk of vertebral fractures begins to rise about 5 to 10 ears later. Vertebral Fractures Ce etd 4,000 Sn a) Men ee ee) Dress SS ce ey eed fom Cooper C etal. Trends Endocrinol Metab ae 2) Vertebral fracture is the most common osteoporotic fracture (approximately 550,000 per year) 3) Marker for future fracture risk: RR for forearm fracture = 1.4, vertebral fracture RR = 4.4, hip fracture RR = 2.3 (Klotzbuecher CM, et al JBMR 2000; 15:721-739) 4) Risk rises in women at age 50-55, in men at age 60-65, and increases linearly with age 5) Many occur with everyday activities (lifting, pushing, pulling, etc.) 6) Patients with "clinical" vertebral fractures may have severe pain and are confirmed with x-ray /) Only 25% to 30% of vertebral fractures seen on x-ray are diagnosed clinically Consequences of vertebral fractures 1) Include back pain, loss of height, deformity (kyphosis, protuberant abdomen), reduced pulmonary function (decrease vital capacity by 9%), Version 10.0. Copyright © 2010 by the Intemational Socioty for Clinical Densitometry 12diminished quality of life (loss of self-esteem, distorted body image, dependence on narcotic analgesics, sleep disorder, depression, loss of independence), and increased mortality (Gold et al Rheum Dis Clin North ‘Am 2001; 27: 255-62; Harrison et al J Bone Miner Res 2007; 22:447-57) Z. — Hip fractures 1) May ocour at the femoral neck (approximately 40%), at the intertrochanteric region (approximately 40%), or at other hip sites. 2) Inwomen, the incidence of hip fractures begins to rise about age 65 and increases exponentially. 3) Inmen, the incidence of hip fractures begins to rise about § to 10 years later. Dearie) one Cn ae rson-ye A Graph modified from Cooper C et al. ear eee 84 4) Second most common osteoporotic fracture (approximately 300,000 per year) 5) Marker for future fracture risk: RR for vertebral fracture = 2.5, hip fracture RR = 2.3. (Klotzbuecher CM, et al JBMR 2000; 15:721-739) 6) Most are caused by fall from standing height; only about 5% are “spontaneous,” and only 1% of falls lead to hip fracture 7) Most are diagnosed clinically, usually confirmed with radiography; most are hospitalized and require surgery 8) Variability in hip fracture incidence worldwide (Kanis et al. J Bone Miner Res 2002;12:1237-1244). 9) Complications of hip fractures. (i) 24-30% excess mortality within 1 year (ii) Nearly 65,000 American women die from complications of hip fracture each year (iii) 50% of hip fracture survivors are permanently incapacitated (iv) 20% of hip fracture survivors require long-term nursing home care 1. Ray NF et al. J Bone Miner Res. 1997;12:24 Version 10.0 - Copyright © 2010 by the Iniernational Society for Clinical Densitometry 132. Col NF et al. JAMA. 19: 27:1140. 3. Consensus Development Conference. Am J Med. 1993;94:646. 4. Chrischilles EA et al. Arch Intern Med. 1991;151:2026. 10) Failure to diagnose or treat osteoporosis after hip fracture (Kamel HK, et al, Am J Med, 2000;109:326-328). In this study of 170 patients hospitalized for hip fracture, diagnosis and treatment for asteoporosis occurred in less than 10%. AA. Patients with prior fracture 1) Are at high risk for future fragility fractures 2) Patients with wrist or vertebral fracture are at increased risk of wrist, spine, and hip fracture 3) Patients with hip fracture are at increased risk of spine and hip fracture Relative Risk of Future Fractures Prior Fracture Wrist_| Vertebra_| Hip ist 3.3. 17 1.9 fertebra 14 44 25 Hip 25 ag Klotzbuecher CM et al. J Bone Miner Res. 2000;15:721 BB. Survival rates after fracture (Adapted from Cooper C, et al. Am J Epidemiol. 1993;137:1001-1005) 1) After hip fracture, mortality is in the first 6-12 months 2) After vertebral fracture, there is a gradual increase in mortality 3) Five-year excess mortality is increased by about 20% in both hip and spine fractures Survival Rates After Fractures eae 2 1993;137:10 Serious Pee Economic costs of osteoporosis (From data in Ray NF, et al. J Bone Miner Version 10.0 - Copyright © 2010 by the International Saciety for Gli 14 ¢ ( 6 6 ® ‘ ‘ é < < ‘ 4 ‘ ‘ ‘ ‘ § ‘ < ‘ s « ‘ ‘ i a i a i aDD. EE. FF GG Res, 1997;12:24-35.) 1) The distribution of health care dollars for osteoporosis amount to about 62% for hospitalization, 28% for nursing home care and 10% for outpatient care. In 1997, the cost of osteoporosis was about 13.8 billion dollars and about 19 billion in 2005 (www.nof.org) 2) Indirect cost due to loss of productivity and wages is difficult to measure but is likely to be substantial 3) Projected cost for total fractures by 2025 is expected to be 25 billion annually (Burge R et al J Bone Miner Res, 2007; 22:465-475.) Prevalence of common chronic disease in the US (Melton LJ Ill. J Bone Miner Res. 1995;10:175-177,). 1) Osteopenia (low bone density) and osteoporosis: 42.4 million (2010 estimate) 2) Hypercholesterolemia: 98.6 million (2010 estimate) 3) Hypertension: /3.5 million (2010 estimate) 4) Diabetes: 23.6 million (2010 estimate) Incidence of common events in women 1) Inolder women, the incidence of osteoporotic fractures (about 2 million) is greater than the incidence of myocardial infarction, stroke, and breast cancer combined. ical Utility of Bone Densitometry 1) Diagnosis - WHO T-score classification 2) Prognosis ~ Fracture risk assessment 3) Monitoring — Requires knowledge of Precision and least significant change (LSC) Value of bone densitometry for diagnosis of osteoporosis 1) Allows diagnosis of osteoporosis in asymptomatic individuals using the WHO classification prior to fracture 2) Caveats of diagnosis based on BMD (i) Diagnosis of osteoporosis by DXA is based on the WHO classification as a T-score of -2.5 or below (a) Some patients with T-score -2.5 or below do not have osteoporosis (b) Some patients with T-score above 2.5 may be diagnosed with osteoporosis (ii) T-scores may differ at different skeletal sites (iii) Diagnosis of osteoporosis does not explain etiology (iv) Patients with the diagnosis of osteoporosis may have substantially different fracture risk 3) Reviewed in detail in lecture 5: diagnosis 4) Low bone mass can evalve in different ways: (i) Low peak BMD followed by normal rate of loss OR (ii) Normal peak BMD with accelerated rate of loss (ii) A-single BMD examination cannot distinguish these two NOTE: Low BMD does not equal bone loss Version 10.0 - Copyright © 2010 by the international Society for Clinical Densitometry 15HH, Value of bone densitometry for fracture risk assessment 1) 1. Rationale for using BMD to predict fracture risk: ())__ BMD is correlated with bone strength in biomechanical studies of cortical and cancellous bone specimens (material properties) and whole bones (structural properties) (i) BMD is predictive of future fractures in epidemiologic studies (low bone mass is the most important risk factor for predicting first fracture, and the most quantifiable) 2) Material properties of bone specimens (i) Cortical bone (a) Ultimate strength decreases by 2%-5% per decade after age 20 (ii) Cancellous bone (a) Material properties highly variable with density, anatomic site, age (b) 60-80% variability in elastic modulus explained by apparent density (bone mass per unit volume of marrow and bone tissue. (Bouxsein ML, Augat P. Biomechanics of Bone. In Njeh CF, ed. Quantitative Ultrasound. London: Martin Dunitz, 1999:21-46.) 3) Structural properties of whole-bone specimens: (i) Vertebra (a) Correlation between vertebral BMD and failure load better for DXA (r= 0.80-0.94) than QCT (r= 0.30-0,66) because BMD assessed by DXA is influenced by size (ii) Proximal femur (a) Strong correlation between femoral BMD and failure load (r > 0.80) (iii) Distal radius {a) _ Best predictors of fracture load are cortical width and cortical area (r= 0.78-0.94). BMD measured at distal radius most predictive. (Bouxsein ML, Augat P. Biomechanics of Bone. In: Njeh CF, ed. Quantitative Ultrasound. London: Martin Dunitz, 1999:21-46 and Eckstein JBMR 2002; 17:162.) 4) Fracture risk assessment with BMD: {i) 10-year probability of fracture, can be calculated using the Swedish population and NHANES III T-score cutoff values (Kanis, Ol, (2001) 12: 989-995) 5) Reviewed in detail in lecture 6: Fracture risk Value of bone densitometry for monitoring serial changes 1) Because bone densitometry examinations allow quantitative assessment of bone mass, serial monitoring of patients is possible (i) Ideal skeletal site: (a) Rapid bone turnover (b) Low precision error (c) Rapid response to therapy (d) Greatest response to therapy Version 10.0 - Gopyright © 2010 by the paper Society for Clinical Densitometry SOAP HPAKR EH OKOKER SE OEM EH CHL OLOLK LECLERC OC OEL CC DbOMMDOOn(ii) Lumbar spine is best (a) Itspine not valid, use total hip (iii) Least significant change (LSC) must be known 2) Covered in detail in lecture 7; Monitoring Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 7Suggested Readings 10. 1 12 13. 14. 15, 16. 17. 18, 19, 20 24 22. Albright F. Osteoporosis. Ann Intern Med. 1947;27:861 Anonymous, Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med. 1993;94:646-650. Anonymous. NIH Consensus Development Panel. JAMA. 2001;285:785-795, Bellantonio S, Fortinsky R, Prestwood K. How well are community-living women treated for osteoporosis after hip fracture? J Am Geriatr Soc. 2001; 49:1197-1204. Bauer DC. Osteoporotic fractures: Ignorance is bliss? Am J Med. 2000; 109:338-339. Compston JE, Papapaulos SE, Blanchard F. Report on osteoporosis in the European Community: current status and recommendations for the future. Working Party from European Union Member States. Osteoporos Int. 1998;8:531-534 Cooper C, Atkinson EJ, Jacobsen SJ, O'Fallon WM, Melton LJ Ill. Population-based study of survival after osteoporotic fractures. Am J Epidemiol. 1993;137:1001-1005. Cooper C, Campion G, Melton LJ 3d. Hip fractures in the elderly: a worldwide projection. Osteoporos Int. 1992;2:285-289. Cuddihy M-T, Gabriel SE, Crowson CS et al. Osteoporosis intervention following distal forearm fractures: a missed opportunity? Arch Intern Med. 2002; 162:421-426, Feldstein AC et al. J Bone and Joint Surg. 2004:85-A:2294-302 Genant HK, Cooper C, Poor G, et al. Interim report and recommendations of the World Health Organization task force for osteoporosis. Osteoporos Int. 1999;10:259-264. Harrington JT, Broy SB, Derosa et al. Hip fracture patients are not treated for osteoporosis: A call to action. Arthritis Rheum. 2002; 47:651-854. Jachna CM et al, Osteoporos Int. 2003;14:665-671 Kanis JA, Melton LJ Ill, Christiansen C, Johnstan CC. Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9:1137-1141 Khan SA, De Geus C, Holroyd B, Russell AS. Osteoporosis follow-up after wrist fractures following minor trauma. Arch Intern Med. 2001; 161:1309-1312. Kiebzak GM, Beinart GA, Perser K, et al. Undertreatment of osteoporosis in men with hip fracture. Arch Intern Med. 2002; 162:2217-2222. Liel Y et al. Osteaparns Int 2003;14-490-495, Lindsay R, Meunier PJ. Osteoporosis: Review of the evidence for prevention, diagnosis and treatment and cost-effectiveness analysis. Osteoporos Int. 1998;8:S1-S88. Looker AC, Orwoll ES, Johnston CC Jr, et al. Prevalence of low femoral bone density in older U.S, adults from NHANES Il. J Bone Miner Res. 1997;12:1761-1768 Looker AC, Wahner HW, Dunn WL, et al. Updated data on proximal femur bone mineral levels of LIS adults. Osteaparos Int. 1998;8(5):468-489, Melton L¥ lll. Epidemiology of hip fractures: implications of the exponential increase with age. Bone. 1996;18(3 suppl):1218-1258. Melton LJ Ill, How many women have osteoporosis now? J Bone Miner Res. 1995;10:175-177, Version 10.0 - Copyright © 2010 by the international Society for Clinical Densitometry 18 :23, 24, 25, 26. 27, 28. 29. 30. 31 32, 33, Melton LJ Ill. The prevalence of osteoporosis. J Bone Miner Res. 1997:12:1769-1771 O'Neill TW. The prevalence of vertebral deformity in European men and women: the European vertebral osteoporosis study. J Bone Miner Res. 1996;11:1010 Orlic ZC, Raisz LG. Causes of secondary osteoporosis. J Clin Densitom. 1998;2:79-92 Panneman MJM et al Osteoporos Int. 2004;15:120-124. Port L, Center J, Briffa NK, et al. Osteoporotic fracture: missed opportunity for intervention. Osteoporos Int. 2003;9:780 784 Rosen CJ. Restoring aging bones. Scientific American. 2003;288(3):70-77. Ross PD, He Y, Yates AJ, Coupland C, Ravn P, McClung M, Thompson D, Wasnich RD. Body size accounts for most differences in bone density between Asian and Caueasian women. The EPIC (Early Postmenopausal Interventional Cohort) Study Group. Calcif Tissue Int. 1996;59:339-343. Rothberg AD, Matshidze PK. Perimenopausal wrist fracture_an opportunity for prevention and management of osteoporosis. S Afr Med J. 2000; 90:1121-1124. Seeman E, Pathogenesis of bone fragility in women and men. Lancet. 2002;359:1841- 1850 Siris ES, Bilezikian JP, Rubin MR et al. Pins and plaster aren't enough: A calll for the evaluation and treatment of patients with osteoporotic fractures. J Clin Endocrinol Metab. 2003; 88:3482-3486, Solomon DH, Finkelstein JS, Katz JN, et al. Underuse of osteoporosis medications in elderly patients with fractures. Am J Med. 2003; 115:398-400. Version 10.0 - Copyright @ 2010 by the international Society for Clinical Densitometry 19ll, BASIC SCIENCE OF BONE DENSITOMETRY AND DEVICE OPERATING PRINCIPLES A. Learning objectives 1) List and describe the available devices for bone density measurement 2) Explain the principles of operation for () DXA (a) Central skeletal DXA, (b) Peripheral DXA (pDXA) (i) QCT and pact (iii) Quantitative Ultrasound (QUS) 3) Compare and contrast the accuracy of the available bone densitometry devices B. Techniques for bone mass measurement 1) Wide range of commercially available bone densitometry devices. 2) Classified according to their capability to measure specific skeletal sites () Central devices are capable of measuring spine and hip. These devices can also measure the forearm and total body (i) Peripheral devices are capable of measuring wrist, heel, finger, etc.) 3) _ Instruments may be classified by their primary technology platform (x-ray based or ultrasound based). 4) Classified according to skeletal sites (i) Central sites are the vertebral column, ribs and sternum, pelvis, and proximal femur. (ii) Peripheral sites include the upper and lower extremities (but not the proximal femur). Coe L Clo Me ae eSL Ciel} BN mee ai Bam O)oYercm ey cli) Coty Bae * Lower extremities SN) eo Ll CCI Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 205) Basic DXA Anatomy (i) Lumbar spine: Regions of Interest (ROIs) {a) _ Identification of vertebral bodies (i) Analysis includes L1-L4 (i) Anatomic variabilty — i.e. number of vertebral bodies (ii) Be consistent with labeling when anatomic variatior are present Surrounding structures that may help with positioning MSR Rea A Wy Correct Labeling eee aE bow-tie or dog bone Sd te Sos] CORRE] Hip: Regions of Interest (ROIs) (a) Femoral neck box (b) Total hip (c) Greater and lesser trochanters (4) Ward's area Version 10.0 - Copyright © 2010 by the Intemational Society for ( a DensitometryIdentify Bone Correctly ISCI 6) Central densitometry devices: Dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT) 7) Central DXA (i) Current “gold standard’ to which everything else is compared (ii) The technique about which the most is known (iii) Excellent reproducibility (precision see lecture 7) (iv) Low radiation dose (effective dose: 1-3 Sv) (vy) Technique that has been used in most epidemiologic studies. (vi) Well known how DXA-measured BMD relates to fracture risk (vii) Used in most pharmaceutical trials to select subjects for therapy and to document response to treatment over time 8) Peripheral densitometry devices: Peripheral DXA (pDXA), single x-ray absorptiometry (SXA), peripheral QCT (pQCT), quantitative ultrasound (QUS), and radiographic absorptiometry (RA) Principles of operation 1) Principles behind absorptiometry (x-ray attenuation): (i) Attenuation refers to a reduction in the number and energy of photons in an x-ray beam (Le., its intensity) (ii) Attenuation is determinad largely by tissue density and thickness {ili) The more dense the tissue, the more electrons it contains (iv) The number of electrons in the tissue determines the ability of tissue to attenuate photons in the x-ray beam (v) Ifthe degree of attenuation can be quantified, then it would be possible to quantitatively assess the tissue density as well (vi) When using a single energy x-ray beam, the incident beam (lq) is attenuated proportionally to the total amount of mass through which it passes and the beam that is transmitted (|) is detected You cannot separate how much of that mass is due to bone or soft tissue or both. 2) Why dual-energy? (i) The proportion of radiation transmitted through the patient Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 22PUTT TLUcualtt- ltl LCE emerged depends on the eneray of x-ray photons, physical density of the body, and body thickness. Using two different x-ray energies allows a DXA device to record attenuation profiles at two different photon energies. At low energy (30-50 keV) bone attenuation is greater than soft tissue attenuation, whereas at high-energy (greater than 70 keV) bone attenuation is similar to soft tissue attenuation. Thus, two types of tissue are distinguished: bone (hydroxyapatite) and soft tissue (everything else Why Dual-Energies? rag High Energy Low energy (30-50 keV) Nea) Bae ery om ica’ Cee ea an nT | PU CaCl Parra) Bee cule eu) Poort mL : To solve for two unknowns (bone and soft-tissue mass) two equations are needed. The equation for attenuation for two different x-ray energies results in two unique equations. As such, one can solve for both bone and soft-tissue mass. Integral bone mass in the path of an x-ray beam (BMC in grams) divided by projected area of bone (all pixels recognized as bone by edge-detection algorithm, cm’) results in BMD (reported in gfom’). DXA systems require x-ray tube, collimator and x-ray detector: “ (ii) (ili) (v) X-ray photons are produced by an x-ray tube. An x-ray tube Consists of a cathode (negatively charged) and an anode (positively charged) encased in a vacuum tube. It uses a high- voltage source. Approximately 99% of x-ray tube energy is lost to heat. Less than 1% appears as x-rays. Before it reaches the patient, the x-ray beam is collimated (shaped) into a narrow pencil-beam (using a pinhole collimator) or fan-beam (using a collimator) Collimation is used to keep the scattere electrons from reaching sion 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 234) 5) iO) wi) «wii wii the detector Beam passes through the palienil and is selectively attenuated by the patient's bone and soft tissue. After the x-ray beam leaves the patient, it passes to the x-ray detector where the intensity of transmitted radiation is recorded Type of detector depends on the type of system (k-edge filter vs. voltage switching, pencil-beam vs. fan-beam). X-ray tube, collimator, and detector are aligned and mechanically linked using a scanner arm. Producing dual-energies: 0) (ii) (ii) Different approaches: (a) K-edge filtering (GE, Norland) (b) Voltage switching (Hologic) K-edge filtering systems use a constant-potential generator and a k-edge filter to split the polyenergetic x-ray beam into high and low energy components. (a) GE-Healthcare Lunar uses a cerium filter that results in energy peaks of 40 and 70 keV (b) Norland uses a samarium filter that results in energy peaks of 45 and 80 keV {c) Because either a low or high energy photon can hit the detector at any given moment, the detector needs to determine if the photon was high or low energy. This is done with an eneray discriminating detector. (d)__ The energy discriminating detector counts the high and low energy photons at each image position, a technique called pulse counting, (2) Because it takes time to discriminate and count, photon counting systems have limited count rate capabilities. However, they are very good at measuring low photon counts. (f) For systems like this, an external calibration phantom is often used Voltage switching systems switch the high-voltage generator, that is connected to the x-ray source, between high and low peak voltages (kVp) during alternate hallf-cycles of the main power supply. (a) During each cycle, a peaked distribution at either 50 keV or 85 keV is produced. (b) Acurrent-integrating detector system is used (c) Current-integrating detectors sum all the signal during the half cycle since it is know all of the photons are either high (or low) energy. No need to count and discern the energy. (4) __ Integrating detector systems do not have a limiting upper count rate, However, they are sometimes challenged by low count rates. (e) These systems are continuously calibrated using a rotating wheel or drum (internal calibration) Dual-energy production, clinical utility Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 24 a a(i) Clinical utility is not affected by: (a) Method of dual-energy production (b) Type of detectors used (c) Except for the ability to compare results between manufacturers 6) Central DXA scanners are either pencil-beam or fan-beam: (i) Pencil-beam scanners have a collimated x-ray beam and a single detector that move in tandem. Scanning occurs point by point (ii) Fan-beam (or array) scanners have an array of x-rays and detectors. Scanning occurs line by line. Different types: (a) Wide-angle fan-beam is oriented transverse to the long axis of the body (Hologic) (b) — Narrow-angle is parallel to it (GE) Pencil-Beam Bam eluate clio} * Fixed gantry * Single detector * Lower cost ee Cee (ela) EploCD Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 25Fan-Beam reece De a * Line acquisition EMV Us eM [ot te Colec * Faster acquisition (iii) In general, the accuracy and precision of pencil-beam and fan- beam scanners are comparable (iv) Some fan-beam scanners have a rotating gantry that allows for lateral spine scanning with the patient in supine position. No pencil-beam scanners have a rotating gantry (v) _ Ingeneral, fan-beam scanners have shorter scan acquisition time, better image resolution and slightly higher radiation doses. (vi) The major practical advantage of fan-beam scanners is shorter scan times allowing increased patient throughput 7) BMD values of different manufacturers are not comparable due to different: (i) Methods of dual-energy production (ii) Calibration (iii) Detectors (iv) Edge detection software (v) _ Regions of interest 8) Compared to central devices, SXA and peripheral DXA are () Smaller (ii) Portable (ii) Lower radiation doses (iv) Shorter scan times (v) Easier to operate (vi) Less expensive 9) Differences between peripheral DXA devices (i) Ability to scan one skeletal site or two (ii) Pencil-beam or cone-beam configuration (iii) Different normative databases 10) Peripheral DXA systems Version 10.0 - Copyriaht 2010 by the International Society for Clinical Densitometry 26 Sa nena nh renee ean Gee en ee kee PenreeneehePenree kh eeneeneetewrts aa(i) Measure forearm, finger or heel (ii) Donot use a water bath because tissue equalization is accomplished using two x-ray energies to differentiate bone and soft-tissue 11) SXAsystems () — Measure heel or forearm (ii) Require a water bath for soft-tissue equalization (iii) Are being replaced by DXA systems 12) QCT ofthe spine (CT based absorptiometry) () Any commercially available CT scanner may be used (ii) Addition of special software is required (ili) Addition of reference phantom is usually required (iv) Software is used to help place regions of interest within the vertebral bodies (usually L1-L3) (v) Reference phantom is used to convert CT attenuation coefficient (Hounsfield Units, HU) to bone equivalent values (BML) (vi) Most systems require that the patient and phantom are scanned at the same time (vii) Other systems require that the patient and phantom are scanned separately (vii) Some systems may not require use a phantom and instead use the patient's fat and muscle as standards (ix) Recent software improvernents have improved precision and decreased radiation dose 13) Potential advantage of QCT: () Unlike DXA, QCT allows a volumetric BMD measurement (ie., mg/cm*) (ii) Such measurement is independent of the area of the vertebral body so that vertebral size does not cause an error in measuroment (iii) This may be useful in patients who are at the extremes for size and weight (iv) Capable of measuring purely cancellous bone. (Vv) Minimal or no effect from degenerative disease of the spine 14) Potential disadvantage of QCT: () Less precise than PA spine DXA that may be improved with 3D (spiral CT). (ii) Higher radiation dose than DXA 15) Areal (DXA) vs. Volumetric Measurement (QCT) Version 10.0 - Copyright © 2010 by the International Soci 7 'y for Clinical DensitometryDXA vs. QCT Areal vs. Volumetric Measurement ence ea is co zr ODO CL Ce ae ee 16) Peripheral QCT (pQCT) (i) Allows true volumetric BMD measurement of the forearm (i) Separation into cortical and cancellous compartments of bone is possible . (iii) Requires a dedicated pQCT scanner (iv) Portable and easy to use (v) Lower radiation dose than spine or hip QCT (vi) Volumetric BMD (gicm?) (vii) Cortical and cancellous (trab: 17) QUS (Quantitative Ultrasound) (i) Greater technologie diversity than DXA (ii) No radiation (QUS uses sound waves (mechanical vibrations), whereas xray devices (DXA, pDXA, SXA, QCT, RA) use ionizing ] radiation. (iii) Does not measure BMD 18) Diversity in technology among QUS devices (i) Measurement site (a) QUS can only be used peripherally at present (b) Best suited for sites with minimal soft-tissue covering because of variable effect of soft tissue on sound attenuation. (c) Available systems measure the calcaneus, finger, tibia, and multiple sites, / (ii) Transmission (a) Transverse-sound travels through bone (¢.9. GF, Achilles™ and Hologic, Sahara™) (b) _Axial-sound travels along cortex of bone (e.g., Sunlight) (iii) Transducer coupling (a) Water-based systems use water with dissolved ultrasound gel to allow coupling between skin and ultrasound ecular) ROL Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 28 ‘ ii al ‘ ‘ ‘ ‘ ‘ ‘ ‘ ‘ ‘ ‘ ‘ 6 ‘ « ‘ ‘ & ~ « « « € « « «19) 20) 21) D. Accuracy: Trueness and prec 1) transducer (b) Gel-based systems use ultrasound gel to allow coupling between skin and ultrasound transducer (c) Some systems use both water and gel for coupling (iv) Data acquisition (a) Most systems are fixed single-point and measure a different portion of bone depending on bone size (b) Imaging systems allow selection of region of interest which may improve reproducibility in serial measurements of the same patient Parameters that QUS measures (i) Either speed of sound (SOS) or broadband ultrasound attenuation (BUA) of sound are measured (or both) (i) SOS is expressed in meters per sec (m/sec) (iii) BUA is expressed in decibels per megahertz (dB/MHz) {iv) SOS and BUA are lower in patients with osteoporosis compared with controls. Calculated parameters with QUS: {i) Stiffness (GE, Achilles") is mathemati and SOS. (ii) Quantitative Ultrasound Index (Hologic, Sahara™) is mathematical combination of BUA and SOS (iii) Estimated BMD (Hologic, Sahara™) is derived from quantitative ultrasound index (QUI) (iv) Calculated parameters are lower in patients with osteoporosis when compared with controls | combination of BUA Correlation with QUS measurements with BMD (i) Correlation with calcaneal BMD (by DXA) is moderately high (r = 0.6-0.8) (ii) Correlation with spine or hip BMD (by DXA) is modest (r is less than 0.5) (ii) Poor correlation between QUS T-scores and central DXA T- scores is explained in part by different reference populations used (Glier CC. J Bone Miner Res 1997;12:1280 and Faulkner KG, et al. J Clin Densitom 1999;2:343) ion in bone densitometry Accuracy (i) Accuracy is defined by the International Standards Organization (ISO 3534:3.11). Accuracy is the ability of a measurement to match the accepted reference value (ii) Accuracy in densitometry can be affected by two types of error. systematic error (trueness) and random error (precision). Accuracy encompasses trueness and precision. Trueness (ISO 3534:3.12). (i) Ability to measure true value (ii) No perfect way to measure the “true value” of bone mineral content in a bone specimen. Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 29(i) (iv) (v) (wi) (wii) Often expressed as systemic error (% error between true and measured value). Systematic error will cause the average measurement value, from multiple measurements of the same person, to be “untrue” or different than the true value. Systematic error affects the “trueness” of the system, Trueness is an updated way of expressing what is commonly known as “accuracy.” All techniques have associated measurement error (FDA 510K clearance requires less than 10% error of BMD devices). Trueness is most important for diagnosis and for assessment of fracture risk. It is less important for monitoring serial changes. 3) Determining trueness using bone ash method. i ) (iii) ) Laboratory method of determining “true value” of bone mineral content (a) Clean specimen of soft tissue and dry (b) Place in titanium crucible and carefully weigh (c) __Incinerate in a furnace and weigh remaining bone ash The ash is ONLY mineral because all else (e.g., collagen) is incinerated Trueness error is determined by comparing grams of ash to previously measured bone mineral content (grams) using DXA If BMC = 0.95 g and ash = 1.0 g, trueness (ur avcuracy) error = 5% 4) Precision (ISO 3534:3.14). @ (ii) (ii) (iv) (v) Comparison between serial measurements of the same object or person. Random errors cause scatter in multiple measures. However, the average value would siill be “true”. Thus, random errors affect the precision, or reproducibility, of a system. Crucial for comparison between serial measurements of the same object or person (e.g. reproducibility) This type of error is often expressed as a precision error: % error between measurements Can be quantified either using phantom (in vitro) or people (in vivo), In vitro precision is best used to monitor the stability of the system for quality assurance, In vivo precision is best used to determine when true change has occurred in serial measurements on the same individual. This is expressed as the “Least Significant Change" (LSC) and will be discussed in Chapter 5 in detail Knowing in vivo precision is essential for distinguishing random measurement errar from true biologic change when monitoring patients. NOTE: There are many factors that affect the accuracy of densitometry devices. Trueness is most affected by the technology, whereas precision is affected mostly by the operator (technologist). Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 30 I I a Me i a i i iin a i ie i i ane a ii i i a i i i iSystematic (Trueness) vs. Random (Precision) Temes) ene eoticra Cele reer ll lenges Poor precision Good precision (eee pL eed Central DXA: Tru Error PA spine 410% Lateral spine 5-15% Femur 6% Forearm 5% Total body 3% Peripheral DXA: sion Error Forearm 1-2% Calcaneus 1.2% Hand 4-2% Other: Precision Error Trueness Error SXA 1-2% 4-6% Spine QGT 1.5-4% 515% Peripheral QCT 1-2% 2-8% (Gased on Genant HK, et ol.) Bone Miner Res. 1996:11(6}707 5) __ Trueness and precision of QUS (Gller CC. J Bone Miner Res 1997; 12:1280) (i) Because QUS measurements are affected not only by bone mineral content but also by other material properties of bone, trueness is difficult to determine and compare with that of x-ray based densitometric techniques (i) Precision of QUS is somewhat poorer than x-ray based densitometric techniques. (iii) Controversy exists as to how express precision of QUS devices Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 31{iv) NOTE: Standardized precision error has been proposed as a way to adjust for signal magnitude between x-ray and QUS devices Approaches for standardizing precision error include normalizing either the coefficient of variation or the standard deviation of the measurement by one of the following: (a) rates of change due to disease or treatment (b) normal annual rate of change (c) difference between healthy and osteoporotic individual (4) normal variability in healthy individuals Suggested Readings 1 2 Augat P, Fuerst T, Genant HK. Quantitative bone mineral assessment at the forearm: a review. Osteoporos Int. 1998;8:299-310. Blake GM, Fogelman |. Technical principles of dual energy x-ray absorptiometry. Semin Nuc! Med. 1997 Jul; 27(3):210-28 Engelke K, Gliier CC, Genant HK. Factors influencing short-term precision of dual x-ray bone absorptiometry (DXA) of spine and femur. Calcif Tissue Int. 1995;56:19-25. Faulkner KG, Von Stetten E, Miller P. Discordance in Patient Classification Using T Scores. J Clin Densitom. 1999;2:343 Formica CA, Nieves JW, Cosman F, Garrett P, Lindsay R. Comparative assessment of bone mineral measurements using dual x-ray absorptiometry and peripheral quantitative computed tomography. Osteoporos int. 1998;8:460-467 Genant HK, Engelke K, Fuerst T, et al. Noninvasive assessment of bone mineral and structure: state of the art. J Bone Miner Res, 1996;11:707-30. Gluer CC. Quantitative ultrasound techniques for the assessment of osteoporosis: expert agreement on current status. The International Quantitative Ultrasound Version 10.0 - Copyright © 2010 by the Intemational Society for Clinical Densitometry 32 SHPH HPA KHMKHHHHKH GHP HSH OK HHH OHH HKEKHEHKLOKHAHK HK SHKeeBssaarn10. "1 Consensus Group. J Bone Miner Res. 1997;12:1280-1288. Grampp S, Lang P, Jergas M, et al. Assessment of the skeletal status by peripheral quantitative computed tomography of the forearm: short-term precision in vivo and comparison to dual x-ray absorptiometry. J Bone Miner Res. 1995;10:1566-1576 Sievanen H, Koskue V, Rauhio A, Kannus P, Heinonen A, Vuori |. Peripheral quantitative computed tomography in human long bones: evaluation of in vitro and in vivo precision. J Bone Miner Res. 1998;13:87 1-882. Yeap SS, Pearson D, Cawte SA, Hosking DJ. The relationship between bone mineral density and ultrasound in postmenopausal and osteoporotic women. Osteoporos Int. 1998;8:14 1-146. Yu W, Gliier CC, Grampp S, et al. Spinal bone mineral assessment in postmenopausal women: a comparison between dual x-ray absorptiometry and quantitative computed tomography. Osteoporos int. 1995;5:433-439 Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 33MM X-RAY SCIENCE, RADIATION SAFETY, AND QUALITY ASSURANCE A D. Learning objectives 1) List the properties of x-rays 2) State and define the units for expressing radiation dose 3) State the typical dose for densitometric examinations 4) Describe biologic effects of radiation 5) Discuss radiation safety and protection 6) _ State influences on quality originating with the equipment, the patient and the operator 7) Describe instrument quality control procedures for bone densitometers 8) Discuss the considerations and cautions when upgrading equipment hardware and software 9) Comparing results from different DXA devices What is Radiation 1) Radiation is the flow of energy through space and matter. (i) Examples: visible light, radio waves, x-rays. 2) Radiation can be in the form of particles or waves. (i) Examples: (a} Electromagnetic waves such as X-rays and gamma rays (b) _ Particles such as neutrons, electrons, alpha particles 3) _ Radiation can penetrate matter to varying degrees (depends on type of radiation). lonizing Radiation and X-rays 1) Ionizing radiation produces ions (charged atomic particles) after penetrating into matter. 2) _lonizing radiation can damage cells by breaking chemical bonds, etc. 3) X-tays are a subset of lonizing radiation. They are waves of energy (electromagnetic) and are like radio waves, microwaves, light, etc., but of higher energy and capable of ionizing atoms. (i) Short wavelength (ii) Polyenergetic (multiple energy levels) (ii) Emitted by electrical devices. (iv) Activates DXA scanner detector(s) (v) Can penetrate into tissues and cause lonization (vi) Have many different energies, travel in straight lines in all directions, cannot be focused by a lens, cause certain crystals to glow, affect photographic film, and ionize certain gases and tissues. Tissue ionization, the interaction of radiation with atomic electrons, is what leads to the harmful effects of radiation, and must be detected by their effect on other media as they cannot be detected by human senses. Radiation units 1) X-ray output (=exposure) (i) Measurement of x-ray tube output. Measure of x-ray ionization in air. Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 343) (ii) Fxpressed in coulambsikg or roantgens. Skin entry dose (=absorbed dose) (i) Measurement of the total amount of radiation entering the body Maybe expressed as entrance surface dose (ESD) (ii) ESD is absorbed dose to skin where x-ray beam enters. ESD is most easily measured; whereas the effective dose is calculated (iii) Skin entry dose does not consider the size of beam and organs exposed. (iv) Reported by the manufacturer (v) Expressed as gray (Gy) or rad NOTE: 1 gray = 100 rad Effective dose (=dose equivalent): (i) This is a calculated dose and calculates the potential biological harm radiation may have on the tissue after being absorbed (ii) Expressed as sievert (Sv) or rem (a) Dose corrected for type of radiation and tissue sensitivity (b) _ Preferred for expressing and comparing dose (c) Effective dose = DQwy D = absorbed dose Q = quality factor (diagnostic x-rays = alpha particles = 20) wT = tissue weighting factor (account for varying radiosensitivity of different tissues, these add up to 1 fora total body exposure) NOTE: 1 Sv = 100 rem; 10 Sv = 1 mrem Skin entry Dose vs. Effective dose (i) Skin entry dose (uGy) is the correct method to check if you device is working within specifications (ii) Fffective dose (uSv) can typically be found in the published literature and differs from the skin entry dose reported by manufacturers (ili) Effective dose (uSv) is the correct method to compare the potential radiation harm of different radiological procedure Tissue weighting factors . protons = 10, Tissue __wt Gonads 0.20 Bone marrow 0.12 Lung 0.12 Colon 0.12 Stomach 0.12 Thyroid 0.05 Breast 0.05 Other _ 0.22 TOTAL 1.00 inleravonal Cmmnision an Radiation Prolacton Publication 60. Ann ICRP. 1991:211-3 Radiation units (i) Entrance dose easily measured (i) Mean marrow and gonadal doses usually calculated (effective dose) (iil) For x-rays grays and sievert are equivalent for total body Version 10.0 - Copyright © 2010 hy the International Seciety for Clinical Densitometry 35E. mn Radiation dose for densitometric examinations 1) Determinants of radiation dose (i) Equipment (fan-beam vs. pencil-beam, scan mode) (il) Patient (body part scanned, patient size) Effective Radiation Doses (uSv) for DXA Systems at Different Skeletal Sites oa oR 1000/4000 | 4500/Delphi enneeetak ary (excl. ovaries) cor (inc, ovaries) 2) For comparison: Natural background 5-8 j1Sv per day Mammography 450 Sv Chest x-ray 50-150 uSv (depends on technique) Lateral lumbar x-ray 700 Sv L-spine +T-spine xray 1800-2000 uSv VFA 30-50 uSv Genant HK, etal J Bone Miner Ras. 1996;11:707, lender WA. Osteoperas int. 1992:2:82 Lewis MK, etal. Osteoporos ini, 19940411 Bonrick $ and Lewis LA‘Bane Denstomety for To is Humana Prass 2008 3) When comparing doses, be aware of whether entry skin dose (ESD) or effective dose (generally much lower) is reported, Skin entry dose is often cited by manufacturers and is much higher than effective dose. Biologic effects of radiation 1) Carcinogenesis (i) Excess cancer deaths in Japanese atamic bomb survivors (ii) Probability of fatal cancer: 1% per Sv (1 million DXA exams) 2) Mutagenesis (exposure of parents) (i) Probability of severe genetic effects in succeeding generations (i) 1% per Sv (1 million DXA exams) 3) Teratogenesis (in-utero exposure) Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 36 SPHLEPF HHH HH ASHSKKEKHKREKEKHO KK KKK OHHH OE HEHE REDE RE Bar(i) Pre-implantation death, congenital anomalies (mental retardation) (ii) Minimum dose of 100 mSv (100,000 DXA exams) 4) Biologic effects of radiation are usually categorized as stochastic or deterministic (American College of Radiology, Radiation Risk: A Primer, 1996.) (i) Stochastic effects of radiation (a) Increase in random adverse effects (b) Occur at low dose (c) Probability of occurrence is a function of dose (d) Examples are cancer and mutation (e) Small risk, no threshold dose () Example: skin cancer will occur in some at a ten to twenty year latency. The number affected will be proportional to the dose (ii) Deterministic effects radiation (a) Occur ata very high dose (b) Occur in each individual receiving sufficient dose (c) Examples are acute radiation sickness and cataracts (d) There is a threshold dose (1.2-3.0 Sv) below which effects are insignificant (e) The threshold dose is much greater than doses used in medical imaging (including DXA and QCT) (f) Example: sunburn will affect all who sunbathe long enough ion dose from central DXA Dose to patient small compared to other radiological exams (1/50" to 1/1000" of the dose) 2) Dose to technologist mostly from scatter radiation is so small that it may be difficult to detect 3) Ata distance greater than 1 meter away from the scanner table the radiation dose is negligible (no different than background) 4) Examples of typical effective radiation doses DXA 1-5 Sv per exam Natural background 5-8 Sv per day LA-NY-LA flight 60 Sy Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 3fAverage Annual Effective Radiation Doses in the USA (uSv) Background 2951 Man-made 650 Radon 1980 Medical X-ray 390 Cosmic 290 Nuclear Medicine 140 Terrestrial 290 Nuclear Industry 20 icles) 0) Consumer Products 100 5) Maximal permissible dose in United States (i) General public (a) Excluding medical or dental (b) 5,000 Sv per year (c) 1,000 Sv per year (International Standard) (ii) Occupational exposure (a) For example, technologist (b) 50,000 Sv per year H. Radiation safety and protection 1) Why teach radiation safety? (i) Patient education (a) People fear what they do not understand (b) Patients deserve and require care from those properly trained and educated (ii) Protection of patients and technologists requires understanding of radiation safety (iii) Communication with (a) Patients (b) Technologists (c) _ Regulatory agencies 2) Elements of radiation safety (i) Justification (a) Medical necessity: Is the information obtained from the test essential for patient care and will it influence medical care? (b) _ Can the information be obtained using other means? (ii) Regulation (a) Practice must comply with all local, state (provincial) and Version 10.0 - Copyright © 2010 by the International Sociaty for Clinical Densitometry 36federal (national) regulations (iii) Optimization (2) ALARA: As Low As Reasonably Achievable 3) Radiation safety for general radiography (i) Time (a) Minimize exposure (i) Distance (a) Maintain safe distance (b) Intensity decreases as the square of distance away from source (ii) Shielding (a) _ Use appropriate shielding when necessary 4) Radiation safety for bone densitometry (i) Time (ii) Distance (a) Maintain safe distance from DXA scanner (b) Technologist greater than 1 meter from edge of table (c) Exposure declines as the square of the distance from the radiation source (doubling distance that the technologist is away from scanner reduces exposure by a factor of four) (iii) Shielding (a) — Room shielding usually not necessary (b) Most densitometers are shielded internally (c) Very limited requirements (iv) Patient (a) Proper collimation (6) Beam scan limits (c) _ Prescreen for contraindications (v) Technologist (a) Keep at least 1 meter trom table edge while scanning (b) May wear personal dosimeter (vi) Public (a) Post room with “caution radiation’ signs (b) Exclude visitors while scanning (c) _ Room shielding not necessary (vil) Check federal, state and local regulation Precautions regardiny pregnancy (patient) (i) Ask all premenopausal or perimenopausal women if they may be pregnant (ii) If possible pregnaney, postpone exam until pregnancy is ruled out 6) Precautions regarding pregnancy (technologist) (i) Technologist should be encouraged to notify employer in writing of possibility of pregnancy (i) Pregnant technologist may be offered reassignment to other duties or shielding with lead apron to reduce concerns (iii) May wear badge at abdomen to monitor fetal radiation (under apron) (iv) Permissible dose for technologist 5000 uSv for duration of pregnancy, not to exceed 500 uSv per month ° Version 10.0 - Copyright © 2010 by the Intemational Society far Clinical Densitometry 39Factors influencing quality 1) Scanner related (i) Accuracy and precision (ii) Machine calibration 2) Patient related (i) Artifacts (ii) Deformities (iii) Patient cooperation (motion) 3) Operator (technologist) related (i) Acquisition (patient positioning) (i) Analysis Clinical quality control procedures 1) Calibration methods (i), Internal (continuous) (a) — Required with oscillating supply (e.g. Hologic scanners) (b) X-ray passes through calibration filter (drum or wheel) while patient is being scanned {c) Calibration filter contains bone, tissue, and air equivalent (4) Point by point calibration (ii) External (periodic) (a) Daily scanning of known bone and tissue standards (e.y. GE-Healtheare Lunar and Norland scanners) — incorporated in daily quality assurance (b) Utilizes a calibration standard (©) May automatically adjust calibration factors as needed (depends on make and model of device) 2) Quality control: (i) Gentral DXA systems include a phantom that should be scanned routinely to assess stability of the system (li) Note: Phantoms monitor the daily performance of your scanner; phantom BMD should remain stable over time (iii) Any observed visual trend in quality control plot away from baseline should be investigated as a possible calibration shift (a) Some peripheral devices including QUS have phantoms 3) _ ISCD position: phantom scanning and calibration (i) Adhere to manufacturer guidelines (ii) Periodic (at least one per week) phantom scans are recommended as an independent check of system quality assurance (iii) Plot and review QC data regularly (iv) Verify phantom mean BMD after any service performed on the system (v) Establish and enforce corrective action thresholds (vi) Maintain service logs (vii) Comply with government inspections, radiation surveys and all regulatory requirements 4) Calibration shift may occur with Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry au() Relocation (ii) Maintenance (ii) Change of x-ray tube or detector Calibration SI 1.08 5 F Es ‘1SCD Mad 5) Calibration drift may occur with (i) Change in room conditions (temperature, humidity) (ii) Change in power supply (ili) Aging of x-ray tube or detector Cc TeuitlamTetig 1047 SSD vem s0 Comparing different DXA systems: Data is not interchangeable. 1) Different DXA Systems , same manufacturer (i) May use different acquisition methods (e.g., pencil vs. fan beam) (ii) May use different software Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 41(ili) May use different young normal databases, (iv) Inter device variability +/- 2% 2) Different DXA Systems, different manufacturers (i) Use different method for dual energy production (ii) Use different methods of x-ray detection (iii) Are calibrated differently (iv) _ Use different edge detection software (v) May use different regions of interest (vi) Use different young normal databases (vii) Inter-device variability +/- 5-7% NOTE: If you have upgraded your software between studies, you may want to reanalyze the baseline study with the new software before comparing it with follow-up study. (viii) Conversions of patient data between manufacturers should be used with caution. Previously published conversion equations that provided standardized BMD (sBMD) used data from older technology. (a) Genant HK, etal. J Bone Miner Res. 1994:9:1503-1514 (b) _ Hanson J. J Bone Miner Res, 1997;12:1316-1317 (ix) SBMD should not be used for individual patients Upgrading of central DXA equipment If cross-calibration study is not performed, no quantitative comparison to the prior machine can be made. Consequently a new baseline BMD and intra- system least significant change (LSC ~ see lecture 7) should be established 1) Hardware changes () When changing hardware or when replacing with the same manufacturer and model, cross calibration should be performed. (li) Have one technologist do 10 phantom scans with repositioning before and after hardware change. (iii) If more than 1% difference in mean BMD, contact manufacturer for service 2) System changes ()) When changing an entire system to one made by the same manufacturer using different technology (fan vs pencil beam) or when changing to a system made by a different manufacturer, one approach to cross calibration is: (a) Scan 30 patients representative of the facilities patient population once on the old system and twice on the new system within 60 days (b) Measure spine and hip (c) Calculate the average BMD relationship and least significant change (LSC — see lecture 7) between the ald and new machine using the ISCD cross calibration tool (ii) Use the LSC for comparison between old and new system. Inter- system quantitative comparison can only be made if cross- calibration is performed on each skeletal site commonly measured Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 42(ili) Once a new precision assessment has been performed on the new system, all future scan should be compared to scans performed on the new system using the newly established intra- system LSC 3) Between Facilities Itis not possible to quantitatively compare BMD or to calculate a LSC between facilities without cross-calibration 4) Software changes (i) Check with manutacturer before installing any software upgrade (li) Know the reason for the upgrade. Examples: Modification of edge detection algorithms; reporting systems; normative database updates; new features (iii) Generally will not affect BMD results but may affect T-scores and ‘ Z-scores such as the Hologic and GE-Healtheare Lunar NHANES updates. (iv) Verify any change in manufacturer's reference database as this may change T-score and/or Z-score. Unintentional consequences can occur with software changes (see Binkley et al JBMR 2005. 20(2); 195-201) (v) After installing new software compare phantom mean BMD with that prior to new software. New mean should be nearly identical (vi) Another alternative is to reanalyze some patient scans previously obtained with old software usiny 1ew suflware (without changing region of interest). Results of old and new analysis should be nearly identical Version 10.0 - Copyright © 2010 by the International Society for Clinical Densitometry 43Suggested Readings ‘American College of Radiology. Radiation Risk: A Primer, 1996. 2, Blunt BA, Jones DJ, Svensen RK, Hans DB, Feinblatt JD, Genant HK. Good clinical practice and audits for dual x-ray absorptiometry and x-ray imaging laboratories and quality assurance centers involved in clinical drug trials, private practice, and research. J Clin Densitom. 1998;1:323-337 3. Faulkner KG, McClung MR. Quality control of DXA instruments in multicenter trials. Osteoporos Int. 1995;5:218-227. 4. Faulkner KG, Von Stetten E, Miller P. Discordance in patient classification using T- scores. J Clin Densitom. 1999;2:343-349. 5. Finkelstein JS, Butler JP, Cleary RL, Neer RM. Comparison of four methods for cross- calibrating dual-energy x-ray absorptiometers to eliminate systematic errors when upgrading equipment. J Bone Miner Res. 1994;9:1945-1952. 6. Genant HK, Grampp S, Gltier CC, et al. Universal standardization for dual x-ray absorptiometry: patient and phantom cross-calibration results. J Bone Miner Res. 1994:9:1503-1514 7. Genant HK, Engelke K, Fuerst T, et al. Noninvasive assessment of bone mineral and structure: state of the art. J Bone Miner Res. 1996;11:707-730. 8, Hanson J. Standardization of femur BMD. J Bone Miner Res. 1997;12:1316-1317 9. Kalender WA. Effective dose values in bone mineral measurements by photon absorptiometry and computed tomography. Osteoporos int. 1992;2:82-87. 10. Lewis MK, Blake GM, Fogeiman I. Patient dose in dual x-ray absorptiometry. Osteoporos Int. 1994;4:11-15. 11. Lloyd T, Eggli DF, Miller KL, Eggli KD, Dodson WC. Radiation dose from DXA scanning to reproductive tissues of females. J Clin Densitom. 1998; 1:379-383 12. Steiger P, Genant HK, German ME, Hangartner T, Hanson J, Kalender WA, Standardization of postero-anterior spine bone mineral density measurements. Eur J Radiol. 1995;20:198-199. 13. Bushong, SC. Radiologic science for technologists, 7” ed. St. Louis, MO: Mosby, Inc; 2001 14. Forshier, S. Essentials of radiation biology and protection. Albany, NY: Delmar Press; 2002. Version 10.0 - Copyright © 2010 by the International Sociely for Ciinical Densitometry 44