Executive Summary of the 2015 ISCD Position Development Conference on Advanced Measures From DXA and QCT: Fracture Prediction Beyond BMD

Executive Summary of the 2015 ISCD Position Development Conference on Advanced Measures From DXA and QCT: Fracture Prediction Beyond BMD

Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health, vol. 18, no. 3, 274e286, 2015 Ó Copyright 2015 by The Internation...

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Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health, vol. 18, no. 3, 274e286, 2015 Ó Copyright 2015 by The International Society for Clinical Densitometry 1094-6950/18:274e286/$36.00 http://dx.doi.org/10.1016/j.jocd.2015.06.013

2015 ISCD Position Development Conference

Executive Summary of the 2015 ISCD Position Development Conference on Advanced Measures From DXA and QCT: Fracture Prediction Beyond BMD John A. Shepherd,*,1 John T. Schousboe,2 Susan B. Broy,3 Klaus Engelke,4,5 and William D. Leslie6,7 1

Department of Radiology and Biomedical Imaging, University of California at San Francisco, San Francisco, CA, USA; 2 Park Nicollet Clinic/Health Partners, Division of Health Policy and Management, University of Minnesota, USA; 3 Department of Medicine, Rosalind Franklin School of Medicine, Chicago Medical School, North Chicago, IL, USA; 4 Institute of Medical Physics, University of Erlangen, Erlangen, Germany; 5Bioclinica, Hamburg, Germany; 6Department of Medicine, University of Manitoba, Winnipeg, Canada; and 7Department of Radiology, University of Manitoba, Winnipeg, Canada

Abstract There have been many scientific advances in fracture risk prediction beyond bone density. The International Society for Clinical Densitometry (ISCD) convened a Position Development Conference (PDC) on the use of dualenergy X-ray absorptiometry beyond measurement of bone mineral density for fracture risk assessment, including trabecular bone score and hip geometry measures. Previously, no guidelines for nonbone mineral density DXA measures existed. Furthermore, there have been advances in the analysis of quantitative computed tomography (QCT) including finite element analysis, QCT of the hip, DXA-equivalent hip measurements, and opportunistic screening that were not included in the previous ISCD positions. The topics and questions for consideration were developed by the ISCD Board of Directors and the Scientific Advisory Committee and were designed to address the needs of clinical practitioners. Three task forces were created and asked to conduct comprehensive literature reviews to address specific questions. The task forces included participants from many countries and a variety of interests including academic institutions and private health care delivery organizations. Representatives from industry participated as consultants to the task forces. Task force reports with proposed position statements were then presented to an international panel of experts with backgrounds in bone densitometry. The PDC was held in Chicago, Illinois, USA, contemporaneously with the Annual Meeting of the ISCD, February 26 through February 28, 2015. This Executive Summary describes the methodology of the 2015 PDC on advanced measures from DXA and QCT and summarizes the approved official positions. Six separate articles in this issue will detail the rationale, discussion, and additional research topics for each question the task forces addressed. Key Words: Dual-energy X-ray absorptiometry; finite element analysis; guidelines; opportunistic screening; quantitative computed tomography.

Introduction

Received 06/30/15; Accepted 06/30/15. *Address correspondence to: John A. Shepherd, PhD, CCD, Department of Radiology and Biomedical Imaging, University of California at San Francisco, 1 Irving Street, Suite A-C108B, San Francisco, CA 94143. E-mail: [email protected]

The International Society for Clinical Densitometry (ISCD) is a nonprofit professional organization dedicated to the advancement of assessment of musculoskeletal health, 274

Executive Summary particularly (but not limited to) bone densitometry. A major focus of the society is the development of guidelines and establishment of standards for bone densitometry, assessment of fracture risk, and other aspects of musculoskeletal measurement. In recognition of the many scientific advances in the use of dual-energy X-ray absorptiometry (DXA) scans for measures other than bone density, and further advances in fracture risk assessment using computed tomography (CT), the ISCD convened a Position Development Conference (PDC) on the use of advanced measures from DXA and quantitative computed tomography (QCT) to assess fracture risk. The society conducts PDCs every 2e3 years to develop guidelines and standards (expressed as position statements) for new technologies used to assess musculoskeletal health and fracture risk, and to update older guidelines and standards as new data become available. The ISCD official positions are widely used by clinicians and densitometry technologists as a reference regarding the indications for, acquisition of, and interpretation and reporting of measures of musculoskeletal health, as well as incorporation of those measures into fracture risk assessment. The curricula of the densitometry educational courses provided by ISCD are heavily influenced by these positions. The ISCD PDC process is designed to summarize and use the best scientific evidence available to develop and update position statements regarding musculoskeletal assessment. Because musculoskeletal assessment technologies are evolving, clinically important issues are sometimes addressed in the absence of robust evidence and thus are largely based on expert opinion. However, the PDC process grades and highlights the limitations of the available evidence pertinent to each statement and indicates where additional research is needed to improve the scientific evidence on which positions are based as well as to resolve areas of ambiguity and controversy. Position statements from prior PDC’s held in 2001, 2003, 2005, 2007, 2010, and 2013 have been published (1e9). The most recent PDC was held in Chicago, IL, USA, February 26 through February 28, 2015. This article describes the methodology of this PDC, and the results from the topics regarding advanced measures from DXA and QCT for fracture prediction beyond BMD.

Methodology Potential topics for the 2015 ISCD PDC were solicited from the ISCD Board of Directors, executive committee, and members of the scientific advisory committee. Candidate topics were then ranked in order of importance. Trabecular bone score (TBS) was identified as an important new application of DXA requiring new guidelines and standards. However, TBS is only one in a class of non-BMD measures from DXA scans that had not been previously reviewed by the ISCD: hip geometry measures including hip structural analysis (HSA), hip axis length (HAL), and neck-shaft angle (NSA). In addition, there have been recent advances in the use of CT to assess fracture risk using either QCT of the hip, advanced analysis algorithms such as finite element analysis (FEA), or the opportunistic evaluation of CT scans acquired for nonbone-related clinical reasons.

275 A steering committee was formed consisting of the President-Elect of ISCD (John A. Shepherd, who served as chair), the current ISCD president (William D. Leslie), and past president (John T. Schousboe), all with extensive experience leading and moderating prior PDCs. Scientific questions within each topical area were chosen by the PDC steering committee. The questions asked of the task forces regarding the clinical utility of the non-BMD measures from DXA and QCT were as follows. B

B

B

B

B

Can the measure be used to diagnose osteoporosis? - Are there adequate reference data to use the measure clinically? - Are reference data for the measure affected by age, sex, and ethnicity? Can the measure be used to assess fracture risk? - How should the measure be used relative to other fracture risk assessment tools? Can the measure be used for monitoring? - Monitoring of individuals not receiving treatment? - Monitoring of individuals receiving treatment? - What is the short-term and long-term precision of the measure in routine practice? - What are the quality assurance and quality control (QA/QC) criteria for the measure? Are there special conditions where the measure has greater or lesser clinical utility? - Clinical role in Glucocorticoid-induced osteoporosis (GIOP) or other secondary osteoporosis? - What are the limitations and contraindications to using the measure? What are the required elements in a clinical report of the measure?

2015 PDC Structure Formation of and function of task forces: 3 task forces were formed to address the questions in 3 primary areas: TBS, hip geometry (including HSA), and QCT. Task force chairs were selected because of their high level of expertise in these areas. Along with the steering committee, they selected additional experts in the field to serve as task force members. Each task force was asked to perform a literature search using the methodology of previous PDCs, focusing on PubMed, MEDLINE, and Embase databases. Informed by the published literature, the task forces had the option to refine the questions initially proposed, in consultation with the steering committee. Each task force then drafted proposed position statements to address the questions assigned. The task force chairs, in consultation with task force members, then wrote detailed reports describing the proposed position statements, supporting rationale and literature. Formation of and function of the expert panel: starting with the adult and pediatric PDCs of 2007, the ISCD PDCs have followed the RAND-UCLA method of rating the appropriateness of candidate position statements RAND/UCLA Appropriateness Method (RAM) that is described in more detail in the next section (10). This method requires that an

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expert panel, completely separate from the task forces, be formed to review and rate the proposed position statements after considering the supporting documents. Expert panel members were chosen on the basis of 4 criteria; (1) acknowledged expertise in at least one of the topic areas; (2) representative of different geographic regions; (3) representative of other professional societies with a commitment to the field of musculoskeletal measurement; and (4) a keen ability to weigh scientific evidence. Accordingly, 12 international experts were invited and agreed to serve on the expert panel, were able to attend all presentations from each task force as well as the deliberations of the expert panel, and rated the proposed position statements.

(3) Strength of recommendation. The strength of the recommendation to implement the statement was rated as; (A) strong recommendation supported by the available evidence; (B) recommendation supported by the available evidence; or (C) recommendation supported primarily by expert opinion. It should be noted that a statement could be rated as being supported by a good quality of evidence and yet have a level C strength of recommendation, if the beneficial consequences of implementation of the statement were judged to be slight or offset by negative consequences. (4) Applicability. Statements were rated as applicable throughout the world (worldwide) or applicable according to local requirements (local).

2015 PDC Procedures

Second round expert panel voting at the PDC in Chicago, IL: based on the initial rating by the expert panel, the task forces revised their initial documents and presented these revised documents in detail to the expert panel in sessions open to the public on February 28, 2015. Statements that were rated as inappropriate in the first round of rating were not considered further or presented. Statements that were rated as appropriate without disagreement in the first round of expert panel voting were presented briefly and, with a few exceptions, accepted and rated again as appropriate in their original wording and content. A few of these statements, however, were altered at the behest of the expert panel before being rated as appropriate during the second round. Most of the time in the open sessions was spent debating statements that were rated as uncertain. Some of these statements were rated as inappropriate on the second round votes, some were again voted as uncertain, and some that were voted as uncertain on the first round were voted appropriate without disagreement on the second round. Final selection of and approval of the 2015 ISCD official positions: the expert panel, task force chairs, and the 2015 PDC steering committee met again in closed session on March 1, 2015, to refine the final wording of the statements that would be submitted to the ISCD Board of Directors for review and approval. The final statements rated as appropriate without disagreement, along with their ratings regarding quality of evidence, strength of recommendation, and applicability, and the supporting literature reviews, were reviewed by the ISCD Board of Directors. The ISCD Board of Directors voted to approve all these statements on May 14, 2015. The rationale supporting these positions is presented in 6 separate articles also published in this issue of JCD (11e16).

The 2015 PDC procedures, including the literature reviews performed by the task forces, formulation of position statements to address the questions posed to the task forces, and the rating of those statements, all followed a modified RAM (2,4,10). The RAM not only includes ratings as to whether or not a statement is appropriate but also explicitly grades the quality of the evidence on which the statement is based. This process recognizes that although based on the currently available evidence, a statement may be considered to be appropriate although the evidence may be weak. Grading of the quality of evidence places the statement in the appropriate context. The task forces presented the proposed statements and the supporting scientific evidence for each statement in 2 steps. The task forces finished their literature reviews and draft documents by January, 2015. These were sent to all expert panelists, who conducted their initial round of rating from January 15 through January 29, 2015 without consulting each other. Grading of the official positions: all statements were rated by each expert panelist in 4 areas. (1) Appropriateness. The appropriateness of each statement was voted on a scale of 1e9 with 1 representing ‘‘highly inappropriate’’ and 9 representing ‘‘highly appropriate’’. Statements that had a median score of 1e3 were rated as ‘‘inappropriate’’, those with a median score of 4e6 as ‘‘uncertain’’, and those with a median score of 7e9 as ‘‘appropriate’’. Statements were considered to be ‘‘appropriate without disagreement’’ if, in addition to a median score of 7e9, no more than 3 expert panelist ratings fell outside this range. (2) Quality of evidence. The quality of the evidence supporting each statement was rated as being good, fair, or poor. ‘‘Good’’ evidence was from 2 or more well-designed prospective studies (randomized controlled trials or high quality observational studies). ‘‘Fair’’ evidence was judged to be sufficient to determine effects on outcomes but limited by the number, quality, or consistency of the available studies. ‘‘Poor’’ evidence was judged to be insufficient to determine effects or consequences of implementing the statement on outcomes, due to the number of available studies, flaws in their design or conduct, major gaps in the chain of evidence, or conflicting evidence.

Participants The list of individuals who comprised the 2015 PDC steering committee, served on each of the task forces, or served on the expert panel is shown in Appendix A. All PDC participants were required to fully disclose any real or perceived conflicts of interest using the ISCD disclosure form. Any potential conflict of interest was thoroughly vetted with the Chair of the respective task force, steering committee liaison to the task force, and the PDC steering committee before

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Executive Summary appointment. Industry scientists and representatives were excluded from participating as task force or expert panel members but were allowed to act as technical consultants to the task force to ensure that position statements were not incompatible with the technology itself.

Financial Support The following industry partners gave financial support that made the PDC possible; Amgen, Inc. (Thousand Oaks, California, USA) and Merck, Inc. (Kenilworth, New Jersey, USA) Industry partners providing financial support played no role in the PDC or its recommendations.

Cumulative ISCD Official Positions A summary of all the ISCD positions for this and all past PDCs that remain current is shown in Appendix B.

New ISCD Official Positions on Advanced Measures From DXA and QCT Trabecular Bone Score (1) TBS is associated with vertebral, hip, and major osteoporotic fracture risk in postmenopausal women. Grade: good-B-W (2) TBS is associated with hip fracture risk in men O50 yr. Grade: fair-B-W (3) TBS is associated with major osteoporotic fracture risk in men O50 yr. Grade: fair-C-W (4) TBS should not be used alone to determine treatment recommendations in clinical practice. Grade: good-A-W (5) TBS can be used in association with FRAX and BMD to adjust FRAX-probability of fracture in postmenopausal women and older men. Grade: good-B-W (6) TBS is not useful for monitoring bisphosphonate treatment in postmenopausal women with osteoporosis. Grade: good-A-W (7) TBS is associated with major osteoporotic fracture risk in postmenopausal women with type II diabetes. Grade: fair-B-L Hip Geometry (8) HAL derived from DXA is associated with hip fracture risk in postmenopausal women. Grade: fair-B-L (9) The following hip geometry parameters derived from DXA (cross-sectional area [CSA], outer diameter [OD], section modulus [SM], buckling ratio [BR], crosssectional moment of inertia [CSMI], NSA) should not be used to assess hip fracture risk. Grade: fair-B-W (10) Hip geometry parameters derived from DXA (CSA, OD, SM, BR, CSMI, HAL, NSA) should not be used to initiate treatment. Grade: fair-B-W

277 (11) Hip geometry parameters derived from DXA (CSA, OD, SM, BR, CSMI, HAL, NSA) should not be used for monitoring. Grade: good-A-W Quantitative CT (12) QCT acquisition of the proximal femur should extend from the femoral head to the proximal shaft. Grade: good-A-W (13) For density-based QCT measurements the in-scan calibration phantom can be replaced by asynchronous calibration if scanner stability is maintained. Grade: fair-B-W (14) Opportunistic CT to screen for patients with low BMD or low bone strength of the spine or proximal femur is possible only if validated machine-specific cutoff values and scanner stability have been established. Grade: Fair-C-W (15) Femoral neck and total hip T-scores calculated from 2D projections of QCT data are equivalent to the corresponding DXA T-scores for diagnosis of osteoporosis in accordance with the WHO criteria. Grade: fair-B-W (16) Total femur trabecular BMD measured by QCT predicts hip fractures and hip BMD measured by DXA in postmenopausal women and older men. Grade: fair-B-W (17) Where QCTand DXA are both available and provide comparable information, DXA is preferred to limit radiation exposure. Grade: fair-C-W (18) Integral and trabecular BMD of the proximal femur measured by QCT can be used to monitor age- and treatment-related BMD changes. Grade: fair-B-W FEA by QCT (19) Vertebral strength as estimated by QCT-based FEA predicts vertebral fracture in postmenopausal women. Grade: fair-B-W (20) Vertebral strength as estimated by QCT-based FEA is comparable to spine DXA for prediction of vertebral fractures in older men. Grade: fair-B-W (21) Femoral strength as estimated by QCT-based FEA is comparable to hip DXA for prediction of hip fractures in postmenopausal women and older men. Grade: fair-B-W (22) FEA cannot be used to diagnose osteoporosis using the current WHO T-score definition. Grade: good-A-W (23) Vertebral or femoral strength as estimated by QCT-based FEA can be used to initiate pharmacologic treatment using validated thresholds and in conjunction with clinical risk factors. Grade: fair-B-W

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278 (24) Vertebral or femoral strength as estimated by QCT-based FEA can be used to monitor age- and treatment-related changes. Grade: fair-B-W

Acknowledgments As was true of prior Position Development Conference’s (PDC’s), the 2015 International Society for Clinical Densitometry (ISCD) PDC was made possible only through the extensive voluntary efforts of large numbers of individuals, notably the clinical and scientific experts who donated countless hours over the past 18 mo as task force chairs, task force members, or expert panel members. The ISCD wishes to acknowledge and thank these individuals for their extraordinary service. Additionally, the staff of ISCD plays a crucial role organizing the logistics and infrastructure of these conferences so they can run smoothly. Those of us on the steering committee of the 2015 ISCD PDC thank them for their efforts and support.

Shepherd et al. 11. Engelke K, Lang T, Khosla S, et al. 2015 Clinical use of quantitative computed tomography (QCT) of the hip in the management of osteoporosis in adults: the 2015 ISCD official positionsdPart I. J Clin Densitom 18:338e358. 12. Zysset P, Qin L, Lang T, et al. 2015 Clinical use of quantitative computed tomographydbased finite element analysis of the hip and spine in the management of osteoporosis in adults: the 2015 ISCD official positionsdPart II. J Clin Densitom 18:359e392. 13. Engelke K, Lang T, Khosla S, et al. 2015 Clinical use of quantitative computed tomographydbased advanced techniques in the management of osteoporosis in adults: the 2015 ISCD official positionsdPart III. J Clin Densitom 18:393e407. 14. Broy SB, Cauley JA, Lewiecki EM, et al. 2015 Fracture risk prediction by non-BMD DXA measures: the 2015 ISCD official positions part 1: hip geometry. J Clin Densitom 18:287e308. 15. Silva BC, Broy SB, Boutroy S, et al. 2015 Fracture risk prediction by non-BMD DXA measures: the 2015 ISCD official positions part 2: trabecular bone score. J Clin Densitom 18: 309e330. 16. Beck TJ, Broy SB. 2015 Measurement of hip geometrydtechnical background. J Clin Densitom 18:331e337.

Appendix A

References

2015 ISCD PDC Steering Committee

1. Baim S, Binkley N, Bilezikian JP, et al. 2008 Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Position Development Conference. J Clin Densitom 11:75e91. 2. Baim S, Leonard MB, Bianchi ML, et al. 2008 Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Pediatric Position Development Conference. J Clin Densitom 11:6e21. 3. Binkley N, Bilezikian JP, Kendler DL, et al. 2006 Official positions of the International Society for Clinical Densitometry and executive summary of the 2005 Position Development Conference. J Clin Densitom 9:4e14. 4. Hans DB, Kanis JA, Baim S, et al. 2011 Joint Official Positions of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX((R)). Executive Summary of the 2010 Position Development Conference on interpretation and use of FRAX(R) in clinical practice. J Clin Densitom 14:171e180. 5. Lenchik L, Leib ES, Hamdy RC, et al. 2002 Executive summary International Society for Clinical Densitometry position development conference Denver, Colorado July 20-22, 2001. J Clin Densitom 5(Suppl):S1eS3. 6. The Writing Group for the ISCD Position Development Conference. 2004 Executive Summary. 2004 J Clin Densitom 7:7e12. 7. Schousboe JT, Shepherd JA, Bilezikian JP, Baim S. 2013 Executive summary of the 2013 International Society for Clinical Densitometry Position Development Conference on bone densitometry. J Clin Densitom 16:455e466. 8. Shepherd JA, Baim S, Bilezikian JP, Schousboe JT. 2013 Executive summary of the 2013 International Society for Clinical Densitometry Position Development Conference on body composition. J Clin Densitom 16:489e495. 9. Bianchi ML, Baim S, Bishop NJ, et al. 2010 Official positions of the International Society for Clinical Densitometry (ISCD) on DXA evaluation in children and adolescents. Pediatr Nephrol 25:37e47. 10. Fitch K, Bernstein SJ, Aguilar MD, et al. 2001 The RAND/UCLA appropriateness method user’s manual. (No. RAND/MR1269-DG-XII/RE). RAND CORP SANTA MONICA CA.

John A. Shepherd PhD, (Chair) University of California at San Francisco, San Francisco, CA, USA. John T. Schousboe MD PhD, Park Nicollet Health Service and University of Minnesota, MN, USA. William D. Leslie MD MSc, University of Manitoba, Winnipeg, Canada.

2015 ISCD PDC Expert Panelists Sanford Baim MD, Rush University Medical Center, Chicago, IL, USA. John P. Bilezikian MD, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Rob D. Blank MD, Medical College of Wisconsin Milwaukee, WI, USA. Mary L. Bouxsein PhD, Harvard Medical School, Boston, MA, USA. John J. Carey MB MS, Merlin Park University Hospital, Galway, Ireland. Roland Chapurlat, MD PhD, INSERM, Lyon, France. Angela Cheung PhD MD, University of Toronto, Toronto, Ontario, Canada. Harry K. Genant MD, University of California, San Francisco, CA USA. Larry G. Jankowski CDT, Illinois Bone and Joint Institute, Chicago, IL, USA. Deborah Kado MD, University of California, San Diego, La Jolla, CA, USA. Kyla Kent CDT, Stanford University, Palo Alto, CA, USA. Pawel Szulc, MD PhD, INSERM, Lyon, France.

2015 ISCD PDC Task Forces Non-BMD DXAeTBS Susan B. Broy MD (Chair) Chicago Medical School, North Chicago, IL, USA.

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Executive Summary Stephanie Boutroy PhD, University of Lyon, Lyon, France. William D. Leslie MD MSc, (Exec. Comm. Liaison) University of Manitoba, Winnipeg, Canada. Barbara C. Silva MD, Santa Casa and Felicio Rocho Hospital, Belo Horizonte, MG, Brazil.

Non-BMD DXAeHip Geometry Susan B. Broy MD, (Chair) Chicago Medical School, North Chicago, IL, USA. Jane A. Cauley DrPH, University of Pittsburgh, Pittsburgh, PA, USA. William D. Leslie MD MSc, (Exec. Comm. Liaison) University of Manitoba, Winnipeg, Canada. E. Michael Lewiecki MD, University of New Mexico School of Medicine, Albuquerque, NM, USA.

Quantitative Computed Tomography Klaus Engelke PhD, (Chair) University of Erlangen, Germany. Sundeep Khosla MD, Mayo Clinic College of Medicine, Rochester, MN, USA. Thomas Lang PhD, UCSF School of Medicine, San Francisco, CA, USA. Ling Qin PhD, The Chinese University of Hong Kong, China. John T. Schousboe MD PhD, (Exec. Comm. Liaison) University of Minnesota, St Louis Park, MN, USA. Philippe Zysset PhD, Institute for Surgical Technology & Biomechanics, University of Bern, Switzerland.

279  Adults taking medications associated with low bone mass or bone loss.  Anyone being considered for pharmacologic therapy.  Anyone being treated to monitor treatment effect.  Anyone not receiving therapy in whom evidence of bone loss would lead to treatment. Women discontinuing estrogen should be considered for bone density testing according to the indications listed previously.

Reference Database for T-Scores  Use a uniform Caucasian (nonrace adjusted) female normative database for women of all ethnic groups. (Note: application of recommendation may vary according to local requirements.)  Use a uniform Caucasian (nonrace adjusted) female reference for men of all ethnic groups. (Note: application of recommendation may vary according to local requirements.)  Manufacturers should continue to use National Health and Nutrition Examination Survey III (NHANES III) data as the reference standard for femoral neck and total hip T-scores.  Manufacturers should continue to use their own databases for the lumbar spine as the reference standard for Tscores.  If local reference data are available they should be used to calculate only Z-scores but not T-scores.

Appendix B These are the adult official positions of the ISCD as updated in 2015. The official positions that are new or revised since 2013 are in bold type.

Indications for Bone Mineral Density (BMD) Testing  women aged 65 yr and older,  for postmenopausal women !65 yr, a bone density test is indicated if they have a risk factor for low bone mass such as; B low body weight, B prior fracture, B high-risk medication use, B disease or condition associated with bone loss.  Women during the menopausal transition with clinical risk factors for fracture, such as low body weight, prior fracture, or high-risk medication use.  Men aged 70 yr and older.  For men !70 yr of age, a bone density test is indicated if they have a risk factor for low bone mass such as; B low body weight, B prior fracture, B high-risk medication use, B disease or condition associated with bone loss.  Adults with a fragility fracture.  Adults with a disease or condition associated with low bone mass or bone loss.

Central DXA for Diagnosis  The WHO international reference standard for osteoporosis diagnosis is a T-score of 2.5 or less at the femoral neck. B The reference standard from which the T-score is calculated is the female, white, age 20e29 yr, NHANES III database.  Osteoporosis may be diagnosed in postmenopausal women and in men aged 50 yr and older if the T-score of the lumbar spine, total hip, or femoral neck is 2.5 or less: (Note: other hip regions of interest, including Ward’s area and the greater trochanter, should not be used for diagnosis. Application of recommendation may vary according to local requirements.) B In certain circumstances the 33% radius (also called one-third radius) may be used.  Skeletal sites to measure. B Measure BMD at both the posterior anterior (PA) spine and hip in all patients. B Forearm BMD should be measured under the following circumstances: - hip and/or spine cannot be measured or interpreted, - hyperparathyroidism, - very obese patients (over the weight limit for DXA table).

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280  Spine region of interest (ROI). B Use PA L1eL4 for spine BMD measurement. B Use all evaluable vertebrae and only exclude vertebrae that are affected by local structural change or artifact. Use 3 vertebrae if 4 cannot be used and 2 if 3 cannot be used. B BMD-based diagnostic classification should not be made using a single vertebra. B If only 1 evaluable vertebra remains after excluding other vertebrae, diagnosis should be based on a different valid skeletal site. B Anatomically abnormal vertebrae may be excluded from analysis if: - they are clearly abnormal and nonassessable within the resolution of the system; or - there is more than a 1.0 T-score difference between the vertebra in question and adjacent vertebrae. B When vertebrae are excluded, the BMD of the remaining vertebrae is used to derive the T-score. B The lateral spine should not be used for diagnosis but may have a role in monitoring  hip ROI B Use femoral neck, or total proximal femur whichever is lowest. B BMD may be measured at either hip. B There are insufficient data to determine whether mean Tscores for bilateral hip BMD can be used for diagnosis. B The mean hip BMD can be used for monitoring, with total hip being preferred  forearm ROI B Use 33% radius (sometimes called one-third radius) of the nondominant forearm for diagnosis. Other forearm ROI are not recommended.

Fracture Risk Assessment  A distinction is made between diagnostic classification and the use of BMD for fracture risk assessment.  For fracture risk assessment, any well-validated technique can be used, including measurements of more than one site where this has been shown to improve the assessment of risk.

Use of the Term ‘‘Osteopenia’’  The term ‘‘osteopenia’’ is retained but ‘‘low bone mass’’ or ‘‘low bone density’’ is preferred.  People with low bone mass or density are not necessarily at high fracture risk.

BMD Reporting in Postmenopausal Women and in Men Aged 50 yr and Older  T-scores are preferred.  The WHO densitometric classification is applicable.

Shepherd et al. BMD Reporting in Females Prior to Menopause and in Males Younger Than Age 50 yr  Z-scores, not T-scores, are preferred. This is particularly important in children.  A Z-score of 2.0 or lower is defined as ‘‘below the expected range for age’’, and a Z-score above 2.0 is ‘‘within the expected range for age.’’  Osteoporosis cannot be diagnosed in men under age 50 yr on the basis of BMD alone.  The WHO diagnostic criteria may be applied to women in the menopausal transition.

Z-Score Reference Database  Z-scores should be population specific where adequate reference data exist. For the purpose of Z-score calculation, the patient’s self-reported ethnicity should be used.

Serial BMD Measurements  Serial BMD testing can be used to determine whether treatment should be started on untreated patients because significant loss may be an indication for treatment.  Serial BMD testing can monitor response to therapy by finding an increase or stability of bone density.  Serial BMD testing can evaluate individuals for nonresponse by finding loss of bone density, suggesting the need for reevaluation of treatment and evaluation for secondary causes of osteoporosis.  Follow-up BMD testing should be done when the expected change in BMD equals or exceeds the least significant change (LSC).  Intervals between BMD testing should be determined according to each patient’s clinical status: typically 1 yr after initiation or change of therapy is appropriate, with longer intervals once therapeutic effect is established.  In conditions associated with rapid bone loss, such as glucocorticoid therapy, testing more frequently is appropriate.

Phantom Scanning and Calibration The quality control (QC) program at a DXA facility should include adherence to manufacturer guidelines for system maintenance. In addition, if not recommended in the manufacturer protocol, the following QC procedures are advised:  Perform periodic (at least once per week) phantom scans for any DXA system as an independent assessment of system calibration.  Plot and review data from calibration and phantom scans.  Verify the phantom mean BMD after any service performed on the densitometer.  Establish and enforce corrective action thresholds that trigger a call for service.  Maintain service logs.

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Executive Summary  Comply with government inspections, radiation surveys, and regulatory requirements.

Precision Assessment  Each DXA facility should determine its precision error and calculate the LSC.  The precision error supplied by the manufacturer should not be used.  If a DXA facility has more than one technologist, an average precision error combining data from all technologists should be used to establish precision error and LSC for the facility, provided the precision error for each technologist is within a pre-established range of acceptable performance.  Every technologist should perform an in vivo precision assessment using patient’s representative of the clinic’s patient population.  Each technologist should do one complete precision assessment after basic scanning skills have been learned (e.g., manufacturer training) and after having performed approximately 100 patient scans.  A repeat precision assessment should be done if a new DXA system is installed.  A repeat precision assessment should be done if a technologist’s skill level has changed.  To perform a precision analysis: B measure 15 patients 3 times, or 30 patients 2 times, repositioning the patient after each scan, B calculate the root mean square standard deviation for the group, B calculate LSC for the group at 95% confidence interval.  The minimum acceptable precision for an individual technologist is: B lumbar spine: 1.9% (LSC 5 5.3%), B total hip: 1.8% (LSC 5 5.0%), B femoral neck: 2.5% (LSC 5 6.9%), B retraining is required if a technologist’s precision is worse than these values.  Precision assessment should be standard clinical practice. Precision assessment is not research and may potentially benefit patients. It should not require approval of an institutional review board. Adherence to local radiologic safety regulations is necessary. Performance of a precision assessment requires the consent of participating patients.

Cross-Calibration of DXA Systems  When changing hardware, but not the entire system, or when replacing a system with the same technology (manufacturer and model), cross-calibration should be performed by having 1 technologist do 10 phantom scans, with repositioning, before and after hardware change. B If a O1% difference in mean BMD is observed, contact the manufacturer for service/correction.

281  When changing an entire system to one made by the same manufacturer using a different technology, or when changing to a system made by a different manufacturer, one approach to cross-calibration is: B scan 30 patients representative of the facility’s patient population once on the initial system and then twice on the new system within 60 d, B measure those anatomic sites commonly measured in clinical practice, typically spine and proximal femur, B facilities must comply with locally applicable regulations regarding DXA, B calculate the average BMD relationship and LSC between the initial and new machine using the ISCD DXA Machine Cross-Calibration Tool (www.ISCD.org), B use this LSC for comparison between the previous and new system. Intersystem quantitative comparisons can only be made if cross-calibration is performed on each skeletal site commonly measured, B once a new precision assessment has been performed on the new system, all future scans should be compared with scans performed on the new system using the newly established intrasystem LSC.  If a cross-calibration assessment is not performed, no quantitative comparison to the prior machine can be made. Consequently, a new baseline BMD and intrasystem LSC should be established.

BMD Comparison Between Facilities  It is not possible to quantitatively compare BMD or to calculate an LSC between facilities without cross-calibration.

Vertebral Fracture Assessment Nomenclature  Vertebral Fracture Assessment (VFA) is the correct term to denote densitometric spine imaging performed for the purpose of detecting vertebral fractures.

Indications for VFA  Lateral spine imaging with standard radiography or densitometric VFA is indicated when T-score is ! 1.0 and of one or more of the following is present: B women age 70 yr or men  age 80 yr, B historical height loss O4 cm (O1.5 inches), B self-reported but undocumented prior vertebral fracture, B glucocorticoid therapy equivalent to  5 mg of prednisone or equivalent per day for  3 mo.

Methods for Defining and Reporting Fractures on VFA  The methodology used for vertebral fracture identification should be similar to standard radiological approaches and be provided in the report.

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282  Fracture diagnosis should be based on visual evaluation and include assessment of grade or severity. Morphometry alone is not recommended because it is unreliable for diagnosis.  The Genant visual semiquantitative method is the current clinical technique of choice for diagnosing vertebral fracture with VFA.  Severity of deformity may be confirmed by morphometric measurement if desired.

Indications for Following VFA With Another Imaging Modality  The decision to perform additional imaging must be based on each patient’s overall clinical picture, including the VFA result.  Indications for follow-up imaging studies include: B two or more mild (grade 1) deformities without any moderate or severe (grade 2 or 3) deformities, B lesions in vertebrae that cannot be attributed to benign causes, B vertebral deformities in a patient with a known history of a relevant malignancy, B equivocal fractures, B unidentifiable vertebrae between T7 and L4, B sclerotic or lytic changes, or findings suggestive of conditions other than osteoporosis Note: VFA is designed to detect vertebral fractures and not other abnormalities.

Baseline DXA Report: Minimum Requirements  Demographics (name, medical record identifying number, date of birth, sex).  Requesting provider.  Indications for the test.  Manufacturer and model of instrument used.  Technical quality and limitations of the study, stating why a specific site or ROI is invalid or not included.  BMD in g/cm2 for each site.  The skeletal sites, ROI, and, if appropriate, the side, that were scanned.  The T-score and/or Z-score where appropriate.  WHO criteria for diagnosis in postmenopausal females and in men aged 50 yr and over.  Risk factors including information regarding previous nontraumatic fractures.  A statement about fracture risk. Any use of relative fracture risk must specify the population of comparison (e.g., young adult or age matched). The ISCD favors the use of absolute fracture risk prediction when such methodologies are established.  A general statement that a medical evaluation for secondary causes of low BMD may be appropriate.  Recommendations for the necessity and timing of the next BMD study.

Shepherd et al. Follow-Up DXA Report  Statement regarding which previous or baseline study and ROI is being used for comparison.  Statement about the LSC at your facility and the statistical significance of the comparison.  Report significant change, if any, between the present and previous study or studies in g/cm2 and percentage.  Comments on any outside study including manufacturer and model on which previous studies were performed and the appropriateness of the comparison.  Recommendations for the necessity and timing of the next BMD study.

DXA Report: Optional Items  Recommendation for further non-BMD testing, such as X-ray, magnetic resonance imaging, computed tomography, and so forth.  Recommendations for pharmacological and nonpharmacological interventions.  Addition of the percentage compared to a reference population.  Specific recommendations for evaluation of secondary osteoporosis.

DXA Report: Items That Should Not Be Included  A statement that there is bone loss without knowledge of previous bone density.  Mention of ‘‘mild,’’ ‘‘moderate,’’ or ‘‘marked’’ osteopenia or osteoporosis.  Separate diagnoses for different ROI (e.g., osteopenia at the hip and osteoporosis at the spine).  Expressions such as ‘‘She has the bones of an 80-yearold,’’ if the patient is not 80 yr old.  Results from skeletal sites that are not technically valid.  The change in BMD if it is not a significant change based on the precision error and LSC.

Components of a VFA Report  Patient identification, referring physician, indication(s) for study, technical quality, and interpretation.  A follow-up VFA report should also include comparability of studies and clinical significance of changes, if any.  VFA reports should comment on the following: B unevaluable vertebrae, B deformed vertebrae and whether or not the deformities are consistent with vertebral fracture, B unexplained vertebral and extra-vertebral pathology.  Optional components include fracture risk and recommendations for additional studies.

Trabecular Bone Score (TBS)  TBS is associated with vertebral, hip, and major osteoporotic fracture risk in postmenopausal women.

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Executive Summary  TBS is associated with hip fracture risk in men over the age of 50 yr.  TBS is associated with major osteoporotic fracture risk in men over the age of 50 yr.  TBS should not be used alone to determine treatment recommendations in clinical practice.  TBS can be used in association with FRAX and BMD to adjust FRAX-probability of fracture in postmenopausal women and older men.  TBS is not useful for monitoring bisphosphonate treatment in postmenopausal women with osteoporosis.  TBS is associated with major osteoporotic fracture risk in postmenopausal women with type II diabetes.

Hip Geometry  HAL derived from DXA is associated with hip fracture risk in postmenopausal women.  The following hip geometry parameters derived from DXA (CSA, OD, SM, BR, CSMI, NSA) should not be used to assess hip fracture risk.  Hip geometry parameters derived from DXA (CSA, OD, SM, BR, CSMI, HAL, NSA) should not be used to initiate treatment.  Hip geometry parameters derived from DXA (CSA, OD, SM, BR, CSMI, HAL, NSA) should not be used for monitoring.

General Recommendations for Noncentral DXA Devices: QCT, peripheral quantitative computed tomography (pQCT), QUS, and pDXA The following general recommendations for QCT, pQCT, quantitative ultrasound (QUS), and pDXA are analogous to those defined for central DXA technologies. Examples of technical differences among devices, fracture prediction ability for current manufacturers, and equivalence study requirements are provided in the full-text documents printed in the Journal of Clinical Densitometry.  Bone density measurements from different devices cannot be directly compared.  Different devices should be independently validated for fracture risk prediction by prospective trials, or by demonstration of equivalence to a clinically validated device.  T-scores from measurements other than DXA at the femur neck, total femur, lumbar spine, or one-third (33%) radius cannot be used according to the WHO diagnostic classification because those T-scores are not equivalent to Tscores derived by DXA.  Device-specific education and training should be provided to the operators and interpreters before clinical use.  QC procedures should be performed regularly.

Baseline Noncentral DXA Devices (QCT, pQCT, QUS, pDXA) Report: Minimum Requirements  Date of test,

283          

   

demographics (name, date of birth or age, sex), requesting provider, names of those receiving copy of report, indications for test, manufacturer and model of instrument and software version, measurement value(s), reference database, skeletal site or ROI, quality of test, limitations of the test including a statement that the WHO diagnostic classification cannot be applied to T-scores obtained from QCT, pQCT, QUS, and pDXA (other than one-third (33%) radius) measurements, clinical risk factors, fracture risk estimation, a general statement that a medical evaluation for secondary causes of low BMD may be appropriate, recommendations for follow-up imaging.

Note: a list of appropriate technical items is provided in the QCT and pQCT sections of the full-text documents printed in the Journal of Clinical Densitometry.

Noncentral DXA Devices (QCT, pQCT, QUS, pDXA) Report: Optional Items  Report may include the following optional item: B recommendations for pharmacological and nonpharmacological interventions.

QCT and pQCT  Acquisition B With single-slice QCT, L1eL3 should be scanned; with 3D QCT, L1eL2 should be scanned. B QCT acquisition of the proximal femur should extend from the femoral head to the proximal shaft. B For density-based QCT measurements the in-scan calibration phantom can be replaced by asynchronous calibration if scanner stability is maintained. B Opportunistic CT to screen for patients with low BMD or low bone strength of the spine or proximal femur is possible only if validated machine-specific cutoff values and scanner stability have been established.  Diagnosis B Femoral neck and total hip T-scores calculated from 2D projections of QCT data are equivalent to the corresponding DXA T-scores for diagnosis of osteoporosis in accordance with the WHO criteria.  Fracture Prediction B Spinal trabecular BMD as measured by QCT has at least the same ability to predict vertebral fractures as AP spinal BMD measured by central DXA in postmenopausal women. There is lack of sufficient evidence to support this position for men. B There is lack of sufficient evidence to recommend spine QCT for hip fracture prediction in either women or men.

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284 Total femur trabecular BMD measured by QCT predicts hip fractures as well as hip BMD measured by DXA in postmenopausal women and older men. B pQCT of the forearm at the ultra-distal radius predicts hip, but not spine, fragility fractures in postmenopausal women. There is lack of sufficient evidence to support this position for men.  Therapeutic Decisions B Central DXA measurements at the spine and femur are the preferred method for making therapeutic decisions and should be used if possible. Where QCT and DXA are both available and provide comparable information, DXA is preferred to limit radiation exposure. B However, if central DXA cannot be done, pharmacologic treatment can be initiated if the fracture probability, as assessed by QCT of the spine or pQCT of the radius using device-specific thresholds and in conjunction with clinical risk factors, is sufficiently high.  Monitoring B Trabecular BMD of the lumbar spine measured by QCT can be used to monitor age-, disease-, and treatmentrelated BMD changes. B Integral and trabecular BMD of the proximal femur measured by QCT can be used to monitor age- and treatment-related BMD changes. B Trabecular and total BMD of the ultra-distal radius measured by pQCT can be used to monitor agerelated BMD changes.  Finite Element Analysis (FEA) B Vertebral strength as estimated by QCT-based FEA predicts vertebral fracture in postmenopausal women. B Vertebral strength as estimated by QCT-based FEA is comparable to spine DXA for prediction of vertebral fractures in older men. B Femoral strength as estimated by QCT-based FEA is comparable to hip DXA for prediction of hip fractures in postmenopausal women and older men. B FEA cannot be used to diagnose osteoporosis using the current WHO T-score definition. B Vertebral or femoral strength as estimated by QCTbased FEA can be used to initiate pharmacologic treatment using validated thresholds and in conjunction with clinical risk factors. B Vertebral or femoral strength as estimated by QCTbased FEA can be used to monitor age- and treatment-related changes.  Reporting B For QCT using whole-body CT scanners the following additional technical items should be reported: - tomographic acquisition and reconstruction parameters, - kV, mAs, - collimation during acquisition, - table increment per rotation, - table height, - reconstructed slice thickness, reconstruction increment,

Shepherd et al.

B

-

reconstruction kernel. For pQCT using dedicated pQCT scanners, the following additional technical items should be reported: - tomographic acquisition and reconstruction parameters, - reconstructed slice thickness, - single or multi-slice acquisition mode, - length of scan range in multi-slice acquisition mode

Quantitative Ultrasound  Acquisition B The only validated skeletal site for the clinical use of QUS in osteoporosis management is the heel.  Fracture prediction B Validated heel QUS devices predict fragility fracture in postmenopausal women (hip, vertebral, and global fracture risk) and men ˃65 yr (hip and all nonvertebral fractures), independently of central DXA BMD. B Discordant results between heel QUS and central DXA are not infrequent and are not necessarily an indication of methodological error. B Heel QUS in conjunction with clinical risk factors can be used to identify a population at very low fracture probability in which no further diagnostic evaluation may be necessary. (Examples of device-specific thresholds and case findings strategy are provided in the full-text documents printed in the Journal of Clinical Densitometry.)  Therapeutic decisions B Central DXA measurements at the spine and femur are preferred for making therapeutic decisions and should be used if possible. However, if central DXA cannot be done, pharmacologic treatment can be initiated if the fracture probability, as assessed by heel QUS, using device-specific thresholds and in conjunction with clinical risk factors, is sufficiently high. (Examples of device-specific thresholds are provided in the full-text documents printed in the Journal of Clinical Densitometry.)  Monitoring B QUS cannot be used to monitor the skeletal effects of treatments for osteoporosis.

pDXA  Fracture prediction B Measurement by validated pDXA devices can be used to assess vertebral and global fragility fracture risk in postmenopausal women; however, its vertebral fracture predictive ability is weaker than central DXA and heel QUS. There is lack of sufficient evidence to support this position for men. B Radius pDXA in conjunction with clinical risk factors can be used to identify a population at very low fracture probability in which no further diagnostic evaluation may be

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Executive Summary necessary. (Examples of device-specific thresholds and case findings strategy are provided in the full-text documents printed in the Journal of Clinical Densitometry.)  Diagnosis B The WHO diagnostic classification can only be applied to DXA at the femur neck, total femur, lumbar spine, and the one-third (33%) radius ROI measured by DXA or pDXA devices using a validated young-adult reference database.  Therapeutic decisions B Central DXA measurements at the spine and femur are the preferred method for making therapeutic decisions and should be used if possible. However, if central DXA cannot be done, pharmacologic treatment can be initiated if the fracture probability, as assessed by radius pDXA (or DXA) using device-specific thresholds and in conjunction with clinical risk factors, is sufficiently high. (Examples of device-specific thresholds are provided in the full-text documents printed in the Journal of Clinical Densitometry.)  Monitoring B pDXA devices are not clinically useful in monitoring the skeletal effects of presently available medical treatments for osteoporosis.

285 B

B

B

B

B

Body Composition  Indications B DXA total body composition with regional analysis can be used in the following conditions: - In patients living with human immunodeficiency virus to assess fat distribution in those using antiretroviral agents associated with a risk of lipoatrophy (currently stavudine [d4T] and zidovudine [ZDV, AZT]). - In obese patients undergoing bariatric surgery (or medical, diet, or weight loss regimens with anticipated large weight loss) to assess fat and lean mass changes when weight loss exceeds approximately 10%. The impact on clinical outcomes is uncertain. - In patients with muscle weakness or poor physical functioning to assess fat and lean mass. The impact on clinical outcomes is uncertain. B Pregnancy is a contraindication to DXA body composition. Limitations in the use of clinical DXA for total body composition or bone mineral density are weight over the table limit, recent administration of contrast material, and/or artifact. Radiopharmaceutical agents may interfere with accuracy of results using systems from some DXA manufacturers.  Acquisition B No phantom has been identified to remove systematic differences in body composition when comparing in vivo results across manufacturers. B An in vivo cross-calibration study is necessary when comparing in vivo results across manufacturers.

B

B

B

B

B

B

Cross-calibrating systems of the same make and model can be performed with an appropriate whole body phantom. Changes in body composition measures can be evaluated between 2 different systems of the same make and model if the systems have been cross-calibrated with an appropriate total body phantom. When changing hardware, but not the entire system, or when replacing a system with the same technology (make and model), cross-calibration should be performed by having one technologist do 10 whole-body phantom scans, with repositioning, before and after hardware change. If a O2% difference in mean percent fat mass, fat mass, or lean mass is observed, contact the manufacturer for service or correction. No total body phantoms are available at this time that can be used as absolute reference standards for softtissue composition or bone mineral mass. The QC program at a DXA body composition facility should include adherence to manufacturer guidelines for system maintenance. In addition, if not recommended in the manufacturer protocol, the following QC procedures are advised: - Perform periodic (at least once per week) body composition phantom scans for any DXA system as an independent assessment of system calibration. - Plot and review data from calibration and body composition phantom scans. - Verify the body composition phantom mean percent fat mass and tissue mass after any service performed on the densitometer. - Establish and enforce corrective action thresholds that trigger a call for service. - Maintain service logs. - Comply with radiation surveys and regulatory government inspections, radiation surveys and regulatory requirements. Consistent positioning and preparation (e.g., fasting state, clothing, time of day, physical activity, empty bladder) of the patient is important for precise measures. Positioning of the arms, hands, legs, and feet whenever possible should be according to the NHANES method (palms down isolated from the body, feet neutral, ankles strapped, arms straight or slightly angled, face up with neutral chin). ‘‘Offset-scanning’’ should be used in patients who are too wide to fit within the scan boundaries, using a validated procedure for a specific scanner model. Every technologist should perform an in vivo precision assessment for all body composition measures of interest using patients who are representative of the clinic’s patient population. The minimum acceptable precision for an individual technologist is 3%, 2%, and 2% for total fat mass, total lean mass, and percent fat mass, respectively. Consistently use manufacturer’s recommendations for ROI placement.

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286 Consistently use manufacturer’s recommendations for artifact removal.  Analysis and reporting B For adults total body (with head) values of body mass index, BMD, BMC, total mass, total lean mass, total fat mass, and percent fat mass should appear on all reports. B Total body BMC as represented in the NHANES 1999e2004 reference data should be used when using DXA in 4-compartment models. B DXA measures of adiposity and lean mass include visceral adipose tissue, appendicular lean mass index (ALMI: appendicular lean mass/ht2), android/gynoid percent fat mass ratio, trunk to leg fat mass ratio, lean mass index (LMI: total lean mass/ht2), fat mass index (FMI: fat mass/ht2) are optional. The clinical utility of these measures is currently uncertain. B When comparing to the US population, the NHANES 1999e2004 body composition data are most appropriate for different races, both sexes, and for ages from 8 to 85 yr. [Note: reference to a population does not imply health status.] B Both Z-scores and percentiles are appropriate to report if derived using methods to adjust for non-normality. B The use of DXA adiposity measures (percent fat mass or fat mass index) may be useful in risk-stratifying patients for cardiometabolic outcomes. Specific thresholds to define obesity have not been established. B ‘‘Low lean mass’’ could be defined using appendicular lean mass divided by height squared (ALM/height2) with Z-scores derived from a young adult, race, and sex-matched population. Thresholds for low lean mass from consensus guidelines for sarcopenia await confirmation. B

Glossary

Shepherd et al. CSMIecross-sectional moment of inertia DXAedual-energy X-ray absorptiometry FEAefinite element analysis FMIefat mass index FRAXeWorld Health Organization Fracture Risk Assessment Tool HALehip axis length ISCDeInternational Society for Clinical Densitometry LMIelean mass index LSCeleast significant change NHANES IIIeNational Health and Nutrition Examination Survey III NSAeneck-shaft angle ODeouter diameter PAeposterior anterior pDXAeperipheral dual-energy x-ray absorptiometry pQCTeperipheral quantitative computed tomography QCequality control QCTequantitative computed tomography QUSequantitative ultrasound ROIeregion(s) of interest SMesection modulus SSIestrain strength index

ALMIeappendicular lean mass index TBLHetotal body less head BMCebone mineral content TBSetrabecular bone score BMDebone mineral density (equivalent to areal BMD, aBMD)

VATevisceral adipose tissue

BMIebody mass index

VFAevertebral fracture assessment

BRebuckling ratio

vBMDevolumetric BMD

CSAecross-sectional area

WHOeWorld Health Organization

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