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Skeletal Health and Bone Strength: DXA and Beyond Growth for the Journal of Clinical Densitometry
Journal of Clinical Densitometry: Assessment of Skeletal Health, vol. 11, no. 1, 1e5, 2008 Ó Copyright 2008 by The International Society for Clinical Densitometry 1094-6950/08/11:1e5/$34.00
Editorial
Skeletal Health and Bone Strength: DXA and Beyond Growth for the Journal of Clinical Densitometry Paul D. Miller, Editor-in-Chief 1,2 1
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA; and 2 Colorado Center for Bone Research, Lakewood, Colorado, USA; and
Osteoporosis Foundation with its international member societies, which have brought together many cultures who have a common stake in this health care arena and led by the enormous energy of Professor Pierre Demas; the Canadian Osteoporosis Society; the American Society for Bone and Mineral Research; and, the International Bone and Mineral Society. All of these societies have had educational interactions with the ISCD that was sprouted by the introduction of DXA. Furthermore, recognition that DXA stands at the forefront for management of osteoporosis led to the congressional Bone Mass Measurement Act (1997), which expanded indications for bone mass measurement Medicare reimbursement (10); the US Prevention Services Task Force position of 2002 that DXA be applied for population screening in postmenopausal women 60 yr of age and older with an additional risk factor for osteoporosis and to women 65þ yr and older regardless of other risk factors (11). In this regard, osteoporosis became the second disease state where mass screening was supported by the US Governmentdthe first population screening being mammography for breast cancer detection. Subsequently, the 2004 US Surgeon General’s report on the status of America’s Bone Health highlighted the underdetection and undertreatment of osteoporosis and put into context the personal and economic impact of osteoporotic fractures in an aging population (12). The efficacy of DXA for diagnosing osteoporosis and preventing fractures is not in dispute. In 2005, the Centers for Medicare and Medicaid Services recognized DXA testing for osteoporosis as one of its key preventive services (13), and in 2006 a final rule was issued to the Bone Mass Measurement Act stating that
When the Society for Clinical Densitometry (SCD) was founded in 1992 by a steering committee with a deep interest in bone mass measurements (see Appendix for Steering Committee Members) the society’s name reflected the dominant technology available for assessing fracture risk, dual-energy X-ray absorptiometry (DXA). 1992 was also the year that the working group of the World Health Organization (WHO), headed by Professor John Kanis, met to formulate criteria for diagnosing postmenopausal osteoporosis in nonfractured women based on specific bone mineral density (BMD) DXA-derived cutpoints, termed ‘‘T-scores.’’ The WHO published their results in 1994 and bone densitometry was launched as a practical clinical tool to diagnose both osteoporosis in nonfractured patients and predict fracture risk (1). In addition, as DXA technology became more accurate and precise (2e4), it evolved into a clinically useful tool to monitor changes in BMD due to diseases that negatively impact bone or pharmacological agents with a positive impact on bone (5e9). The science of DXA is well grounded. The consistent trust in DXA is recognized by multiple international professional societies: The now International Society for Clinical Densitometry (ISCD), (which also created the first international certification course for education in DXA utilization headed up by Sydney Bonnick, Ken Faulkner, and Paul Miller in 1994); the Brazilian SCD which started the first densitometry certification course outside of the United States in 1995 led by Dr Sergio Rage Eis and the late Dr. Antonio Carlos Arturo de Souza; the National Osteoporosis Foundation, the first organization developed to deal with patient and public policy in this vital area; the International
1
2 DXA (hip & spine) is the only approved technology to measure response to therapy over time and ‘‘the single best predictor of fracture risk’’ (14). Finally, the 2007 Physician Quality Reporting Initiative (PQRI) lists DXA testing for osteoporosis among its quality measures in Medicare’s new PQRI (15). Recognizing that DXA utilization principles change as information grows, the ISCD has held Position Development Conferences (PDCs) (4 adult and 1 pediatric) to wrestle with and debate the controversial issues that naturally evolve in biological sciences as more data are acquired and more research is completed (16e18). In this manner, the PDCs have provided ongoing guidance in DXA application, issues that are often revisited as concepts become more refined (19). The ISCD and the PDCs have helped define the usefulness of DXA-determined vertebral fracture assessment for a low X-ray energy and lower cost means of detecting asymptomatic vertebral fractures, which may change a patient’s risk (and often diagnosis) independent of their ‘‘T-score’’ (20e27); have offered guidance on the use of DXA for body fat and body composition that may lead to broad application in practice as the links between ‘‘obesity,’’ adipocytes, and bone become better defined (28e31); on use of DXA for the detection of vascular calcification where the link between bone and cardiovascular disease is an exciting and intense area of research (32,33); and, on the use of DXA to define hip strength independent of hip BMD as more data on the determinants of hip strength and hip structural analysis (HSA) become available (34e37). Hence, DXA has been and will continue to be the ‘‘workhorse’’ of clinical osteoporosis management. However, we have also come to recognize that there is more to bone strength than bone mineral content, BMD, or bone mass (38). Although baseline BMD as measured by 2-dimensional DXA captures w70% of the basal bone strength, there is a substantial amount of bone strength that cannot be captured by DXA measurements. For example, the risk for a low-trauma fracture doubles for each decade above the age of 50 yr at the equivalent level of BMD (39,40). DXA does not capture what ‘‘bone quality’’ means in explaining the differential levels of risk as a function of age (38e40); nor the ability to explain why a bone breaks with minimal trauma (nonpathological) even though the ‘‘T-score’’ may be perfectly normal (41e46). There are measurable changes in bone microstructure, collagen orientation, crystal size, cortical thickness, differential cross-sectional diameter as a function of differential Journal of Clinical Densitometry: Assessment of Skeletal Health
Miller rates of endosteal vs periosteal resorption, and formation that can each independently contribute to bone strength independent of DXA-measured BMD (47e54). Likewise, whereas pharmacologically induced increases in BMD as measured by DXA are associated with reductions in fracture risk, the relationship between change in BMD and change in risk is neither linear nor proportional (55e58). Although some of these differences in findings among studies examining the relationship between drug-induced change in 2-dimensional BMD and fracture risk reduction are methodological and statistical (59e64), there is evolving evidence that both antiresorptive and anabolic agents improve, in part, bone strength independent of changes in DXA-measured BMD (65e67). Hence, developing technologies that further explain how our therapies improve bone strength beyond BMD changes are very important. For clinicians, having additional office-based methods that help explain to our patients why no change in their DXA-measured BMD on treatment may be ‘‘OK’’ and that their bone strength has really increased on their therapy would certainly facilitate patient management. From inception, the ISCD clearly stated that ISCD cannot be or become a DXA-only society and must embrace newer technologies that measure ‘‘bone’’ as long as the science justifies that embracement. That time has come. This first issue of the Journal of Clinical DensitometrydAssessment of Skeletal Health for 2008 (11.1) represents a new era for the ISCD and its journal. In addition to changing part of the journal’s name, the entire issue is devoted to the fourth ISCD PDC and the first such pediatric conference, spearheaded by the upcoming ISCD President, Dr. Sandy Baim (68). The journal’s color has been changed to reflect a new era, and will have rotating images of the newer technologies that are rapidly emerging to measure bone ‘‘beyond DXA’’ that may ultimately find their way into clinical medicine and become an adjunct to DXA. Would it not be a great advancement if we all had an office-based bone-strength testing tool? Micro-magnetic resonance imaging (MRI), highresolution MRI, 3-D quantitative computerized tomography, HSA, high-resolution ultrasound all offer these potentials. Hence, the title of the journal has been modified to include ‘‘assessment of skeletal health’’ to reflect the growth that has occurred in the field of bone mass measurements and as science Volume 11, 2008
Editorial better defines ‘‘bone quality’’ and strives to provide means of real-world application of these new technologies. In addition, though the journal’s growth is steady as measured by the increasing number of submitted papers, increase in citations, and impact factor, we can do better. Hence, we have added 4 Editorial Board Review Section Editors, Drs. Nelson Watts, E. Michael Lewiecki, Ken Faulkner, and Glen Blake to seek high-quality review articles in the field of bone and offer our readership more top-notch general reviews, which are always in demand by the medical community. To seek short, 1-page key clinical or technical cases (or case reports) that seem attractive to trainees and established clinician technologists alike, we have added a ‘‘Clinical and Technical Hot Topic’’ section headed by Dr. Edgar Lerma and Larry Jankowski, RT, CDT to solicit and review these interesting practical experiences. We invite all of our colleagues to submit interesting cases to these key members. The ISCD is proud of its contributions to promote both the science and the clinical applications of measuring bone strength, and facilitate both competent patient management in the field of metabolic bone disease and cooperative efforts among the many professional societies dedicated to ‘‘bone.’’ In this regard, the JCD and now the ‘‘JCD and Assessment of Skeletal Health’’ will continue to foster growth in this vital area of disease(s) that effect bone metabolism. Finally, in addition many thanks to our management company, Association Resources, our publisher, Elsevier, the ISCD Board of Directors, and the publication committee for their unwavering support. The Editor-in-Chief also gives thanks to the managing editor, Linda E. Miller, BS, RT, for her tireless dedication to the journal’s excellence. Likewise, we both recognize the many hard hours of volunteer work that goes into the fine peer reviews that our members and reviewers provide. A very special thanks also goes to Dr. Nelson Watts for his willingness to always be available to seek and find capable reviewersda great value as the demand for excellent reviews increases.
Acknowledgments
Funding for the ISCD organizational start-up provided by Proctor and Gamble Pharmaceuticals, and P þ G Manager: Mr. Perry Owen, Norwich, NY. Journal of Clinical Densitometry: Assessment of Skeletal Health
3
References 1. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. 1994 World Health Organ Tech Rep Ser 843: 1e129. 2. Miller PD, Bonnick SL, Rosen CJ. 1996 Clinical utility of bone mass measurements in adults: consensus of an international panel. Semin Arthritis Rheum 25:361e372. 3. Miller PD, Bonnick SL. 1999 Clinical application of bone densitometry. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. p. 152e159. 4. Kanis JA, Gluer CC. 2000 An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, International Osteoporosis Foundation. Osteoporos Int 11(3):192e202. 5. Bonnick SL, Johnston CC Jr, Kleerekoper M, et al. 2001 Importance of precision in bone density measurements. J Clin Densitom 4:105e110. 6. Bonnick SL, Shulman L. 2006 Monitoring osteoporosis therapy: bone mineral density, bone turnover markers, or both? Am J Med 119(4 Suppl 1):S25eS31. 7. Miller PD. 2007 Monitoring osteoporosis therapies. Curr Osteoporos Rep 5:38e43. 8. Miller PD, Zapalowski C, Kulak CAM, et al. 1999 Bone densitometry: the best way to detect osteoporosis and to monitor therapy. J Clin Endocrinol Metab 84:1867e1871. 9. Gluer CC. 1999 Monitoring skeletal changes by radiological techniques. J Bone Miner Res 14(11):1952e1962. 10. Department of Health and Human Services. 1998 Medicare coverage of and payment for bone mass measurements. Fed Regist 63(121):34320e34328. 11. United States Prevention Services Task Force: screening for osteoporosis. Available at: www.ahrq.gov/clinic/uspstf/ usposte.htm. Accessed: June 10, 1996. 12. US Surgeon General’s Report on America’s Bone Health. Available at: www.surgeongeneral.gov/library. Accessed: October 14, 2004. 13. CMS Centers for Medicare and Medicaid Services. Medicare and You. Available at: www.medicare.gov/publications/ pubs/pdf/10050.pdf. Accessed: October 2, 2007. 14. BMMD #2 42 CFR 410.31 (Bone Mass Measurement: Conditions for Coverage and Frequency Standards). 15. PQRI P.L. 109-432 (H.R. 6111 Tax Relief and Health Care Act of 2006). 16. Leib E, Lewiecki M, Binkley N, et al. 2004 Official positions of the international society for clinical densitometry. J Clin Densitom 7:1e6. 17. Leib ES, Binkley N, Bilezikian JP, et al. 2005 Position Development Conference of the International Society for Clinical Densitometry. Vancouver, BC, July 15e17, 2005. 18. 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. J Clin Densitom 9(1). 19. Lewiecki EM, Binkley N, Petak SM. 2006 DXA quality matters. J Clin Densitom 9(4):388e392. 20. Vokes T, Bachman D, Baim S, et al. 2006 Vertebral fracture assessment: the 2005 ISCD official positions. J Clin Densitom 9(1):37e46.
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4 21. Lewiecki EM, Laster A. 2006 Clinical review: clinical applications of vertebral fracture assessment by dual-energy x-ray absorptiometry. J Clin Endocrinol Metab 91(11): 4215e4222. 22. Laster AJ, Lewiecki EM: ISCD Board of Directors. 2007 Vertebral fracture assessment by dual-energy X-ray absorptiometry: insurance coverage issues in the United States. A White Paper of the International Society for Clinical Densitometry. J Clin Densitom 10(3):227e238. Epub 2007 Jun 28. Review. 23. Genant HK, Li J, Wu CY, et al. 2000 Vertebral fractures in osteoporosis: a new method for clinical assessment. J Clin Densitom 3(3):281e290. 24. Duboeuf F, Bauer DC, Chapurlat RD, et al. 2007 Assessment of vertebral fracture using densitometric morphometry. J Clin Densitom 8(3):362e368. Review. 25. Chapurlat RD, Duboeuf F, Marian-Audibert HO, et al. 2006 Effectiveness of instant vertebral assessment to detect prevalent vertebral fracture. Osteoporos Int 17(8):1189e1195. Epub 2006 Jun 7. 26. Greenspan SL, von Stetten E, Emond SK, et al. 2001 Instant vertebral assessment: a noninvasive dual X-ray absorptiometry technique to avoid misclassification and clinical mismanagement of osteoporosis. J Clin Densitom 4(4):373e380. 27. Genant HK, Delmas PD, Chen P, et al. 2007 Severity of vertebral fracture reflects deterioration of bone microarchitecture. Osteoporos Int 18(1):69e76. Epub 2006 Oct 7. 28. Zhao LJ, Jiang H, Papasian CJ, et al. 2008 Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis. J Bone Miner Res 10:17e29. 29. De Laet C, Kanis JA, Oden A, et al. 2005 Body mass index as a predictor of fracture risk: a metaanalysis. Osteoporos Int 16:1330e1338. 30. Thomas T, Burguear B. 2002 In Leptin the link between fat and bone mass? J Bone Miner Res 17:1563e1569. 31. Lenchik L, Register TC, Hsu FC, et al. 2003 Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone 33:646e651. 32. Sioka C, Goudevenos J, Pappas K, et al. 2007 Bone mineral density and coronary atherosclerosis. Calcif Tissue Int 81:333. 33. Hyder JA, Allison MA, Criqui MH, et al. 2007 Association between systemic calcified atherosclerosis and bone density. Calcif Tissue Int 80:301e306. 34. Faulkner KG, Wacker WK, Barden HS, et al. 2005 Femur strength index predicts hip fracture independent of bone density and hip axis length. Osteoporos Int 17:1e7. 35. Mayhew PM, Thomas CD, Clement JG, et al. 2005 Relation between age, femoral neck cortical stability, and hip fracture risk. Lancet 366(9480):129e135. 36. Uusi-Rasi K, Semanick LM, Zanchetta JR, et al. 2005 Effects of teriparatide [rhPTH (1-34)] treatment on structural geometry of the proximal femur in elderly osteoporotic women. Bone 36(6):948e958. 37. Khoo BC, Beck TJ, Qiao QH, et al. 2005 In vivo short-term precision of hip structure analysis variables in comparison with bone mineral density using paired dual-energy X-ray absorptiometry scans from multi-center clinical trials. Bone 37(1):112e121. 38. Bouxsein ML. 2003 Bone quality: where do we go from here? Osteoporos Int 14(Suppl 5):118e127. 39. Hui SL, Slemenda CW, Johnston CC Jr. 1988 Age and bone mass as predictors of fracture in a prospective study. J Clin Invest 81:1804e1809.
Journal of Clinical Densitometry: Assessment of Skeletal Health
Miller 40. Kanis JA, Oden JA, Johannsson H, et al. 2007 Expressing fracture risk. Osteoporos Int. 41. Wainwright SA, Marshall LM, Ensrud KE, et al. 2005 Hip fracture in women without osteoporosis. J Clin Endocrinol Metab 90(5):2787e2793. 42. Siris E, Miller P, Barrett-Connor E, et al. 2001 Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment (NORA). JAMA 286:2815e2822. 43. Black DM, Steinbuch M, Palmero L, et al. 2001 An assessment tool for predicting fracture risk in postmenopausal women. Osteoporos Int 12(7):519e528. 44. Miller PD, Barlas S, Brenneman SK, et al. 2004 An approach to identifying osteopenic women at increased short-term risk of fracture. Arch Intern Med 164:1113e1120. 45. Nevitt MC, Cummings SR, Stone KL, et al. 2005 Risk factors for a first-incident radiographic vertebral fracture in women O or 5 65 years of age: the study of osteoporotic fractures. J Bone Miner Res 20(1):131e140. 46. Papaioannou A, Joseph L, Ioannidis G, et al. 2005 Risk factors associated with incident clinical vertebral and nonvertebral fractures in postmenopausal women: the Canadian Multicentre Osteoporosis Study (CaMos). Osteoporos Int 16(5):568e578. 47. Borah B, Dufrense TE, Ritman EL, et al. 2006 Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture: sequential triple biopsy studies with micro-computed tomography. Bone 39(2):345e352. Epub 2006 Mar 29. 48. Hordon LD, Itoda M, Shore PA, et al. 2006 Preservation of thoracic spine microarchitecture by alendronate: comparison of histology and microCT. Bone 38(3):444e449. Epub 2005 Dec 19. 49. Borah B, Gross GJ, Dufrense TE, et al. 2001 Three-dimensional microimaging (MRmicroI and microCT), finite element modeling, and rapid prototyping provide unique insights into bone architecture in osteoporosis. Anat Rec 265(2):101e110. Review. 50. Ji B. 2007 A study of the interface strength between protein and mineral in biological materials. J Biomech. 51. Boivin G, Meunier P. 2003 The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Osteoporos Int 14(Suppl 3):S19eS24. Epub 2003 Mar 18. Review. 52. Knott L, Bailey AJ. 1998 Collagen cross-links in mineralizing tissues: a review of their chemistry, function, and clinical relevance. Bone 22(3):181e187. Review. 53. Wagner HD, Weiner S. 1992 On the relationship between the microstructure of bone and its mechanical stiffness. J Biomech 25(11):1311e1320. 54. Ruppel ME, Burr DB, Miller LM. 2006 Chemical makeup of microdamaged bone differs from undamaged bone. Bone 39(2):318e324. Epub 2006 Apr 11. 55. Wasnich RD, Miller PD. 2000 Antifracture efficacy of antiresportive agents are related to changes in bone density. J Clin Endocrinol Metab 85:1e6. 56. Hochberg MC, Greenspan S, Wasnich RD, et al. 2002 Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 87:1586e1592.
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Editorial 57. Miller PD, Deltas PD, Huss H, et al. 2008 Increases in hip and spine bone mineral density are predictive for antifracture efficacy with ibandronate. In press. 58. Cummings SR, Karpf DB, Harris F, et al. 2002 Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with anti-resorptive drugs. Am J Med 112:281e289. 59. Delmas PD, Li Z, Cooper C. 2004 Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with meta-analyses. J Bone Miner Res 19(2):330e337. 60. Watts NB, Cooper C, Lindsay R, et al. 2004 Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: greater increases in bone mineral density do not relate to greater decreases in fracture risk. J Clin Densitom 7(3):255e261. 61. Miller PD. 2005 Bone density and markers of bone turnover in predicting fracture risk and how changes in these measures predict fracture risk reduction. Curr Osteoporos Rep 3(3):103e110. 62. Lenchick L, Watts NB. 2001 Regression to the mean: what does it mean? Using bone density results to monitor treatment of osteoporosis. J Clin Densitom 4(1):1e4. 63. Delmas PD, Seeman E. 2004 Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy. Bone 34:599e604. 64. Freedman LS, Graubard BI, Schatzkin A. 1992 Statistical validation of intermediate endpoints for chronic diseases. Stat Med 11:167e178.
Journal of Clinical Densitometry: Assessment of Skeletal Health
5 65. Miller PD, Hochberg MC, Wehren LE, et al. 2005 How useful are measures of BMD and bone turnover? Curr Med Res Opin 21(4):545e553. 66. McClung M, San Martin J, Miller PD, et al. 2005 Teriparatide and alendronate increase bone mass by opposite effects on bone remodeling. Arch Intern Med 165:1762e1768. 67. Chen P, Miller PD, Delmas PD, et al. 2006 Change in lumbar spine bone mineral density and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis. J Bone Miner Res 21:1786e1790. 68. Baim S, Leonard MB, Bianchi M-L, et al. 2008 Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 Pediatric Position Development Conference. J Clin Densitom 11(1):6e21.
Appendix
ISCD Original Steering Committee Members, First Organizational Meeting: Chicago, IL, April 1992.
Sydney Lou Bonnick, MD (Denton, TX, USA) Maria Greenwald, MD (Palm Springs, CA, USA) Paul D. Miller, MD (Chair-Lakewood, CO, USA) Al Moffett, MD (Leesburg, FL, USA) Clifford Rosen, MD (Bangor, ME, USA) David Sartoris, MD (San Diego, CA, USA)
Volume 11, 2008
Editorial
Skeletal Health and Bone Strength: DXA and Beyond Growth for the Journal of Clinical Densitometry Paul D. Miller, Editor-in-Chief 1,2 1
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA; and 2 Colorado Center for Bone Research, Lakewood, Colorado, USA; and
Osteoporosis Foundation with its international member societies, which have brought together many cultures who have a common stake in this health care arena and led by the enormous energy of Professor Pierre Demas; the Canadian Osteoporosis Society; the American Society for Bone and Mineral Research; and, the International Bone and Mineral Society. All of these societies have had educational interactions with the ISCD that was sprouted by the introduction of DXA. Furthermore, recognition that DXA stands at the forefront for management of osteoporosis led to the congressional Bone Mass Measurement Act (1997), which expanded indications for bone mass measurement Medicare reimbursement (10); the US Prevention Services Task Force position of 2002 that DXA be applied for population screening in postmenopausal women 60 yr of age and older with an additional risk factor for osteoporosis and to women 65þ yr and older regardless of other risk factors (11). In this regard, osteoporosis became the second disease state where mass screening was supported by the US Governmentdthe first population screening being mammography for breast cancer detection. Subsequently, the 2004 US Surgeon General’s report on the status of America’s Bone Health highlighted the underdetection and undertreatment of osteoporosis and put into context the personal and economic impact of osteoporotic fractures in an aging population (12). The efficacy of DXA for diagnosing osteoporosis and preventing fractures is not in dispute. In 2005, the Centers for Medicare and Medicaid Services recognized DXA testing for osteoporosis as one of its key preventive services (13), and in 2006 a final rule was issued to the Bone Mass Measurement Act stating that
When the Society for Clinical Densitometry (SCD) was founded in 1992 by a steering committee with a deep interest in bone mass measurements (see Appendix for Steering Committee Members) the society’s name reflected the dominant technology available for assessing fracture risk, dual-energy X-ray absorptiometry (DXA). 1992 was also the year that the working group of the World Health Organization (WHO), headed by Professor John Kanis, met to formulate criteria for diagnosing postmenopausal osteoporosis in nonfractured women based on specific bone mineral density (BMD) DXA-derived cutpoints, termed ‘‘T-scores.’’ The WHO published their results in 1994 and bone densitometry was launched as a practical clinical tool to diagnose both osteoporosis in nonfractured patients and predict fracture risk (1). In addition, as DXA technology became more accurate and precise (2e4), it evolved into a clinically useful tool to monitor changes in BMD due to diseases that negatively impact bone or pharmacological agents with a positive impact on bone (5e9). The science of DXA is well grounded. The consistent trust in DXA is recognized by multiple international professional societies: The now International Society for Clinical Densitometry (ISCD), (which also created the first international certification course for education in DXA utilization headed up by Sydney Bonnick, Ken Faulkner, and Paul Miller in 1994); the Brazilian SCD which started the first densitometry certification course outside of the United States in 1995 led by Dr Sergio Rage Eis and the late Dr. Antonio Carlos Arturo de Souza; the National Osteoporosis Foundation, the first organization developed to deal with patient and public policy in this vital area; the International
1
2 DXA (hip & spine) is the only approved technology to measure response to therapy over time and ‘‘the single best predictor of fracture risk’’ (14). Finally, the 2007 Physician Quality Reporting Initiative (PQRI) lists DXA testing for osteoporosis among its quality measures in Medicare’s new PQRI (15). Recognizing that DXA utilization principles change as information grows, the ISCD has held Position Development Conferences (PDCs) (4 adult and 1 pediatric) to wrestle with and debate the controversial issues that naturally evolve in biological sciences as more data are acquired and more research is completed (16e18). In this manner, the PDCs have provided ongoing guidance in DXA application, issues that are often revisited as concepts become more refined (19). The ISCD and the PDCs have helped define the usefulness of DXA-determined vertebral fracture assessment for a low X-ray energy and lower cost means of detecting asymptomatic vertebral fractures, which may change a patient’s risk (and often diagnosis) independent of their ‘‘T-score’’ (20e27); have offered guidance on the use of DXA for body fat and body composition that may lead to broad application in practice as the links between ‘‘obesity,’’ adipocytes, and bone become better defined (28e31); on use of DXA for the detection of vascular calcification where the link between bone and cardiovascular disease is an exciting and intense area of research (32,33); and, on the use of DXA to define hip strength independent of hip BMD as more data on the determinants of hip strength and hip structural analysis (HSA) become available (34e37). Hence, DXA has been and will continue to be the ‘‘workhorse’’ of clinical osteoporosis management. However, we have also come to recognize that there is more to bone strength than bone mineral content, BMD, or bone mass (38). Although baseline BMD as measured by 2-dimensional DXA captures w70% of the basal bone strength, there is a substantial amount of bone strength that cannot be captured by DXA measurements. For example, the risk for a low-trauma fracture doubles for each decade above the age of 50 yr at the equivalent level of BMD (39,40). DXA does not capture what ‘‘bone quality’’ means in explaining the differential levels of risk as a function of age (38e40); nor the ability to explain why a bone breaks with minimal trauma (nonpathological) even though the ‘‘T-score’’ may be perfectly normal (41e46). There are measurable changes in bone microstructure, collagen orientation, crystal size, cortical thickness, differential cross-sectional diameter as a function of differential Journal of Clinical Densitometry: Assessment of Skeletal Health
Miller rates of endosteal vs periosteal resorption, and formation that can each independently contribute to bone strength independent of DXA-measured BMD (47e54). Likewise, whereas pharmacologically induced increases in BMD as measured by DXA are associated with reductions in fracture risk, the relationship between change in BMD and change in risk is neither linear nor proportional (55e58). Although some of these differences in findings among studies examining the relationship between drug-induced change in 2-dimensional BMD and fracture risk reduction are methodological and statistical (59e64), there is evolving evidence that both antiresorptive and anabolic agents improve, in part, bone strength independent of changes in DXA-measured BMD (65e67). Hence, developing technologies that further explain how our therapies improve bone strength beyond BMD changes are very important. For clinicians, having additional office-based methods that help explain to our patients why no change in their DXA-measured BMD on treatment may be ‘‘OK’’ and that their bone strength has really increased on their therapy would certainly facilitate patient management. From inception, the ISCD clearly stated that ISCD cannot be or become a DXA-only society and must embrace newer technologies that measure ‘‘bone’’ as long as the science justifies that embracement. That time has come. This first issue of the Journal of Clinical DensitometrydAssessment of Skeletal Health for 2008 (11.1) represents a new era for the ISCD and its journal. In addition to changing part of the journal’s name, the entire issue is devoted to the fourth ISCD PDC and the first such pediatric conference, spearheaded by the upcoming ISCD President, Dr. Sandy Baim (68). The journal’s color has been changed to reflect a new era, and will have rotating images of the newer technologies that are rapidly emerging to measure bone ‘‘beyond DXA’’ that may ultimately find their way into clinical medicine and become an adjunct to DXA. Would it not be a great advancement if we all had an office-based bone-strength testing tool? Micro-magnetic resonance imaging (MRI), highresolution MRI, 3-D quantitative computerized tomography, HSA, high-resolution ultrasound all offer these potentials. Hence, the title of the journal has been modified to include ‘‘assessment of skeletal health’’ to reflect the growth that has occurred in the field of bone mass measurements and as science Volume 11, 2008
Editorial better defines ‘‘bone quality’’ and strives to provide means of real-world application of these new technologies. In addition, though the journal’s growth is steady as measured by the increasing number of submitted papers, increase in citations, and impact factor, we can do better. Hence, we have added 4 Editorial Board Review Section Editors, Drs. Nelson Watts, E. Michael Lewiecki, Ken Faulkner, and Glen Blake to seek high-quality review articles in the field of bone and offer our readership more top-notch general reviews, which are always in demand by the medical community. To seek short, 1-page key clinical or technical cases (or case reports) that seem attractive to trainees and established clinician technologists alike, we have added a ‘‘Clinical and Technical Hot Topic’’ section headed by Dr. Edgar Lerma and Larry Jankowski, RT, CDT to solicit and review these interesting practical experiences. We invite all of our colleagues to submit interesting cases to these key members. The ISCD is proud of its contributions to promote both the science and the clinical applications of measuring bone strength, and facilitate both competent patient management in the field of metabolic bone disease and cooperative efforts among the many professional societies dedicated to ‘‘bone.’’ In this regard, the JCD and now the ‘‘JCD and Assessment of Skeletal Health’’ will continue to foster growth in this vital area of disease(s) that effect bone metabolism. Finally, in addition many thanks to our management company, Association Resources, our publisher, Elsevier, the ISCD Board of Directors, and the publication committee for their unwavering support. The Editor-in-Chief also gives thanks to the managing editor, Linda E. Miller, BS, RT, for her tireless dedication to the journal’s excellence. Likewise, we both recognize the many hard hours of volunteer work that goes into the fine peer reviews that our members and reviewers provide. A very special thanks also goes to Dr. Nelson Watts for his willingness to always be available to seek and find capable reviewersda great value as the demand for excellent reviews increases.
Acknowledgments
Funding for the ISCD organizational start-up provided by Proctor and Gamble Pharmaceuticals, and P þ G Manager: Mr. Perry Owen, Norwich, NY. Journal of Clinical Densitometry: Assessment of Skeletal Health
3
References 1. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. 1994 World Health Organ Tech Rep Ser 843: 1e129. 2. Miller PD, Bonnick SL, Rosen CJ. 1996 Clinical utility of bone mass measurements in adults: consensus of an international panel. Semin Arthritis Rheum 25:361e372. 3. Miller PD, Bonnick SL. 1999 Clinical application of bone densitometry. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. p. 152e159. 4. Kanis JA, Gluer CC. 2000 An update on the diagnosis and assessment of osteoporosis with densitometry. Committee of Scientific Advisors, International Osteoporosis Foundation. Osteoporos Int 11(3):192e202. 5. Bonnick SL, Johnston CC Jr, Kleerekoper M, et al. 2001 Importance of precision in bone density measurements. J Clin Densitom 4:105e110. 6. Bonnick SL, Shulman L. 2006 Monitoring osteoporosis therapy: bone mineral density, bone turnover markers, or both? Am J Med 119(4 Suppl 1):S25eS31. 7. Miller PD. 2007 Monitoring osteoporosis therapies. Curr Osteoporos Rep 5:38e43. 8. Miller PD, Zapalowski C, Kulak CAM, et al. 1999 Bone densitometry: the best way to detect osteoporosis and to monitor therapy. J Clin Endocrinol Metab 84:1867e1871. 9. Gluer CC. 1999 Monitoring skeletal changes by radiological techniques. J Bone Miner Res 14(11):1952e1962. 10. Department of Health and Human Services. 1998 Medicare coverage of and payment for bone mass measurements. Fed Regist 63(121):34320e34328. 11. United States Prevention Services Task Force: screening for osteoporosis. Available at: www.ahrq.gov/clinic/uspstf/ usposte.htm. Accessed: June 10, 1996. 12. US Surgeon General’s Report on America’s Bone Health. Available at: www.surgeongeneral.gov/library. Accessed: October 14, 2004. 13. CMS Centers for Medicare and Medicaid Services. Medicare and You. Available at: www.medicare.gov/publications/ pubs/pdf/10050.pdf. Accessed: October 2, 2007. 14. BMMD #2 42 CFR 410.31 (Bone Mass Measurement: Conditions for Coverage and Frequency Standards). 15. PQRI P.L. 109-432 (H.R. 6111 Tax Relief and Health Care Act of 2006). 16. Leib E, Lewiecki M, Binkley N, et al. 2004 Official positions of the international society for clinical densitometry. J Clin Densitom 7:1e6. 17. Leib ES, Binkley N, Bilezikian JP, et al. 2005 Position Development Conference of the International Society for Clinical Densitometry. Vancouver, BC, July 15e17, 2005. 18. 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. J Clin Densitom 9(1). 19. Lewiecki EM, Binkley N, Petak SM. 2006 DXA quality matters. J Clin Densitom 9(4):388e392. 20. Vokes T, Bachman D, Baim S, et al. 2006 Vertebral fracture assessment: the 2005 ISCD official positions. J Clin Densitom 9(1):37e46.
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4 21. Lewiecki EM, Laster A. 2006 Clinical review: clinical applications of vertebral fracture assessment by dual-energy x-ray absorptiometry. J Clin Endocrinol Metab 91(11): 4215e4222. 22. Laster AJ, Lewiecki EM: ISCD Board of Directors. 2007 Vertebral fracture assessment by dual-energy X-ray absorptiometry: insurance coverage issues in the United States. A White Paper of the International Society for Clinical Densitometry. J Clin Densitom 10(3):227e238. Epub 2007 Jun 28. Review. 23. Genant HK, Li J, Wu CY, et al. 2000 Vertebral fractures in osteoporosis: a new method for clinical assessment. J Clin Densitom 3(3):281e290. 24. Duboeuf F, Bauer DC, Chapurlat RD, et al. 2007 Assessment of vertebral fracture using densitometric morphometry. J Clin Densitom 8(3):362e368. Review. 25. Chapurlat RD, Duboeuf F, Marian-Audibert HO, et al. 2006 Effectiveness of instant vertebral assessment to detect prevalent vertebral fracture. Osteoporos Int 17(8):1189e1195. Epub 2006 Jun 7. 26. Greenspan SL, von Stetten E, Emond SK, et al. 2001 Instant vertebral assessment: a noninvasive dual X-ray absorptiometry technique to avoid misclassification and clinical mismanagement of osteoporosis. J Clin Densitom 4(4):373e380. 27. Genant HK, Delmas PD, Chen P, et al. 2007 Severity of vertebral fracture reflects deterioration of bone microarchitecture. Osteoporos Int 18(1):69e76. Epub 2006 Oct 7. 28. Zhao LJ, Jiang H, Papasian CJ, et al. 2008 Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis. J Bone Miner Res 10:17e29. 29. De Laet C, Kanis JA, Oden A, et al. 2005 Body mass index as a predictor of fracture risk: a metaanalysis. Osteoporos Int 16:1330e1338. 30. Thomas T, Burguear B. 2002 In Leptin the link between fat and bone mass? J Bone Miner Res 17:1563e1569. 31. Lenchik L, Register TC, Hsu FC, et al. 2003 Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone 33:646e651. 32. Sioka C, Goudevenos J, Pappas K, et al. 2007 Bone mineral density and coronary atherosclerosis. Calcif Tissue Int 81:333. 33. Hyder JA, Allison MA, Criqui MH, et al. 2007 Association between systemic calcified atherosclerosis and bone density. Calcif Tissue Int 80:301e306. 34. Faulkner KG, Wacker WK, Barden HS, et al. 2005 Femur strength index predicts hip fracture independent of bone density and hip axis length. Osteoporos Int 17:1e7. 35. Mayhew PM, Thomas CD, Clement JG, et al. 2005 Relation between age, femoral neck cortical stability, and hip fracture risk. Lancet 366(9480):129e135. 36. Uusi-Rasi K, Semanick LM, Zanchetta JR, et al. 2005 Effects of teriparatide [rhPTH (1-34)] treatment on structural geometry of the proximal femur in elderly osteoporotic women. Bone 36(6):948e958. 37. Khoo BC, Beck TJ, Qiao QH, et al. 2005 In vivo short-term precision of hip structure analysis variables in comparison with bone mineral density using paired dual-energy X-ray absorptiometry scans from multi-center clinical trials. Bone 37(1):112e121. 38. Bouxsein ML. 2003 Bone quality: where do we go from here? Osteoporos Int 14(Suppl 5):118e127. 39. Hui SL, Slemenda CW, Johnston CC Jr. 1988 Age and bone mass as predictors of fracture in a prospective study. J Clin Invest 81:1804e1809.
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Miller 40. Kanis JA, Oden JA, Johannsson H, et al. 2007 Expressing fracture risk. Osteoporos Int. 41. Wainwright SA, Marshall LM, Ensrud KE, et al. 2005 Hip fracture in women without osteoporosis. J Clin Endocrinol Metab 90(5):2787e2793. 42. Siris E, Miller P, Barrett-Connor E, et al. 2001 Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment (NORA). JAMA 286:2815e2822. 43. Black DM, Steinbuch M, Palmero L, et al. 2001 An assessment tool for predicting fracture risk in postmenopausal women. Osteoporos Int 12(7):519e528. 44. Miller PD, Barlas S, Brenneman SK, et al. 2004 An approach to identifying osteopenic women at increased short-term risk of fracture. Arch Intern Med 164:1113e1120. 45. Nevitt MC, Cummings SR, Stone KL, et al. 2005 Risk factors for a first-incident radiographic vertebral fracture in women O or 5 65 years of age: the study of osteoporotic fractures. J Bone Miner Res 20(1):131e140. 46. Papaioannou A, Joseph L, Ioannidis G, et al. 2005 Risk factors associated with incident clinical vertebral and nonvertebral fractures in postmenopausal women: the Canadian Multicentre Osteoporosis Study (CaMos). Osteoporos Int 16(5):568e578. 47. Borah B, Dufrense TE, Ritman EL, et al. 2006 Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture: sequential triple biopsy studies with micro-computed tomography. Bone 39(2):345e352. Epub 2006 Mar 29. 48. Hordon LD, Itoda M, Shore PA, et al. 2006 Preservation of thoracic spine microarchitecture by alendronate: comparison of histology and microCT. Bone 38(3):444e449. Epub 2005 Dec 19. 49. Borah B, Gross GJ, Dufrense TE, et al. 2001 Three-dimensional microimaging (MRmicroI and microCT), finite element modeling, and rapid prototyping provide unique insights into bone architecture in osteoporosis. Anat Rec 265(2):101e110. Review. 50. Ji B. 2007 A study of the interface strength between protein and mineral in biological materials. J Biomech. 51. Boivin G, Meunier P. 2003 The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Osteoporos Int 14(Suppl 3):S19eS24. Epub 2003 Mar 18. Review. 52. Knott L, Bailey AJ. 1998 Collagen cross-links in mineralizing tissues: a review of their chemistry, function, and clinical relevance. Bone 22(3):181e187. Review. 53. Wagner HD, Weiner S. 1992 On the relationship between the microstructure of bone and its mechanical stiffness. J Biomech 25(11):1311e1320. 54. Ruppel ME, Burr DB, Miller LM. 2006 Chemical makeup of microdamaged bone differs from undamaged bone. Bone 39(2):318e324. Epub 2006 Apr 11. 55. Wasnich RD, Miller PD. 2000 Antifracture efficacy of antiresportive agents are related to changes in bone density. J Clin Endocrinol Metab 85:1e6. 56. Hochberg MC, Greenspan S, Wasnich RD, et al. 2002 Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 87:1586e1592.
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Editorial 57. Miller PD, Deltas PD, Huss H, et al. 2008 Increases in hip and spine bone mineral density are predictive for antifracture efficacy with ibandronate. In press. 58. Cummings SR, Karpf DB, Harris F, et al. 2002 Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with anti-resorptive drugs. Am J Med 112:281e289. 59. Delmas PD, Li Z, Cooper C. 2004 Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with meta-analyses. J Bone Miner Res 19(2):330e337. 60. Watts NB, Cooper C, Lindsay R, et al. 2004 Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: greater increases in bone mineral density do not relate to greater decreases in fracture risk. J Clin Densitom 7(3):255e261. 61. Miller PD. 2005 Bone density and markers of bone turnover in predicting fracture risk and how changes in these measures predict fracture risk reduction. Curr Osteoporos Rep 3(3):103e110. 62. Lenchick L, Watts NB. 2001 Regression to the mean: what does it mean? Using bone density results to monitor treatment of osteoporosis. J Clin Densitom 4(1):1e4. 63. Delmas PD, Seeman E. 2004 Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy. Bone 34:599e604. 64. Freedman LS, Graubard BI, Schatzkin A. 1992 Statistical validation of intermediate endpoints for chronic diseases. Stat Med 11:167e178.
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5 65. Miller PD, Hochberg MC, Wehren LE, et al. 2005 How useful are measures of BMD and bone turnover? Curr Med Res Opin 21(4):545e553. 66. McClung M, San Martin J, Miller PD, et al. 2005 Teriparatide and alendronate increase bone mass by opposite effects on bone remodeling. Arch Intern Med 165:1762e1768. 67. Chen P, Miller PD, Delmas PD, et al. 2006 Change in lumbar spine bone mineral density and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis. J Bone Miner Res 21:1786e1790. 68. Baim S, Leonard MB, Bianchi M-L, et al. 2008 Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 Pediatric Position Development Conference. J Clin Densitom 11(1):6e21.
Appendix
ISCD Original Steering Committee Members, First Organizational Meeting: Chicago, IL, April 1992.
Sydney Lou Bonnick, MD (Denton, TX, USA) Maria Greenwald, MD (Palm Springs, CA, USA) Paul D. Miller, MD (Chair-Lakewood, CO, USA) Al Moffett, MD (Leesburg, FL, USA) Clifford Rosen, MD (Bangor, ME, USA) David Sartoris, MD (San Diego, CA, USA)
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