Lumbar Spine Bone Mineral Apparent Density in Children: Results From the Bone Mineral Density in Childhood Study

C LI NI CA L RE SE AR CH A RT IC LE Lumbar Spine Bone Mineral Apparent Density in Children: Results From the Bone Mineral Density in Childhood Study Joseph M. Kindler,1 Joan M. Lappe,2 Vicente Gilsanz,3 Sharon Oberfield,4 John A. Shepherd,5 Andrea Kelly,6,7 Karen K. Winer,8 Heidi J. Kalkwarf,9* and Babette S. Zemel1* Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; 2Division of Endocrinology, Department of Medicine, Creighton University, Omaha, Nebraska 68131; 3Department of Radiology, Children’s Hospital Los Angeles, Los Angeles, California 90027; 4Division of Pediatric Endocrinology, Diabetes, and Metabolism, Department of Pediatrics, Columbia University Medical Center, New York, New York 10032; 5Cancer Center, University of Hawaii, Honolulu, Hawaii 96813; 6Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; 7Department of Pediatrics, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104; 8Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 21117; and 9Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229 ORCiD numbers: 0000-0001-7613-4548 (J. M. Kindler). Context: Dual-energy X-ray absorptiometry (DXA) is a cornerstone of pediatric bone health assessment, yet differences in height-for-age confound the interpretation of areal bone mineral density (aBMD) measures. To reduce the confounding of short stature on spine bone density, use of bone mineral apparent density (BMAD) and height-for-age Z-score (HAZ)‒adjusted aBMD (aBMDHAZ) are recommended. However, spine BMAD reference data are sparse, and the degree to which BMAD and aBMDHAZ account for height-related artifacts in bone density remains unclear. Objective: We developed age-, sex-, and population ancestry‒specific spine BMAD reference ranges; compared height-adjustment methods in accounting for shorter stature; and assessed the stability of these measures over time. Design: Secondary analysis of data from a previous longitudinal study. Participants: Children and adolescents aged 5 to 19 years at baseline (n = 2014; 922 males; 22% black) from the Bone Mineral Density in Childhood Study. Main Outcome Measures: Lumbar spine BMAD and aBMDHAZ from DXA. Results: Spine BMAD increased nonlinearly with age and was greater in blacks and females (all P , 0.001). Age-specific spine BMAD z-score reference curves were constructed for black and non‒black males and females. Overall, both BMAD and aBMDHAZ z scores reduced the confounding influence of shorter stature, but neither was consistently unbiased across all age ranges. Both BMAD and aBMDHAZ z scores tracked strongly over 6 years (r = 0.70 to 0.80; all P , 0.001). Conclusion: This study provided robust spine BMAD reference ranges and demonstrated that BMAD and aBMDHAZ partially reduced the confounding influence of shorter stature on bone density. (J Clin Endocrinol Metab 104: 1283–1292, 2019) ISSN Print 0021-972X ISSN Online 1945-7197 Printed in USA Copyright © 2019 Endocrine Society Received 10 August 2018. Accepted 24 September 2018. First Published Online 27 September 2018 doi: 10.1210/jc.2018-01693 *H.J.K. and B.S.Z. contributed equally to this work. Abbreviations: aBMD, areal bone mineral density; aBMDHAZ, height-for-age Z-score adjusted areal bone mineral density; BMAD, bone mineral apparent density; BMDCS, Bone Mineral Density in Childhood Study; DXA, dual-energy X-ray absorptiometry; HAZ, height-for-age Z-score; L, power for the Box-Cox transformation; M, median; S, standard deviation. J Clin Endocrinol Metab, April 2019, 104(4):1283–1292 https://academic.oup.com/jcem 1283 1 1284 Kindler et al Spine Bone Mineral Apparent Density in Children D these measures are predictive of future risk for osteoporosis and fracture. The only pediatric reference data for spine BMAD from Hologic fan-beam densitometers are based on 587 white children and adolescents (262 females) aged 4.5 to 20 years from a single clinical center in the United Kingdom (11). To meet criteria for robust reference ranges, a larger, multicenter sample of data including other population ancestry groups is needed. To address this need, we used data from the Bone Mineral Density in Childhood Study (BMDCS), a large, multicenter, multiethnic study of healthy children and adolescents that provides pediatric reference data for aBMD and BMC at several skeletal sites, including the whole body, hip, forearm, and lumbar spine (3, 5). We assessed age-, sex-, and ancestry-dependent changes in spine BMAD during childhood. Second, we developed age-specific spine BMAD reference ranges for black and non‒black males and females. Finally, we compared spine BMAD with aBMD and aBMDHAZ with respect to (i) reducing the effects of shorter stature on bone density and (ii) the stability (i.e., tracking) of these indices within individuals over time. Methods Study population The BMDCS was a multiethnic prospective study of healthy children from five clinical centers across the United States, including Children’s Hospital of Los Angeles (Los Angeles, CA), The Children’s Hospital of Philadelphia (Philadelphia, PA), Cincinnati Children’s Hospital Medical Center (Cincinnati, OH), Columbia University (New York, NY), and Creighton University (Omaha, NE). The study protocols and procedures have been described previously (2, 3, 5). Initially, 1554 healthy children aged 6 to 16 years were enrolled from July 2002 to November 2003 and followed up annually for up to 6 years for seven possible visits. To expand this age range, additional children aged 5 and 19 years were enrolled in the fourth year of the study. These participants were evaluated annually for 2 years, for a maximum of three total visits. Participants were enrolled and evaluated throughout the calendar year. Exclusion criteria included height, weight, or body mass index below the third percentile or above the 97th percentile; delayed or advanced pubertal development; premature birth; scoliosis; use of medications known to influence bone metabolism; or medical conditions that threatened normal bone accretion. In addition, individuals younger than 10 years were excluded for having experienced two or more fractures, and individuals older than 10 years were excluded for having experienced three or more fractures. For participants younger than 18 years, a parent/guardian provided written informed consent and the participant provided assent. Participants 18 years of age or older provided written informed consent. All study protocols and procedures were approved by the institutional review board for human subjects at each clinical center. ual-energy X-ray absorptiometry (DXA) is a cornerstone of bone health assessment (1). However, the (...truncated)