Vibha Singhal1, Smriti Sanchita2, Sonali Malhotra3, Amita Bose2, Landy Paola Torre Flores2, Ruben Valera2, Fatima Cody Stanford4, Meghan Slattery2, Jennifer Rosenblum5, Mark A Goldstein5, Melanie Schorr2, Kathryn E Ackerman6, Karen K Miller2, Anne Klibanski2, Miriam A Bredella7, Madhusmita Misra8. 1. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, United States of America; Division of Pediatric Endocrinology, Massachusetts General Hospital for Children, Harvard Medical School, United States of America; MGH Weight Center, United States of America. Electronic address: vsinghal1@partners.org. 2. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, United States of America. 3. Division of Pediatric Endocrinology, Massachusetts General Hospital for Children, Harvard Medical School, United States of America. 4. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, United States of America; MGH Weight Center, United States of America. 5. Division of Adolescent Medicine, Massachusetts General Hospital for Children, Harvard Medical School, United States of America. 6. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, United States of America; Divison of Sports Medicine, Boston Children's Hospital, Harvard Medical School, United States of America. 7. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, United States of America. 8. Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, United States of America; Division of Pediatric Endocrinology, Massachusetts General Hospital for Children, Harvard Medical School, United States of America.
Abstract
BACKGROUND: Despite their higher areal bone mineral density (aBMD), adolescents with obesity (OB) have an increase in fracture risk, particularly of the extremities, compared with normal-weight controls. Whereas bone parameters that increase fracture risk are well characterized in anorexia nervosa (AN), the other end of nutritional spectrum, these data are lacking in adolescents with obesity. OBJECTIVE: Our objective was to compare bone parameters in adolescent girls across the nutritional spectrum, to determine whether suboptimal bone adaptation to increased body weight may explain the increased fracture risk in OB. METHODS: We assessed bone endpoints in 153 adolescent girls 14-21 years old: 50 OB, 48 controls and 55 AN. We used (i) DXA to assess aBMD at the lumbar spine, proximal femur and whole body, and body composition, (ii) high resolution peripheral quantitative CT (HRpQCT) to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and (iii) finite element analysis to assess failure load (a strength estimate) at the distal radius and tibia. All aBMD, microarchitecture and FEA analyses were controlled for age and race. RESULTS: Groups did not differ for age or height. Areal BMD Z-scores at all sites were highest in OB, intermediate in controls and lowest in AN (p < 0.0001). At the radius, cortical area and thickness were higher in OB compared to AN and control groups (p = 0.001) while trabecular area did not differ across groups. Compared to controls, OB had higher cortical porosity (p = 0.003), higher trabecular thickness (p = 0.024), and higher total, cortical and trabecular vBMD and rod BV/TV (p < 0.04). Plate BV/TV did not differ in OB vs. controls, but was higher than in AN (p = 0.001). At the tibia, total, cortical, and trabecular area and cortical thickness were higher in OB vs. controls and AN (p < 0.005). OB also had higher cortical porosity (p < 0.007) and lower trabecular thickness (p < 0.02) than the other two groups. Trabecular number, total and trabecular vBMD, and rod BV/TV were higher in OB vs. controls and AN (p < 0.02), while cortical vBMD and plate BV/TV did not differ in OB vs. the other two groups. Finally, failure load (a strength estimate) was higher in OB at the radius and tibia compared to controls and AN (p < 0.004 for all). However, after adjusting for body weight, failure load was lower in OB vs. controls at both sites (p < 0.05), and lower than in AN at the distal tibia. CONCLUSION: Not all bone parameters demonstrate appropriate adaptation to higher body weight. Cortical porosity and plate BV/TV at the radius and tibia, and cortical vBMD and trabecular thickness at the tibia are particularly at risk. These effects may contribute to the higher risk for fracture reported in OB vs. controls.
BACKGROUND: Despite their higher areal bone mineral density (aBMD), adolescents with obesity (OB) have an increase in fracture risk, particularly of the extremities, compared with normal-weight controls. Whereas bone parameters that increase fracture risk are well characterized in anorexia nervosa (AN), the other end of nutritional spectrum, these data are lacking in adolescents with obesity. OBJECTIVE: Our objective was to compare bone parameters in adolescent girls across the nutritional spectrum, to determine whether suboptimal bone adaptation to increased body weight may explain the increased fracture risk in OB. METHODS: We assessed bone endpoints in 153 adolescent girls 14-21 years old: 50 OB, 48 controls and 55 AN. We used (i) DXA to assess aBMD at the lumbar spine, proximal femur and whole body, and body composition, (ii) high resolution peripheral quantitative CT (HRpQCT) to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and (iii) finite element analysis to assess failure load (a strength estimate) at the distal radius and tibia. All aBMD, microarchitecture and FEA analyses were controlled for age and race. RESULTS: Groups did not differ for age or height. Areal BMD Z-scores at all sites were highest in OB, intermediate in controls and lowest in AN (p < 0.0001). At the radius, cortical area and thickness were higher in OB compared to AN and control groups (p = 0.001) while trabecular area did not differ across groups. Compared to controls, OB had higher cortical porosity (p = 0.003), higher trabecular thickness (p = 0.024), and higher total, cortical and trabecular vBMD and rod BV/TV (p < 0.04). Plate BV/TV did not differ in OB vs. controls, but was higher than in AN (p = 0.001). At the tibia, total, cortical, and trabecular area and cortical thickness were higher in OB vs. controls and AN (p < 0.005). OB also had higher cortical porosity (p < 0.007) and lower trabecular thickness (p < 0.02) than the other two groups. Trabecular number, total and trabecular vBMD, and rod BV/TV were higher in OB vs. controls and AN (p < 0.02), while cortical vBMD and plate BV/TV did not differ in OB vs. the other two groups. Finally, failure load (a strength estimate) was higher in OB at the radius and tibia compared to controls and AN (p < 0.004 for all). However, after adjusting for body weight, failure load was lower in OB vs. controls at both sites (p < 0.05), and lower than in AN at the distal tibia. CONCLUSION: Not all bone parameters demonstrate appropriate adaptation to higher body weight. Cortical porosity and plate BV/TV at the radius and tibia, and cortical vBMD and trabecular thickness at the tibia are particularly at risk. These effects may contribute to the higher risk for fracture reported in OB vs. controls.
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Authors: Melanie Schorr; Pouneh K Fazeli; Katherine N Bachmann; Alexander T Faje; Erinne Meenaghan; Allison Kimball; Vibha Singhal; Seda Ebrahimi; Suzanne Gleysteen; Diane Mickley; Kamryn T Eddy; Madhusmita Misra; Anne Klibanski; Karen K Miller Journal: J Clin Endocrinol Metab Date: 2019-10-01 Impact factor: 5.958
Authors: Madhusmita Misra; Vibha Singhal; Brian Carmine; Amita Bose; Megan M Kelsey; Fatima Cody Stanford; Jennifer Bram; Jeremy Aidlen; Thomas Inge; Mary L Bouxsein; Miriam A Bredella Journal: Bone Date: 2020-02-19 Impact factor: 4.398
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