Vibha Singhal1,2, Amita Bose1, Meghan Slattery1, Melanie S Haines1, Mark A Goldstein3, Nupur Gupta3, Kathryn S Brigham3, Seda Ebrahimi4, Kristin N Javaras5,6, Mary L Bouxsein7, Kamryn T Eddy8, Karen K Miller1, David Schoenfeld9, Anne Klibanski1, Madhusmita Misra1,2. 1. Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 2. Division of Pediatric Endocrinology, Massachusetts General Hospital for Children and Harvard Medical School, Boston, MA, USA. 3. Division of Adolescent Medicine, Massachusetts General Hospital for Children and Harvard Medical School, Boston, MA, USA. 4. Cambridge Eating Disorders Center, Cambridge, MA, USA. 5. Department of Psychiatry, Harvard Medical School, Boston, MA, USA. 6. Division of Women's Mental Health, McLean Hospital, Belmont, MA, USA. 7. Division of Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 8. Eating Disorders Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. 9. Biostatistics Center at Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Abstract
CONTEXT: Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency. OBJECTIVE: To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes. DESIGN: Double-blind, randomized, placebo-controlled 12-month longitudinal study. PARTICIPANTS: Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study. INTERVENTION: Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range. MAIN OUTCOME MEASURES: Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates. RESULTS: Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups. CONCLUSIONS: We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.
CONTEXT: Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency. OBJECTIVE: To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes. DESIGN: Double-blind, randomized, placebo-controlled 12-month longitudinal study. PARTICIPANTS: Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study. INTERVENTION: Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range. MAIN OUTCOME MEASURES: Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates. RESULTS: Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups. CONCLUSIONS: We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.
Authors: Pouneh K Fazeli; Irene S Wang; Karen K Miller; David B Herzog; Madhusmita Misra; Hang Lee; Joel S Finkelstein; Mary L Bouxsein; Anne Klibanski Journal: J Clin Endocrinol Metab Date: 2014-01-23 Impact factor: 5.958
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Authors: Madhusmita Misra; Rajani Prabhakaran; Karen K Miller; Mark A Goldstein; Diane Mickley; Laura Clauss; Patrice Lockhart; Jennalee Cord; David B Herzog; Debra K Katzman; Anne Klibanski Journal: J Clin Endocrinol Metab Date: 2007-12-18 Impact factor: 5.958
Authors: Madhusmita Misra; Rajani Prabhakaran; Karen K Miller; Mark A Goldstein; Diane Mickley; Laura Clauss; Patrice Lockhart; Jennalee Cord; David B Herzog; Debra K Katzman; Anne Klibanski Journal: J Clin Endocrinol Metab Date: 2007-12-18 Impact factor: 5.958
Authors: Vibha Singhal; Amita Bose; Meghan Slattery; Melanie S Haines; Mark A Goldstein; Nupur Gupta; Kathryn S Brigham; Seda Ebrahimi; Kristin N Javaras; Mary L Bouxsein; Kamryn T Eddy; Karen K Miller; David Schoenfeld; Anne Klibanski; Madhusmita Misra Journal: J Clin Endocrinol Metab Date: 2021-06-16 Impact factor: 5.958