title: A randomized controlled trial testing an adherence-optimized Vitamin D regimen to mitigate bone change in adolescents being treated for acute lymphoblastic leukemia.
abstract: Adolescents with acute lymphoblastic leukemia (ALL) develop osteopenia early in therapy, potentially exacerbated by high rates of concurrent Vitamin D deficiency. We conducted a randomized clinical trial testing a Vitamin D-based intervention to improve Vitamin D status and reduce bone density decline. Poor adherence to home supplementation necessitated a change to directly observed therapy (DOT) with intermittent, high-dose Vitamin D3 randomized versus standard of care (SOC). Compared to SOC, DOT Vitamin D3 successfully increased trough Vitamin 25(OH)D levels (p = .026) with no residual Vitamin D deficiency, 100% adherence to DOT Vitamin D3, and without associated toxicity. However, neither Vitamin D status nor supplementation impacted bone density. Thus, this adherence-optimized intervention is feasible and effective to correct Vitamin D deficiency in adolescents during ALL therapy. Repletion of Vitamin D and calcium alone did not mitigate osteopenia, however, and new, comprehensive approaches are needed to address treatment-associated osteopenia during ALL therapy.
authors.affiliation: a Children's Center for Cancer and Blood Diseases , Children's Hospital Los Angeles , Los Angeles , CA , USA.|b Keck School of Medicine , University of Southern California , Los Angeles , CA , USA.
authors.forename: Etan
authors.identifier: http://orcid.org/0000-0002-1487-6818
authors.initials: E
authors.lastname: Orgel
authors.affiliation: c Children's Orthopaedic Center , Children's Hospital Los Angeles , Los Angeles , CA , USA.
authors.forename: Nicole M
authors.identifier: http://orcid.org/0000-0003-4459-8289
authors.initials: NM
authors.lastname: Mueske
authors.affiliation: a Children's Center for Cancer and Blood Diseases , Children's Hospital Los Angeles , Los Angeles , CA , USA.|b Keck School of Medicine , University of Southern California , Los Angeles , CA , USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.affiliation: b Keck School of Medicine , University of Southern California , Los Angeles , CA , USA.|d Department of Radiology , Children's Hospital Los Angeles , Los Angeles , CA , USA.
authors.forename: Vicente
authors.initials: V
authors.lastname: Gilsanz
authors.affiliation: b Keck School of Medicine , University of Southern California , Los Angeles , CA , USA.|c Children's Orthopaedic Center , Children's Hospital Los Angeles , Los Angeles , CA , USA.
authors.forename: Tishya A L
authors.initials: TAL
authors.lastname: Wren
authors.affiliation: a Children's Center for Cancer and Blood Diseases , Children's Hospital Los Angeles , Los Angeles , CA , USA.|b Keck School of Medicine , University of Southern California , Los Angeles , CA , USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Freyer
authors.affiliation: a Children's Center for Cancer and Blood Diseases , Children's Hospital Los Angeles , Los Angeles , CA , USA.|b Keck School of Medicine , University of Southern California , Los Angeles , CA , USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Butturini
authors.affiliation: b Keck School of Medicine , University of Southern California , Los Angeles , CA , USA.|e Center for Endocrinology, Diabetes & Metabolism , Children's Hospital Los Angeles , Los Angeles , CA , USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Mittelman
mesh_terms: D000293:Adolescent; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D002762:Cholecalciferol / Q000008:administration & dosage; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy; D014808:Vitamin D Deficiency / Q000150:complications* / Q000188:drug therapy
chemical_list: D050071:Bone Density Conservation Agents; D002762:Cholecalciferol
keywords: Acute lymphoblastic leukemia; Vitamin D; adolescent and young adult; bone mineral density; medication adherence; osteopenia