title: Chronic exposure to methylphenidate impairs appendicular bone quality in young rats.
abstract: Methylphenidate (MP) is a psychostimulant widely prescribed to treat Attention Deficit Hyperactivity Disorder (ADHD). Although generally well tolerated, growth deficits have been reported in children and adolescents undergoing MP treatment. This study was designed to elucidate the skeletal effects of chronic MP administration in adolescent rats. Male, 4-week-old rats received one of two doses of MP (MP-Low or MP-High) delivered for 8 h a day via drinking water, or were untreated (water only). After 13 weeks, half were sacrificed (N=12/group) and the remaining rats were left to recover, untreated for 5 additional weeks. Femora, tibiae, and L5 vertebra were analyzed using calipers, DXA, and mechanical testing. Immediately following treatment, MP decreased femoral anterior-posterior diameter (5% and 9% for MP-Low and MP-High, respectively), femoral and tibial bone mineral density (BMD) (6% and 5% for MP-High femora and tibiae, respectively), and bone mineral content (BMC) (9% for MP-High femora and tibiae). In addition, femora from MP treated rats had reduced ultimate force (20% for MP-High) and energy to failure (20% and 33% for MP-Low and MP-High, respectively). However, after recovery, there were no statistically significant differences for any measured parameters. Despite these effects on the appendicular skeleton, no differences were identified between vertebral samples at either time-point. In summary, MP treatment resulted in smaller, less mineralized, and weaker bones at appendicular sites, but did not affect the axial site. Although these effects were ameliorated within 5 weeks, these data suggest that adolescents undergoing MP treatment may be at an increased risk for long bone fractures.
authors.affiliation: Department of Orthopaedics, Stony Brook University, HSC Level 18, Room 085, Stony Brook, NY 11794-8181, USA. david.komatsu@sbumed.org
authors.forename: David E
authors.initials: DE
authors.lastname: Komatsu
authors.forename: Panayotis K
authors.initials: PK
authors.lastname: Thanos
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Mary
authors.forename: Haden A
authors.initials: HA
authors.lastname: Janda
authors.forename: Christine M
authors.initials: CM
authors.lastname: John
authors.forename: Lisa
authors.initials: L
authors.lastname: Robison
authors.forename: Mala
authors.initials: M
authors.lastname: Ananth
authors.forename: James M
authors.initials: JM
authors.lastname: Swanson
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Michael
authors.initials: M
authors.lastname: Hadjiargyrou
mesh_terms: D000293:Adolescent; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects*; D001846:Bone Development / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D024042:Collagen Type I / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000633:toxicity*; D023421:Models, Animal; D010455:Peptides / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D013739:Testosterone / Q000097:blood; D013997:Time Factors
chemical_list: D015415:Biomarkers; D000697:Central Nervous System Stimulants; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D008774:Methylphenidate; D013739:Testosterone; D000469:Alkaline Phosphatase