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Journal of Child Neurology
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Effects of Valproic Acid on Longitudinal Bone Growth

Shufang Wu, PhD

Sections of Endocrinology and Diabetes, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, PA

Agustin Legido, MD

Section of Child Neurology, Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, PA

Francesco De Luca, MD

Sections of Endocrinology and Diabetes, Drexel University College of Medicine, St. Christopher's Hospital for Children, Philadelphia, PA, francesco.deluca{at}drexel.edu

Valproic acid is widely used in the treatment of children with epilepsy. Evidence indicates that valproic acid has teratogenic effects on the skeletal system. In addition, the use of valproic acid in children has been associated with short stature. Thus, we hypothesized that valproic acid could also affect bone growth after skeletal morphogenesis is completed. To test this hypothesis, we cultured fetal rat metatarsal bones in the presence of valproic acid. Valproic acid markedly suppressed metatarsal longitudinal growth. To determine the underlying mechanisms, we studied cell proliferation and hypertrophy in the growth plate, the site where bone growth takes place. At the end of the culture period, valproic acid—treated bones exhibited narrow growth plate proliferative and hypertrophic zones and an expanded ossification center. In addition, valproic acid suppressed chondrocyte proliferation in the metatarsal rudiments. Our results suggest that valproic acid suppresses longitudinal bone growth by inhibiting cartilage formation and accelerating ossification of the growth plate. These findings warrant a prospective study on the effects of valproic acid on growth in children treated with valproic acid. (J Child Neurol 2004;19:26—30).

Journal of Child Neurology, Vol. 19, No. 1, 26-30 (2004)
DOI: 10.1177/088307380401900105011
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A. M. Pack, M. J. Morrell, A. Randall, D. J. McMahon, and E. Shane
Bone health in young women with epilepsy after one year of antiepileptic drug monotherapy
Neurology, April 29, 2008; 70(18): 1586 - 1593.
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