Effects of pharmacologic agents on bone in childhood: an editorial overview.

ON APRIL 14, 2005, a workshop on the skeletal effects of pharmacologic agents in children was held at the National Institutes of Health. Jointly sponsored by the American Society for Bone and Mineral Research (ASBMR) and the National Institute of Child Health and Human Development, the meeting was organized in response to suggestions from the Pediatric Bone Initiative of the ASBMR.1 Previous discussions at the 2003 ASBMR symposium on the state of pediatric bone research1 led to the conclusion that there was a lack of information on the effects of Food and Drug Administration–approved therapeutic agents on bone in children. Advances in pediatric medicine have produced a new population of children who are able to live into adulthood with chronic illnesses and were previously thought to have a poor prognosis for survival beyond their childhood years. Medications and direct effects of illness may compromise normal bone mineralization, leading to skeletal deformities and osteopenia at a relatively young age. Several topics discussed at the 2003 ASBMR symposium were further examined and developed in the recent National Institutes of Health workshop, such as the limitations of currently available pediatric bone density–reference data, the challenges of measuring bone mass and strength in children, clinicaltrial design, chronic drug effects on growing bone, and therapeutic agents for pediatric bone disorders. The following is a summary of all the presentations from the National Institutes of Health workshop on pediatric bone. Detailed summaries of selected talks are provided as well. The first session provided basic background on normal bone accrual in children, the regulation of skeletal growth, and the effects of calcium, phosphorus, and vitamin D on growing bone. Dr Jeffrey Baron and his co-workers2,3 reviewed the role of the growth plate in linear skeletal growth and work from his own laboratory to elucidate mechanisms of growth at the growth plate. Addressing specifically the role of the resting zone of the growth plate in longitudinal growth, he presented evidence that the resting zone contains chondrocyte stem-like cells that can regenerate the entire growth plate in the absence of the other 2 zones, the proliferative and hypertrophic. He then discussed growth-plate senescence and, with the use of rabbit and rat models, hypothesized that this phenomenon is a result of the finite capacity of chondrocytes to proliferate. Dr Baron proposed that “catchup” growth, which occurs after recovery from a specific condition that inhibits growth, is explained by changes in the tempo of growth-plate senescence. In this model, inhibition of linear growth slows growth-plate senescence. When the inhibiting condition is resolved, the growth-plate chondrocytes have more of their proliferative capacity remaining and, thus, catch-up growth occurs. Conversely, estrogen accelerates growth-plate senescence, which leads to earlier “exhaustion” of