Study: ADHD drugs delay bone healing in children, UB researchers report

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BUFFALO, NY – Children who take psychostimulants prescribed for psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), and who experience a common childhood fracture take longer to heal than children who do not take these medications, report researchers from the University at Buffalo.

The findings were published in September in the Journal of Pediatric Orthopedics B. The researchers note that this finding is not only important for children taking these medications for ADHD and specific disorders, but that it is concerning in light of the fact that many children in middle and high school – as many as one in four – may be using the drugs. illegal, according to a recent national report.

The research grew out of the UB researchers’ preclinical work in which they developed a pharmacokinetic animal model to investigate how these drugs affect bone. They found that bone strength and density weakened in rats given these drugs. This sparked the researchers’ interest in investigating whether this was a problem for children prescribed these drugs, which are among the most commonly prescribed drugs for children.

Most common psychiatric disorder in children

ADHD is the most common psychiatric disorder in children. A 2020 national survey found that 9.3% (5.6 million) of children in the US between the ages of 3 and 17 have been diagnosed with it. Methylphenidate and mixed amphetamine salts (MAS), marketed as Ritalin and Adderall respectively, are the most commonly prescribed medications for the condition.

The UB researchers conducted a retrospective review of pediatric patient data and X-rays over a period of ten years. They looked at the bone density of 62 children between the ages of 6 and 18 who were taking these medications and who had a distal fracture, and compared them with 126 matched controls who had had such fractures but were not taking these medications.

Patients taking methylphenidate and MAS showed significantly reduced bone healing by approximately 20% after experiencing a distal radius fracture, the most common type of fracture, accounting for a quarter of all pediatric fractures. It usually occurs when the child falls on an outstretched or bent hand.

The longer a patient took the drug, the lower the bone density, up to as much as 52% less, compared to the control group. However, that effect leveled off after five years of treatment.

“This is useful for orthopedic physicians because if a patient is taking this medication, it may impact the time it takes to heal from a fracture,” said Panayotis (Peter) K. Thanos, PhD, corresponding author and senior research scientist in the Department of Pharmacology and Toxicology at the Jacobs School of Medicine and Biomedical Sciences and the Clinical Research Institute on Addictions at UB. “Physicians should ask questions about the use of psychostimulants and consider that these patients may require additional time for such fractures to heal.”

Research into a possible mechanism

Thanos says his team’s previous work has shown that these drugs affect bone at the cellular level. He says the drugs affect the differentiation and activity of osteoclasts during healing; Osteoclasts are bone cells that play a crucial role in normal bone remodeling, the final stage of fracture repair.

“This would explain the reduced rate of bone healing we observed in the experimental group in this study,” the authors write, adding that additional research into the specific mechanisms involved in humans is needed.

Thanos notes that it is currently unknown whether this healing problem persists after the patient stops taking the drug, or whether the bone density problem persists into adulthood. The finding from previous studies that women are affected significantly more often also needs to be further studied.

What’s also concerning, he adds, is that many children and young adults are known to use these drugs to improve cognition, often illegally or by obtaining the drug from a friend or family member.

“Orthopedic surgeons planning elective surgeries should be aware of this as a potential problem in recovery and should optimize bone health preoperatively, counseling patients and their families,” he says.

Layla M. Ortiz, a graduate student in Thanos’ lab at UB’s Clinical Research Institute on Addictions, is the first author. Other co-authors are Natasha O’Malley of the University of Rochester, Kenneth Blum of Western University of Health Sciences, Michael Hadjiargyrou of the New York Institute of Technology and David E. Komatsu of Stony Brook University.

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