Does stimulant use affect bone health?

Stimulant Use and Bone Health

Stimulant medications used to treat ADHD are associated with reduced bone mineral density (BMD) and bone mineral content (BMC) in children and adolescents, with effects most pronounced in males and with treatment duration of 3 months or longer.

Evidence of Bone Health Impact

Primary Findings from Population Studies

• A nationally representative NHANES analysis (2011-2018) of 5,472 children aged 8-16 years found that stimulant users had significantly lower BMC and BMD at the lumbar spine, pelvis, and total body compared to non-users, particularly in males 1

• Children using stimulants for ≥3 months showed significantly reduced BMC at the lumbar spine (β = -1.35), pelvis (β = -9.06), and total body (β = -52.96), along with reduced BMD at the pelvis (β = -0.03) and total body (β = -0.01) 1

• A separate NHANES analysis (2005-2010) of 6,489 participants aged 8-20 years confirmed these findings, showing stimulant users had lower lumbar spine BMC (12.76 g vs 13.38 g, P=0.02), lower lumbar spine BMD (0.90 g/cm² vs 0.94 g/cm², P=0.03), and lower femoral neck BMC (4.34 g vs 4.59 g, P=0.03) compared to non-users 2

Duration-Dependent Effects

• Treatment duration matters critically: participants using stimulants for ≥3 months had significantly lower lumbar spine BMD (0.89 g/cm² vs 0.94 g/cm², P=0.02) and femoral neck BMD (0.87 g/cm² vs 0.91 g/cm², P=0.048) compared to non-users 2

• A prospective study following children for 3 years on stimulant treatment showed significant reductions in sex and height-corrected Z-scores for lean tissue (-0.84), BMC (-0.55), and BMD (-0.41) 3

• Children taking psychostimulants for 1-5 years showed approximately 52% lower bone density following distal radius fractures compared to controls, though this effect plateaued after 5 years 4

Mechanism and Early Changes

• Bone turnover markers (propeptide of type I collagen) showed significant reduction after just 3 months of treatment (564 to 458 ng/ml, P=0.019), though this recovered by 3 years 3

• The mechanism likely involves sympathetic nervous system activation by stimulants, which leads to decreased bone mass through altered bone remodeling 2

• Early fat loss of 1.4 kg occurred within the first 6 months of treatment, with lean tissue including bone increasing more slowly than expected for normal growth 3

Sex Differences

• The bone density effects are predominantly seen in males, with BMC and BMD at lumbar spine, pelvis, and total body generally lower among male stimulant users (all P<0.001), while differences in females were not statistically significant 1

• Body mass index and serum alkaline phosphatase may serve as predictors for loss of BMC and BMD in stimulant users 1

Adult Data (Less Conclusive)

• Limited data in adults aged 18-50 years showed stimulant use associated with decreased BMD in the skull (-6.6%, P<0.05) and thoracic spine (-6.0%, P<0.05), but no differences in other skeletal regions 5

• The adult findings are inconclusive and require further study to determine if ADHD itself or stimulant medication use independently affects bone health 5

Clinical Implications for Fracture Healing

• Children taking psychostimulants showed approximately 20% reduced bone healing following distal radius fractures, with duration of use (1-5 years) playing a significant role 4

• Orthopedic surgeons planning elective bone procedures should preoperatively optimize bone health and counsel patients and families about potential delayed healing 4

Growth Monitoring Context

• While the 2002 AACAP guidelines noted that prospective follow-up into adult life revealed no significant impairment of final height attained 6, these guidelines predate the specific bone density research

• Small weight decrements are reported during short-term trials, and the MTA study showed significant decrements in rates of weight acquisition with chronic stimulant treatment 6

• The guidelines recommend monitoring height and weight regularly, though they do not specifically address bone density monitoring 6

Clinical Monitoring Recommendations

• Given the evidence of reduced bone density, particularly in males and with treatment duration ≥3 months, clinicians should:
  • Monitor growth parameters (height, weight) at baseline and regularly during treatment 6
  • Consider the bone health implications when planning long-term stimulant therapy, especially in males
  • Optimize nutrition and ensure adequate calcium and vitamin D intake
  • Be aware of potentially slower fracture healing in children on chronic stimulant therapy 4
  • Consider bone density assessment in high-risk patients or those on long-term therapy, though this is not yet a guideline recommendation

Important Caveats

• The bone density reductions occur despite stimulants remaining the first-line treatment for ADHD due to their superior efficacy (effect size ~1.0) 7

• The clinical significance of these bone density reductions for long-term fracture risk in adulthood remains unknown and requires prospective study 3, 2

• These findings should not deter appropriate stimulant use for ADHD, but rather inform monitoring and counseling practices 4