Fracture risk of young adults receiving proton-pump inhibitors and H2-receptor antagonists.

INTRODUCTION: Proton-pump inhibitors (PPI) and histamine (type 2) receptor antagonists (H2RA) have the potential to interfere with calcium metabolism. Several authors have evaluated the effect of these medications on fracture incidence in older adults. A recent large epidemiologic study demonstrated a higher risk of fractures in young adults receiving PPI. AIM: To evaluate the effect of PPI and H2RA use on fracture incidence in a large retrospective cohort of military recruits representative of general population of young adults. METHODS: A retrospective cohort of 254 265 male and 234 670 female non-combat military conscripts ages 18-25. Subjects were divided into three groups by PPI use (no PPI use, 1-100 tablets and more than 100 tablets) and two groups by H2RA use (no H2RA use, any H2RA use). Multivariate logistic regression was used to adjust fracture risk for age, BMI, education level, socio-economic level, ethnic origin, occupation and duration of follow-up in months. MAIN OUTCOME MEASURES: At least one fracture during the study period. RESULTS: Use of PPI and H2RA was not associated with an increased risk of fractures. In men, the predictors of an increased fracture risk were higher BMI (OR = 1.007, P < 0.001), origin from a developing country (OR = 1.15, P < 0.001) and service as a driver (OR = 1.11, P < 0.001). Higher education, higher socioeconomic status and service as an officer or as an administrative worker had a protective effect on fracture incidence. In women, fractures were associated with higher BMI (OR = 1.035, P < 0.001). Origin from a developed country, as well as service as an officer or an administrative worker was associated with lower fracture risk. CONCLUSIONS: There was no association between the use of PPI or H2-antagonists and fracture incidence in this retrospective cohort of healthy young military recruits.

Lower risk of stress fractures in young adults with ADHD under chronic treatment with methylphenidate.

INTRODUCTION: Methylphenidate (MP) use is highly prevalent among children and young adults. Previous basic and epidemiological research demonstrated an adverse effect of MP on bone mass. Studies in military recruits have shown that history of MP use before conscription was a risk factor for stress fractures (SF) during the service. METHODS: This study is part of the project in which the association between MP use and incidence of SF was retrospectively investigated in a cohort of healthy conscripts aged 18-25, who served for at least 12 months between 2008 and 2017. Baseline information included sex, age, weight, height, geographic origin, socioeconomic status, and education. Subjects were divided into five groups: subjects without ADHD; untreated subjects with ADHD; and subjects with ADHD and prescriptions of 1-90, 91-180, or 181+ tablets during the study period. The primary outcome was at least one diagnosis of stress fracture during the study. RESULTS: Among 682,110 subjects (409,175 men [60%]), 29,888 (4.4%) had fractures. MP was used by 1681 (0.4%) men and 2828 (1%) women. In both men and women, SF incidence was significantly higher among subjects with untreated ADHD (7.9% and 5.4%, respectively) and significantly lower in subjects with treated ADHD (1.9-3%; 0.3-4.3%), compared to healthy controls (5.3% and 2.9%). After multivariate adjustment, subjects with untreated ADHD remained at an increased risk of fracture (men OR = 1.66, p < 0.001 and women OR = 1.33, p = 0.007), whereas only subjects with highest exposure to MP (180+ tablets) had significantly lower chances for fracture (men OR = 0.49, p = 0.08 and women OR = 0.09, p = 0.02), compared to healthy controls. DISCUSSION: The study has demonstrated lower risk of stress fractures with concurrent MP use. The findings in this population challenge our understanding of the MP effect on bone integrity and prompt further basic research.