Introduction: Increased fat mass may increase bone mass through greater biomechanical load on bones [1]. Further, fat mass is a regulator of endocrine function which may influence bone metabolism both positively and negatively [2]. The mediating role of endocrine factors in the positive relationship between fat mass and bone mass in pre- and early-pubertal children is unclear. The aim of this study was to examine the association between fat mass and bone mineral content (BMC), and to investigate whether this relationship is mediated by insulin, free leptin index, adiponectin, dehydroepiandrosterone sulphate (DHEAS), testosterone and estradiol in girls and boys aged 9 to 11 years. Methods: We utilised cross-sectional data from the 2-year follow-up of the Physical Activity and Nutrition in Childhood study, an ongoing longitudinal study in a population sample of Finnish children (n = 396, 203 girls). The study protocol was approved by the Research Ethics Committee of the Hospital District of Northern Savo. The parents or caregivers of the children provided their written informed consent, and the children provided their assent to participation. Total body less head (TBLH) BMC and fat mass were assessed with dual-energy X-ray absorptiometry. Endocrine factors were assessed from fasted venous blood samples. Serum insulin was measured by electrochemiluminescence immunoassay. Plasma leptin was analysed using a competitive radioimmunoassay. Plasma leptin receptor, serum high-molecular-weight adiponectin and serum DHEAS were analysed using enzyme linked immunosorbent assay kits. Testosterone and estradiol were measured using liquid chromatography-mass spectrometry. We applied the novel 4-way decomposition method [3] to analyse associations between fat mass, endocrine factors, and BMC, adjusting for age, stature, pubertal status, lean mass and baseline BMC. The 4-way decomposition method allows the total relationship between fat mass and BMC to be separated into four components: controlled direct effect, reference interaction, mediated interaction, and pure indirect effect.  Results: Fat mass had a positive controlled direct effect on BMC in girls and boys (β = 0.033 to 0.68, p < 0.001). We observed a negative interaction between fat mass and adiponectin with BMC in girls (β = -0.003, p = 0.033). We observed a negative mediated interaction between fat mass and free leptin index with BMC in boys (β = -0.007, p = 0.007).  Conclusions: In children with greater levels of adiponectin and free leptin index, the relationship between fat mass and BMC became less positive, in girls and boys respectively. Fat mass primarily positively influenced BMC through pathways not related to the endocrine factors we assessed, likely through mechanical loading. As the relationship between fat mass and endocrine factors with BMC is likely moderated by weight status and pubertal stage, further research is needed to assess whether these observations extend to children and adolescents with overweight and obese weight status.   Figure 1. Summary of significant mediation and moderation effects from the 4-way decomposition, adjusted for age, stature, pubertal status, lean mass, and baseline TBLH BMC. Girls: n = 191, Boys: n = 181.