Higher Peptide YY Levels Are Associated With Lower Bone Mineral Density in Low Weight Adolescent Girls With Avoidant/Restrictive Food Intake Disorder

Background: Avoidant/Restrictive Food Intake Disorder (ARFID) is a condition characterized by lack of interest in eating or food, sensory sensitivity, and/or fear of aversive consequences of eating; as opposed to the body image disturbance and fear of weight gain that characterize anorexia nervosa (AN). While appetite regulating hormones and their associations with bone mineral density (BMD) have been well studied in AN, little is known regarding BMD and its association with appetite regulating hormones in ARFID. Peptide YY (PYY), a gut derived anorexigenic hormone, acts via the Y2 receptor to inhibit osteoblastic activity in mammals. In AN, levels of PYY are higher than in healthy controls (HC) and are negatively associated with BMD. We hypothesized that similar to AN, low-weight female adolescents with ARFID would have lower BMD and higher PYY levels than in HC and that PYY levels would be inversely associated with BMD. Methods: We studied 24 adolescent females (10 low weight with ARFID and 14 HC). BMD variables were measured by Dual-Energy X-ray Absorptiometry. We performed cross sectional analysis to compare BMD and fasting PYY levels between low weight ARFID and HC and to determine the relationship between BMD and PYY levels. Results: ARFID and HC were 15.1±2.9 (mean ± SEM) and 17.1±3.8 years old, respectively (p=0.178), with mean BMI Z-scores of -1.74±0.88 kg/m(2) and 0.24±0.51 kg/m(2), respectively (p<0.0001). Total body BMD Z-scores were significantly lower in ARFID (-1.59±1.19, n=10) compared to HC (-0.41±1.11, n=14) (p=0.022), and lumbar BMD Z-scores were numerically lower in ARFID (-1.13±1.40, n=9) vs. HC (-0.44±0.86, n=14) (p=0.212). Mean PYY levels trended higher in ARFID (104.6±39.9 pg/ml, n=8) vs. HC (71.4±24.5 pg/ml, n=9) (p=0.054). In a combined analysis of participants with ARFID and HC, PYY levels were negatively correlated with lumbar BMD and BMD Z-scores (r=-0.52, p=0.038 and r=-0.54 p=0.031, n=16). In multivariable regression analysis, PYY remained a primary determinant of lumbar BMD after adjusting for age and height (p=0.035, β= -0.36) and a borderline significant predictor of lumbar BMD Z-scores after adjusting for height (p=0.064, β=-0.5). Similar associations were noted within the ARFID group alone, with PYY being a significant predictor of lumbar BMD (p=0.031, β=-0.97) after adjusting for age and height. Conclusion: Female adolescents with low-weight ARFID have lower BMD and a trend toward higher levels of PYY compared with HC. Increased PYY levels may contribute to the lower BMD observed in ARFID. These findings are an initial step in understanding the neuroendocrine dysregulation in low weight adolescents with ARFID, which may predict bone outcomes in this condition.