The Effect of Hypothalamic Suppression and Caloric Restriction on Bone Strength and Geometry during Puberty

Abstract

INTRODUCTION: Low energy availability and hypothalamic amenorrhea are both risk factors for developing insufficient bone mineral density (BMD) in young physically active women. The prevalence of osteopenia in women athletes is estimated to be between 22-50%. PURPOSE: Determine the effect of calorie restriction and hypothalamic suppression on bone strength and geometrical measures. METHODS: 30 female Sprague-Dawley rats, age day 23, were randomly assigned to a control (C, n=8) group that received daily saline injections (0.2cc) for 27 days and sacrificed at age day 50, or two experimental groups; delayed puberty (GnRH-a, n=14) that received daily injections of gonadotropin releasing hormone antagonist (GnRH-a, 0.2cc, dosage 0.2mg*kg-1) or food restricted and delayed puberty (FR-G, n=8) that received daily injections of gonadotropin releasing hormone antagonist and had a 30% caloric restriction (no deficit in micronutrients) based on the C group's average daily food consumption. All animals were sacrificed at age day of 50. RESULTS: Body weight on day of sacrifice of the FR-G was significantly lower than C (15%, p < 0.001) while GnRH-a was significantly higher than C (8%, p=0.013). The GnRH-a treatment was successful indicated by significantly lower uterine and ovary weights in both the FR-G and GnRH-a groups (p < 0.001). The percent muscle to fat ratio of the FR-G group was significantly higher than control (64%, p=0.038). There was no difference in absolute femoral peak moment, however when normalized for body weight the FR-G and GnRH-a groups were significantly higher than control (19%, p = 0.004 and 20%, p < 0.001 respectively). Cortical bone total area was significantly less in the FR-G group as compared to control (10%, p = 0.043) however, FR-G had a larger cortical thickness compared to control (15%, p = 0.036). In the trabecular both the GnRH-a and FR-G groups had a significantly lower percent bone volume per total volume (BV/TV) compared to control (p < 0.001). However, when normalized for body weight, the percent bone volume of the FR-G group was higher than both control (p = 0.046) and GnRH-a (p < 0.001). The structure was also affected, GnRH-a and FR-G had a higher structural model index (SMI) values than control (p = 0.002, p = 0.007). CONCLUSION: Hypothalamic suppression and caloric restriction before puberty reduced body weight, body fat, and muscle weight while increasing femoral peak moment relative to body weight and increasing cortical thickness in the femur while maintaining trabecular volume per body weight. These results could suggest bone strength is more correlated with body composition than hypothalamic function.