7858 Increasing Severity of Growth Hormone Deficiency is Associated with Lower Vertebral Strength

Abstract Disclosure: R. Boutin: None. M. Haines: None. R. Shahid: None. C. Mark: None. C. Gill: None. M. Bredella: None. K.K. Miller: Other; Self; Pfizer, Inc. L.E. Dichtel: Consulting Fee; Self; Lumos Pharma. Grant Recipient; Self; Lumos Pharma, Perspectum Ltd. Research Investigator; Self; Recordati, Novo Nordisk. Stock Owner; Self; Marea Therapeutics. Other; Self; Third Rock Ventures. Objective: Growth hormone (GH) stimulates osteoblast differentiation, while insulin-like growth factor-1 (IGF-1) stimulates osteoblast proliferation and bone formation. Retrospective studies have demonstrated a 2-to-3-fold increased fracture risk in adults with GH deficiency (GHD) due to organic hypothalamic or pituitary disease, particularly at vertebral sites. Adults with overweight/obesity produce relatively less GH than lean individuals, and serum IGF-1 levels are associated positively with BMD in adults with obesity. Yet, no published studies have examined the relationship between degree of GHD across these groups and vertebral strength, an understudied measure of bone quality in part because HR-pQCT cannot image this skeletal site. We hypothesized that there would be an inverse association between degree of GHD and vertebral strength, independent of age and BMI. Methods: Cross-sectional study of 134 estrogen-replete (with regular menses or taking estrogen) women: 16 with GHD secondary to hypopituitarism (HP, severe GHD), 91 with obesity (OB) without a hypothalamic/pituitary disorder (relative GHD), and 37 lean controls (LC) without a hypothalamic/pituitary disorder (normal GH production). Peak-stimulated GH was assessed by GHRH-arginine testing. CT imaging at the L4 vertebra was performed to determine vertebral cross-sectional area and total integrated volumetric bone mineral density (Int.vBMD), from which estimates of vertebral strength were calculated. Results: Mean age [44±9 (mean±SD) (HP) vs. 35±7 (OB) vs. 30±7 (LC) y, p<0.005] and BMI [30±6 (HP) vs. 34±6 (OB) vs. 22±2 (LC) kg/m2, p<0.004] differed between all groups. As expected, peak-stimulated GH was highest in LC (28.3 ± 9.5 ng/mL) followed by OB (12.4 ± 8.9 ng/mL) and HP (2.4 ± 1.7 ng/mL), p<0.0001. IGF-1 Z-scores were higher in LC (0.0 ± 0.6) and OB (0.0 ± 0.7) vs. HP (-1.4 ± 0.7), p<0.0001. Int.vBMD and vertebral strength were higher in LC and OB vs. HP [Int.vBMD (g/cm3) LC 0.21±0.04 and OB 0.21±0.04 vs. HP 0.16±0.03, and vertebral strength (N) LC 4540±850 and 4743±91 vs. HP 3542±651, both p<0.0001], which remained significant when adjusted for age and BMI (p≤0.01). Peak-stimulated GH and IGF-1 Z-scores were positively associated with vertebral strength (GH R=0.33, p=0.003 and IGF-1 Z-score R=0.41, p<0.0001) and Int.vBMD (GH R=0.46, p<0.0001 and IGF-1 Z-score R=0.40, p<0.0001), which remained significant when adjusted for age and BMI. Among the subset of patients without organic pituitary disease (LC and OB only), IGF-1 Z-scores remained positively associated with vertebral strength (R=0.24, p<0.03) and Int.vBMD (R=0.22, p<0.05). Conclusions: These findings suggest that severe GHD is associated with impaired vertebral volumetric bone density and strength. Moreover, the relative GHD of obesity may contribute to lower vertebral bone density and strength in otherwise healthy adults with overweight/obesity. Presentation: 6/3/2024