Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency

Abstract

Objective: Few studies have determined the effects of more than 5-10 years of GH replacement in adults on bone mineral content (BMC) and bone mineral density (BMD).

Design/patients: In this prospective, single-centre, open-label study, the effects of 15 years of GH replacement on BMC and BMD, measured using dual-energy X-ray absorptiometry, were determined in 126 hypopituitary adults (72 men) with adult-onset GH deficiency (GHD). Mean age was 49.4 (range 22-74) years at the initiation of the study.

Results: The mean initial GH dose of 0.63 (s.e.m. 0.03) mg/day was gradually lowered to 0.41 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.69 (0.11) at baseline to 0.63 (0.16) at the study end (P<0.001 vs baseline). The 15 years of GH replacement induced a sustained increase in total body BMC (+5%, P<0.001) and BMD (+2%, P<0.001). Lumbar (L2-L4) spine BMC increased by 9% (P<0.001) and BMD by 5% (P<0.001). In femur neck, a peak increase in BMC and BMD of 7 and 3%, respectively, was observed after 7 years (both P<0.001). After 15 years, femur neck BMC was 5% above the baseline value (P<0.01), whereas femur neck BMD had returned to the baseline level. In most variables, men had a more marked response to GH replacement than women.

Conclusions: Fifteen-year GH replacement in GHD adults induced a sustained increase in total body and lumbar (L2-L4) spine BMC and BMD. In femur neck, BMC and BMD peaked at 7 years and then decreased towards baseline values.

Figure 1

The gender differences in the effects of 15 years of GH replacement in 126 GH-deficient adults on IGF1 SDS (A) and BMD in total body (B), lumbar (L2–L4) spine (C) and femur neck (D). IGF1 SDS are shown as s.d. for men and women. The grey rectangle shows the normal range of −2 to +2 s.d. The results in BMD are shown as percent change from baseline. The vertical bars indicate the s.e.m. values shown. P values for men vs women are based on a two-way ANOVA of the percent change from baseline in each group. *P<0.05; ***P<0.001 vs baseline.

Figure 2

The percentage of patients with normal BMD adjusted for age, i.e. z-score >0, in total body (A), lumbar (L2–L4) spine (B) and femur neck (C) during 15 years of GH replacement to 126 adults with GH deficiency. In all locations, the percentage of patients with z-score >0 increased throughout the study period.