Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial

Abstract

Objective: To evaluate the effect of physiological adult growth hormone (GH) replacement on bones. Design: Thirty-six prospective severely growth hormone-deficient (GHD) adults (22 females and 14 males) were randomised to either 18 months of GH (0.03 mU/kg/day) or placebo treatment. Methods: Bone mineral density and content (BMD, BMC) and body composition were evaluated by dual energy X-ray absorptiometry at baseline and after 6, 12 and 18 months. Serum concentrations of insulin-like growth factor-I (IGF-I), IGF binding protein 3, osteocalcin, carboxyterminal propeptide of type I collagen, carboxyterminal crosslink telopeptide of type I collagen, amino-terminal propeptide of type III procollagen and urine pyridinolin and deoxypyridinolin were determined. Results: IGF-I levels increased from 63.2 mg/l (^10.1) to 193.6 (^25.8) mg/l (mean (^S.E.)) (P , 0:001 compared with placebo). Markers of bone turnover increased significantly from 142% to 227% of baseline values (all P , 0:001 compared with placebo). Body composition changes were an increase of lean body mass and a decrease of fat mass resulting in a reduction of percentage body fat of 21.8 (^3.8) in the GH-treated group vs an increase of 1.0 (^2.9)) in the placebo-treated group ðP ¼ 0:002Þ: Conclusions: No significant difference in BMD or BMC between the GH and placebo groups was found after 18 months. At several sites the variances of changes from baseline were significantly greater in the GH than in the placebo group, indicating an impact of the treatment. From baseline to 6 months an insignificant reduction of total BMD was seen while an increase of BMD was found from 6 to 18 months in the GH group compared with the placebo group.This placebo-controlled trial confirmed the longer term open studies on the effect on bones in patients with GHD, with an initial overrepresentation of bone resorption followed by an increase in BMD which at 18 months had reached baseline level.

GH replacement therapy increases plasma osteoprotegerin levels in GH-deficient adults

“…The concomitant increase of both BGP and Dpd rule out a selective stimulation of bone formation as a potential factor responsible for the late anabolic effect of GH therapy on bone mass of adults with GHD (15)(16)(17)(18)(19).…”

Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency? A systematic literature analysis

“…The effects of GH therapy on BMD/BMC are also reflected by increased levels of biochemical markers of bone metabolism as well as altered expression of genes in bone, related to a stimulation of bone remodeling (18,33,34,36,38,39,41,42,46,54,59,60,62,(66)(67)(68)(69).…”

“…the carboxy-terminal telopeptide of type I collagen and urine pyridinolin, are reported to increase significantly from baseline values after 3-6 months of GH therapy in GHD patients (18,33,36,38,39,41,42,46,60,67). Markers of bone formation, e.g.…”

“…Markers of bone formation, e.g. bonespecific alkaline phosphatase, osteocalcin, and the epitope of C-terminal propeptide (PICP) have similarly been reported to increase significantly from baseline values after 3-24 months of GH therapy (18,33,34,36,38,39,41,42,46,54,59,60,66,67).…”

“…The results seem rather inconclusive with a slight majority of trials, however, reporting insignificant differences between the GH and placebo groups (data not shown) (12,39,47,49,52,60). …”