Growth hormone and sex steroid effects on bone metabolism and bone mineral density in healthy aged women and men.
BACKGROUND
Aging is associated with concomitant declines in activity of the growth hormone (GH) and gonadal steroid axes, and in bone mineral density (BMD), in both sexes. Long-term estrogen replacement slows bone loss and prevents fractures in postmenopausal women, whereas the effects of supplementation of GH or testosterone on bone metabolism and BMD in aged individuals remains uncertain.


METHODS
Using a randomized, placebo-controlled, double-blind study design, we investigated the separate and interactive effects of 6 months of administration of recombinant human GH and/or gonadal steroids on bone biochemical markers and BMD in 125 healthy, older (>65 years) women (n = 53) and men (n = 72) with age-related reductions in GH and gonadal steroids.


RESULTS
In women, administration of GH, but not GH + hormone replacement therapy (HRT), increased serum levels of osteocalcin and procollagen peptide (PICP) and increased urinary excretion of deoxypyridinoline (DPD) crosslinks. Urinary calcium excretion decreased after HRT. In men, GH, and to a greater extent GH + T, increased osteocalcin. GH increased serum PICP, and GH + T increased urinary DPD. Urinary calcium excretion was unaffected by hormone treatment in men. In women, administration of HRT and GH + HRT, but not GH, increased BMD at the lumbar spine, femoral neck, and distal radius. In men, GH + T led to a small decrease in BMD at the proximal radius; there were no other significant effects of hormone administration on BMD.


CONCLUSIONS
These data suggest that short-term administration of HRT exerts beneficial effects on bone metabolism and BMD in postmenopausal women, which are not significantly altered by the coadministration of GH. In andropausal men, T administration to achieve physiologic levels did not result in significant effects on bone metabolism or BMD, whereas GH + T increased one marker of bone formation and decreased one marker of bone resorption. Given the known biphasic actions of GH on bone and the apparent favorable biochemical effects of GH + T in men, the longer-term effects of GH + T on BMD in aged men remain to be clarified.
Christmas
Colleen
C
Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
O'Connor
Kieran G
KG
Harman
S Mitchell
SM
Tobin
Jordan D
JD
Münzer
Thomas
T
Bellantoni
Michele F
MF
Clair
Carol St
CS
Pabst
Katharine M
KM
Sorkin
John D
JD
Blackman
Marc R
MR
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism*; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D015914:Estrogen Replacement Therapy; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013739:Testosterone / Q000097:blood
D012739:Gonadal Steroid Hormones; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D013739:Testosterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I