Administration of growth hormone in selectively protein-deprived rats decreases BMD and bone strength.
BACKGROUND
Isocaloric protein undernutrition is associated with decreased bone mass and decreased bone strength, together with lower IGF-I levels. It remains unclear whether administration of growth hormone (GH) corrects these alterations in bone metabolism.


METHODS
Six-month-old female rats were fed isocaloric diets containing either 2.5% or 15% casein for 2 weeks. Bovine growth hormone (bGH, 0.5 or 2.5mg/kg of body weight) or vehicle was then administered as subcutaneous injections, twice daily, to rats on either diet for 4 weeks. At the proximal tibia, analysis of bone mineral density (BMD), maximal load and histomorphometry were performed. In addition, urinary deoxypyridinoline, plasma osteocalcin and IGF-I concentrations were measured. Weight was monitored weekly.


RESULTS
bGH caused a dose-dependent increase in plasma IGF-I regardless of the dietary protein content. However, bGH dose-dependently decreased BMD and bone strength in rats fed the low-protein diet. There was no significant effect of bGH on BMD in rats fed the normal protein diet within this short-term treatment period, however bone formation as detected by histomorphometry was improved in this group but not the low-protein group. Osteoclast surface was increased in the low-protein bGH-treated animals only. Changes in bone turnover markers were detectable under both normal and low-protein diets.


CONCLUSIONS
These results emphasize the major importance of dietary protein intake in the bone response to short-term GH administration, and highlight the need for further investigation into the effects of GH treatment in patients with reduced protein intake.
Ammann
Patrick
P
Service of Bone Diseases, Department of Rehabilitation and Geriatrics, University Hospitals of Geneva, Switzerland. patrick.ammann@unige.ch
Brennan
Tara C
TC
Mekraldi
Samia
S
Aubert
Michel L
ML
Rizzoli
René
R
D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D001835:Body Weight; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D002364:Caseins; D002417:Cattle; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D002364:Caseins; D013006:Growth Hormone