Histologic evidence: growth hormone completely prevents reduction in cortical bone gain and partially prevents cancellous osteopenia in the tibia of hypophysectomized rats.

BACKGROUND

In previous studies we found that the cause of bone loss in young hypophysectomized (HX) animals was due primarily to an inhibition in growth-dependent bone gain and a decrease in bone turnover. The aim of this study was to determine whether growth hormone, which has stimulatory effects on bone growth and turnover, can prevent HX-induced skeletal alterations in rats.

METHODS

Female Sprague-Dawley rats were divided into baseline control (BASAL), age-matched control (CON), HX, HX plus low-dose GH (1.5 mg/kg/d, subcutaneously), and HX plus high-dose GH (4.5 mg/kg/d) groups. The BASAL group was sacrificed at 2 months of age and the remaining groups were sacrificed after 6 weeks of treatment. Cancellous and cortical bone histomorphometry was performed on double-fluorescent-labeled 40 microm-thick sections of the proximal tibia and tibial shaft.

RESULTS

Both low- and high-dose GH prevented the HX-induced decrease of IGF-I serum levels. High-dose GH also significantly increased the body weight and the wet weight of the gastrocnemius muscle when compared to the CON groups. In the tibial shaft, the periosteal labeled surface, mineral apposition rate and bone formation rate were higher in both of the GH-treated groups than in the HX group (P < 0.05). The tissue area and cortical bone area of the high-dose GH-treated rats were greater than those of the HX rats, but did not differ from those of the CON rats. In the proximal tibia, both low- and high-dose GH prevented an HX-induced decrease in the longitudinal growth rate and growth plate width, and increased surface-based bone formation compared to the HX and CON. Cancellous bone volume, tissue-based bone formation rate, and eroded surface in both of the GH-treated groups were higher than those of the HX group, but lower than those of the BASAL and CON groups (P < 0.05). Bone architecture of the HX rats was also improved after GH treatment.

CONCLUSIONS

This study clearly demonstrates that GH replacement at the dosage of 4.5 mg/kg/d can completely prevent the HX-induced reduction in cortical bone gain in the tibial shaft, but can only partially prevent cancellous osteopenia in the proximal tibia after six weeks.