Growth hormone effects on healing efficacy, bone resorption and renal morphology of rats: histological and histometric study in rat calvaria

Abstract

Previous reports demonstrated the utility of systemic application of growth hormone (GH) in the treatment of bone defects. Very few studies correlated bone repair efficacy with hepatic and renal side effects promoted by locally-delivered GH. The objectives of this study were to assess the bone repair properties along with hepatic and renal adverse effects promoted by local application of GH in a rat model. Thirty-two rats were randomly divided (4 groups; n = 8/group), as follows: (i) AB (autogenous bone + local application of saline solution [SS]), (ii) AB+ (autogenous bone + SS local application + SS irrigation), (iii) AB/GH+ (autogenous bone + SS local application + GH irrigation) and (iv) AB/GHL+ (autogenous bone + GH local application + GH irrigation). Critical-sized defects (diameter = 5.0 mm) were surgically created by a single operator in the calvaria of rats. Defects were filled with ground autogenous bone. Defects pertaining to AB+ and AB/GH+ received a mixture of autogenous bone and a SS-saturated (0.02 mL) collagen sponge covered with bovine cortical membrane. Defects in group AB/GHL+, were filled with the same biomaterials saturated with GH (0.02 mL). SS (0.1 mL) or GH (0.1 mL, equivalent to 0.4 IU) were applied locally on alternate days (8 weeks) in animals in groups AB, AB+ and AB/GH+ or AB/GHL+, respectively. Bone repair properties was determined in hematoxylin/eosin-stained slices using traditional histologic and histomorphometric techniques along with optical microscopy and digital image analysis. Statistical differences among groups was determined using Kruskal-Wallis and Tukey post hoc tests (α = 0.05). Histology results indicated that AB and AB+ displayed greater presence of autogenous bone as compared to AB/GH+ and AB/GHL+. Histomorphometric results indicated significantly higher osteoid matrix formation in AB and AB+ when compared to AB/GHL+ (p = 0.009). Kidneys and livers were found to have their glomeruli preserved in AB and AB+. Strong glomeruli necrosis and large areas of protein deposition were found in AB/GH+. Abnormal small-sized glomeruli were found in AB/GHL+. The utilization of autogenous bone graft associated with local application and irrigation with GH was shown to not improve the bone repair in calvarial critical-sized defects in a rat model.