A HISTOMORPHOMETRIC STUDY OF BONE CHANGES IN THYROID-DYSFUNCTION IN RATS

Clinical studies in thyrotoxicosis reveal a state of high bone turnove r leading, eventually, to osteoporosis. Recently there has been concer n that thyroxine (T-4) treatment may have a similar effect on bone. Ra t models have been used to study the effects of T-4 on bone, but the m ajority of studies have looked at the effects of T-4 after only 3 week s of treatment. The aim of this study was to evaluate histomorphometri c changes in rats after 12 weeks of thyroxine overtreatment or 12 week s of hypothyroidism compared with untreated control animals. Animals r eceived either T-4 200 mu g/kg per day, 0.1% propylthiouracil, or vehi cle for 12 weeks. Tetracycline was administered 1 week and 3 weeks pri or to killing, Iliac crest bone was used for histomorphometry. Serum T -4 measurements (taken at killing) confirmed hyper- and hypothyroidism in the appropriate animal groups (between group difference p < 0.001 by ANOVA). In hyperthyroid animals there was an increase in mineral ap position rate (MAR; 0.94 vs. 0.59 mu m/day, p ( 0.001) and mineral for mation rate (MFR/BS; 0.24 vs. 0.12 x 10(-2) mu m(3)/mu m(2) per day, p < 0.001) and a slight increase in eroded surfaces (ES/BS%; 1.54 vs, 1 .36, p < 0.05) compared with controls, consistent with previous in vit ro and in vivo observations. In hypothyroid rats there was a marked re duction in osteoid surfaces (OS/BS%; 1.7 vs. 24.8, p < 0.001) and MAR (0.3 vs, 0.59 mu g/day, p < 0.001), a reduction in ES/BS% (0.51 vs. 1. 36, p < 0.05), and an increase in cancellous bone volume (BV/TV%; 30.2 9 vs. 19.6, p < 0.05), suggesting that thyroid hormones are a requirem ent for normal bone turnover. This study characterizes the histomorpho metric changes following 12 weeks of T-4 overtreatment in rats and dem onstrates profound changes due to hypothyroidism in a rat model. To th e best of our knowledge, it is the first study to show such effects in an animal model.