A histomorphometric study of bone changes in thyroid dysfunction in rats

Clinical studies in thyrotoxicosis reveal a state of high bone turnover leading, eventually, to osteoporosis. Recently there has been concern that thyroxine (T4) treatment may have a similar effect on bone. Rat models have been used to study the effects of T4 on bone, but the majority of studies have looked at the effects of T4 after only 3 weeks of treatment. The aim of this study was to evaluate histomorphometric changes in rats after 12 weeks of thyroxine overtreatment or 12 weeks of hypothyroidism compared with untreated control animals. Animals received either T4 200 μg/kg per day, 0.1% propylthiouracil, or vehicle for 12 weeks. Tetracycline was administered 1 week and 3 weeks prior to killing. Iliac crest bone was used for histomorphometry. Serum T4 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 apposition rate (MAR; 0.94 vs. 0.59 μm/day, p< 0.001) and mineral formation rate (MFR/BS; 0.24 vs. 0.12 × 10−2 μm3/μm2 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 vitro and in vivo observations. In hypothyroid rats there was a marked reduction in osteoid surfaces (OS/BS%; 1.7 vs. 24.8, p< 0.001) and MAR (0.3 vs. 0.59 μg/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%; 30.29 vs. 19.6, p< 0.05), suggesting that thyroid hormones are a requirement for normal bone turnover. This study characterizes the histomorphometric changes following 12 weeks of T4 overtreatment in rats and demonstrates profound changes due to hypothyroidism in a rat model. To the best of our knowledge, it is the first study to show such effects in an animal model.