*4.1.3. Subclinical hypothyroidism and skeletal changes*

Subclinical hypothyroidism is a relatively frequent clinical condition, particularly among aged population, characterized by a low-normal free T4 level and a slightly elevated TSH level. The prevalence of subclinical hypothyroidism has been reported between 3.9 and 6.5% (Hollowell et al, 2002; Huber et al, 2002)

In Trosmo study, Grimnes et al. (2008) have demonstrated that, after multivariate adjustment, 25 out of 950 postmenopausal women with serum TSH above the 97.5 percentile had significantly higher BMD at the femoral neck than women with serum TSH in the normal range. However, there was no association between TSH and BMD, and serum TSH as a continuous variable had no effect on BMD.

Thyroid Disorders and Bone Mineral Homeostasis 259

After initiation of anti-thyroid treatment, biochemical markers of bone resorption, such as urinary hydroxyproline, serum pyridinoline, serum deoxypiridinoline cross-links, have been found to fall, with a subsequent rise of the bone formation markers (Mosekilde et al 1990; Siddiqi et al, 1997; Garnero et al, 1994). Elevation of serum PTH has been reported in some patients with severe thyrotoxicosis under anti-thyroid treatment (Pantazi et al, 2000). This rise in PTH was suggested to play a role in inducing some temporal changes in mineral metabolism and participate to the reversal of the catabolic bone status of hyperthyroidism to anabolic. Furthermore, another study found that in hyperthyroidism, despite normal or high IGF-I levels, IGF-I bioactivity is reduced, probably because of high levels of IGF-binding protein-1 (Miell et al, 1993). Treatment of thyrotoxicosis reverses this abnormality. The rise

in IGF-I bioactivity may therefore have a positive effect on the bone metabolism.

Pathological skeletal changes, including osteopenia and osteoporosis, with higher incidence of fracture rates have been reported in hyperthyroid patients. Accordingly, hyperthyroidism was found 2.5-fold more often in postmenopausal women presenting with hip fracture than in controls. Among postmenopausal women, risk of hip fracture was significantly higher in patients with overt untreated hyperthyroidism and a history of past hyperthyroidism (Wejda et al, 1995). These findings were confirmed by a prospective follow-up study realized in 9516 Caucasian women, 65 years of age or older (Cummings et al, 1995). The authors demonstrated a higher risk of hip fracture among women who had previous hyperthyroidism. Another study reported that the prevalence of all types of fractures in patients with a history of thyroid disease was not different from that of

However, women with a history of hyperthyroidism or thyroid cancer appeared to have their first fracture earlier than women without thyroid disease (Solomon et al, 1993). Median lumbar BMD in patients with thyrotoxicosis was shown to be 12.6% lower than that of normal individuals before the initiation of treatment (Krolner et al, 1983). Decreased BMD in hyperthyroid patients was demonstrated particularly in areas consisting of cortical bone. The risk of hip fracture increased significantly with age at diagnosis of hyperthyroidism (Campos-Pastor et al, 1993; Udayakmar et al, 2006; Vestergaard et al, 2002, 2005). The etiology of hyperthyroidism is not believed to play a role in the severity of hyperthyroid

A recent meta-analysis (Vestergaard et al, 2005) evaluated data regarding BMD and fracture risk in 20 (962 patients) and 5 publications, respectively (62 830 patients and controls). The results showed that patients with hyperthyroidism have a significantly decreased BMD. These values were lower in untreated patients compared to those under treatment, particularly for the lumbar spine (-0.83 vs. -0.27 Z-score) and the femoral site (-0.75 vs. -0.15 Z-score). The risk of hip fracture at the moment of diagnosis of hyperthyroidism was 1.6 (95% CI 0.7 to 3.4), and the value of BMD alone was associated with a risk of hip fracture

*4.2.2. Overt hyperthyroidism and skeletal changes* 

control subjects.

bone disease (Jodar et al, 1997).

corresponding to 1.2 (95% CI 0.9-1.5).

Bone quality was studied by Nagata et al. using quantitative ultrasound in postmenopausal women with subclinical hypothyroidism. The results demonstrated that calcaneo osteo sono assessment indices of right feet measured by ultrasound bone densitometer decreased according to the increase in TSH concentration. The authors have suggested that hypothyroidism affects bone structure (Nagata et al, 2007).
