acid-phosphatase and Thyrotoxicosis

Thyrotoxicosis is more frequent in postmenopausal women than in the general population, effectively accelerating bone turnover. Interleukin-6 has been shown to be involved in the pathogenesis of bone disorders. Thus, the aim of the present study was to assess the role of IL-6 and its soluble receptor in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women.. The study was carried out in 40 subjects with toxic nodular goitre in three groups: Group 1 - 13 premenopausal females, mean age 36 ± 15 years (PremTx→PremEu); Group 2 - 12 postmenopausal females, mean age 66 ± 14 years (PostTx→PostEu); and Group 3 - 15 males, mean age 45 ± 21 years (MTx→MEu). Overt thyrotoxicosis and euthyreosis after treatment with thyrostatics were confirmed by thyrotropin, free thyroxine and free triiodothyronin concentrations. Serum levels of bone turnover markers: TRACP5b and osteocalcin as well as serum IL-6 and IL-6sR were determined using ELISA kits.. TRACP5b/osteocalcin quotient was significantly elevated in the PostTx females compared to the PremTx women (p < 0.02). There was a positive correlation between serum TRACP5b and osteocalcin in the studied patients (R = 0.45, p < 0.001). Levels of serum IL-6 values were significantly elevated in PostTx: 3.0 (2.14-6.40) and MTx: 2.24 (1.60-5.10), compared to PremTx females: 1.39 (0.96-2.14) (p < 0.01 and p < 0.05 respectively). There were significant positive correlations between IL-6 and IL-6sR concentrations (R = 0.22, p < 0.05) and between IL-6sR and TRACP5b serum levels (R = 0.23, p < 0.05).. The results of our study suggest that interleukin-6 plays a considerable role in the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen-deficient women.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Bone Density; Bone Diseases; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Isoenzymes; Male; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Receptors, Interleukin-6; Sex Factors; Tartrate-Resistant Acid Phosphatase; Thyrotoxicosis; Young Adult

Interleukin-6 (IL-6) has been shown to be involved in the pathogenesis of several bone diseases characterized by a negative balance between bone resorption and formation. The aim of the study was to estimate serum markers of bone turnover: osteoclast-derived tartrate-resistant acid phosphatase form 5a (TRACP 5b) reflecting resorption, and osteocalcin as a marker of bone formation in IL-6 knock-out mice to assess the role of IL-6 in the pathogenesis of thyrotoxicosis-related disturbances of bone metabolism. The study was performed on forty, 14-15 weeks old, female mice: C57BL/6J (wild-type; WT) and C57BL/6J (IL6-/-Kopf) (IL-6 knock-out; IL6KO). The mice were randomly divided into 4 groups with 10 mice in each one: 1. WT mice in thyrotoxicosis (WT-thx), 2. WT controls (WT-ctrl), 3. IL6KO mice with thyrotoxicosis (IL6KO-thx), and 4. IL6KO controls. Experimental model of hyperthyroidism was induced by intraperitoneal injection of levothyroxine at a dose of 1 microg/g, daily over 21 days. The serum levels of TRACP 5b and osteocalcin were determined by ELISA. Serum concentration of TRACP 5b (median and interquartile ranges) were significantly increased in both groups of mice with thyrotoxicosis: WT [28.2(18.8-41.6) U/l] and IL6KO [26.4(23.0-31.2) U/l] as compared to the respective controls. Osteocalcin serum levels in IL6KO-thx mice [111.9(103.1-175.6) ng/ml] were significantly elevated in comparison to WT-thx animals [46.1(32.5-58.9) ng/ml]. In summary, the results of the present study suggest that IL-6 plays a crucial role in thyrotoxicosis-related disturbances of bone turnover in mice, determining the imbalance between bone resorption and bone formation caused by excess of thyroid hormones predominantly by inhibition of bone formation.

Topics: Acid Phosphatase; Animals; Biomarkers; Bone Density; Bone Diseases; Densitometry; Female; Genotype; Interleukin-6; Isoenzymes; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteocalcin; Tartrate-Resistant Acid Phosphatase; Thyroid Gland; Thyrotoxicosis