The effects of recombinant TSH on bone turnover markers and serum osteoprotegerin and RANKL levels.
OBJECTIVE
Recently it was found that thyrotropin (TSH) receptors are present both in osteoclast and osteoblast and that TSH can modulate bone remodeling independent of thyroid hormones. The aim of this study was, firstly, to evaluate the effects of acute administration of TSH on bone remodeling markers both in men and in women and, secondly, to evaluate if these effects are mediated by variations in serum osteoprotegerin (OPG) and receptor activator of nuclear factor-KB ligand (RANKL).


METHODS
We studied 30 thyroidectomized patients (10 premenopausal and 10 postmenopausal women, 10 men) affected by thyroid carcinoma on l-thyroxine therapy. Eighty age- and sex-matched subjects were used as controls. A blood sample was drawn from each patient at baseline and 3 and 5 days after recombinant human TSH (rhTSH) administration, in preparation for (131)I whole body scan, to assess serum bone markers and serum OPG and RANKL levels.


RESULTS
At baseline, postmenopausal women and men had significantly higher values of bone turnover markers and serum OPG compared to control subjects. In all thyroidectomized patients serum RANKL was lower than in controls. After rhTSH administration, serum N-terminal propeptide of type-I procollagen (PINP), a marker of bone formation, increased significantly in postmenopausal women, while serum RANKL significantly increased after 3 days in postmenopausal patients and men returning to baseline values at day 5. Serum OPG levels did not change significantly.


CONCLUSIONS
The low serum TSH observed in thyroidectomized patients on l-thyroxine therapy is associated with an increase of bone turnover in postmenopausal women and men that is associated with an increase of OPG and a decrease of serum RANKL levels. The acute TSH administration results in an increase of PINP, an index of osteoblastic activity, associated with an increase of serum RANKL. The lack of this response in premenopausal women suggests an influence of estrogen status on bone reactivity to TSH.
Martini
Giuseppe
G
Department of Internal Medicine, Endocrinology & Metabolism and Biochemistry, Section of Internal Medicine, University of Siena, Siena, Italy. martinig@unisi.it
Gennari
Luigi
L
De Paola
Vincenzo
V
Pilli
Tania
T
Salvadori
Stefania
S
Merlotti
Daniela
D
Valleggi
Fabrizio
F
Campagna
Stella
S
Franci
Beatrice
B
Avanzati
Annalisa
A
Nuti
Ranuccio
R
Pacini
Furio
F
D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000601:surgery*; D013965:Thyroidectomy; D013972:Thyrotropin / Q000627:therapeutic use*; D013974:Thyroxine / Q000627:therapeutic use; D016896:Treatment Outcome
D053244:Osteoprotegerin; D053245:RANK Ligand; D011994:Recombinant Proteins; D013972:Thyrotropin; D013974:Thyroxine