Serum osteoprotegerin and soluble receptor activator of nuclear factor kappaB ligand levels in patients with a history of differentiated thyroid carcinoma: a case-controlled cohort study.
Overt hyperthyroidism is associated with changes in bone metabolism, whereas the effect of levothyroxine (L-T4) load in patients with differentiated thyroid carcinoma (DTC) is controversial. The aim of our study was to evaluate osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappaB ligand (RANK-L) in patients with DTC with suppressed endogenous thyrotropin due to L-T4 regimen. A cohort of 80 subjects with DTC (68 women and 12 men; age range, 27-81 years) was studied. A cohort of 55 subjects with a history of partial or total surgery for nonmalignant thyroid pathology served as a control group. Groups were matched for sex, age, and body mass index. Per-week dosage of L-T4 was significantly higher in patients with DTC than in controls (P < .001). More elevated free T(4) concentrations (P < .001) and more suppressed thyrotropin and thyroglobulin levels (P < .001) were found in subjects with DTC than in controls. No difference in serum or urinary parameters related to bone metabolism or dual-energy x-ray absorptiometry was noted between the groups. Overall, OPG levels were similar in both groups but were significantly (P = .03) lower in postmenopausal women with DTC than in postmenopausal control women. Only control women showed lower OPG levels in premenopausal than in postmenopausal (P = .002) conditions. Overall, RANK-L levels were significantly higher (P = .03) in subjects with DTC than in controls. In both groups, OPG and RANK-L levels were unrelated to each other. A significant positive correlation was seen between OPG levels and age in both subjects with DTC (P < .001) and controls (P < .001). Serum RANK-L correlated negatively with age in subjects with DTC (P = .05). Although there were several differences in L-T4 dosages, OPG and RANK-L levels were similar in patients with a history of DTC and those with a history of nonmalignant thyroid diseases. The correlation between circulating OPG and RANK-L levels was not significant. The increase in OPG with age indicates its protective role in bone loss. The cause of bone loss after long-term L-T4 load will be more extensively studied.
Giusti
Massimo
M
UO Clinica Endocrinologica, Azienda Ospedaliera Universitaria San Martino, Genoa, Italy. magius@unige.it
Cecoli
Francesca
F
Fazzuoli
Laura
L
De Franchis
Vincenzina
V
Ceresola
Enrica
E
Ferone
Diego
D
Mussap
Michele
M
Minuto
Francesco
F
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D053245:RANK Ligand / Q000097:blood*; D013963:Thyroid Hormones / Q000097:blood; D013964:Thyroid Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000652:urine; D013972:Thyrotropin / Q000037:antagonists & inhibitors; D013974:Thyroxine / Q000008:administration & dosage*
D053244:Osteoprotegerin; D010281:Parathyroid Hormone; D053245:RANK Ligand; D013963:Thyroid Hormones; D010758:Phosphorus; D013972:Thyrotropin; D003404:Creatinine; D000469:Alkaline Phosphatase; D013974:Thyroxine; D002118:Calcium