The role of
type 2 deiodinase (D2) in the human skeleton remains unclear. The D2 polymorphism Thr92Ala has been associated with lower enzymatic activity, which could result in lower local
triiodothyronine (T(3)) availability in bone. We therefore hypothesized that the D2 Thr92Ala polymorphism may influence bone mineral density (BMD) and bone turnover. We studied 154 patients (29 men, 125 women: 79
estrogen-replete, 46
estrogen-deficient) with cured differentiated
thyroid carcinoma. BMD and bone turnover markers [bone-specific
alkaline phosphatase (BAP), cross-linking terminal
C-telopeptide of
type I collagen (CTX),
procollagen type 1 amino-terminal propeptide (P1NP), and cross-linked
N-telopeptide of
type I collagen (NTX)] were measured. Effects of the D2 Thr92Ala polymorphism on BMD and bone turnover markers were assessed by a linear regression model, with age, gender,
estrogen state, body mass index (BMI), serum
calcium,
25-hydroxyvitamin D,
parathyroid hormone (PTH),
thyroid-stimulating hormone (TSH), and free triiodothyroxine (T(4)) as covariables. Sixty patients were wild type (Thr/Thr), 66 were heterozygous (Thr/Ala), and 28 were homozygous (
Ala/Ala) for the D2 polymorphism. There were no significant differences in any covariables between the three genotypes. Subjects carrying the D2 Thr92Ala polymorphism had consistently lower femoral neck and total hip densities than wild-type subjects (p = .028), and this was accompanied by significantly higher serum P1NP and CTX and urinary NTX/
creatinine levels. We conclude that in patients with cured differentiated
thyroid carcinoma, the D2 Thr92Ala polymorphism is associated with a decreased femoral neck BMD and higher bone turnover independent of serum
thyroid hormone levels, which points to a potential functional role for D2 in bone.