Antithyroid therapy improves bony manifestations and bone metabolic markers in patients with Graves' thyrotoxicosis.
OBJECTIVE
Abnormal bone metabolism in patients with Graves' thyrotoxicosis is well documented, but the precise time-course of its recovery remains poorly understood. The present study was undertaken to clarify longitudinal improvement in bony manifestations, especially in cortical bone, and bone metabolic markers in thyrotoxicosis.


METHODS
Two year prospective follow-up study in patients with Graves' disease.


METHODS
Ten consecutive patients with Graves' disease (seven males and three females, of mean (+/-SEM) age 39.3 +/- 3.9 years) were enrolled in the study and treated with antithyroid drugs. Thirteen sex- and age-matched patients with the disease in remission served as controls.


METHODS
Bony manifestations were evaluated both by fine cortical bone striations in the metacarpals on magnified roentgenograms and lumbar bone mineral density (BMD) measurement. Urinary deoxypyridinoline (dPYR) and serum pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) were monitored as markers of bone resorption, as well as serum osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP) and alkaline-phosphatase (ALP) as markers of bone formation.


RESULTS
Initial elevated free thyroid hormone levels were normalized within a month of starting therapy. Striation indices of the metacarpals were 1.89 +/- 0.16 before therapy, higher than those of 0.49 +/- 0.12 in the controls (P < 0.0001); the indices gradually decreased to 1.00 +/- 0.20 (12 months) and 0.48 +/- 0.12 (24 months). Lumbar BMD Z-scores increased from -0.22 +/- 0.46 to 0.21 +/- 0.47 (12 months) and 0.68 +/- 0.48 (24 months) (P = 0.0029). Before therapy, urinary dPYR and serum ICTP concentrations were much higher than the control values (dPYR, +553%; ICTP, -396%, P < 0.0001), which declined promptly in the 2nd month. Serum OC, PICP and ALP were also significantly higher than in controls at first (OC, +287%; PICP, +225%; ALP, +196%), and remained elevated until 4 or 8 months.


CONCLUSIONS
Bone resorption and cortical bone striations occur in untreated patients with Graves' thyrotoxicosis. The bone resorption rapidly ameliorates after normalization of thyroid hormone levels. In contrast, the accelerated bone formation persists for at least 4-8 months, suggesting positive uncoupling of bone remodelling. This dominant bone formation could result in the improvement in cortical bone striations and the increase in bone mineral density of trabecular bone.
Nagasaka
S
S
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Sugimoto
H
H
Nakamura
T
T
Kusaka
I
I
Fujisawa
G
G
Sakuma
N
N
Tsuboi
Y
Y
Fukuda
S
S
Honda
K
K
Okada
K
K
Ishikawa
S
S
Saito
T
T
D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D013956:Antithyroid Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D005260:Female; D005500:Follow-Up Studies; D006111:Graves Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008713:Methimazole / Q000627:therapeutic use*; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies
D000596:Amino Acids; D013956:Antithyroid Agents; D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D008713:Methimazole; C036020:deoxypyridinoline; D003094:Collagen; D000469:Alkaline Phosphatase