Bone turnover and cortical bone mineral density in the distal radius in patients with hyperthyroidism being treated with antithyroid drugs for various periods of time.
OBJECTIVE
Whether patients, who have lost bone mass, can be restored to age-matched control levels by some means is still controversial. We investigated how the thyroid status after antithyroid drug therapy for various periods of time affects bone metabolism in patients with hyperthyroidism by assessing currently used biochemical markers of bone turnover and distal radius bone mineral density (BMD).


METHODS
The biochemical markers of bone turnover and BMD at the distal one third of the radius were measured in 79 women with hyperthyroidism treated with antithyroid drugs for various periods of time. The patients were divided into two groups according to thyroid function at the time of study: a hyperthyroid group (serum thyroid stimulating hormone (TSH) < 0.4 mU/l) and an euthyroid group (TSH 0.4-4.0 mU/l). Second, each group was further divided according to the duration of therapy: short-term (less than 3 years) and long-term (3 or more years).


METHODS
Urinary type I collagen degradation products (CTx) were measured by the CrossLapsTM ELISA kit. Urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured by high performance liquid chromatography (HPLC) after acid hydrolysis. Serum N-mid osteocalcin (OCN-mid) was measured by a recently developed enzyme-linked immunosorbent assay. Serum alkaline phosphatase (ALP) was determined by routine laboratory methods. Bone mineral density (BMD) at the distal one third of the radius was measured using dual energy X-ray absorptiometry (DEXA; DCS-600EX, Aloka, Tokyo).


RESULTS
There were statistically significant positive correlations of FT3 and FT4 with the biochemical markers of bone turnover. There were significant negative correlations between the biochemical markers and BMD only in patients undergoing long-term therapy. In a comparison between hyperthyroid and euthyroid groups based on duration of treatment (long-term and short-term), and in a comparison without regard for length of treatment (all patients), it was evident that ALP and CTx levels were significantly higher in the hyperthyroid than in the euthyroid groups. Significantly lower BMD Z-scores in the hyperthyroid group compared to those in the euthyroid group were observed only in patients undergoing long-term therapy.


CONCLUSIONS
Urinary type I collagen degradation products were a sensitive marker for evaluating the bone turnover in patients with hyperthyroidism. Our data suggested that it might be important to control the levels of TSH within normal ranges during long-term antithyroid drug therapy in order to prevent bone loss.
Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, Japan.
M
M
Olkawa
K
K
Kushida
M
M
Takahashi
T
T
Ohishi
H
H
Hoshino
M
M
Suzuki
H
H
Ogihara
J
J
Ishigaki
T
T
Inoue
D000328:Adult; D000368:Aged; D013956:Antithyroid Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy* / Q000378:metabolism*; D008875:Middle Aged; D011884:Radius / Q000378:metabolism; D013997:Time Factors
D013956:Antithyroid Agents; D015415:Biomarkers