Thyroid function within the upper normal range is associated with reduced bone mineral density and an increased risk of nonvertebral fractures in healthy euthyroid postmenopausal women.
BACKGROUND
The relationship between thyroid function and bone mineral density (BMD) is controversial. Existing studies are conflicting and confounded by differences in study design, small patient numbers, and sparse prospective data.


OBJECTIVE
We hypothesized that variation across the normal range of thyroid status in healthy postmenopausal women is associated with differences in BMD and fracture susceptibility.


METHODS
The Osteoporosis and Ultrasound Study (OPUS) is a 6-yr prospective study of fracture-related factors.


METHODS
We studied a population-based cohort from five European cities.


METHODS
A total of 2374 postmenopausal women participated. Subjects with thyroid disease and nonthyroidal illness and those receiving drugs affecting thyroid status or bone metabolism were excluded, leaving a study population of 1278 healthy euthyroid postmenopausal women.


METHODS
There were no interventions.


METHODS
We measured free T(4) (fT4) (picomoles/liter), free T(3) (fT3) (picomoles/liter), TSH (milliunits/liter), bone turnover markers, BMD, and vertebral, hip, and nonvertebral fractures.


RESULTS
Higher fT4 (beta = -0.091; P = 0.004) and fT3 (beta = -0.087; P = 0.005) were associated with lower BMD at the hip, and higher fT4 was associated with increasing bone loss at the hip (beta = -0.09; P = 0.015). After adjustment for age, body mass index, and BMD, the risk of nonvertebral fracture was increased by 20% (P = 0.002) and 33% (P = 0.006) in women with higher fT4 or fT3, respectively, whereas higher TSH was protective and the risk was reduced by 35% (P = 0.028). There were independent associations between fT3 and pulse rate (beta = 0.080; P = 0.006), increased grip strength (beta = 0.171; P<0.001), and better balance (beta = 0.099; P < 0.001), indicating that the relationship between thyroid status and fracture risk is complex.


CONCLUSIONS
Physiological variation in normal thyroid status is related to BMD and nonvertebral fracture.
Murphy
Elaine
E
Molecular Endocrinology Group, 7th Floor Commonwealth Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom.
Glüer
Claus C
CC
Reid
David M
DM
Felsenberg
Dieter
D
Roux
Christian
C
Eastell
Richard
R
Williams
Graham R
GR
D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015519:Bone Density / Q000502:physiology*; D005260:Female; D050723:Fractures, Bone / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D017698:Postmenopause / Q000502:physiology*; D011446:Prospective Studies; D012016:Reference Values; D012044:Regression Analysis; D012307:Risk Factors; D013960:Thyroid Function Tests; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*; D016387:Women's Health
D014284:Triiodothyronine; D013974:Thyroxine