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May 22, 1991, Vol 265, No. 20 >
Original Contributions | May 22, 1991

Bone Mineral Density in Premenopausal Women Receiving Long-term Physiological Doses of Levothyroxine

Annie W. C. Kung, MD, MRCP; K. K. Pun, MD, PhD, MRCP
[+] Author Affiliations

Reprint requests to Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong (Dr Kung).


From the Department of Medicine, University of Hong Kong, Queen Mary Hospital.


JAMA. 1991;265(20):2688-2691. doi:10.1001/jama.1991.03460200068037
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Total body and regional bone mineral density (BMD) levels were determined in 26 premenopausal women with Hashimoto's thyroiditis receiving long-term physiological doses of levothyroxine sodium replacement therapy. The BMD levels of each patient were compared with the mean of the BMD levels of age-matched normal controls. The mean levothyroxine sodium dose was 111 ±6 μg/d, and the mean duration of treatment was 7.5 ±5.3 years (range, 1 to 24 years). Dietary calcium intake was similar in both groups, as were serum thyroxine, triiodothyronine, free thyroxine index, and thyrotropin levels. Women receiving the levothyroxine treatment had normal total body BMD levels but had significantly lower BMD levels at the femoral neck ( - 5.7%), femoral trochanter ( - 7.0%), Ward's triangle ( -10.6%), both arms (right, - 7.8%; left, - 8.9%), and pelvis (-4.9%). In contrast, lumbar spine BMD levels were similar in the two groups. There was no correlation between the total body or different regional BMD levels and the duration or dosage of levothyroxine treatment or thyroid function test results. However, the z score of the femoral neck of these patients showed a significant negative correlation with their serum free thyroxine index levels. We conclude that patients receiving physiological doses of levothyroxine may have decreased bone density. Thyroid functions in patients receiving long-term levothyroxine treatment should be closely monitored and bone densitometry should be performed in patients at risk for osteoporosis.

(JAMA. 1991;265:2688-2691)

REFERENCES

1 +
Meunier PJ, Bianchi GGS, Edouard CM, Bernard JC, Courprou P, Vignou GE.  Bone manifestations of thyrotoxicosis . Orthop Clin North Am. 1972;;3:745-774.
2 +
Melsen F, Mosekilde L.  Morphometric and dynamic studies of bone change in hyperthyroidism . Acta Pathol Microbiol Scand. 1977;;85:141-150.
3 +
Riggs BL, Melton LJ III.  Involutional osteoporosis . N Engl J Med. 1986;;314:1676-1686.
4 +
Ettinger B, Wingerd J.  Thyroid supplements: effect on bone mass . West J Med. 1982;;136:473-476.
5 +
Fallon MD, Perry HM III, Bergfeld M, Droke D, Teitelbaum SL, Avioli LV.  Exogenous hyperthyroidism with osteoporosis . Arch Intern Med. 1983;;143:442-444.
6 +
Coindre JM, David JP, Riviere L, et al.  Bone loss in hypothyroidism with hormone replacement: a histomorphometric study . Arch Intern Med. 1986;;146:48-53.
7 +
Daniell HW.  Replacement treatment of hypothyroidism . N Engl J Med. 1974;;291:102.
8 +
Richelson LS, Wahner HW, Melton LJ III, Riggs BL.  Relative contributions of aging and estrogen deficiency to postmenopausal bone loss . N Engl J Med. 1984;;311:1273-1275.
9 +
McDermott MT, Kidd GS, Blue P, Ghead V, Hofeldt FD.  Reduced bone mineral content in totally thyroidectomized patients: possible effect of calcitonin deficiency . J Clin Endocrinol Metab. 1983;;56:936-939.
10 +
Tiegs RD, Body JJ, Rolfe J, Brennan MD, Heath H III.  Calcitonin deficiency follows thyroid damage by surgery or radiation . Calcif Tissue Int. 1983;;369:479. Abstract.
11 +
Muller BJ, Krantzler NJ, Grivetti LE, Schultz HG, Miselman HL.  Validity of a food frequency questionnaire for the determination of individual food intake . Am J Clin Nutr. 1984;;39:136-143.
12 +
Pun KK, Chan LWL, Chung V, Wong FHW.  Calcium and other dietary constituents in Hong Kong Chinese in relation to age and osteoporosis . J Appl Nutr. In press.
13 +
Nord RH, Payne PK, Hoonneman G.  Computation of bone density from dual energy x-ray data: an empirical method . Presented at the XXI European Symposium on Calcified Tissue; March 17, 1989 ; Jerusalem, Israel.
14 +
Pun KK, Wong FHW, Loh T.  Rapid postmenopausal loss of total body and regional bone mass in normal southern Chinese females in Hong Kong . Osteoporosis Int . In press.
15 +
Tiegs RD, Body JJ, Wahner HW, Barta J, Riggs BL, Health H III.  Calcitonin secretion in postmenopausal osteoporosis . N Engl J Med. 1985;;312:1097-1100.
16 +
Lee MS, Kim SY, Lee MC, et al.  Negative correlation between the change in bone mineral density and serum osteocalcin in patients with hyperthyroidism . J Clin Endocrinol Metab. 1990;; 70:766-770.
17 +
Fraser SA, Anderson JB, Smith DA, Wilson GM.  Osteoporosis and fractures following thyrotoxicosis . Lancet . 1971;;1:981-983.
18 +
Nielsen HE, Mosekilde L, Charles P.  Bone mineral content in hyperthyroid patients after combined medical and surgical treatment . Acta Radiol Oncol. 1979;;18:122-128.
19 +
Ross DS, Neer RM, Ridgway EC, Daniels GH.  Subclinical hyperthyroidism and reduced bone density as a possible result of prolonged suppression of the pituitary-thyroid axis with L-thyroxine . Am J Med. 1987;;82:1167-1170.
20 +
Meema HE, Schatz DL.  Simple radiologic demonstration of cortical bone loss in thyrotoxicosis . Radiology . 1970;;97:9-15.
21 +
Paul TL, Kerrigan J, Kelly AM, Braverman LE, Baran DT.  Long-term L-thyroxine therapy is associated with decreased hip bone density in premenopausal women . JAMA. 1988;;259:3137-3141.
22 +
Eriksen EF, Mosekilde L, Melsen F.  Kinetics of trabecular bone resorption and formation in hypothyroidism: evidence for a positive balance per remodeling cycle . Bone . 1986;;7:101-105.
23 +
Hennessy JV, Evaul JE, Tseng YC, et al.  L-thyroxine dosage: a reevaluation of therapy with contemporary preparations . Ann Intern Med. 1986;;105:11-15.
24 +
Caldwell G, Kellett HA, Gow SM, et al.  A new strategy for thyroid function testing . Lancet . 1985;;1:1117-1119.
25 +
Perry HM III.  Thyroid replacement and osteoporosis . Arch Intern Med. 1986;;146:41-42.
26 +
Krolner B, Jorgensen JV, Nielsen SP.  Spinal bone mineral content in myxoedema and thyrotoxicosis: effects of thyroid hormone(s) and antithyroid treatment . Clin Endocrinol. 1983;;18:439-446.
27 +
Garrel DR, Delmas PD, Malaval L, Tourniaire J.  Serum bone Gla protein: a marker of bone turnover in hyperthyroidism . J Clin Endocrinol Metab. 1986;;62:1052-1055.
28 +
Frame B, Marel GM.  Clinical disorders of bone and mineral metabolism . Ann Intern Med. 1983;; 99:725-727.
29 +
Gonalez D, Ghiringhelli G, Mautelan E.  Acute antiosteoclastic effect of salmon calcitonin in osteoporotic women . Calcif Tissue Int. 1986;;38:71-75.
30 +
Fleish H.  Biphosphonates: an introduction . In: Christiansen C, Johansen JS, Riis BJ, eds. Osteoporosis . Copenhagen, Denmark: Osteopress ApS; 1987;:1159-1164.

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1 +
Meunier PJ, Bianchi GGS, Edouard CM, Bernard JC, Courprou P, Vignou GE.  Bone manifestations of thyrotoxicosis . Orthop Clin North Am. 1972;;3:745-774.
2 +
Melsen F, Mosekilde L.  Morphometric and dynamic studies of bone change in hyperthyroidism . Acta Pathol Microbiol Scand. 1977;;85:141-150.
3 +
Riggs BL, Melton LJ III.  Involutional osteoporosis . N Engl J Med. 1986;;314:1676-1686.
4 +
Ettinger B, Wingerd J.  Thyroid supplements: effect on bone mass . West J Med. 1982;;136:473-476.
5 +
Fallon MD, Perry HM III, Bergfeld M, Droke D, Teitelbaum SL, Avioli LV.  Exogenous hyperthyroidism with osteoporosis . Arch Intern Med. 1983;;143:442-444.
6 +
Coindre JM, David JP, Riviere L, et al.  Bone loss in hypothyroidism with hormone replacement: a histomorphometric study . Arch Intern Med. 1986;;146:48-53.
7 +
Daniell HW.  Replacement treatment of hypothyroidism . N Engl J Med. 1974;;291:102.
8 +
Richelson LS, Wahner HW, Melton LJ III, Riggs BL.  Relative contributions of aging and estrogen deficiency to postmenopausal bone loss . N Engl J Med. 1984;;311:1273-1275.
9 +
McDermott MT, Kidd GS, Blue P, Ghead V, Hofeldt FD.  Reduced bone mineral content in totally thyroidectomized patients: possible effect of calcitonin deficiency . J Clin Endocrinol Metab. 1983;;56:936-939.
10 +
Tiegs RD, Body JJ, Rolfe J, Brennan MD, Heath H III.  Calcitonin deficiency follows thyroid damage by surgery or radiation . Calcif Tissue Int. 1983;;369:479. Abstract.
11 +
Muller BJ, Krantzler NJ, Grivetti LE, Schultz HG, Miselman HL.  Validity of a food frequency questionnaire for the determination of individual food intake . Am J Clin Nutr. 1984;;39:136-143.
12 +
Pun KK, Chan LWL, Chung V, Wong FHW.  Calcium and other dietary constituents in Hong Kong Chinese in relation to age and osteoporosis . J Appl Nutr. In press.
13 +
Nord RH, Payne PK, Hoonneman G.  Computation of bone density from dual energy x-ray data: an empirical method . Presented at the XXI European Symposium on Calcified Tissue; March 17, 1989 ; Jerusalem, Israel.
14 +
Pun KK, Wong FHW, Loh T.  Rapid postmenopausal loss of total body and regional bone mass in normal southern Chinese females in Hong Kong . Osteoporosis Int . In press.
15 +
Tiegs RD, Body JJ, Wahner HW, Barta J, Riggs BL, Health H III.  Calcitonin secretion in postmenopausal osteoporosis . N Engl J Med. 1985;;312:1097-1100.
16 +
Lee MS, Kim SY, Lee MC, et al.  Negative correlation between the change in bone mineral density and serum osteocalcin in patients with hyperthyroidism . J Clin Endocrinol Metab. 1990;; 70:766-770.
17 +
Fraser SA, Anderson JB, Smith DA, Wilson GM.  Osteoporosis and fractures following thyrotoxicosis . Lancet . 1971;;1:981-983.
18 +
Nielsen HE, Mosekilde L, Charles P.  Bone mineral content in hyperthyroid patients after combined medical and surgical treatment . Acta Radiol Oncol. 1979;;18:122-128.
19 +
Ross DS, Neer RM, Ridgway EC, Daniels GH.  Subclinical hyperthyroidism and reduced bone density as a possible result of prolonged suppression of the pituitary-thyroid axis with L-thyroxine . Am J Med. 1987;;82:1167-1170.
20 +
Meema HE, Schatz DL.  Simple radiologic demonstration of cortical bone loss in thyrotoxicosis . Radiology . 1970;;97:9-15.
21 +
Paul TL, Kerrigan J, Kelly AM, Braverman LE, Baran DT.  Long-term L-thyroxine therapy is associated with decreased hip bone density in premenopausal women . JAMA. 1988;;259:3137-3141.
22 +
Eriksen EF, Mosekilde L, Melsen F.  Kinetics of trabecular bone resorption and formation in hypothyroidism: evidence for a positive balance per remodeling cycle . Bone . 1986;;7:101-105.
23 +
Hennessy JV, Evaul JE, Tseng YC, et al.  L-thyroxine dosage: a reevaluation of therapy with contemporary preparations . Ann Intern Med. 1986;;105:11-15.
24 +
Caldwell G, Kellett HA, Gow SM, et al.  A new strategy for thyroid function testing . Lancet . 1985;;1:1117-1119.
25 +
Perry HM III.  Thyroid replacement and osteoporosis . Arch Intern Med. 1986;;146:41-42.
26 +
Krolner B, Jorgensen JV, Nielsen SP.  Spinal bone mineral content in myxoedema and thyrotoxicosis: effects of thyroid hormone(s) and antithyroid treatment . Clin Endocrinol. 1983;;18:439-446.
27 +
Garrel DR, Delmas PD, Malaval L, Tourniaire J.  Serum bone Gla protein: a marker of bone turnover in hyperthyroidism . J Clin Endocrinol Metab. 1986;;62:1052-1055.
28 +
Frame B, Marel GM.  Clinical disorders of bone and mineral metabolism . Ann Intern Med. 1983;; 99:725-727.
29 +
Gonalez D, Ghiringhelli G, Mautelan E.  Acute antiosteoclastic effect of salmon calcitonin in osteoporotic women . Calcif Tissue Int. 1986;;38:71-75.
30 +
Fleish H.  Biphosphonates: an introduction . In: Christiansen C, Johansen JS, Riis BJ, eds. Osteoporosis . Copenhagen, Denmark: Osteopress ApS; 1987;:1159-1164.

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