J Bone Metab.  2019 Feb;26(1):31-38. 10.11005/jbm.2019.26.1.31.

Effects of Thyrotropin Suppression on Bone Health in Menopausal Women with Total Thyroidectomy

• Kim EH
• Jeon YK
• Pak K
• Kim IJ
• Kim SJ
• Shin S
• Kim BH
• Kim SS
• Lee BJ
• Lee JG
• Goh TS
• Kim K

• KMID: 2440643
• DOI: http://doi.org/10.11005/jbm.2019.26.1.31

Abstract

BACKGROUND
This study examined the change in the trabecular bone score (TBS), areal bone mineral density (aBMD), and osteoporosis in postmenopausal women who underwent thyrotropin (TSH)-suppressive therapy for treating papillary thyroid cancer after a total thyroidectomy procedure.
METHODS
We evaluated 36 postmenopausal women who received a total thyroidectomy for papillary thyroid cancer and were undergoing TSH suppressive therapy with levothyroxine. Postmenopausal women (n=94) matched for age and body mass index were recruited as healthy controls. The aBMD and TBS of the lumbar spine were compared between dual energy X-ray absorptiometry (DXA) at baseline and at follow-up after an average of 4.92 years.
RESULTS
There was no significant difference in the rate of diagnoses of osteoporosis, osteopenia, or normal bone status between the 2 groups during the baseline DXA evaluation. However, the TBS was significantly lower whereas aBMD did not show significant difference at the time of baseline DXA measurement (1st DXA, 1.343±0.098 vs. 1.372±0.06317, P < 0.001; 2nd DXA, 1.342±0.095 vs. 1.370±0.062, P < 0.001). The TBS and aBMD did not differ significantly between the initial and follow-up DXA images in both groups of TSH suppressive patients and controls.
CONCLUSIONS
The average value of TBS and aBMD did not significantly change during the follow-up period. The TSH suppressive therapy was revealed as not a significant factor for the progressive deterioration of bone status during long term follow-up.

Keyword

Absorptiometry, photon; Bone density; Postmenopause; Thyroid neoplasms

MeSH Terms

Absorptiometry, Photon
Body Mass Index
Bone Density
Bone Diseases, Metabolic
Diagnosis
Female
Follow-Up Studies
Humans
Osteoporosis
Postmenopause
Spine
Thyroid Neoplasms
Thyroidectomy*
Thyrotropin*
Thyroxine
Thyrotropin
Thyroxine

Figure

• 

  Fig. 1 Diagnosis of dual energy X-ray absorptiometry (DXA) during follow-up. For DXA, T-scores ≥−1.0 standard deviations (SDs) from the reference mean were defined as normal; T-scores between −2.5 and −1.0 SDs from the reference mean were defined as osteopenia; T-scores ≤−2.5 SDs from the reference mean were defined as osteoporosis. This follows the World Health Organization criteria. TSH, thyroid-stimulating hormone.

• 

  Fig. 2 Changes of mean areal bone mineral density (aBMD) and trabecular bone score (TBS) at the 1st dual energy X-ray absorptiometry scan and 2nd follow-up scan. Both (A) aBMD and (B) TBS did not change significantly during follow-up using paired t-test. TSH, thyroid-stimulating hormone.

Reference

1. Abe E, Marians RC, Yu W, et al. TSH is a negative regulator of skeletal remodeling. Cell. 2003; 115:151–162.

2. Sendak RA, Sampath TK, McPherson JM. Newly reported roles of thyroid-stimulating hormone and follicle-stimulating hormone in bone remodelling. Int Orthop. 2007; 31:753–757.

3. Eriksen EF, Mosekilde L, Melsen F. Trabecular bone remodeling and bone balance in hyperthyroidism. Bone. 1985; 6:421–428.

4. Mosekilde L, Melsen F, Bagger JP, et al. Bone changes in hyperthyroidism: interrelationships between bone morphometry, thyroid function and calcium-phosphorus metabolism. Acta Endocrinol (Copenh). 1977; 85:515–525.

5. Biondi B, Cooper DS. Benefits of thyrotropin suppression versus the risks of adverse effects in differentiated thyroid cancer. Thyroid. 2010; 20:135–146.

6. Cady B, Cohn K, Rossi RL, et al. The effect of thyroid hormone administration upon survival in patients with differentiated thyroid carcinoma. Surgery. 1983; 94:978–983.

7. Klein Hesselink EN, Klein Hesselink MS, de Bock GH, et al. Long-term cardiovascular mortality in patients with differentiated thyroid carcinoma: an observational study. J Clin Oncol. 2013; 31:4046–4053.

8. Flynn RW, Bonellie SR, Jung RT, et al. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab. 2010; 95:186–193.

9. de Melo TG, da Assumpção LV, Santos Ade O, et al. Low BMI and low TSH value as risk factors related to lower bone mineral density in postmenospausal women under levothyroxine therapy for differentiated thyroid carcinoma. Thyroid Res. 2015; 8:7.

10. Bauer DC, Ettinger B, Nevitt MC, et al. Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med. 2001; 134:561–568.

11. Ross DS, Neer RM, Ridgway EC, et al. 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.

12. Ross DS. Hyperthyroidism, thyroid hormone therapy, and bone. Thyroid. 1994; 4:319–326.

13. Solomon BL, Wartofsky L, Burman KD. Prevalence of fractures in postmenopausal women with thyroid disease. Thyroid. 1993; 3:17–23.

14. Grimnes G, Emaus N, Joakimsen RM, et al. The relationship between serum TSH and bone mineral density in men and postmenopausal women: the Tromso study. Thyroid. 2008; 18:1147–1155.

15. Wang LY, Smith AW, Palmer FL, et al. Thyrotropin suppression increases the risk of osteoporosis without decreasing recurrence in ATA low- and intermediate-risk patients with differentiated thyroid carcinoma. Thyroid. 2015; 25:300–307.

16. Pothuaud L, Carceller P, Hans D. Correlations between greylevel variations in 2D projection images (TBS) and 3D microarchitecture: applications in the study of human trabecular bone microarchitecture. Bone. 2008; 42:775–787.

17. Lee JE, Kim KM, Kim LK, et al. Comparisons of TBS and lumbar spine BMD in the associations with vertebral fractures according to the T-scores: a cross-sectional observation. Bone. 2017; 105:269–275.

18. Hwangbo Y, Kim JH, Kim SW, et al. High-normal free thyroxine levels are associated with low trabecular bone scores in euthyroid postmenopausal women. Osteoporos Int. 2016; 27:457–462.

19. Moon JH, Kim KM, Oh TJ, et al. The effect of TSH suppression on vertebral trabecular bone scores in patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2017; 102:78–85.

20. Silva BC, Bilezikian JP. Trabecular bone score: perspectives of an imaging technology coming of age. Arq Bras Endocrinol Metabol. 2014; 58:493–503.

21. Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009; 19:1167–1214.

22. Biondi B, Filetti S, Schlumberger M. Thyroid-hormone therapy and thyroid cancer: a reassessment. Nat Clin Pract Endocrinol Metab. 2005; 1:32–40.

23. Pacini F, Schlumberger M, Dralle H, et al. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol. 2006; 154:787–803.

24. Balme HW. Metastatic carcinoma of the thyroid successfully treated with thyroxine. Lancet. 1954; 266:812–813.

25. McGriff NJ, Csako G, Gourgiotis L, et al. Effects of thyroid hormone suppression therapy on adverse clinical outcomes in thyroid cancer. Ann Med. 2002; 34:554–564.

26. Sugitani I, Fujimoto Y. Effect of postoperative thyrotropin suppressive therapy on bone mineral density in patients with papillary thyroid carcinoma: a prospective controlled study. Surgery. 2011; 150:1250–1257.

27. Kung AW, Yeung SS. Prevention of bone loss induced by thyroxine suppressive therapy in postmenopausal women: the effect of calcium and calcitonin. J Clin Endocrinol Metab. 1996; 81:1232–1236.

28. Heemstra KA, Hamdy NA, Romijn JA, et al. The effects of thyrotropin-suppressive therapy on bone metabolism in patients with well-differentiated thyroid carcinoma. Thyroid. 2006; 16:583–591.

29. Quan ML, Pasieka JL, Rorstad O. Bone mineral density in well-differentiated thyroid cancer patients treated with suppressive thyroxine: a systematic overview of the literature. J Surg Oncol. 2002; 79:62–69.

30. Lee MY, Park JH, Bae KS, et al. Bone mineral density and bone turnover markers in patients on long-term suppressive levothyroxine therapy for differentiated thyroid cancer. Ann Surg Treat Res. 2014; 86:55–60.

31. Franklyn JA, Betteridge J, Daykin J, et al. Long-term thyroxine treatment and bone mineral density. Lancet. 1992; 340:9–13.

32. Kim CW, Hong S, Oh SH, et al. Change of bone mineral density and biochemical markers of bone turnover in patients on suppressive levothyroxine therapy for differentiated thyroid carcinoma. J Bone Metab. 2015; 22:135–141.

33. WHO Study Group. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994; 843:1–129.

34. Leslie WD, Johansson H, Kanis JA, et al. Lumbar spine texture enhances 10-year fracture probability assessment. Osteoporos Int. 2014; 25:2271–2277.

35. Bousson V, Bergot C, Sutter B, et al. Trabecular bone score (TBS): available knowledge, clinical relevance, and future prospects. Osteoporos Int. 2012; 23:1489–1501.

36. Sampath TK, Simic P, Sendak R, et al. Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats. J Bone Miner Res. 2007; 22:849–859.

37. Kim HY, Mohan S. Role and mechanisms of actions of thyroid hormone on the skeletal development. Bone Res. 2013; 1:146–161.

38. Kim MK, Yun KJ, Kim MH, et al. The effects of thyrotropin-suppressing therapy on bone metabolism in patients with well-differentiated thyroid carcinoma. Bone. 2015; 71:101–105.