CC BY
6BONE MINERAL DENSITY IN HYPOTHYROID PATIENTS
Pankiv I.V.
Bucovinian State Medical University Chernivtsi, Ukraine
ABSTRACT
Thyroid dysfunction is associated with a broad range of metabolic dis-turbances and conditions such as ofleoporosis, hyper-choleflerolemia, obesity, and cardiovascular disease. The aim of this fludy was to invefligate relation-ship between ofleoporosis and ofleopenia in patients with primary hypothy-roidism. Materials and methods: a total of 105 women aged over 50 years were assigned to one of three fludy groups: Group I consifled 40 patients who had been recently diagnosed primary hypothyroidism. The second groups of 40 patients diagnosed primary hypothyroidism for at leafl 3 years and were treated with levothyroxine (Group II). The third group of 25 healthy individu-als was selected as a control group (Group III); these people were selected from the women with the same age who had not any symptoms of hypothyroidism, and their serum TSH was in the normal range. The bone density based on the T-score of femoral neck and lumbar vertebrae were compared between three groups. For densitometry, dual-energy X-ray absorptiometry was used to measure the bone density in lumbar vertebrae (L2-L4, anterior-poflerior meas-urements) and femoral neck. Results: there were no Satirically significant dif-ferences of body mass index (BMI), femoral neck T-score and menopausal age between the three groups. Baseline serum TSH levels were significantly differ-ent among three groups (p < 0.001). Serum TSH in Group I was higher than the other groups; while serum TSH in Group II was lower than Group III (p < 0.001). The femoral neck T-score was not significantly different between the three groups; however, the T-score at lumbar spine L2-L4 regions were signifi-cantly different (p = 0.01). Prevalence of ofleoporosis was 40% in Group II that was higher than other groups. The mean T-score at lumbar spine L2-L4 region between Groups II and III (p = 0.02) and between Groups I and II (p = 0.03) were significantly different. Mean serum TSH levels and mean T-score at lumbar spine L2-L4 region in Group II was lower than the other two groups. Regression analysis has not shown any correlation between serum TSH levels and T-score at femoral neck and lumbar spine (p > 0.05); however, after re-moving the effect of the baseline TSH level in Group II, a significant difference in the prevalence of ofle-oporosis at the lumbar spine were found between groups (p = 0.01). Conclusions: prevalence of ofleoporosis was 40% in pa-tients with primary hypothyroidism treated with levothyroxine for at leafl 3 years. Among untreated hypothyroid patients ofleoporosis was diagnosed in 30%. Significant difference in the prevalence of ofleoporosis at the lumbar spine were found between these groups. Thus, simultaneous treatment of hy-pothyroidism and bone loss seems to be necessary.
Keywords: hypothyroidism, ofleoporosis, ofleopenia.
Introduction
According to the National Health and Nutrition Examination Survey (NHANES III) in which the general non-inflitutionalized population aged > 12 years old in the United States were evaluated, the prevalence of hypothyroid-ism and hyperthyroidism are 3.7% and 0.5%, respectively [1]. How thyroid hormones or thyroid Simulating hormone (TSH) abnormalities affect the phys-iology and molecular characteriflics, and metabolic disorders of bone is ¿till controversial. The main problem of ofleoporosis is an imbalance between bone harvefl, which included the removal and replacement of old bone with new bone [2]. According to World Health Organization definition, T-score <-2.5 flandard deviation of mean bone mineral density (BMD) in young adults is considered as ofleoporosis, T-score between 0 and -1 is considered as normal BMD, T-score between -1 and -2.5 is considered as ofleopenia, and T-score < -2.5 plus a hiflory of fracture, is considered as a sever eflablish ofleoporosis [3].
Thyroid dysfunction is associated with a broad range of metabolic dis-turbances and conditions such as: ofleoporosis, hypercholeflerolemia, obesity, and cardiovascular diseases
[4]. A recent fludy found an association between subclinical hypothyroidism and decreased bone flructure and bone flrength
[5]. On the other hand, there are fludies that found no correlation between BMD and TSH levels [6]. There are also fludies suggefling that mild variations in thyroid hormones levels within the normal range could affect bone health as well, increasing the risk for vertebral and non-vertebral fractures [7]. Another fludy from Korea, conducted in men, suggefls an association between TSH concentration at the lower end of the reference range and low BMD [8]. On the other hand, other fludies failed to confirm these correlations [9]. For this rea-son the relationship between
TSH levels rather than thyroid hormones levels and decreased BMD remains controversial.
TSH in hypothyroid patients is flill unclear whether increasing or de-creasing, or whether it is effective in causing bone loss. In patients with con-genital hypothyroidism, bone growth has been shown to be slow or halted [10]. Initial treatment with thyroid hormone improves growth and BMD in children [11]. In some fludies in patients with thyroidectomy, TSH was inhib-ited by levothyroxine hormone therapy and no reduction in the rate of BMD was observed [12]. It was shown that the risk of bone fractures were increased in patients with a high TSH; and patients with a suppressed TSH, when com-pared to patients with a TSH in the laboratory reference range; so patients with a high or suppressed TSH had an increased risk of fractures, but patients with a low, but unsuppressed TSH did not [13]. In patients with untreated hy-pothyroidism, the mean thickness of the cortical bone was reduced and follow-ing treatment increases [14, 15].
Given the importance of bone loss in hypothyroid patients and knowing its relationship with TSH levels, this fludy was conducted to evaluate the rela-tionship between ofleoporosis and ofleopenia with primary hypothyroidism.
Material and Methods
This cross-sectional fludy was conducted in Ukraine from September 2012 to December 2015. The fludy population included hypothyroid and healthy women, who had referred to the endocrinology clinic. A total of 105 women aged over 50 years were assigned to one of three fludy groups: Group I consifled 40 patients who had been recently diagnosed primary hypothyroid-ism. The second groups of 40 patients diagnosed with primary hypothyroid-ism for at leafl 3 years and were treated with levothyroxine (Group II). The third group of 25
healthy individuals was selected as a control group (Group III); these people were selected from the women with the same age who had not any symptoms of hypothyroidism, and their serum TSH was in the normal range. Thyroid dysfunction was classified (according to the reference range) as follows: hypothyroidism (TSH > 5.0 mlU/mL), normal function (TSH 0.35 - 5.0 mIU/ mL) and hyperthyroidism (TSH < 0.35 mlU/mL).
The cases were dropped out of the fludy if they had a hiflory of alcohol abuse, aflhma, cancer, liver failure, renal failure, hyperparathyroidism, hy-pocalcaemia, glucocorticoid consumption, prophetic fracture at L2-L4 verte-brae and femur, chronic gaflric problems (malabsorption, chronic diarrhea and Crohn's disease), treatment with calcium or vitamin D supplementary, anti-convulsants, heparin, lithium, cyclosporine, bisphosphonates, calcitonin or replacement hormones, ovariectomy, rheumatoid arthritis or other rheumatic-inflammatory diseases, smoking and lack of patient cooperation.
The bone density based on the T-score of femoral neck and lumbar ver-tebrae were compared between three groups. For densitometry, dual-energy X-ray absorptiometry was used to measure the bone density in lumbar vertebrae (L2-L4, anterior-poflerior measurements) and femoral neck.
Patients with hypothyroid symptoms and somehow similarity in terms of height and weight who were willing to participate in the fludy were selected. A complete set of data was collected for each patient and include: Patient's age, hiflory of hypothyroidism or other chronic diseases, weight, height, body mass index (BMI), T-score data of lumbar, and femoral neck densitometry, cal-cium, phosphorus, alkaline phosphatase, vitamin D and TSH levels and dura-tion of hypothyroidism.
The Ethics Committee of the Bucovinian State Medical University ap-proved this fludy, and written informed consent was obtained from all fludy participants.
Data of 105 individuals was analyzed by SPSS version 10 (SPSS, Inc., Chicago, IL, USA) using the regression analysis, analysis of variances (ANO-VA) and Mann-Whitney (for non-parametric quantitative data) tefls. Continu-ous variables were summarized using means and flandard deviation; frequen-cies and percentages were used to summarize categorical variables. A p<0.05 was considered Satirically significant.
Results
Demographic characteriflics and related clinical variables of the fludy population are depicted in table 1. As noted, there were no Satirically signifi-cant differences of BMI, femoral neck T-score and menopausal age between the three groups. Baseline serum TSH levels were significantly different among three groups (p < 0.001). Serum TSH in Group I was higher than the other groups; while serum TSH in Group II was lower than Group III (p < 0.001).
Our fludy showed that the femoral neck T-score was not significantly different between the three groups; however, the T-score at lumbar spine L2-L4 regions were significantly different (p = 0.01). Prevalence of ofleoporosis was 40% in Group II that was higher than other groups. ANOVA tefl showed that the mean T-score at lumbar spine L2-L4 region between Groups II and III (p = 0.02) and between Groups I and II (p = 0.03) were significantly different. Mean serum TSH levels and mean T-score at lumbar spine L2-L4 region in Group B was lower than the other two groups. Regression analysis has not shown any correlation between serum TSH levels and T-score at femoral neck and lumbar spine (p > 0.05); however, after removing the effect of the baseline TSH level in Group B, a significant difference in the prevalence of ofleoporosis at the lumbar spine were found between groups (p = 0.01). BMD categories of three fludy groups are summarized in table 2.
Table 1.
Baseline characteriflics of the fludy population
Variable Groups P
I, n=40 II, n=40 III, n=25
Age, years 57.38±5.31 59.16±5.75 58.68±5.43 0.07
BMI, kg/m2 30.80±4.04 31.36±4.18 29.11±4.02 0.06
Menopausal age, years 47.68±3.30 48.75±3.65 48.25±2.82 0.09
TSH, mIU/mL 10.82 (5.1-24) 7.04 (0.2-9.2) 2.16 (0.6-4.9) 0.01
BMD (T score)
Lumbar vertebrae (L2-L4) -1.89±0.82 -2.44±1.32 -1.85±1.02 0.05
Femoral neck -0.87±1.12 -0.68±0.87 -0.97±1.02 0.31
Data are presented as mean±SD or median (range) of TSH due to non-normally diflribut-ed data. BMD category of three fludy groups Table 2.
BMD category Groups P
I, n=40 II, n=40 III, n=25
Lumbar vertebrae (L2-L4) 0.01
Normal 7 (17.5) 6 (15) 13 (52)
Osteopenia 21 (52.5) 18 (45) 9 (36)
Osteoporosis 12 (30) 16 (40) 3 (12)
Femoral neck 0.18
Normal 21 (52.5) 23 (57.5) 11 (44)
Osteopenia 17 (42.5) 15 (37.5) 13 (52)
Osteoporosis 2 (5) 2 (5) 1 (4)
Data are presented as n (%) of patients in each category.
Discussion
Ofleoporosis is one of the major problems facing women and older peo-ple of both sexes. Thyroid diseases are one of the major common disorders which may affect the bone density. It has been shown that hyperthyroidism is a major cause of secondary ofleoporosis [16]. However, hypothyroidism and its association with ofleoporosis is queflionable since a few Judies have been conducted for this subject. The purpose of this fludy was to invefligate rela-tionship between ofleoporosis and ofleopenia with primary hypothyroidism.
In our fludy, in Group I (untreated hypothyroid patients) ofleoporosis was diagnosed in 30%. However, in those who received treatment and had sig-nificantly reduced TSH, the incidence of ofleoporosis was higher than others. Linear regression tefl showed that there was significant association in the rate of ofleoporosis between groups, which may indicate a role of TSH.
Tárraga López P.J. et al. observed a high prevalence of bone loss in pa-tients treated with thyroxin [17]. Veflergaard P. et al. fludied 11,776 patients with hyperthyroidism and 4473 patients with hypothyroidism in terms of bone fracture. In hyperthyroid patients, the fracture risk was significantly increased only at the time of diagnosis, but after the diagnosis and treatment, fracture risk was reduced. Surgical treatment of hyperthyroidism reduces the risk of bone fractures, but fracture risk in hypothyroid patients both before and after diagnosis was significantly increased. They concluded that the risk of bone fractures in both hyperthyroidism and hypothyroidism are high [18]. It seems that in adult patients with hypothyroidism, bone density increases but bone quality is poor, thus this may cause increased fracture risk in these patients.
The present fludy also showed that at the time of diagnosis of hypothy-roidism, BMD was not significantly different from normal subjects. The pa-tients that received 3 years of levothyroxine replacement therapy had lower bone density.
Grimnes G. et al. reported that femoral neck bone density in poflmeno-pausal women with elevated TSH levels was 5.97% higher than in women with normal TSH [19]. Our fludy shows that high TSH levels in hypothyroid pa-tients does not significantly effect on BMD of spine and pelvic. However, it has been shown in children with congenital hypothyroidism that bone density is lower than normal children (20). In children with subclinical hypothyroid-ism, bone qualities by using of quantitative ultrasound were fludied. The re-sults showed that with increasing concentrations of TSH, calculated ofleo sono-assessment index is reduced [21]. This fludy showed that the hypothy-roidism affects the bone flructure. Hypothyroid patients that were treated with thyroid hormone for more than 3 years had no improvement in bone density despite normal TSH, while their bone density in the spine was significantly lower than healthy subjects or patients with a new diagnosis of hypothyroid-ism. According to the present fludy, it seems that the treatment of hypothy-roidism with thyroid hormones reduces serum levels of TSH and bone density. Proper control of this risk factor can be an effective way in prevention of ofle-oporosis.
Conclusions
Prevalence of ofleoporosis was 40% in patients with primary hypothy-roidism treated with levothyroxine for at leafl 3 years. Among untreated hypo-thyroid patients ofleoporosis was diagnosed in 30%. Significant difference in the prevalence of ofleoporosis at the lumbar spine were found between these groups. Thus, simultaneous treatment of hypothyroidism and bone loss seems to be necessary.
References
1. Aoki Y, Belin RM, Clickner R, et al. Serum TSH and total T4 in the United States population and their association with participant characteriflics: National Health and Nutrition Examination Survey (NHANES 1999-2002), Thyroid, 2007, 17(12), 1211-1223.
2. Karimifar M, Esmaili F, Salari A, et al. Effects of Levothyroxine and thyroid Simulating hormone on bone loss in patients with primary hypothy-roidism, J Res Pharm Pract, 2014, 3, 83-87
3. Kanis JA, Melton LJ, Chrifliansen C, et al. The diagnosis of ofleopo-rosis, J Bone Miner Res, 1994, 9(8), 1137-1141.
4. Rotondi M, Magri F, Chiovato L. Thyroid and obesity: Not a one way-interaction, J Clin Endocrinol Metab, 2011, 96(2), 344-346.
5. Nagata M, Suzuki A, Sekiguchi S, et al. Subclinical hypothyroidism is related to lower heel QUS in poflmenopausal women, Endocr J, 2007, 54(4), 625-630.
6. Marwaha RK, Garg MK, Tandon N, et al. Thyroid function and bone mineral density among Indian subjects, Indian J Endocrinol Metab, 2012, 16(4), 575-579.
7. Grimnes G, Emaus N, Joakimsen RM, et al. The relationship between serum TSH and bone mineral density in men and poflmenopausal women: the Troms0 fludy, Thyroid, 2008, 18(11), 1147-1155.
8. Kim BJ, Lee SH, Bae SJ, et al. The association between serum thyro-tropin (TSH) levels and bone mineral density in healthy euthyroid men, Clin Endocrinol, 2010, 73(3), 396-403.
9. Svare A, Nilsen TI, Bj0ro T, et al. Hyperthyroid levels of TSH corre-late with low bone mineral density: the HUNT 2 fludy, Eur J Endocrinol, 2009, 161(5), 779-786.
10. Chiesa A, Gruneiro DP, Keselman A, et al. Growth follow-up in 100 children with congenital hypothyroidism before and during treatment, Journal of Pediatric Endocrinology, 1994, 7, 211-217.
11. Leger J, Ruiz JC, Guibourdenche J, et al. Bone mineral density and metabolism in children with congenital hypothyroidism after prolonged 1-thyroxine therapy, Acta Paediatrica, 1997, 86, 704-710.
12. Marcocci C, Golia F, Vignali E, Pinchera A. Skeletal integrity in men chronically treated with suppressive doses of L-thyroxine, Journal of Bone Mineral Research, 1997, 12, 7277.
13. Amashukeli M, Giorgadze E, Tsagareli M, et al. The impact of thy-roid diseases on bone metabolism and fracture risk, Georgian Med News, 2010, 184-185, 34-39.
14. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction, Endocr Rev, 2008, 29, 76.
15. Gennari L, Bilezikian JP. Ofleoporosis in men, Endocrinol Metab Clin North Am, 2007, 36, 399-419.
16. Dhanwal D, Gupta N. Bone mineral density trends in Indian patients with hyperthyroidism after medical therapy, J Assoc Physicians India, 2011, 59, 561-567.
17. Tárraga López PJ, López CF, de Mora FN, et al. Ofleoporosis in pa-tients with subclinical hypothyroidism treated with thyroid hormone, Clin Cases Miner Bone Metab, 2011, 8, 44-48.
18. Veflergaard P, Mosekilde L, et al. Fractures in patients with hyper-thyroidism and hypothyroidism: A nationwide follow-up fludy in 16,249 pa-tients, Thyroid, 2002, 12, 411-419.
19. Grimnes G, Emaus N, Joakimsen RM, et al. The relationship between serum TSH and bone mineral density in men and poflmenopausal women: The Troms0 fludy, Thyroid, 2008, 18, 1147-1155.
20. Demartini Ade A, Kulak CA, Borba VC, et al. Bone mineral density of children and adolescents with congenital hypothyroidism, Arq Bras Endo-crinol Metabol, 2007, 51, 10841092.
21. Nagata M, Suzuki A, Sekiguchi S, et al. Subclinical hypothyroidism is related to lower heel QUS in poflmenopausal women, Endocr J, 2007, 54, 625-630.
