The Risk: Thyroid Hormone Replacement and Osteoporosis

To estimate the prevalence of osteoporosis in patients being treated with thyroid hormone. The receptors for TSH (TSHR) are located not only in thyroid follicular cells, but also in osteoblasts and osteoclasts 4,5. Data from scientific reports indicates that TSH is considered as a negative regulator of bone turnover 4. Its direct action on bone tissue cells leads to enhanced bone remodeling and osteoporosis 15,16.

Studies on humans are limited to the effect of different TSH concentration on serum markers of bone metabolism. Interesting studies analyzed the effect of acute administration of recombinant human TSH (rhTSH) in patients without thyroid glands and with constant free thyroxine (FT4) level due to their L-thyroxine (L-T4) supply. This test is commonly used as a part of follow-up in patients with differentiated thyroid cancer and gives the opportunity to test in vivo the effect of increased concentration of TSH on bone turnover markers. On the other hand, another study reported no effect of rhTSH on serum osteoprotegerin and RANKL 26. Suppressive doses of L-T4 are used in patients with differentiated thyroid carcinoma as a complementary treatment after thyroidectomy and radioactive iodine therapy. Although an endogenous hyperthyroidism is a risk factor of secondary osteoporosis, the effects supraphysiological doses of levothyroxine on bone are still under discussion.

Heemstra et al. suggested that in postmenopausal women after long-term suppressive thyroxine replacement therapy decreased BMD and increased risk of osteoporosis was observed, whereas it wasn’t noted among men and premenopausal women 46. Quan et al. analyzed 11 researches concerning the effects of suppressive thyroxine therapy in patients with well-differentiated thyroid cancer on bone metabolism. They didn’t notice significant change in bone mineral density among premenopausal women and men. Findings for postmenopausal women remained unclear and needed further studies 47.

Thyroid Research

As with patients with overt hypothyroidism, clinicians who treat subclinical hypothyroidism should be cautious to avoid over treatment. Whether treatment of subclinical hypothyroidism is needed or helpful is another question. According to the present study, it seems that the treatment of hypothyroidism with thyroid hormones reduces serum levels of TSH and bone density. Hence, proper control of this risk factor can be an effective way in prevention of osteoporosis. This chapter reviews clinical studies of bone health in people receiving treatment with LT4 in these settings.

Treatment of Subclinical Thyroid Disorders

Hyperthyroidism increases the rate of turnover of bone, with a net synthroid questions loss of bone mineralisation; accordingly, suboptimally managed hyperthyroidism can be a cause of osteoporosis and increased fracture risk 1, 2. Restoration of euthyroid status reverses the loss of bone mineral content and also ameliorates the excess fracture risk in patients with hyperthyroidism 5. During normal aging, regulatory functions such as thyroid hormone production and degradation decrease, and therefore the required doses for elderly patients with hypothyroidism differ from those for younger patients 6,7. Chronic under or over-replacement is common in clinical practice, and data indicate that over-replacement occurs in approximately 20% of levothyroxine patients who are treated with levothyroxine due to non-adherence or a lack of levothyroxine replacement monitoring 8-10. Bone loss due to levothyroxine over-replacement frequently occurs in postmenopausal women 11,12.

Thus, the amount of bone formation decreases with age, leading to a more fragile skeleton.
However, more recent data suggest that this clinical condition may affect bone metabolism resulting in decreased bone mineral density (BMD) and increased risk of fracture, particularly in postmenopausal women.
Their expression in bone directly means that this tissue is under the influence of thyroid hormones.
A case-control study from Denmark, where all 124,655 patients with a fracture served as cases and 373,962 randomly selected age- and gender-matched people without fractures served as controls, found no association between LT4 treatment and risk of fracture 24.

Experiences of young people living with an endocrine disorder

In Korea, a cohort study by Choi et al. 2 reported that the subclinical hypothyroidism prevalence was 18.9% in elderly Korean women. Therefore, more than 20% of elderly patients receive long-term levothyroxine replacement therapy 1. Despite the importance of this treatment, previous studies on the association between levothyroxine use and fracture risk have reported controversial results 3-5. However, it has been shown in children with congenital hypothyroidism that bone density is lower than normal children.39 In children with subclinical hypothyroidism, bone qualities by using of quantitative ultrasound were studied.

Studies that analyzed the effect of the treatment of subclinical hyperthyroidism on lumbar spine bone mass density and femoral bone mass density. The relation between thyroid hormones and bone metabolism is well documented in children with hypothyroidism. In severe untreated hypothyroidism, delayed skeletal development, defective endochondral ossification, short stature, and epiphyseal dysgenesis are well known clinical features that can be reversed particularly when early and prompt replacement therapy is started. Thyroid hormone is crucial for cartilage growth and differentiation and enhances the response to growth hormone. Thyroid hormones have multiple effects on body homeostasis 10,11 and metabolism 12, and their increased concentration may lead to different complications, mainly at the cardiovascular level 13.

Both women and men had a BMD that was significantly decreased compared to the control. Longitudinal studies also evaluated whether bone loss could be reversed by treatment of hyperthyroidism. A study by Dhanwal et al. reported an early recovery at hip and lumbar spine after eight weeks of carbimazole therapy 43. Another study reported that the increased level of OPG found in hyperthyroid, normalized after medical treatment, even in the presence of persistent abnormal bone structure 44. Collectively, all the data demonstrate that the severity of hyperthyroidism appears to influence the degree of bone mass and increase the probability of osteoporosis.

Hemopoietic cells of the monocyte/macrophage lineage differentiate to mature osteoclasts and resorb bone 27.
This has led to a series of disputes among experts regarding the management and diagnosis of these patients (17, 18).
Thus, simultaneous treatment of hypothyroidism and bone loss seems to be necessary.
She proceeded to break ribs, wrists, femurs, vertebrae, and hips just by opening a window, coughing, or losing her balance and falling.

There are a number of contributors to osteoporosis, including genetics, peak bone mass acquired during youth, and factors that contribute to increased breakdown ofbone and/or a decrease in formation of new bone.
Very few studies analyzed the effect of the treatment of thyroid disorders on bone metabolism (Table 6).
The conversion of vitamin D into its active form is also reduced by low parathormone thus reducing gastrointestinal calcium absorption and resultant fecal calcium losses.
OP is a health issue with important implications for individuals, families and the community.
A total of 162 individuals, all over 65 years of age with subclinical hypothyroidism, were divided in 2 groups.

Long-term treatment with high doses of LT4 may be administered to suppress the activity of residual thyroid tumour cells after total thyroidectomy for well-differentiated thyroid carcinoma (see chapter, “Levothyroxine and Cancer”). This setting has been likened to a state of “subclinical hyperthyroidism” by some authors 29. While the treatment of overt thyroid disease is mandatory due to its effect on the cardiovascular system, lipid metabolism, and metabolic consequences, the treatment of subclinical disorders are still under debate 89. The decision of their treatment is based on different factors and the possible reduction of the BMD cannot be considered the main reason to start appropriate therapy. The accelerated remodeling cycle causes an increased release of calcium into the systemic circulation 36. High levels of calcium reduce parathyroid hormone secretion leading to an increased urinary calcium loss and a negative calcium balance.

REFERENCES

Although at an appropriate dose thyroxin is a very safe medicine, before treatment begins a number of possible side effects must be considered including restoration of euthyroidism, the exacerbation of ischemic heart disease and the production of acute adrenal insufficiency. Care must be taken to get the dose right, since an excess can lead to decreased bone mineral density, the onset of atrial arrhythmias and the precipitation of angina pectoris. This is not the case with elevated TSH and normal T4 as the adverse effects of thyroxin outweigh the benefits in patients with subclinical hypothyroidism scheduled for urgent or semi-elective surgery or invasive methods. Such procedures should not be delayed because there is no evidence of increased risk of complications or mortality, even in cases of established hypothyroidism (12–14).