Effects of Levothyroxine and thyroid stimulating hormone on bone loss in patients with primary hypothyroidism

Untreated hypothyroidism in childhood leads to growth retardation or even growth arrest, disturbances of endochondral ossification, delayed bone age and persistent short stature 8,13,19. Osteoporosis is defined as “a disease characterized by low bone mass and microarchitectural deterioration of bone tissue leading to enhanced fragility and increased fracture risk”. 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. Hyperthyroidism itself produces an increase in bone loss, and if the disease is treated early, this can be minimized. In the same manner, excessive amounts of thyroid hormone replacementcan result in bone loss. For this reason, it is important that patients onthyroid hormone replacement be checked regularly ( every 6-12 months) to makecertain that the dose of replacement results in a TSH within a normal range.

The relationship between bone mass and thyroid functional status is an issue of utmost importance and currently controversial. Thyroid hormones are essential for growth and development during childhood and for the maintenance of bone in adulthood. In children with hypothyroidism one sees stunted growth with epiphyseal dysgenesis and delayed skeletal maturation while in adults the phases of bone renewal are prolonged with reduced osteoblast activity and increased cortical bone thickness. However, the most pronounced effects of thyroid hormones on bone in adults are seen in hyperthyroidism.

Overview of the Effects of Thyroid Hormones on the Skeleton

Lee et al. concluded that men over 65years old with subclinical hypothyroidism were at increased risk for hip fracture. Whether treatment of the subclinical syndrome reduced this risk was unknown 38. Loss of bone mineral density due to osteoporosis is the main cause of fragility fractures and leads to dropped synthroid types quality of life and increased mortality. Disturbance of balance between bone formation and bone resorption is dangerous, can cause loss of bone mass and disruption of it’s architecture. Correct development, achievement of peak bone mass and normal functioning of human skeleton depend on different factors. Both excess as well as deficiency of fT4 and fT3 can be potentially deleterious for bone tissue.

The knockout of the thyroid hormone TRα gene results in delayed bone maturation, while the lack of all isoforms of TRβ has no effect on bone cells 18. In this review, we summarize the systemic and local effects of thyroid hormone action and the bone consequence of long-term effects of thyroid dysfunction including the subclinical forms of these diseases. Decreased bone mass and increased fragility in age-related osteoporosis can occur because of failure to achieve optimal peak bone mass. Although genetic determinants are responsible for up to 85% of the variation in peak bone mass, other factors during childhood and adolescence can affect the ability to achieve optimal peak bone mass. These variables include nutrition, particularly calcium intake, delayed puberty, physical activity, a wide variety of intercurrent illnesses, and social factors such as low family income 2. Levothyroxine is still the gold standard in hypothyroidism treatment, Schulman pointed out.

No prospective studies have been done for patients with subclinical hypothyroidism. Overt hypothyroidism is defined as increased TSH together with T3 and T4 below the lower limit of the reference range. It impairs bone turnover by reducing both osteoclastic bone resorption and osteoblastic activity.

Underactive thyroid (hypothyroidism)

Thyroid hormones might have a direct effect on osteoclasts, or their action on bone resorption might be mediated by osteoblasts or other cell types. With regard to the association between TSH and fasting glucose, a predominance of unaltered fasting glucoses (up to 110) was found, regardless of the TSH range and there was no statistically significant relationship found. The information on this website is not intended to diagnose, treat, cure, or prevent any disease or condition. It is for informational purposes only and is not a substitute for advice from your physician or other healthcare professional. You’ll also receive regular, helpful insights from us on thyroid, general hormone, cognitive, and immune health. She proceeded to break ribs, wrists, femurs, vertebrae, and hips just by opening a window, coughing, or losing her balance and falling.

In consequence thyrotoxicosis leads to increased risk of fractures 8,13,20,22. Elevated serum concentrations of IL-6 are observed in people with hyperthyroidism 23,24. IL-6 stimulates the production of osteoclasts and may be a mediator of parathyroid hormone on bone tissue 23,24. Adverse changes in bone metabolism seen in hyperthyroidism are connected with negative calcium balance, hypercalcaemia and hypercalciuria 13,23. Nuclear T3 receptor has been found in osteoblastic cell lines 19 as well as in osteoclastoma-derived osteoclasts 20. Moreover, T3 directly stimulates bone resorption in vitro 21 possibly through the involvement of interleukin 6, a potent stimulator of osteoclastic activity.

• Furthermore, these incidence rates were standardized to the age distribution of all Korean elderly women in 2005.
• Given that the loss of bone mass resulting from hyperthyroidism, is only partially reversible, it seems logical that we should treat this condition situation as soon as possible, if it is shown that it is altering the bone metabolism.
• “Levothyroxine remains the safest and most widely used option to treat underactive thyroid,” he said.
• Additionally, a study on the association between fracture risk and levothyroxine use in Korean patients has not yet been performed.
• Decreased BMD was observed in a small group of patients with subclinical hyperthyroidism with nodular goiter 50.

New Study Links Popular Thyroid Drug to Increased Bone Loss

Moreover, the majority of studies in hyperthyroid postmenopausal women demonstrated a reduction in BMD. Furthermore, a prior history of hyperthyroidism is an independent risk factor for hip and vertebral fracture (relative risk 1.8) 45. Data seem also to suggest that treatment of hyperthyroidism has a beneficial effect on bone metabolism, but studies are too scanty to draw firm conclusions. But the excess of thyroid hormones in childhood can lead to premature accretion of growth plates and cranial sutures and finally short stature and craniosynostosis 8,13,17,19. In adults, overt hyperthyroidism leads to acceleration of bone turnover and loss of mineral density in 10-20%, mainly in cortical bone 8,13,19. The cycle of bone remodeling is shortened in almost 50% (from 200 to 113 days), and the proportions between bone formation and bone resorption are disturbed 20.

Bone consists of a mineralized matrix and a highly metabolic active cellular component. Cortical bone is a dense bone, which represents up to 80% of skeletal mass, and is present in the shafts of long bones. The bone remodeling cycle is initiated and orchestrated by osteocytes, which are embedded within mineralized bone and communicate via ramifications of dendritic processes. Bone remodeling may result from changes in mechanical load, structural damage, or exposure to systemic or paracrine factors. Hemopoietic cells of the monocyte/macrophage lineage differentiate to mature osteoclasts and resorb bone 27.

However, in those who received treatment and had significantly reduced TSH, the incidence of osteoporosis was higher than others. Linear regression test showed that there was no significant association in the rate of osteoporosis between groups, which may indicate a weak role of TSH. 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-posterior measurements) and femoral neck. The measurement was performed by an expert technician using the Explorer™-Hologic’s bone densitometer manufactured in USA (Hologic QDR 2000). The study included participants aged 65 or older with hypothyroidism, 81 of whom were taking levothyroxine daily, and 364 non-users.