Does Long-term Levothyroxine Use Cause Bone Loss?

Gayle Nicholas Scott, PharmD

Disclosures

September 20, 2011

Question

Does chronic thyroid supplementation cause bone loss? If so, how does this occur?

Response from Gayle Nicholas Scott, PharmD
Assistant Professor, Eastern Virginia Medical School, Norfolk, Virginia; Clinical Pharmacist, Chesapeake Regional Medical Center, Chesapeake, Virginia

Many factors, such as age and menopausal status, contribute to bone loss.[1,2] Both hypo- and hyperthyroidism have been associated with an increased fracture risk in adults.[2] Lower bone mass associated with hyperthyroidism may be caused by increased bone turnover as a result of imbalance between bone reabsorption and formation. Decreased bone mineral density and increased bone turnover markers could result.[1] This negative effect of hyperthyroidism on bone may not be limited to women.[2] As hyperthyroidism is associated with fracture risk, does exogenous levothyroxine use increase the risk for fractures?

The prevalence of levothyroxine use in older patients can be explained by a decline of thyroid hormone production and secretion. However, a decline of thyroid degradation also occurs with aging. Thus, patients who begin taking levothyroxine in middle age may need lower doses with advancing age. Overtreatment is common[3] despite requirements for regular thyroid-stimulating hormone (TSH) monitoring. Excessive intake of thyroid supplements resulting in subclinical hyperthyroidism may occur in as many as 20% of patients, particularly the elderly.[1]

In a nested case-control study, current levothyroxine treatment was associated with increased risk for fracture in elderly patients (aged ≥ 70 years) compared with matched controls of remote users of levothyroxine. Fracture risk was significantly increased in current users, particularly women. A strong dose-relation between risk for fracture and levothyroxine dosing existed. High cumulative doses (> 93 µg daily) and medium cumulative doses (44-93 µg daily) were associated with a higher risk for fractures compared with low cumulative doses (< 44 µg daily).[3]

Level of TSH suppression may be associated with fracture risk -- research suggests that suppressed TSH is associated with increased bone turnover markers.[1] An observational cohort study found that patients with a suppressed TSH had increased risk for fracture while patients with a low but unsuppressed TSH did not.[4]Elderly patients and postmenopausal women may be at risk for TSH suppression.[3]

TSH levels should be obtained at least annually in patients taking levothyroxine.[5] In addition, patients should be instructed on how to take levothyroxine properly. Levothyroxine should be taken at a consistent time to avoid fluctuations in TSH levels. Some research suggests bedtime administration of levothyroxine may be more effective than morning administration.[6] Levothyroxine should not be taken concomitantly with multivalent cations (ie, iron and calcium) or food due to risk for altered absorption.[6]

Current guidelines for osteoporosis screening do not address hyperthyroidism.[7] However, bone mineral density scanning may be particularly important for elderly women and younger women with additional risk factors for bone loss (eg, small stature, smoking, family history of fracture) who are receiving long-term levothyroxine therapy.

Although the risk for fracture associated with long-term levothyroxine is low,[8] iatrogenic hyperthyroidism should be avoided. TSH should be monitored closely according to published guidelines,[5] particularly in patients at risk for fracture. Lower than expected doses of levothyroxine may be required in order to avoid TSH suppression and adverse effects on bone.

The author wishes to acknowledge Andi Scott, PharmD candidate, for her contributions in researching and compiling this response.

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