Perhaps the biggest question question mark over long term thyroxine is its ability to cause osteoporosis. One study of long term thyroxine users showed no evidence of reduced bone density (Lancet, 1992; 340: 9-13), while another study of premenopausal women with Hashimoto's disease on thyroid replacement therapy demonstrated that they had lower bone mineral density than normal in certain areas of the leg and pelvis.
However, it's not known whether the hyperthyroidism that occurs early in the disease before the thyroid burns out was actually responsible for lowering bone density (JAMA, 1991; 265: 2688-91). One definite area of concern is hypothyroid women who are being given too high doses of thyroxine replacement who become hyperthyroid without obvious symptoms. In those cases, studies have demonstrated that this group do have lowered bone density (Thyroid, 1994; 4 (3): 319-26), as do women on thyroxine replacement doses that send levels of the hormone TSH plunging (Semin Nucl Med, 1995; 25: 205-20).