Search

Purpose: To determine if bone mineral density is decreased in postmenopausal women treated with 1-thyroxine, and, if any decrease is observed, whether it is related to overtreatment with thyroid hormone, to deficiency of calcitonin, or to other factors., Patients and Methods: The study consisted of 19 postmenopausal women between 50 and 75 years of age treated with 1-thyroxine for 5 years or longer, and 19 matching control subjects with no thyroid disease. Bone mineral density of the spine and hip was measured by dual-photon absorptiometry. Plasma calcitonin concentrations and serum thyroid hormone levels were determined by radioimmunoassays., Results: The 1-thyroxine-treated women had lower bone density in the lumbar spine (1.013 g/cm2 [95% confidence interval, 0.945 to 1.081] versus 1.134 g/cm2 [1.026 to 1.242], p = 0.043); in the femoral neck (0.736 g/cm2 [0.694 to 0.778] versus 0.809 g/cm2 [0.747 to 0.872], p = 0.040); in Ward's triangle (0.576 g/cm2 [0.530 to 0.623] versus 0.694 g/cm2 [0.617 to 0.770], p = 0.011); and in the trochanteric area (0.626 g/cm2 [0.581 to 0.672] versus 0.722 g/cm2 [0.651 to 0.794], p = 0.027). The maximal increase in calcitonin following calcium infusion was 1.37 ng/L (95% confidence interval, -0.44 to 3.17) in the 1-thyroxine-treated patients versus 18.8 ng/L (95% confidence interval, 10.0 to 27.5) in normal women, p less than 0.001. The average dose of 1-thyroxine was 120 micrograms/day; 16 of the 19 patients had normal serum thyroxine levels. However, TSH levels were low in 13 of the 19, suggesting that 1-thyroxine treatment was supraphysiologic. Seven of the 19 patients had a history of hyperthyroidism in the distant past; these patients, considered separately, had significantly reduced bone density in the hip. The other 12 patients, considered separately, did not have a statistically significant loss of bone density., Conclusions: Long-term 1-thyroxine therapy is associated with decreased density of the spine and hip. Since subclinical hyperthyroidism, decreased calcitonin responsiveness, and a history of hyperthyroidism were demonstrated in some or all of these patients, these factors must be considered as possible causes of the decreased bone density.

The mineral apposition rate of trabecular bone was determined in several skeletal sites of young adult beagles. Tetracycline derivatives were administered intravenously or orally on 2 separate occasions preceding the day of sacrifice in order to label actively mineralizing bone surfaces. The rate of mineral apposition was calculated by dividing the distance between the 2 tetracycline markers by the time interval between their administration. The lumbar vertebra, proximal humerus, and pelvis, each of which contains red marrow, were found to have a significantly higher (P less than 0.001) rate of mineral apposition in trabecular bone than the skeletal sites containing yellow marrow--the proximal ulna and distal humerus. The mean apposition rate in the former 3 sites was 1.3 +/- 0.3 micrometers/day, while that in the latter 2 was 0.9 +/- 0.2 micrometers/day (uncorrected for plane of sectioning). It is tempting to speculate that this finding may be a consequence of differences in vascularity between red and yellow marrow.

Methylene diphosphonate (MDP) was formulated as a complex of 99mTc for skeletal imaging. This agent was compared with three other bone-seeking technetium agents: ethane-1-hydroxy-1, 1-diphosphonate (EHDP), pyrophosphate, and polyphosphate. In tissue radioassay experiments in rodents, the technetium complexes of MDP and EHDP were similar, but skeletal concentration with both of these agents was higher than that with pyrophosphate or polyphosphate. The total-body retention of MDP and EHDP complexed with 95mTc was studied in beagle dogs for 35 days by excretion measurements and total-body counting and compared with polyphosphate and pertechnetate. The long-term retention was greater for MDP. The 5-day cumulative fecal excretion of 95mTc was low when administered as EHDP or polyphosphate complexes and negligible when administered as MDP complex. In six human volunteers the blood clearance of 99mTc-mdp was similar to that of 18F and significantly faster than that of 99mTc-EHDP. Pyrophosphate cleared from the blood much faster than polyphosphate but slower than the diphosphonates. The urinary excretion of the MDP complex was greater than for EHDP within the first 2-3 hr after injection. The 24-hr urinary excretion of pyrophosphate and polyphosphate complexes was not as complete as for the diphosphonates. All four 99mTc complexes proved satisfactory for clinical imaging studies. The MDP complex produced images of superior quality as early as 2 hr after administration, attributable to its more rapid clearance from the blood and soft tissues. On the contrary, a longer interval of 3-4 hr after injection was usually needed for 99mTc-EHDP; pyrophosphate and polyphosphate complexes regularly required a waiting period of 4 hr. Comparitive radiation dose estimates were made based on the available biologic distribution data for these 99mTc skeletal-localizing agents.

Two radiocolloid preparations, differing in particle size by a factor of 5 to 20, were compared in each of 15 patients. The smaller colloid, measuring less than 80 nm, showed a relative decrease in the calculated target to background ratios for the liver and spleen and an increase for the bone marrow. The increased uptake of the smaller particle in the bone marrow, as measured by the bone marrow to soft-tissue background ratio, was about 50% higher than that of the larger colloidal particles. Comparable marrow images can be obtained in a half to a third of the time with the smaller particle size for a given administered dose.