Friday, December 16, 2011

Role of hypogonadism in development of bone alterations in thalassemic patients: Causes of hypogonadism in adult TM patients

It has been suggested that in TM patients the hypothalamus and the pituitary are damaged by the iron overload. In fact the pituitary gland is very sensitive to iron and also a modest deposition may impair its functionality. Histological studies have confirmed the damage of the pituitary gland by iron overload in TM patients and MRI has shown a signif-icantly smaller anterior pituitary volume. Other studies have shown that iron overload may also directly damage the gonads. Therefore, it may be assumed that the hypogo- nadism of adult TM patients is mainly a consequence of the iron deposit.

Some authors have reported higher ferritin levels in subjects who had hypogonadism compared to those with normal go- nadal function. Ferritin is the protein that stores iron intra- cellularly and when its capability is exceeded an excess of active iron is released and catalyses the formation of free radicals. Free radicals may damage membrane lipids, leading to mitochondrial and lysosomal damage and finally to cell death. Because of these findings it has been suggested that improvement of chelation treatments may prevent or reduce the appearance of hypogonadism in TM patients. While it may be probable, other studies did not find such correlations and our normogonadic patients had the same transfusion and chelation treatment than hypogonadic patients. Moreover, while hypogonadic patients had slightly higher ferritin circulating levels, the difference with normogonadic patients was not significant.

Relationships between hypogonadism and bone mass deficiency in TM

It is well known that sexual hormone deficiency determines an alteration of bone metabolism with increased bone resorption and progressive evolution towards osteoporosis. While most studies have been conducted in menopausal women, it is clear, from clinical and experimental data, that sexual hormone deficiency may determine osteopenia or osteoporosis at any age and in both sexes. Because of it and although many other possible causes are present in thalassemia, hypogonadism may have a main role in determining bone mass deficiency.


Figure 2 - Z score differences between eugonadal and hypogonadal thalassemic patients.

Consistent with this hypothesis, we have shown that in adult TM patients a direct correlation between low bone mass and reduced estradiol exists, suggesting that reduced bone mass in many TM patients is mostly dependent on sex hormone deficiency. Moreover, hypogonadic TM patients had lower L1- L4 z score (Figure 2) and higher levels of bone markers (Figure 3) than eugonadal TM patients. All these data confirm that gonadal failure plays a main role in inducing bone mass deficiency of adult TM patients. Need medication you can't afford? buy asthma inhalers online


Figure 3 - Difference in bone alkaline phosphatase and CTX between eugonadal and hypogonadal thalassemic patients.

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