Effect of lithium carbonate on subchondral bone in sexually mature Wistar rats

Clinical and experimental studies have shown that lithium carbonate causes a number of clinical manifestations such as hyperparathyroidism, hypothyroidism, renal toxicity, and diabetes insipidus. The effect of this drug on the bone biology of experimental animals has not been studied to date. Therefore, the aim of the present experimental work was to study the effect of lithium on bone tissue in healthy sexually mature Wistar rats. Ten female Wistar rats, aged 3 1 2 – 4 1 2 months, 210–220 g body weight, were assigned to one of the following groups: untreated control group and experimental group receiving 45 mg/kg body weight/day of lithium carbonate in their drinking water during 3 months. Prior to euthanasia, blood samples were obtained in order to determine plasma phosphorus, calcium alkaline phosphatase, and lithium. After sacrifice, the tibiae were resected, processed, and embedded in paraffin. The following histomorphometric parameters were determined on digital photographs of the histologic sections: BV/TV (%), bone volume; Tb.Th (μm), trabecular thickness; Tb.N (mm −2/mm), trabecular number; Tb.Sp (μm), trabecular separation; Ob.S/BS (%), osteoblast surface; ES/BS (%), total erosive surface; Lc.S (%), lining cells surface; and GPC.Th (μm), thickness of growth plate cartilage. The results showed that administration of lithium carbonate cause bone loss in healthy sexually mature Wistar rats. Although the mechanism involved in bone toxicity remains to be clarified, the results obtained in the present study suggest that patients under long-term lithium therapy should be thoroughly evaluated, particularly those presenting other risk factors of osteopenia, such as menopause, low calcium intake, alcohol consumption, and glucocorticoid therapy.