Bone Abstracts

Proton pump inhibitors (PPIs) are a class of drugs particularly used in gastric disorders. They promote a decrease on gastric acid secretion by inhibiting the H⁺/K⁺ ATPases. Osteoclasts are cells specialized in bone resorption by H⁺ translocation to the bone surface. Thus, PPIs might be regarded as potential tools to modulate osteoclast resorption activity, particularly in conditions that are associated with a hyperactivation of osteoclasts, like it happens, in bone osteolytic metastasis. Breast cancer is one of the most frequent tumours that originate bone osteolytic metastasis. In this context, this work intended to characterize the effects of three PPIs on human osteoclastogenesis in co-cultures of human osteoclasts and breast cancer cells.

Osteoclastic precursors were isolated from human peripheral blood and were co-cultured with two different breast cancer cell lines (T47D and SK-BR-3). Cell cultures were treated with a concentration range (10⁻⁷ to 10⁻³ M) of omeprazole, esomeprazole and lansoprazole. Cell cultures were characterized throughout a 21-day period for total protein content, tartarate-resistant acid phosphatase (TRAP) activity, TRAP+ multinucleated cells and the presence of cells with actin rings and expressing vitronectin and calcitonin receptors.

The presence of breast cancer cells, particularly T47D cells, greatly induced osteoclastogenesis. The tested PPIs caused a dose-dependent inhibition of osteoclast development. The osteoclastogenic inhibition was verified at levels higher than 10⁻⁶ M for the three PPIs. Although the highest concentrations seemed to be toxic for osteoclastic cells, the inhibition observed at lower levels appeared to result from specific effects on the osteoclasts, rather than to a significant decrease on the cellular viability.

Taken together, PPIs had the ability to decrease human osteoclastogenesis, when osteoclastic precursors were co-cultured with breast cancer cells. Understanding the subjacent mechanisms can open new perspectives in the utilization of such compounds in pathological conditions characterized by a hyperactivation of osteoclastic cells.