Effects of Tributyltin (TBT) on Rat Bone and Mineral Metabolism

Abstract

Background/aims: Tributyltin (TBT) is an organotin (OTs) and biohazard organometallic pollutant. Recently our group has shown that TBT, even in very low doses, has deleterious effects on several tissues most likely due to its role as an endocrine-disrupting molecule. Other studies have confirmed that OT exposure could be responsible for neural, endocrine, and reproductive dysfunctions via in vitro and in vivo models. However, TBT effects on bone lack concise data despite the fact that bone turnover is regulated by endocrine molecules, such as parathormone (PTH), estrogen (E2), etc. Our group has already shown that TBT disrupts adrenal and female gonadal functions.

Methods: We studied the effects of TBT on bone metabolism and structure using DXA, microCT scan, and SEM. We also determined the calcium (Ca²⁺) and phosphate (Pi) metabolism in TBT-treated rats as well as some biomarkers for bone formation and resorption.

Results: Surprisingly, we found that TBT leads to higher bone mineral density (BMD) although lesions in spinal bone were observed by either microCT scan or SEM. Biomarkers for bone resorption, such as the urinary deoxipyridinolines (DPD) excretion ratio was increased in TBT-treated animals versus mock-treated controls. Osteocalcin (OC) and alkaline phosphatase (AP) are markers of bone formation and are also elevated suggesting that the bone matrix suffers from a higher turnover. Serum Ca²⁺ (total and ionized) do not changed by TBT treatment although hypercalciuria is observed.

Conclusion: It is known that Sn atoms have three valence states (Sn²⁺, Sn³⁺, and Sn⁴⁺); hence, we hypothesized that Sn (more likely Sn²⁺) could be competing with Ca²⁺ and/or Mg²⁺ in hydroxyapatite mineral matrix to disturb bone turnover. Further work is needed to confirm this hypothesis.

Keywords: Bone; Estrogen; Mineral metabolism; TBT; Ultrastructural changes.