05–15 mg kg−1 of [14C]-alendronate was injected IV. Furthermore, reports from the literature have shown that nBPs not only acted on osteoclast bone resorption, but also affected the behaviour and metabolism of other bone-related cells,

such as osteoblasts, osteocytes and macrophages.13 and 14 Therefore, we aimed to evaluate BALP serum levels after treatment with ALD. BALP, an isoform of TALP, acts specifically as a bone formation marker. Its mechanism of action is based on inorganic pyrophosphate hydrolysis, removing this osteogenic Ku-0059436 datasheet inhibitor, while it creates inorganic phosphate, required for the generation and deposition of hydroxyapatite.15 BALP is secreted from osteoblast membrane toward matrix vesicles, allowing the mineralisation process to occur.15 It is known that mammalian-tissue BALP is strongly activated by divalent cations such as Mg2+ and Zn2+, and has an active site and contains two Zn2+ ions that stabilise its tertiary

structure.14 The intestinal and placental isoenzymes are less influenced by these cations.16 In this study, we have shown that the lowest doses of ALD (0.01 and 0.05 mg kg−1) prevented the reduction of BALP serum levels, when compared to its baseline data. On the other hand, the highest dose of ALD (0.25 mg kg−1) prevented BALP reduction when compared to saline after 11 days of periodontitis, but it was significantly different on BALP serum levels Epacadostat supplier when compared to its baseline. Although slight, the lower level of BALP after treatment with ALD may be related to two aspects: the chemical structure, which is closely linked to the anti-resorptive

effect of this drug, and its concentration.17 and 18 nBPs, like ALD, have two radicals linked to the carbon atom, one, called R1 that has a hydroxyl group ( OH) and improves mineral affinity, and the other one, called R2, which increases nBP potency to inhibit bone resorption.14 This chemical structure elicits the development of a structural motif called ‘bone hook’ that binds to the Thalidomide mineral by chelation of divalent cations.18 Therefore, considering that BALP needs divalent cations to become activated and that the ALD bone hook reduces the offer of these cations, our present observations suggest that the highest dose of ALD inhibited BALP activity through divalent cation chelation within the bone hook structure. This suggestion is based on a previous report where BALP inhibition was reversed by an excess of Zn2+ or Mg2+.13 However, it was seen that lower doses of ALD prevented BALP reduction while the highest dose did not, when compared to its respective baseline; therefore, we can infer that ALD may have a dose-dependent effect on BALP serum levels. In fact, reports from the literature had already confirmed our finding.17 and 18 For Still et al.