Engineered Multifunctional Nanomedicine for Simultaneous Stereotactic Chemotherapy and Inhibited Osteolysis in an Orthotopic Model of Bone Metastasis.

A novel multifunctional Ag2 S quantum dot (QD)-based nanomedicine of alendronate (Ald)/doxorubicin (DOX)@Ag2 S is developed for highly effective bone tumor therapy in an orthotopic model. The bone-targeting and osteolysis inhibition of Ald and the chemotherapeutic effect of DOX on the bone tumor are in situ visualized by Ag2 S QDs with emission in the second near-infrared window.

Calcitonin, sodium alendronate and high intensity laser in the treatment of traumatized teeth: a preliminary study.

The aim of this study was to evaluate the influence of erbium:yttrium-aluminum-garnet (Er:YAG) laser compared with traditional treatment on dentin permeability to calcitonin and sodium alendronate. Forty bovine roots were sectioned and divided into eight groups. Groups 1 and 2 (G1/G2) were immersed in saline solution; G1T/G2T were immersed in ethylene diamine tetra-acetic acid plus sodium lauryl ether sulfate (EDTA-T) and sodium hypochlorite (NaOCl); G1I/G2I were irradiated with Er:YAG laser (2.94 microm, 6 Hz, 40.4 J/cm(2)); G1TI/G2TI were immersed in EDTA-T, NaOCl and subjected to Er:YAG irradiation. After 4 h the radioactivity of the saline solution was measured. Statistical analysis revealed a significant difference (P < 0.05) when the groups treated with EDTA-T and NaOCl followed by Er:YAG laser irradiation were compared with the groups treated with EDTA-T only and with the groups that received no treatment. Er:YAG laser associated with traditional procedures significantly increased the diffusion of calcitonin and sodium alendronate through dentin. All groups showed calcitonin and sodium alendronate diffusion.

Absorption of the oral bisphosphonate alendronate in osteoporotic patients with Crohn's disease.

The absorption of bisphosphonates from the gut is poor. The question arises whether the absorption of alendronate, and thus its bioavailability, is further altered by the local inflammatory process in patients with Crohn's disease, thereby potentially affecting clinical outcome when used in the treatment of osteoporosis. To address this question, urinary excretion of alendronate was evaluated 3 months and 6 months after start of treatment with oral alendronate at a dose of 10 mg/day in 19 osteoporotic patients with stable Crohn's disease, 12 of whom had an intestinal resection. Biochemical parameters of bone turnover and BMD were also measured at start and at 6 months. Thirteen patients had been previously treated with glucocorticoids and five were currently using them. The average 24-h urinary excretion of alendronate was 0.5-0.6% of the dose administered, a figure comparable to that reported for osteoporotic patients without gut pathology. There was a significant decrease from baseline in urine N-telopeptides of collagen cross-links (NTx)/creatinine (60%) associated with an increase in lumbar spine BMD of already 2% after 6 months of treatment. Our data suggest that in patients with Crohn's disease, alendronate is adequately absorbed from the intestine and retained in the skeleton. This adequacy is confirmed by appropriate suppression of bone resorption and increase in lumbar spine BMD. These data hold significant implications for the clinical management of patients with Crohn's disease and osteoporosis.

Pharmacokinetic and pharmacodynamic evaluation of intermittent versus continuous alendronate administration in rats.

We studied the differences in pharmacokinetics and pharmacodynamics of the same dose of alendronate administered subcutaneously as intermittent bolus injection or continuous infusion in rats. Two rat models of bone disease were applied. Bone cancer was produced by intratibial inoculation of Walker carcinosarcoma cells, and a model of augmented bone resorption was produced by vitamin D(3) treatment of rats that had undergone thyroidparathyroidectomy. Higher amounts of alendronate were found in bones and in internal organs after bolus drug administration as compared with continuous infusion. Drug effects on plasma calcium levels and on urine calcium excretion were similar in both modes of alendronate administration. Results of the study indicate that the pharmacokinetics (disposition) of alendronate is administration-dependent. The total amount found in bone does not directly represent the amount of alendronate that is pharmacologically active at the site of action in the bone and that affects bone remodeling. The findings suggest that there is no pharmacodynamic advantage for continuous infusion of alendronate. It is concluded that the preferred mode of administration should be selected according to secondary clinical criteria (like incidence of adverse effects and convenience of administration).

Preclinical evidence of normal bone with alendronate.

This review summarises the results of preclinical studies aimed at elucidating the mode of action of alendronate and assessing its effects on bone quality. Alendronate preferentially localises at bone resorption sites, where the drug inhibits osteoclastic activity. In a variety of estrogen-deficient animal models, alendronate normalised bone turnover, promoted normal mineralisation and increased bone mass and strength. In these studies, bone formed during alendronate therapy was histologically normal and was not associated with spontaneous fractures. Therefore, preclinical studies have established that the antiresorptive activity of alendronate results in the prevention of bone loss and the accretion of normal-quality bone.