Evaluation of La(XT), a novel lanthanide compound, in an OVX rat model of osteoporosis

Yunyun Di; Ellen K Wasan; Jacqueline Cawthray; Jaweria Syeda; Munawar Ali; David M L Cooper; Ahmad Al-Dissi; Nima Ashjaee; Wubin Cheng; James Johnston; David M Weekes; Thomas I Kostelnik; Chris Orvig; Kishor M Wasan

doi:10.1016/j.bonr.2021.100753

Evaluation of La(XT), a novel lanthanide compound, in an OVX rat model of osteoporosis

Bone Rep. 2021 Feb 11:14:100753. doi: 10.1016/j.bonr.2021.100753. eCollection 2021 Jun.

Authors

Affiliations

¹ College of Pharmacy and Nutrition, University of Saskatchewan, 104 Clinic Place, Saskatoon, SK S7N 2Z4, Canada.
² Department of Anatomy Physiology and Pharmacology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
³ Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK S7N 5B4, Canada.
⁴ College of Engineering, University of Saskatchewan, 57 Campus Drive, Saskatoon, SK S7N 5A9, Canada.
⁵ Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada.
⁶ Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

Purpose: The purpose of this study was to evaluate the efficacy and toxicity of a novel lanthanum compound, La(XT), in an ovariectomized (OVX) rat model of osteoporosis.

Methods: Twenty-four ovariectomized female Sprague Dawley rats were divided into 3 groups receiving a research diet with/without treatment compounds (alendronate: 3 mg/kg; La(XT) 100 mg/kg) for three months. At the time of sacrifice, the kidney, liver, brain, lung and spleen were collected for histological examination. The trabecular bone structure of the tibiae was evaluated using micro-CT and a three-point metaphyseal mechanical test was used to evaluate bone failure load and stiffness.

Results: No significant differences were noted in plasma levels of calcium, phosphorus, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) between the La(XT) treatment compared to the non-treated OVX group. Alendronate-treated animals (positive control) showed higher BV/TV, Tb.N and lower Tb.Th and Tb.Sp when compared to the non-treated OVX group. Mechanical analysis indicated that stiffness was higher in the alendronate (32.88%, p = 0.04) when compared to the non-treated OVX group. Failure load did not differ among the groups.

Conclusions: No kidney or liver toxicities of La(XT) treatments were found during the three-month study. The absence of liver and kidney toxicity with drug treatment for 3 months, as well as the increased trabecular bone stiffness are encouraging for the pursuit of further studies with La(XT) for a longer duration of time.

Keywords: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMD, bone mineral density; BV/TV, bone volume fraction; CRF, chronic renal failure; Ca2+, calcium; Cr, creatinine; HAP, hydroxyapatite; La(XT); La3+, lanthanum; Lanthanum; OVX; OVX, ovariectomized; Osteoporosis; SD, Sprague Dawley; Tb.N, trabecular number; Tb.Sp, trabecular separation; Tb.Th, trabecular thickness; Toxicity.