Sequential administration of alendronate and strontium ranelate: histomorphometry and bone biomechanics in ovariectomized animals

• Published in: Acta odontológica latinoamericana Vol. 29; no. 2; pp. 168 - 177
• Main Authors: Díaz, Diego H, Rodas, Julieta A, Bozzini, Clarisa E, Mandalunis, Patricia M, Escudero, Natalia D
• Format: Journal Article
• Language: English; Portuguese
• Published: Argentina Sociedad Argentina de Investigación Odontológica 01.09.2016
• Subjects: Alendronate - administration & dosage; Animals; Biomechanical Phenomena; Bone and Bones - drug effects; Bone and Bones - pathology; Bone and Bones - physiopathology; Bone Density Conservation Agents - administration & dosage; Dentistry; DENTISTRY, ORAL SURGERY & MEDICINE; Female; Ovariectomy; Rats; Rats, Wistar; Thiophenes - administration & dosage; strontium ranelate; Bone tissue; alendronate; Strontium ranelate; Ranelato de estroncio; Alendronate; Tejido óseo; Alendronato
• ISSN: 1852-4834; 1852-4834

Bisphosphonates are the first choice therapy for the pharmaco logical treatment of osteoporosis. Following reports of cases of bisphosphonaterelated osteonecrosis of the jaw and atypical femur fracture, the safety of longterm use of bisphosphonates has been evaluated, resulting in the proposal of strontium as an alternative drug. No experimental study using a sequential administration design has been reported to date. Hence, the aim of this study was to evaluate the effect on bone tissue of ovariectomized rats of administration of alendronate followed by strontium ranelate. Fortyeight female Wistar rats were ovariectomized on day 1 of the experiment. Beginning on day 30, they were administered 0.3 mg/kg/week of alendronate (ALN) or vehicle (VEH) for 8 weeks. Two groups (ALN and corresponding control) were euthanized at this time, and the remaining animals were divided into 4 groups and given 290 mg/kg/day of strontium ranelate (SR) in their drinking water (TW) or only water for 4 months. Experimental groups were: ALN+SR, ALN+TW, VEH+SR, VEH+TW, ALN and VEH. The tibiae and hemimandibles were resected for histomorphometric evaluation, and the right femur was used to perform biomechanical studies. ANOVA and Bonferroni test were applied. Diaphyseal stiffness, maximum elastic load and fracture load increased in animals that received alendronate, regardless of whether or not they received subsequent SR treatment. Fracture load also increased in VEH+ SR versus control (VEH+TW). Subchondral and interradicular bone volumes were significantly higher in animals that received ALN than in those that received vehicle. No difference was observed in cortical area or thickness of the tibia among treatments. The results obtained with the model presented here, evaluating tibial and mandibular interradicular bone, showed that the combination of ALN and SR and administration of ALN alone are equally effective in preventing bone loss associated with ovariectomyinduced estrogen depletion.