The effect of ovariectomy and 2 antiresorptive therapeutic agents on bone response in rats: A 3-dimensional imaging analysis Priscilla Coutinho Romualdo, PhD, a Nayane Barbosa Fernandes Furlanetto Cunha, DDS, a Graziela Bianchi Leoni, PhD, b Manoel Damião Sousa-Neto, PhD, b Alberto Consolaro, PhD, c Alexandra Mussolino de Queiroz, PhD, a Raquel Assed Bezerra da Silva, PhD, a Lea Assed Bezerra da Silva, PhD, a and Paulo Nelson-Filho, PhD a Objective. The aim of this study was to evaluate bone mineral density (BMD) and microarchitecture in femurs and maxillary bones of ovariectomized (OVX) rats treated or not treated with alendronate (ALD) or odanacatib (ODN). Study Design. Twenty rats were divided into groups: SHAM, OVX, OVX/ALD, and OVX/ODN.After 12 weeks, the femurs and maxillae were removed and subjected to 3-dimensional analysis by micro–computed tomography. Results were analyzed with 1-way analysis of variance and Tukey’s post hoc test (α = 0.05). Results. OVX decreased maxillary and femoral BMD and altered femoral microarchitecture (P < .05). The drugs increased BMD of both types of bones, but only ALD maintained the phenotype similar to the SHAM group. The action of ALD was limited to the femoral trabecular separation (Tb.Sp). OVX and the drugs had no effect on the microarchitecture of the maxilla (P > .05). Conclusions. ALD and ODN therapy increased BMD in both bones after ovariectomy. ALD was more successful than ODN in preserving the morphology of bone similar to the SHAM group. ALD maintained the phenotype for Tb.Sp in the femur, but ODN did not. In the maxillae, neither ovariectomy nor the 2 antiresorptive drugs had significant effects on microarchitecture. (Oral Surg Oral Med Oral Pathol Oral Radiol 2018;■■:■■–■■) Osteoporosis is a metabolic bone disease characterized by decrease of bone mineral density (BMD), leading to skeletal fragility and increased risk of fractures. 1,2 Studies evaluating osteoporosis and the therapeutic agents for the prevention and treatment of this disease often use ovari- ectomized rats as an experimental model, approved by the U.S. Food and Drug Administration, to mimic post- menopausal conditions, such as reduced BMD. 3 Micro– computed tomography (micro-CT) is considered the gold standard to evaluate bone morphology and microarchitecture in rodents and other animal models, presenting excellent reproducibility and accuracy. 4,5 The effect of osteoporosis on BMD and the microarchitecture of maxillary bones has been studied, but the results are still controversial. 6,7 There have been reports of a decrease in BMD after ovariectomy (OVX) in rats, with differences of results depending on the type of bone. Long bones and vertebrae are more sensitive than maxillary bones to the estrogen deficiency that occurs after OVX. 8 Some studies have shown that maxillary bones are minimally affected by OVX, 8-10 whereas some others have demonstrated changes in alveolar bone po- rosity, with a resulting decrease in BMD in the mandibles of ovariectomized rats. 7,11 In addition, there are large dis- crepancies among the studies using ovariectomized rats 8 with regard to animal age at the time of surgery, type of bone, and duration of the experimental period. The prevention and treatment of bone loss and osteo- porosis after menopause is of utmost importance in maintaining bone integrity and preventing possible fractures. 12 Bisphosphonates are the first-choice drugs for the pharmacologic treatment of osteoporosis. 13 Alendronate (ALD), a bisphosphonate containing nitro- gen, is considered a drug capable of preventing bone loss induced by estrogen deficiency 12,14 and is associated with increased BMD and reduced risk of fracture. 15 However, an association between the systemic use of alendronate and a high incidence of osteonecrosis of the jaw has been suggested. 16 Therefore, there is an urgent need to develop new potential alternative antiresorptive agents, 17 with the mechanism of action based on the inhibition of bone resorption. Odanacatib (ODN) is an antiresorptive drug that acts specifically on the inhibition of cathepsin K, an enzyme secreted by osteoclasts that degrades type I collagen. ODN has been shown to increase BMD of the spine and hips, 18 as well as the radius and tibia, 19 and has the ability to reduce bone resorption without decreasing the number of osteoclasts and preserving bone formation. 20 ODN leaves the osteoclasts alive and unaffected but inhibits bone resorption by inhibiting cathepsin K activity. 21 The mechanisms by which cathepsin K inhibition increases This work was supported by the São Paulo Research Foundation (FAPESP) grant 2013/18231-9 and 2014/13238-8. a Department of Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. b Department of Restorative Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. c Department of Oral Pathology, Bauru Dental School, University of São Paulo, Bauru, SP, Brazil. Received for publication Nov 28, 2017; returned for revision Mar 14, 2018; accepted for publication Apr 6, 2018. © 2018 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter https://doi.org/10.1016/j.oooo.2018.04.002 Vol. ■■ No. ■■ ■■ 2018 1 ARTICLE IN PRESS