Resumen de Investigating the Effects of Systemically Administered Strontium Ranelate on Alveolar Bone Loss Histomorphometrically and Histopathologically on Experimental Periodontitis in Rats
Nebi Cansın Karakan, Aysun Akpınar, Fahrettin Göze, Ömer Poyraz
Background: The aim of this study is to investigate effects of strontium ranelate (SR) on alveolar bone loss (ABL) in rats with experimental periodontitis.
Methods: Forty Wistar rats were randomly divided into five groups: 1) control (n = 8); 2) ligated (n = 8); 3) 300 mg/kg SR (SR300, n = 8); 4) 625 mg/kg SR (SR625, n = 8); and 5) 900 mg/kg SR (SR900, n = 8). To create experimental periodontitis, 4/0 silk ligatures were inserted submarginally around first molars at the right mandible. After 11 days, rats were sacrificed. ABL was calculated by measuring cemento-enamel junction and alveolar crest distance. Interleukin (IL)-1β, osteoprotegerin (OPG), and bone-specific alkaline phosphatase (BALP) serum levels were determined by enzyme-linked immunosorbent assay. Histopathologic analysis was used to evaluate inflammatory cell infiltration, numbers of osteoblasts and osteoclasts, and receptor activator of nuclear factor-kappa B ligand (RANKL) activity.
Results: ABL was significantly lower in SR900 group than in the ligated group (P <0.05). Osteoclast numbers in ligated group were significantly higher than in the control, SR300, and SR900 groups (P <0.05). In ligated, SR625, and SR900 groups, significantly higher osteoblast numbers were detected than in control group (P <0.05). Osteoblast numbers in SR625 group were significantly higher than in the SR300 group (P <0.05). RANKL activities in SR900 and control groups were close to each other (P >0.05). Serum IL-1β, OPG, and BALP levels revealed no significant difference (P >0.05).
Conclusion: It can be concluded that SR can reduce RANKL activity and osteoclast numbers, as well as ABL.
Periodontitis is a chronic, multifactorial, and inflammatory disease of periodontal tissues characterized as a non-reversible and destructive process. Tooth mobility and loss may occur when the disease is not treated.1,2 Several mechanisms have a role in the etiology of periodontitis. However, periodontal tissue destruction is caused by microbial dental plaque that initiates immunoinflammatory host response.3 Microbial dental plaque is not sufficient for initiating periodontal tissue destruction. There must be adequate concentrations of periodontopathogens in the microbial dental plaque. Supragingival and subgingival microbial plaque includes different bacteria species. In a subgingival plaque sample, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Tannerella forsythia, Campylobacter rectus, Eikenella corrodens, Treponema denticola, and spirochetes were found to be related to periodontitis and termed “periodontal pathogens.”2,3 Bacteria species must overcome a number of host defense mechanisms and must be present in tissues at adequate concentrations. Host response mechanisms to periodontal pathogens are thought to cause periodontal tissue destruction as well as alveolar bone resorption.2,3 Periodontal tissue destruction begins with host response to periodontal pathogens via inflammatory cells and inflammatory mediators.4 Interleukin (IL)-1β and tumor necrosis factor (TNF)-α are common proinflammatory mediators that lead to periodontal tissue damage via decreasing osteoprotegerin (OPG) expression and increasing receptor activator of nuclear factor-kappa B ligand (RANKL) expression.5 Consequently, periodontal tissue destruction and alveolar bone resorption occur.5,6 OPG has an important role in reacting to inhibition of bone resorption. OPG binds on RANKL and inhibits RANK–RANKL connection.7,8 Bone-specific alkaline phosphatase (BALP) is a bone formation marker that improves bone mineralization, and levels of BALP are decreased in periodontitis. It is produced by osteoblasts and is related to early osteoblastic activities.9,10 In host response modulation, different agents such as non-steroidal anti-inflammatory drugs, doxycycline hyclate, and bisphosphonates are used.11 As antiosteoporotic drugs, bisphosphonates have effects on bone in terms of inhibiting osteoclastic activity. Hence, reduction of bone turnover and negative effects of these drugs on bone healing have been reported previously.8,12 Strontium is a soft, silver-white metallic element deposited mainly in areas where mineralization of new bone takes place, such as regions undergoing intramembranous or endochondral ossification.13 Strontium ranelate (SR) is a dual-acting agent that reduces bone resorption by reducing osteoclastic activity and stimulating bone formation by stimulating preosteoblast replication.14 This dual-acting mechanism of SR reveals a superiority to bisphosphonates. SR is mainly used as a therapeutic or prophylactic in patients who are osteoporotic.15,16 An SR molecule consists of one ranelic acid and two stable strontium atoms.17 Strontium is known as a divalent cation that has atomic and ionic properties related to calcium, as well as being involved in bone mineralization.18,19 SR is able to increase biomechanical and structural properties of bone such as mineral density.20 SR binds to hydroxyapatite crystal surfaces such as calcium and has a critical role in bone mineralization process.19 There are two possible mechanisms of action presented in literature about SR:21 1) activating calcium-sensing receptor or another cation-sensing receptor; and 2) increasing expression of OPG in addition to decreasing RANKL expression by osteoblasts.
It has been stated that SR may be a calcium-sensing receptor agonist due to atomic and ionic properties related to calcium.21 Based on favorable aspects of SR, the authors hypothesized that SR may prevent alveolar bone loss (ABL) when it is used as an adjunct to mechanical therapy in periodontitis. In the literature, to the best of the authors’ knowledge, there are no studies examining effects of SR on periodontitis. The aim of the present study is to investigate the morphometric and histopathologic effects of different dosages of SR on ABL in rats with experimental periodontitis.
