Effect of strontium ranelate on pain behavior in an experimental model of osteoarthritis

Abstract

Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects of decreasing the risk of fractures and an indication of reducing the progression of osteoarthritis (OA). This study aimed to investigate the effects of SrRan as either a prophylactic or a treatment drug, using an OA rat model to assess pain behavior. A monoiodoacetate (MIA)-induced knee joint OA model in Wistar rats was used. Thirty Wistar rats (both sexes, 60 days old) were distributed in five groups of 6 rats each: the control group, that received no intervention; a prophylactic group, that received oral administration of 25 mg·kg-1·day-1 of SrRan for 28 days before induction of OA; a group treated with 25 mg·kg-1·day-1 of SrRan for 28 days after OA induction; a group treated with 50 mg·kg-1·day-1 during 28 days after OA induction; and a group that received oral saline for 28 days after induction. The assessment of pain behavior was performed considering articular incapacitation (weight-bearing test), mechanical hyperalgesia (Randall Selitto test) and motor activity (rotarod test), on days 0, 7, 14, 21, and 28. This experiment did not yield a significant difference when comparing the group that received SrRan prophylactically with the groups treated with 25 or 50 mg·kg-1·day-1 and the group that received oral saline. Thus, SrRan did not provide analgesia in either treated rats or as a prophylactic drug with the tested doses. Higher doses should be tested further to achieve possible significant results.

Prophylactic and Therapeutic Use of Strontium Ranelate Reduces the Progression of Experimental Osteoarthritis

“…A study performed using a different rat model of OA induced with zymosan, a potent inducer of cyclooxygenase (COX)-2 expression, used doses ranging from 30 to 300 mg/kg/day for a shorter period ( Nunes et al, 2015 ) and yielded similar results to those of this study. An experiment using much lower doses (25 and 50 mg/kg/day) and a method of OA induction similar to that used in the current study showed no reduction of joint incapacitation in animals treated prophylactically with SrRan or in those treated after the establishment of OA ( Rodrigues et al, 2017 ). Therefore, the present study was the first to identify the beneficial effects of the preventive use of SrRan on joint activity.…”

“…The benefit of the prophylactic use of SrRan was also verified by analyzing its effects on hyperalgesia induced by increasing the pressure on the rat’s paw, based on the fact that inflammation lowers the threshold of pain reactions. SrRan showed similar effects in other studies; however, these studies treated already established OA models and did not investigate the preventive effects ( Alves et al, 2017 ; Rodrigues et al, 2017 ).…”

“…Strontium ranelate (SrRan), an antiresorptive agent and bone proforming agent already proven effective in patients with severe osteoporosis, has been the subject of clinical and experimental studies in OA because of a probable effect on both bone turnover and inflammation associated with this disease ( Reginster et al, 2005 ; Reginster, 2014 ; Tenti et al, 2014 ; Rodrigues et al, 2017 ).…”

Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

“…The Brazilian National Agency of Sanitary Surveillance (ANVISA) and other regulatory agencies in Latin America, in turn, maintain SrRan registry for treatment of severe osteoporosis in men and women, especially in cases in which other anti-osteoporosis medications are inappropriate ( 58 ). Although there are still issues associated with adverse effects related to drug use, recent publications, still seeking a better understanding of the mechanisms involved in the action of SrRan, continue to aggregate important information about its clinical effects, as described in the present review ( 22 , 26 , 32 – 36 ).…”

“…In a recent survey of rats that had knee OA induced by intra-articular injection of MIA (sodium monoiodoacetate), prophylactic administration of SrRan at daily doses of 25 mg/kg and post-induction use of this drug at doses of 25 and 50 mg·kg −1 ·day −1 did not promote improvement in mechanical hyperalgesia (assessed by the Randall Selitto test), joint incapacitation (assessed by the weight-bearing test) and motor activity (assessed by the rotarod test) ( 22 ).…”