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

Abstract

Introduction: Strontium ranelate (SrRan) has the potential to interfere in the progression of osteoarthritis (OA), multifactorial disease associated with mechanical problems and articular inflammatory changes.Objectives: This study aimed to test the effects of prophylactic and therapeutic use of SrRan on clinical parameters of pain, the inflammatory process, and degradation of the articular cartilage.Methods: This was an experimental study, using a model of knee OA induced by intra-articular injection of monoiodoacetate. Thirty Wistar rats were divided into five groups and treated as indicated: control, without intervention; prophylactic, received SrRan at a daily oral dose of 250 mg/kg for 28 days before OA induction; SrRan treatments, administered 250 or 500 mg/kg/day for 28 days after the induction; and model control, received saline solution after the induction. Behavioral tests (joint incapacity, mechanical hyperalgesia, tactile sensitivity, and forced ambulation), histological evaluation of articular cartilage, and determination of inflammatory cytokines in the synovial fluid (interleukin [IL]-6, IL-10, tumor necrosis factor [TNF]-α, and interferon [INF]-γ) were performed.Results: Both prophylactic and therapeutic treatments improved the articular discomfort. A prophylactic dose of 500 mg/kg/day also improved mechanical hyperalgesia and the same dose was beneficial on tactile sensitivity. SrRan did not improve ambulation. Levels of IL-6, IL-10, TNF-α, and IFN-γ in SrRan-treated groups with OA were not significantly different compared with those in the normal control animals. The histopathological evaluation showed less articular damage in the SrRan-treated and control groups compared to the saline-treated group.Conclusion: The prophylactic and therapeutic administration of SrRan was associated with improved behavioral patterns of pain, especially joint discomfort. SrRan administration mitigated histological changes in the articular cartilage and reduced the inflammatory process, which beneficially reduced the progression of OA in the experimental model studied.

Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis

“…98 There are other antiresorptive agents (such as OPG, cathepsin K (CTSK) inhibitors and strontium ranelate) that may exert protective effects on subchondral bone and cartilage in animal models and serve as disease-modifying OA drugs for clinical treatment of OA. [99][100][101] Intriguingly, calcitonin, which is known for targeting subchondral bone remodelling, also leads to intracellular cAMP accumulation and then promotes chondrocyte anabolism by binding to its receptors on human OA chondrocytes. 102 Two phase III trials have reported a beneficial effect of bioactive oral calcitonin on joint pain and biochemical indicators of bone and cartilage degradation in patients with OA.…”

On the Amazing Reactivity of the Ranelate Ion: New Applications of an Old Antiosporotic Drug

“…Strontium ranelate, an old antiosporotic drug, [1,2] remains of great interest in bone healing, [3][4][5][6] dentistry [7][8][9] and several biological applications. [10][11][12][13][14][15][16] Despite its low toxicity, the drug was discontinued by the producer after the European Medicines Agency reported a slight increase (from 1.1 to 1.7% ) in cardiovascular events involving 7000 tested patients who used placebo or strontium ranelate, respectively.…”

Therapeutic Use of Scoparia dulcis Reduces the Progression of Experimental Osteoarthritis

“…A histopathological analysis of the synovial membrane and articular cartilage showed encouraging results, suggesting the possible efficacy of S. dulcis in the treatment of OA at the dose tested. Hyaline cartilage is the most relevant articular tissue in the pathogenesis of this disease [6]. Although OA is characterized by subchondral bone sclerosis, it is uncertain that bone changes are the cause or consequence of the lesions, given that the cartilage properties depend on the bone bed, which can be affected by the mechanical function of the cartilage [53].…”

“…Osteoarthritis (OA) is a chronic, complex disease characterized by loss, alteration and progressive degeneration of cartilage and subchondral bone; reduction of joint space; synovitis; pain, and formation of osteophytes [1,2]. OA mainly affects the joints that are given greater weight, such as the knees, [3] It alters an individual’s the quality of life [4,5], is the most frequent cause of musculoskeletal disease and pain [6,7], and impacts daily living and work activities [8].…”

“…There has been a constant search for substances that can be combined with conventional therapy for OA. Currently, conventional therapy consists of a combination of nonpharmacological measures such as aerobic exercises, weight loss, and joint protection techniques, as well as symptomatic pharmacological treatments including anti- inflammatory nonsteroidal analgesics and corticosteroids or local intra-articular lubricants until, eventually, surgical intervention is required [6].…”