Effects of strontium ranelate on wear particle‑induced aseptic loosening in female ovariectomized mice

Abstract

Aseptic loosening and menopause‑induced osteoporosis are caused by an imbalance between bone formation and osteolysis. With an aging population, the probability of simultaneous occurrence of such conditions in an elderly individual is increasing. Strontium ranelate (SR) is an anti‑osteoporosis drug that promotes bone formation and inhibits osteolysis. The present study compared the effects of SR with those of the traditional anti‑osteoporosis drug alendronate (ALN) using an ovariectomized mouse model of osteolysis. The degree of firmness of the prosthesis and the surrounding tissue was examined, a micro‑CT scan of the prosthesis and the surrounding tissue was performed, and the levels of inflammatory and osteogenic and osteoclast factors were examined. It was observed that treatment with SR and ALN improved the bond between the prosthesis and the surrounding bone tissue by reducing the degree of osteolysis, thus improving the quality of bone around the prosthesis. SR increased the secretion of osteocalcin, runt‑related transcription factor 2 and osteoprotegerin (OPG). It additionally decreased the expression of the receptor activator of nuclear factor‑κB ligand (RANKL) and consequently increased the protein ratio OPG/RANKL, whereas ALN exhibited the opposite effect. Furthermore, SR and ALN suppressed tumor necrosis factor‑α and interleukin‑1β production, with SR exerting a more marked effect. The present results demonstrate that SR and ALN may stimulate bone formation and inhibit bone resorption in the ovariectomized mouse model of wear particle‑mediated osteolysis, with SR demonstrating better effects compared with ALN.

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

“…Strontium ranelate, an old antiosporotic drug, remains of great interest in bone healing, dentistry and several biological applications . 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.…”

Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections In Vivo

“…Pull-out testing is frequently used in implant-associated infection in vivo models where the metallic or polymeric implant integrates with native bone for a period, dependent upon the animal species and age and the rate of bone remodeling . Upon completion of the study, tibial/femoral tissue is excised and fixed in PMMA bone cement and uniaxial tensile loading is used to determine the force required to remove the osseointegrated implant from the bone. ,− Push-out testing serves an analogous function to pull-out testing. Despite the similar goals of pull- and push-out studies it is challenging to compare interfacial shear strength values across studies.…”

“…Despite the similar goals of pull- and push-out studies it is challenging to compare interfacial shear strength values across studies. Specifically, a wide range of loading rates have been used in pull- and push-out testing, depending upon the species, from 0.0083 to 0.5 mm/s, which can influence the resultant interfacial pull-out strength. ,,− Calculation of interfacial shear strength from raw load–displacement plots is also highly variable. For example, some studies define interfacial shear strength as the peak force on the load–displacement plots when the implant is fully removed from the bone or the bone is fractured, while others interpret interfacial shear strength as the force resulting when the implant is only slightly displaced in the bone. ,, Interfacial strength can also vary based upon several factors including the geometry of the bone and the implant placement within the bone ( e.g.…”