The Effect of Strontium Ranelate on Fracture Healing: An Animal Study

Luo

et al. 2023

MedComm

Osteoporosis is a type of bone loss disease characterized by a reduction in bone mass and microarchitectural deterioration of bone tissue. With the intensification of global aging, this disease is now regarded as one of the major public health problems that often leads to unbearable pain, risk of bone fractures, and even death, causing an enormous burden at both the human and socioeconomic layers. Classic anti‐osteoporosis pharmacological options include anti‐resorptive and anabolic agents, whose ability to improve bone mineral density and resist bone fracture is being gradually confirmed. However, long‐term or high‐frequency use of these drugs may bring some side effects and adverse reactions. Therefore, an increasing number of studies are devoted to finding new pathogenesis or potential therapeutic targets of osteoporosis, and it is of great importance to comprehensively recognize osteoporosis and develop viable and efficient therapeutic approaches. In this study, we systematically reviewed literatures and clinical evidences to both mechanistically and clinically demonstrate the state‐of‐art advances in osteoporosis. This work will endow readers with the mechanistical advances and clinical knowledge of osteoporosis and furthermore present the most updated anti‐osteoporosis therapies.

Section: Anti‐osteoporosis Therapiesmentioning

confidence: 99%

Section: Strontium Saltmentioning

confidence: 99%

Mechanistic advances in osteoporosis and anti‐osteoporosis therapies

Luo

et al. 2023

MedComm

“…The results of the meta-analysis demonstrated that the administration of Sr ranelate (SrRa) is associated with a 31% and 40% decrease in osteoporotic fractures and vertebral fractures in postmenopausal osteoporosis cases, respectively [ 267 ]. Sr ranelate was also shown to promote bone fracture healing [ 268 ]. However, SrRa did not improve wrist fracture healing in advanced-age Italians suffering from wrist fracture, while being administered during the acute phase [ 269 ].…”

Section: Strontium (Sr)mentioning

confidence: 99%

The Role of Trace Elements and Minerals in Osteoporosis: A Review of Epidemiological and Laboratory Findings

et al. 2023

The objective of the present study was to review recent epidemiological and clinical data on the association between selected minerals and trace elements and osteoporosis, as well as to discuss the molecular mechanisms underlying these associations. We have performed a search in the PubMed-Medline and Google Scholar databases using the MeSH terms “osteoporosis”, “osteogenesis”, “osteoblast”, “osteoclast”, and “osteocyte” in association with the names of particular trace elements and minerals through 21 March 2023. The data demonstrate that physiological and nutritional levels of trace elements and minerals promote osteogenic differentiation through the up-regulation of BMP-2 and Wnt/β-catenin signaling, as well as other pathways. miRNA and epigenetic effects were also involved in the regulation of the osteogenic effects of trace minerals. The antiresorptive effect of trace elements and minerals was associated with the inhibition of osteoclastogenesis. At the same time, the effect of trace elements and minerals on bone health appeared to be dose-dependent with low doses promoting an osteogenic effect, whereas high doses exerted opposite effects which promoted bone resorption and impaired bone formation. Concomitant with the results of the laboratory studies, several clinical trials and epidemiological studies demonstrated that supplementation with Zn, Mg, F, and Sr may improve bone quality, thus inducing antiosteoporotic effects.

“…The unique dual action of SRR on bone metabolism is attributed to its ability to influence osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells) activities [14]. This equilibrium not only enhances bone mineral density but also reduces the risk of fractures, a frequent complication of osteoporosis [15]. Transitioning to the context of intervertebral discs, the health and integrity of the adjacent vertebral bones play a significant role in determining disc health.…”

Section: Ivyspringmentioning

confidence: 99%

Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis

Sun,

Zhu,

Sun

et al. 2023

Int. J. Med. Sci.

Intervertebral disc degeneration (IVDD) is a prevalent and debilitating condition characterized by chronic back pain and reduced quality of life. Strontium ranelate (SRR) is a compound traditionally used for treating osteoporosis via activating TGF-β1 signaling pathway. Recent studies have proved the anti-inflammatory effect of SRR on chondrocytes. Although the exact mechanism of IVDD remains unclear, accumulating evidences have emphasized the involvement of multifactorial pathogenesis including inflammation, oxidative stress damage, and etc. However, the biological effect of SRR on IVDD and its molecular mechanism has not been investigated. Firstly, this study proved the decreased expression of Transforming Growth Factor-beta 1(TGF-β1) in degenerated human intervertebral disc tissues. Subsequently, we confirmed for the first time that SRR could promote cell proliferation, mitigate inflammation and oxidative stress in human nucleus pulposus cells in vitro via increasing the expression of TGF-β1 and suppressing the Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) pathway. The molecular docking result proved the interaction between SRR and TGF-β1 protein. To further verify this interaction, gain- and loss- of function experiments were conducted. We discovered that both TGF-β1 knockdown and overexpression influenced the activation of the NF-κB pathway. Taken together, SRR could mitigate IL-1β induced-cell dysfunction in human nucleus pulposus cells by regulating TGF-β1/NF-κB axis in vitro . Finally, the in vivo therapeutic effect of SRR on IVDD was confirmed. Our findings may contribute to the understanding of the complex interplay between inflammation and degenerative processes in the intervertebral disc and provide valuable insights into the development of targeted treatment-based therapeutics for IVDD.