Emerging therapeutic targets for osteoporosis

Gennari, Luigi; Merlotti, Daniela; Falchetti, Alberto; Vainicher, Cristina Eller; Cosso, Roberta; Chiodini, Iacopo

doi:10.1080/14728222.2020.1726889

Cited by 20 publications

(20 citation statements)

References 169 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 15 ] The prevalence of osteoporosis and its sequelae is rising substantially as a consequence of the increased life expectancy, becoming one of the largest global healthcare burdens. [ 16 , 17 ] The osteoporosis treatments mainly enclose orally administrated tablets or capsules (some bisphosphonates), subcutaneous injections (teriparatide) or intravenous perfusions (zoledronate), among others. [ 15 , 18 ] While these conventional drugs are effective, they present some limitations and side effects, such as osteonecrosis of the jaw or increased risk of breast cancer, which restrict their long‐term administration and adherence.…”

Section: Introductionmentioning

confidence: 99%

Osteoporosis Remission and New Bone Formation with Mesoporous Silica Nanoparticles

et al. 2021

View full text Add to dashboard Cite

Nanotechnology changed the concept of treatment for a variety of diseases, producing a huge impact regarding drug and gene delivery. Among the different targeted diseases, osteoporosis has devastating clinical and economic consequences. Since current osteoporosis treatments present several side effects, new treatment approaches are needed. Recently, the application of small interfering RNA (siRNA) has become a promising alternative. Wnt/β‐catenin signaling pathway controls bone development and formation. This pathway is negatively regulated by sclerostin, which knock‐down through siRNA application would potentially promote bone formation. However, the major bottleneck for siRNA‐based treatments is the necessity of a delivery vector, bringing nanotechnology as a potential solution. Among the available nanocarriers, mesoporous silica nanoparticles (MSNs) have attracted great attention for intracellular delivery of siRNAs. The mesoporous structure of MSNs permits the delivery of siRNAs together with another biomolecule, achieving a combination therapy. Here, the effectiveness of a new potential osteoporosis treatment based on MSNs is evaluated. The proposed system is effective in delivering SOST siRNA and osteostatin through systemic injection to bone tissue. The nanoparticle administration produced an increase expression of osteogenic related genes improving the bone microarchitecture. The treated osteoporotic mice recovered values of a healthy situation approaching to osteoporosis remission.

show abstract

Section: Introductionmentioning

confidence: 99%

Osteoporosis Remission and New Bone Formation with Mesoporous Silica Nanoparticles

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The Wnt signaling enters into many biological processes, including embryogenesis, postnatal development, and tissue homeostasis in adults [37]. More recently, the Wnt signaling also revealed a regulatory role in bone formation and healing [38], so that proteins as sclerostin, LRP5/6, and Dickkopf-related protein 1 (Dkk-1), which are crucial actors of this signaling pathway, have been the targets of randomized clinical trials (RCTs) for the development of anti-fracture therapies [39]. Studies in animal models confirmed a reduced mineralization rate and a reduced trabecular bone volume in T2DM subjects, probably due to the decreased RUNX2 gene expression and reduction of OC, OPG, BMP-2, and ALP expression [18,[40][41][42][43][44].…”

Section: The Role Of Wingless-type Mouse Mammary Virus Integration Simentioning

confidence: 99%

Energy Metabolism and Ketogenic Diets: What about the Skeletal Health? A Narrative Review and a Prospective Vision for Planning Clinical Trials on this Issue

Merlotti

Cosso

Eller-Vainicher

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

The existence of a common mesenchymal cell progenitor shared by bone, skeletal muscle, and adipocytes cell progenitors, makes the role of the skeleton in energy metabolism no longer surprising. Thus, bone fragility could also be seen as a consequence of a “poor” quality in nutrition. Ketogenic diet was originally proven to be effective in epilepsy, and long-term follow-up studies on epileptic children undergoing a ketogenic diet reported an increased incidence of bone fractures and decreased bone mineral density. However, the causes of such negative impacts on bone health have to be better defined. In these subjects, the concomitant use of antiepileptic drugs and the reduced mobilization may partly explain the negative effects on bone health, but little is known about the effects of diet itself, and/or generic alterations in vitamin D and/or impaired growth factor production. Despite these remarks, clinical studies were adequately designed to investigate bone health are scarce and bone health related aspects are not included among the various metabolic pathologies positively influenced by ketogenic diets. Here, we provide not only a narrative review on this issue, but also practical advice to design and implement clinical studies on ketogenic nutritional regimens and bone health outcomes. Perspectives on ketogenic regimens, microbiota, microRNAs, and bone health are also included.

show abstract

“…( 2 ) BMD is highly heritable, with genome‐wide–association studies (GWASs) having already identified hundreds of loci associated with disease risk in both adults ( 1 , 3 ) and children. ( 4 , 5 ) Although some progress has been made in recent years with the development of new methods to treat osteoporosis, 6 , 7 ) functional investigation of BMD loci identified by GWASs should reveal target genes that represent potentially novel therapeutic avenues for prevention and treatment of this debilitating disease.…”

Section: Introductionmentioning

confidence: 99%

CRISPR‐Cas9–Mediated Genome Editing Confirms EPDR1 as an Effector Gene at the BMD GWAS‐Implicated ‘STARD3NL’ Locus

et al. 2021

View full text Add to dashboard Cite

show abstract

Emerging therapeutic targets for osteoporosis

Cited by 20 publications

References 169 publications

Osteoporosis Remission and New Bone Formation with Mesoporous Silica Nanoparticles

Osteoporosis Remission and New Bone Formation with Mesoporous Silica Nanoparticles

Energy Metabolism and Ketogenic Diets: What about the Skeletal Health? A Narrative Review and a Prospective Vision for Planning Clinical Trials on this Issue

CRISPR‐Cas9–Mediated Genome Editing Confirms EPDR1 as an Effector Gene at the BMD GWAS‐Implicated ‘STARD3NL’ Locus

Contact Info

Product

Resources

About