Pharmacological Topics of Bone Metabolism: Recent Advances in Pharmacological Management of Osteoporosis

Suzuki, Atsushi; Sekiguchi, Sahoko; Asano, Shogo; Itoh, Mitsuyasu

doi:10.1254/jphs.fm0070218

Cited by 27 publications

(20 citation statements)

References 42 publications

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“…Postmenopausal women generally lose bone due to diminished ovarian estrogen and a subsequent increase in bone resorption (32,48). Previous studies have shown that inflammatory cytokines such as interleukin (IL)-1 and prostaglandin E 2 (PGE 2 ) may be involved in the mechanism of bone loss attributable to estrogen insufficiency (49e51).…”

Section: Discussionmentioning

confidence: 99%

3,3′-Diindolylmethane increases bone mass by suppressing osteoclastic bone resorption in mice

Pang

Yang

2015

Journal of Pharmacological Sciences

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3,3'-Diindolylmethane (DIM), a major acid-condensation product or metabolite of indole-3-carbinol which is found in cruciferous vegetables, has been shown to have anticancer, anti-inflammatory, and multiple immune stimulating effects. However, its function in bone metabolism is poorly understood. This study evaluated the effect of DIM on bone mass in mice under physiological and pathological conditions. Eight-week-old female mice received injections of a vehicle or 0.1mg/g of DIM, twice a week for four weeks. We found that DIM treatment significantly increased bone mass as assessed by dual-energy X-ray absorptiometry (DEXA) and micro-computed tomography (μCT). Further, Bone histomorphometric analyses showed that this treatment significantly reduced bone resorption parameters, but did not increase bone formation parameters. Furthermore, we use ovariectomized (OVX)-induced osteoporotic mouse model, and explore function of DIM in skeletal pathological processes. Bone phenotype analyses revealed that the administration of DIM in this study effectively prevented OVX-induced bone loss resulting from increased bone resorption. Our results demonstrated that DIM increased bone mass by suppressing osteoclastic bone resorption in bone metabolism under both physiological and pathological conditions. Accordingly, DIM may be of value in the treatment and the possible prevention of bone diseases characterized by bone loss, such as postmenopausal osteoporosis.

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Section: Discussionmentioning

confidence: 99%

3,3′-Diindolylmethane increases bone mass by suppressing osteoclastic bone resorption in mice

Pang

Yang

2015

Journal of Pharmacological Sciences

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“…The proper balance between bone formation and resorption is regulated by various hormones and cytokines that modulate bone metabolism. If this balance is disrupted, metabolic bone diseases such as osteoporosis and osteopetrosis result (4,5). Osteoclasts are members of the monocyte/macrophage lineage and are formed by fusion of their mononuclear cellular precursors.…”

Section: Introductionmentioning

confidence: 99%

Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells

et al. 2011

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Abstract.Recent research has shown that platinum nanoparticles (nano-Pt) efficiently quench reactive oxygen species (ROS) as a reducing catalyst. ROS have been suggested to regulate receptor activator of NF-κB ligand (RANKL)-stimulated osteoclast differentiation. In the present study, we examined the direct effects of platinum nano-Pt on RANKL-induced osteoclast differentiation of murine pre-osteoclastic RAW 264.7 cells. The effect of the nano-Pt on the number of osteoclasts was measured and their effect on the mRNA expression for osteoclast differentiation was assayed using real-time PCR. Nano-Pt appeared to have a ROS-scavenging activity. Nano-Pt decreased the number of osteoclasts (2+ nuclei) and large osteoclasts (8+ nuclei) in a dose-dependent manner without affecting cell viability. In addition, this agent significantly blocked RANKL-induced mRNA expression of osteoclastic differentiation genes such as c-fms, NFATc1, NFATc2, and DC-STAMP as well as that of osteoclast-specific marker genes including MMP-9, Cath-K, CLC7, ATP6i, CTR, and TRAP. Although nano-Pt attenuated expression of the ROS-producing NOXfamily oxidases, Nox1 and Nox4, they up-regulated expression of Nox2, the major Nox enzyme in macrophages. These findings suggest that the nano-Pt inhibit RANKL-stimulated osteoclast differentiation via their ROS scavenging property. The use of nano-Pt as scavengers of ROS that is generated by RANKL may be a novel and innovative therapy for bone diseases.

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“…Furthermore, the rapid increase in the elderly population means that the prevention of osteoporotic fracture is a socioeconomic priority [Suzuki et al 2008]. …”

Section: Introductionmentioning

confidence: 99%

Strontium ranelate: long-term efficacy against vertebral, nonvertebral and hip fractures in patients with postmenopausal osteoporosis

Reginster

Hiligsmann

Bruyère

2010

Therapeutic Advances in Musculoskeletal

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Osteoporosis treatments need to combine an unequivocally demonstrated reduction of fractures, at various skeletal sites, long-term safety, and a user-friendly profile, optimizing therapeutic adherence. Strontium ranelate is the first compound to simultaneously decrease bone resorption and stimulate bone formation. Its antifracture efficacy, at various skeletal sites, has been established up to 8 years, through studies of the highest methodological standards. Increases in bone mineral density, observed after 1 year of treatment, are predictive of the long-term fracture efficacy, hence suggesting, for the first time in osteoporosis, that bone densitometry can be used as a monitoring tool for both efficacy and compliance. Owing to a positive benefit/risk ratio, strontium ranelate may now be considered as a first-line treatment in the management of osteoporosis.

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Pharmacological Topics of Bone Metabolism: Recent Advances in Pharmacological Management of Osteoporosis

Cited by 27 publications

References 42 publications

3,3′-Diindolylmethane increases bone mass by suppressing osteoclastic bone resorption in mice

3,3′-Diindolylmethane increases bone mass by suppressing osteoclastic bone resorption in mice

Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells

Strontium ranelate: long-term efficacy against vertebral, nonvertebral and hip fractures in patients with postmenopausal osteoporosis

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