Abaloparatide: A new pharmacological option for osteoporosis

Sleeman, Allyson; Clements, Jennifer N.

doi:10.1093/ajhp/zxy022

Cited by 58 publications

(26 citation statements)

References 10 publications

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“…However, their uses in long-term treatment are limited due to their adverse effects such as osteosarcoma, osteonecrosis of jaw, and atypical femur fractures 6 , 7 . Although there are various new drugs (Romosozumab 8 , Abaloparatide 9 , Cathepsin K inhibitors 10 , etc.) and novel therapeutic targets (Semaphorin 3A 11 , EphrinB2/EphB4 12 , etc.…”

Section: Introductionmentioning

confidence: 99%

Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations

Deng²,

et al. 2020

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Age-related osteoporosis is characterized by the deterioration in bone volume and strength, partly due to the dysfunction of bone marrow mesenchymal stromal/stem cells (MSCs) during aging. Alpha-ketoglutarate (αKG) is an essential intermediate in the tricarboxylic acid (TCA) cycle. Studies have revealed that αKG extends the lifespan of worms and maintains the pluripotency of embryonic stem cells (ESCs). Here, we show that the administration of αKG increases the bone mass of aged mice, attenuates age-related bone loss, and accelerates bone regeneration of aged rodents. αKG ameliorates the senescence-associated (SA) phenotypes of bone marrow MSCs derived from aged mice, as well as promoting their proliferation, colony formation, migration, and osteogenic potential. Mechanistically, αKG decreases the accumulations of H3K9me3 and H3K27me3, and subsequently upregulates BMP signaling and Nanog expression. Collectively, our findings illuminate the role of αKG in rejuvenating MSCs and ameliorating age-related osteoporosis, with a promising therapeutic potential in age-related diseases.

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Section: Introductionmentioning

confidence: 99%

Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations

Deng²,

et al. 2020

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“…On the contrary, RG, a G-protein dependent receptor targeted by abaloparatide, reversibly binds to PTHrP with high affinity resulting in transient activation that maximizes initial bone formation while limiting late bone resorption and osteoclast differentiation [ Figure 1]. 22,23 The effectiveness of abaloparatide has been demonstrated in multiple rodent and primate studies. Varella et al demonstrated that long-term daily administration of abaloparatide resulted in dose-dependent gains in bone mass, bone architecture, and up to 2.7-fold greater peak load to failure over controls in the lumbar spine of ovariectomized osteopenic rats.…”

Section: Basic Sciencementioning

confidence: 99%

<p>Abaloparatide and the Spine: A Narrative Review</p>

Thompson¹,

Wanderman²,

Anderson³

et al. 2020

CIA

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Osteoporosis is a common and debilitating condition characterized by diminished bone mass and architecture leading to bone fragility. Antiresorptive medicines like bisphosphonates (and less commonly denosumab) are the typical first-line agents for the medical treatment of osteoporosis. However, newer anabolic agents have been shown to improve bone mass and architecture, as well as reduce fracture risk, to a greater degree than traditional antiresorptive therapies. Teriparatide (human recombinant parathyroid hormone (PTH) 1-34, Forteo, Ely Lilly, Indianapolis, IN), which was the first in class to be approved in the United States, is the most widely used anabolic osteoporosis medicine and has shown significant benefit over traditional antiresorptive therapies. However, abaloparatide (synthetic parathyroid-related peptide (PTHrP), Tymlos, Radius Health, Waltham, MA), the second drug in this family, has recently become available for use. In this narrative review, we review the mechanism, effects, and benefits of abaloparatide compared to alternative treatments as well as discuss the current literature in regard to its effect on osteoporosis-related complications in the spine.

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“…1,2 Previous studies have reported that no less than 18,000,000 people suffer from osteoporosis. [2][3][4] With developments in technology, the treatment for osteoporosis has been improved greatly. 5 However, gene modulation in osteoporosis still remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Osteoporosis is identified as a skeletal dysfunction with symptoms including decreased bone quality and decreased bone mass 1,2 . Previous studies have reported that no less than 18,000,000 people suffer from osteoporosis 2–4 . With developments in technology, the treatment for osteoporosis has been improved greatly 5 .…”

Section: Introductionmentioning

confidence: 99%

Circ‐SLC8A1 regulates osteoporosis through blocking the inhibitory effect of miR‐516b‐5p on AKAP2 expression

Lin

Zhong

Wei

et al. 2020

The Journal of Gene Medicine

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Background: Osteoporosis is a disease characterized by bone loss, imbalance of bone metabolism and destruction of trabecular microarchitecture. Circular RNAs (cir-cRNAs) have been revealed as important biological regulators in human diseases. The expression characteristics and mechanism of circRNAs in osteoporosis are unclear. Methods: The binding sites of miR-516b-5p on circ-SLC8A1 and AKAP2 mRNA were predicted using circAtlas (http://circatlas.biols.ac.cn) and miRDB (http://mirdb.org). Target sites of miR-516b-5p on circ-SLC8A1 and AKAP2 mRNA were confirmed by a dual luciferase assay. The relationship between miR-516b-5p and AKAP2 was determined by a quantitative reverse transcriptase-polymerase chain reaction. Alizarin red S staining and alkaline phosphatase staining were used to observe the level of osteogenic differentiation after transfection. Results: The first six circRNAs captured from the 30 circRNAs with highest expression in the bone marrow were examined in a mouse model of osteoporosis and the expression of circ-SLC8A1 was found to be significantly reduced in osteoporosis. Circ-SLC8A1 negatively regulated the expression of miR-516b-5p. Overexpression of circ-SLC8A1 blocked the inhibition of AKAP2 by miR-516b-5p. Conclusions: Circ-SLC8A1 blocks the inhibitory effect of miR-516b-5p on the downstream target gene AKAP2 and promotes osteoporosis. The findings of the present might help to provide a new strategy for the treatment of osteoporosis.

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Abaloparatide: A new pharmacological option for osteoporosis

Cited by 58 publications

References 10 publications

Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations

Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations

<p>Abaloparatide and the Spine: A Narrative Review</p>

Circ‐SLC8A1 regulates osteoporosis through blocking the inhibitory effect of miR‐516b‐5p on AKAP2 expression

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