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Review
. 2024 Jul 23;12(8):1635.
doi: 10.3390/biomedicines12081635.

Mechanistic Insights and Therapeutic Strategies in Osteoporosis: A Comprehensive Review

Nyruz Ramadan Elahmer  1   2 , Sok Kuan Wong  1 , Norazlina Mohamed  1 , Ekram Alias  3 , Kok-Yong Chin  1 , Norliza Muhammad  1
Affiliations
Review

Mechanistic Insights and Therapeutic Strategies in Osteoporosis: A Comprehensive Review

Nyruz Ramadan Elahmer et al. Biomedicines. .

Abstract

Osteoporosis, a metabolic bone disorder characterized by decreased bone mass per unit volume, poses a significant global health burden due to its association with heightened fracture risk and adverse impacts on patients' quality of life. This review synthesizes the current understanding of the pathophysiological mechanisms underlying osteoporosis, with a focus on key regulatory pathways governing osteoblast and osteoclast activities. These pathways include RANK/RANKL/OPG, Wingless-int (Wnt)/β-catenin, and Jagged1/Notch1 signaling, alongside the involvement of parathyroid hormone (PTH) signaling, cytokine networks, and kynurenine in bone remodeling. Pharmacotherapeutic interventions targeting these pathways play a pivotal role in osteoporosis management. Anti-resorptive agents, such as bisphosphonates, estrogen replacement therapy/hormone replacement therapy (ERT/HRT), selective estrogen receptor modulators (SERMs), calcitonin, anti-RANKL antibodies, and cathepsin K inhibitors, aim to mitigate bone resorption. Conversely, anabolic agents, including PTH and anti-sclerostin drugs, stimulate bone formation. In addition to pharmacotherapy, nutritional supplementation with calcium, vitamin D, and vitamin K2 holds promise for osteoporosis prevention. However, despite the availability of therapeutic options, a substantial proportion of osteoporotic patients remain untreated, highlighting the need for improved clinical management strategies. This comprehensive review aims to provide clinicians and researchers with a mechanistic understanding of osteoporosis pathogenesis and the therapeutic mechanisms of existing medications. By elucidating these insights, this review seeks to inform evidence-based decision-making and optimize therapeutic outcomes for patients with osteoporosis.

Keywords: Notch receptors; RANKL; Wnt; bone remodeling; cytokines; osteoblast; osteoclast; osteoporosis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The cellular mechanisms responsible for the control of bone remodeling process.
Figure 2
Figure 2
RANK/RANKL/OPG signaling pathway.
Figure 3
Figure 3
Wnt/β-catenin signaling pathway.
Figure 4
Figure 4
Jagged1/Notch1 signaling pathway.
Figure 5
Figure 5
Parathyroid hormone PTH signaling pathway.
Figure 6
Figure 6
Kynurenine (KYN) pathway.
Figure 7
Figure 7
Bisphosphonates’ chemical structure.
Figure 8
Figure 8
Bisphosphonates: nitrogen-containing and non-nitrogen-containing agents.
Figure 9
Figure 9
Mechanism of action of nitrogen-containing bisphosphonates.
Figure 10
Figure 10
Illustrates the integration between crucial pathways and pharmacological therapies of osteoporosis and their mechanism of action. PTH: parathyroid hormone, SR: strontium ranelate, ERT/HRT: estrogen replacement therapy/hormone replacement therapy, BPs: bisphosphonates.
See this image and copyright information in PMC

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