**12. miRNAs as biomarkers**

Circulatory miRNAs that are available in the extracellular fluids, e.g., serum, plasma, tears, etc., are potent to be utilized as essential biomarkers in the bone associated issues. Circulatory miRNAs are generally secreted in the form of exosomes or microvesicles, and thus they are guarded against the action of nucleases. Blood plasma miRNAs have been reported as biomarkers in the diagnosis of Non-small-cell lung carcinoma stage I and II [98]. Further, miRNAs present in the human saliva have also been described as biomarkers during the menstrual cycle in women [99]. Serum biomarkers from the osteoporotic patients representing precise

**221**

**14. Conclusion**

**Table 5.**

*MicroRNAs as Next Generation Therapeutics in Osteoporosis*

**13. miRNA as potential new generation drugs**

drug development at the preclinical and clinical stages [104, 105].

miR-3 Mimic replacement Cancers including

miR-122 miR-122 Antisense

inhibitor

*List of few miRNAs which are presently in the development.*

**miRNA Drug format Disease Stage of clinical trial**

Let-7 Mimic Replacement Cancer Preclinical miR-103/105 miR-inhibitor Insulin resistance Preclinical miR-10b miR-10b inhibitor Glioblastoma Preclinical

RG-012 Anti-miR-21 Alport syndrome At the initiating stage of the

hepatocellular

HCV Phase II

phase II trial

Phase I

pathological condition may serve as crucial diagnostic tools in the clinical practice. Studies in the past years have depicted the relevance of extracellular miRNAs in the plasma or serum samples from the osteoporotic patients relative to healthy controls. miRNAs viz. hsa-miR-122-5p and hsa-miR-4516 have been documented as putative markers in the diagnosis of osteoporosis [100]. Similarly, in another study, miR-21, miR-23a, miR-24, miR-93 and miR-100 are highly upregulated in the serum of osteoporotic patients [101]. Even in the investigation of postmenopausal osteoporosis, miR-422 has been regarded as an essential biomarker gene [102]. Based on several validated studies, it can precisely be concluded that miRNAs may act as useful potential biomarkers in the examination of distinct medical implications,

miRNAs are emerging as promising drugs in the pharmaceutical market. They are endogenous and hence associated with less harmful events for the body. Employing miRNAs as therapeutic targets have one key benefit that nucleotide content of the miRNAs can be easily modified by chemicals for the improved pharmacokinetics and pharmacodynamics of the potential miRNA-based drugs. Besides, miRNA has the capability of targeting multiple genes at a time. Moreover, nowadays chemical locked nucleic acid modifications are present for addressing the issues related to the susceptibility of miRNAs to the intracellular nucleases. Likewise, phosphorothioate alteration is another way of improving the efficacy of miRNAs in the in vivo systems [103]. Recently FDA approved drug, Onpattro against polyneuropathy marks the foundation of RNAi technology-based medicines in the commercial space. **Table 5** describes a few miRNA-based therapeutic compounds that are on the success path of

In healthy body conditions, miRNAs are expected to assist in the maintenance of a regulated balance between the osteoblast-based bone-forming activity and osteoclast dependent bone-resorbing activity. This balance is dependent on the action of miRNAs on the biochemical signaling pathways operating inside the bone. While, during pathologies, the aberrant expression of the miRNAs due to misregulated

*DOI: http://dx.doi.org/10.5772/intechopen.91223*

including osteoporosis.

*MicroRNAs as Next Generation Therapeutics in Osteoporosis DOI: http://dx.doi.org/10.5772/intechopen.91223*

*Clinical Implementation of Bone Regeneration and Maintenance*

During osteoporosis, the balance between bone formation and bone elimination is disrupted [89]. Bone dissolution dominates the bone formation and thereby results in the weakened matrix and compromised bone strength. miRNA attempts to correct the imbalance and preserves the bone homeostasis towards bone development during the process of remodeling. miRNAs suppress the genes or proteins involved in the biological signaling pathway and hence aid the pathway to proceed in accurate and normal fashion [90]. This normalization of the pathway further facilitates the optimum differentiation of the mesenchymal stem cells to the osteoblastic lineage. In the past few years, several investigations have emerged which conveys the role of miRNAs in the prognosis and treatment of osteoporosis

> **Disease (osteoporotic models)**

mice

miR-7b miR-7b mimic OVX mice Augmented bone

at the bone marrow cavity in the femur)

femoral metaphysis critical size defect

BALB/c mice

**Effect Reference**

[91]

[92]

[93]

[71]

[94]

[95]

[96]

[97]

OVX mice Diminished bone resorption

and enhanced bone mass

Neutralized the loss of bone, better bone mass

and increased osteoblastogenesis

Improved bone microarchitecture

defect

volume

the tibia-defects

Sprague-Dawley rats Better bone regeneration in

OVX mice Improved bone strength

Healing of critical size

and increased bone mineralization

vascularization and bone

Reduced osteoclastogenesis

Circulatory miRNAs that are available in the extracellular fluids, e.g., serum, plasma, tears, etc., are potent to be utilized as essential biomarkers in the bone associated issues. Circulatory miRNAs are generally secreted in the form of exosomes or microvesicles, and thus they are guarded against the action of nucleases. Blood plasma miRNAs have been reported as biomarkers in the diagnosis of Non-small-cell lung carcinoma stage I and II [98]. Further, miRNAs present in the human saliva have also been described as biomarkers during the menstrual cycle in women [99]. Serum biomarkers from the osteoporotic patients representing precise

*Representation of the current studies where miRNAs are used as therapeutics in the treatment of osteoporosis.*

**11.1 miRNA-based therapeutics in osteoporosis**

(**Table 4**).

**miRNA Treatment: gain/**

miR-148a Loss of

**loss of function of the miRNA**

function using AntagomiR-148a

miR-103a AntagomiR-103a Hindlimb unloaded

miR-31a-5p AnatgomiR-31a-5p Aged rats (Injections

miR-1187 Anti-miR-1187 Ovariectomized

miR-214 miR-214 sponges OVX rat with

using miR-451a mimic

**220**

**Table 4.**

**12. miRNAs as biomarkers**

miR-199a-5p miR-199a-5p

agomiR

miR-451a Gain of function

pathological condition may serve as crucial diagnostic tools in the clinical practice. Studies in the past years have depicted the relevance of extracellular miRNAs in the plasma or serum samples from the osteoporotic patients relative to healthy controls. miRNAs viz. hsa-miR-122-5p and hsa-miR-4516 have been documented as putative markers in the diagnosis of osteoporosis [100]. Similarly, in another study, miR-21, miR-23a, miR-24, miR-93 and miR-100 are highly upregulated in the serum of osteoporotic patients [101]. Even in the investigation of postmenopausal osteoporosis, miR-422 has been regarded as an essential biomarker gene [102]. Based on several validated studies, it can precisely be concluded that miRNAs may act as useful potential biomarkers in the examination of distinct medical implications, including osteoporosis.
