MicroRNA and Markers and Therapeutic Response to Romosozumab and Abaloparatide in Postmenopausal Osteoporosis (ROMIRNA)

May 23, 2026 updated by: Istituto Auxologico Italiano

MicroRNA and Circulating Markers Predictive of the Therapeutic Response to Romosozumab and Abaloparatide Treatment in Women With Postmenopausal Osteoporosis

Osteoporosis is a systemic skeletal disorder affecting approximately 10% of individuals over 50 years of age. It is characterised by an increased risk of fragility fractures, which constitute a major source of morbidity, mortality, and healthcare burden worldwide.

A range of pharmacological therapies has been approved for osteoporosis, with demonstrated efficacy in reducing fracture risk. These include anabolic agents that stimulate osteoblast-mediated bone formation (teriparatide, abaloparatide), antiresorptive agents that inhibit osteoclast-driven bone resorption (bisphosphonates, denosumab), and dual-action agents such as romosozumab, which, through sclerostin inhibition, simultaneously enhances bone formation and suppresses resorption. In clinical practice, these agents are administered sequentially or in combination to optimise therapeutic outcomes.

The primary goal of anti-osteoporotic therapy is to reduce the risk of incident and subsequent fractures. In postmenopausal osteoporosis, this objective is closely linked to meaningful gains in bone mineral density (BMD), as measured by dual-energy X-ray absorptiometry (DEXA), with attainment of osteopenic ranges associated with low fracture probability (<15% for major osteoporotic fractures and <3% for hip fractures, according to FRAX). However, selecting the most effective therapeutic strategy remains challenging, as robust predictors of individual treatment response are lacking. Although bone turnover markers are widely used to monitor treatment effects, their value in predicting clinical outcomes is limited.

MicroRNAs (miRNAs) are small (~22 nucleotides), single-stranded, non-coding RNAs that regulate gene expression at the post-transcriptional level through binding to complementary sequences in target mRNAs. Circulating miRNAs are stabilised by association with proteins and extracellular vesicles, making them attractive candidates as biomarkers. Increasing evidence indicates that miRNAs play key roles in osteoblast and osteoclast differentiation, proliferation, and apoptosis, and distinct miRNA expression profiles have been associated with osteoporosis and fragility fractures.

An emerging area of interest is the interaction between osteoactive therapies and circulating miRNA signatures. To date, available data are largely limited to antiresorptive agents and teriparatide. No studies have yet addressed miRNA expression profiles in patients treated with romosozumab or abaloparatide.

Beyond miRNAs, additional molecular pathways implicated in osteoimmunological crosstalk and ageing are gaining attention as potential biomarkers. Nitric oxide (NO) plays a multifaceted role in bone homeostasis, inhibiting osteoclast activity while promoting osteoblast function. Reduced circulating NO levels have been identified as an independent predictor of osteoporotic fractures in postmenopausal women. Autophagy is increasingly recognised as a critical regulator of bone remodelling, influencing both osteoblastic and osteoclastic activity. Dysregulation of autophagic pathways disrupts bone homeostasis and contributes to bone loss. These processes are tightly controlled by complex molecular networks, including miRNAs, and are closely linked to lysosomal function. In this context, cathepsin K has emerged as a promising therapeutic target in osteoporosis.

The present study primarily aims to identify circulating microRNAs, whose early treatment-induced changes are predictive of the outcome of the therapy in terms of changes in BMD. Secondary, it aims to identify correlations of the changes in microRNAs serum concentrations with variations in biomarkers of bone metabolism as well as of aging.

The study enrols women with diagnosis of severe postmenopausal osteoporosis addressed to treatment with romosozumab or with abaloparatide. All women will be assessed at baseline and after 2, 6 and 12 months of treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

42

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
    • Lombardy
      • Miano, Lombardy, Italy, 20149
        • Recruiting
        • Istituto Auxologico Italiano IRCCS
        • Contact:
      • Milan, Lombardy, Italy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female sex
  • Postmenopause
  • Densitometric diagnosis of osteoporosis
  • Normal calcium diet
  • Supplement with cholecalciferol or calcifediol

Exclusion Criteria:

  • Premenopause
  • Chronic therapy with glucocorticosteroids, or other treatments that may affect bone metabolism
  • Diseases and conditions that may affect bone metabolism

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Romosozumab treatment
Postmenopausal women treated with romosozumab for twelve months
Diagnostic test: miRNA typing
Identification circulating miRNAs
Experimental: Abaloparatide treatment
Postmenopausal women treated with abaloparatide for twelve months
Diagnostic test: miRNA typing
Identification circulating miRNAs

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
miRNA expression profile
Time Frame: Baseline, 2, 6 and 12 months of treatment
Expression profile of circulating miRNA correlated to osteoporosis
Baseline, 2, 6 and 12 months of treatment
Bone Mineral Density
Time Frame: Baseline, 2, 6 and 12 months of treatment
Bone Mineral Density (BMD), tested via a DEXA scan and expressed in T-score
Baseline, 2, 6 and 12 months of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Auxologico Italiano

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 31, 2025

Primary Completion (Estimated)

August 31, 2029

Study Completion (Estimated)

August 31, 2029

Study Registration Dates

First Submitted

May 23, 2026

First Submitted That Met QC Criteria

May 23, 2026

First Posted (Actual)

June 1, 2026

Study Record Updates

Last Update Posted (Actual)

June 1, 2026

Last Update Submitted That Met QC Criteria

May 23, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 32C501

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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