MicroRNA and Markers and Therapeutic Response to Romosozumab and Abaloparatide in Postmenopausal Osteoporosis

Status

Recruiting

Phase

Not applicable

Enrollment

42 participants (estimated)

Sponsor

Istituto Auxologico Italiano · Other

Design

Not randomized · Open label (no masking)

Countries

1 country

Italy

Start

31 Aug 2025

Primary completion

31 Aug 2029 (estimated)

Completion

31 Aug 2029 (estimated)

First posted

1 Jun 2026

Last update posted

1 Jun 2026

Conditions

Osteoporosis · Menopause

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.

• Experimental

  Romosozumab treatment

  Postmenopausal women treated with romosozumab for twelve months

• Experimental

  Abaloparatide treatment

  Postmenopausal women treated with abaloparatide for twelve months

1. miRNA expression profile

   Time frame · Baseline, 2, 6 and 12 months of treatment

   Registry description

   Expression profile of circulating miRNA correlated to osteoporosis

2. Bone Mineral Density

   Time frame · Baseline, 2, 6 and 12 months of treatment

   Registry description

   Bone Mineral Density (BMD), tested via a DEXA scan and expressed in T-score

No study cites this trial.