Clinical trial NCT06551155: Peripheral Mononuclear Cells to Screen, Monitor and Stratify the Population at Risk of Osteoporosis and Fractures
Official title: Identification, Monitoring, and Classification of Patients at Risk of Osteoporosis and Fractures Using a Method Based on the Use of Mononuclear Cells From Peripheral Blood
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Osteoporosis
Osteopenia
Osteoporosis Fracture
Keywords: peripheral blood mononuclear cells
screening
diagnosis
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliero Universitaria Policlinico G.Rodolico - San Marco
First posted: 2024-08-13
Enrollment: 120
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Healthy patients (at risk and undergoing periodic follow-up and/or attending outpatient visits for preventive screening), osteopenic patients, and those with osteoporosis (fractured and non-fractured) with an available DXA or, for fractured patients, a DXA prescribed as part of clinical practice, aged ≥ 40 years of both sexes, with a Body Mass Index (BMI) between 18.5 and 29.9.

Brief summary: Osteoporosis (OP) is one of most common age-associated and chronic metabolic bone diseases, featured by a decrease of bone mineral density (BMD) that increases the risk of bone fractures.OP guidelines agree that Dual-X-ray Absorptiometry (DXA) is the gold standard for BMD assessment, but for the different OP stages screening and diagnosis, BMD by itself is not an accurate predictor. Thus, OP is often misdiagnosed. Aim of the this study is to improve a tool for OP diagnosis based on the ability of circulating peripheral blood mononuclear cells (PBMCs) to maintain or not their in vitro viability (IRCCS Istituto Ortopedico Rizzoli European patent n.3008470 March 21, 2018) for the measurement of the different OP severity levels, also considering specific gender related differences.

Detailed description: Inadequate assessment, diagnosis, and stratification of patients with bone mass loss can lead to an increased risk of osteoporotic fractures. Therefore, alternative and advanced methods to support screening and diagnosis of osteoporosis (OP) are becoming increasingly essential, particularly considering specific gender differences. In this context, evaluating new methods and innovative techniques is a global challenge. To address this challenge, in 2018, the IRCCS Istituto Ortopedico Rizzoli (IOR) filed a European patent (European Patent No. 3008470, March 21, 2018; Inventors: Fini M, Giardino R, Salamanna F) related to an in vitro method for correlating the vitality of peripheral blood mononuclear cells (PBMCs) with bone metabolism alterations and OP through simple optical microscope observation. Additionally, specific gender-related differences have been observed in the number, size, differentiation time, and gene and protein expression profiles of PBMCs from osteoporotic patients of different sexes. In this context, the purpose of this study is to fully expand and develop the patent filed by IRCCS IOR in 2018 in order to: a) improve the understanding of the mechanisms of action and observed behavior in PBMCs on which the IOR patent is based; b) correlate the in vitro behavior of PBMCs with different levels of bone metabolism alteration (from osteopenia to fragility fractures); c) evaluate the correlation between the Dual-X-ray Absorptiometry (DXA) T-score and other blood factors related to OP (parameters related to platelets, pro- and anti-inflammatory cytokines, lymphocyte subpopulations) with the in vitro behavior of PBMCs in the presence of different levels of bone metabolism alteration, considering specific gender differences.

Eligibility criteria: Inclusion Criteria:

* Healthy patients (at risk and undergoing periodic follow-up and/or attending outpatient visits for preventive screening)
* Osteopenic patients with an available DXA
* Osteoporotic patients (fractured and non-fractured) with an available DXA or, for fractured patients, a DXA prescribed as part of clinical practice
* Aged ≥ 40 years of both sexes
* Body Mass Index (BMI) between 18.5 and 29.9

Exclusion Criteria:

* Hematopoietic system disorders (hemolytic, aplastic, and neoplastic anemias)
* Coagulation disorders (hereditary or secondary to other disorders)
* Infections (including HIV-HBV-HCV positivity)
* Neoplastic diseases (primary and/or secondary tumors)
* Pregnancy or breastfeeding
* Alcohol consumption (\>20 g of alcohol per day currently or in the past)
* Smoking (\>10 cigarettes per day, currently or in the past)
* Diabetes
* Treatment with therapeutic agents that may interfere with hematopoiesis (corticosteroids, immunosuppressive agents, cytotoxic drugs)

Primary outcomes:
measure: Sensitivity and specificity
timeFrame: January 2026
Secondary outcomes:
measure: Correlation
timeFrame: January 2026
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico G.Rodolico - San Marco
Study officials:
References:
citation: Salamanna F, Maglio M, Giavaresi G, Pagani S, Giardino R, Fini M. In vitro method for the screening and monitoring of estrogen-deficiency osteoporosis by targeting peripheral circulating monocytes. Age (Dordr). 2015 Aug;37(4):9819. doi: 10.1007/s11357-015-9819-4. Epub 2015 Aug 7.
citation: Salamanna F, Maglio M, Borsari V, Giavaresi G, Aldini NN, Fini M. Peripheral Blood Mononuclear Cells Spontaneous Osteoclastogenesis: Mechanisms Driving the Process and Clinical Relevance in Skeletal Disease. J Cell Physiol. 2016 Mar;231(3):521-30. doi: 10.1002/jcp.25134. Epub 2015 Sep 9.
citation: Salamanna F, Giardino R, Fini M. Spontaneous osteoclastogenesis: Hypothesis for gender-unrelated osteoporosis screening and diagnosis. Med Hypotheses. 2017 Nov;109:70-72. doi: 10.1016/j.mehy.2017.09.028. Epub 2017 Sep 28.
citation: Salamanna F, Maglio M, Sartori M, Tschon M, Fini M. Platelet Features and Derivatives in Osteoporosis: A Rational and Systematic Review on the Best Evidence. Int J Mol Sci. 2020 Mar 4;21(5):1762. doi: 10.3390/ijms21051762.