Retrospective Monocentric Evaluation of Biomarkers Associated With Bone, Muscle and Energy Metabolism (OVAD)

Bone is a metabolically active tissue undergoing continuous remodeling through the coordinated actions of osteoclasts (resorption), osteoblasts (formation), and osteocytes (regulation). Under physiological conditions, bone formation and resorption are balanced and regulated by systemic hormones (PTH, vitamin D, estrogens) and local mediators. However, aging, metabolic disorders, physical inactivity, or pharmacological treatments may disrupt this equilibrium, leading to the predominance of one process over the other. Circulating biochemical markers of bone turnover-classified into formation markers (P1NP, osteocalcin, bone alkaline phosphatase) and resorption markers (CTx-I, NTx-I, DPD)-provide a means to monitor these dynamics.

Beyond its mechanical role, bone also functions as an endocrine organ: osteocalcin, secreted by osteoblasts, modulates insulin secretion and sensitivity, linking bone to muscle and adipose tissue in the regulation of energy metabolism. Adipokines such as leptin and adiponectin further contribute to this complex crosstalk. Bone biomarkers are therefore essential for evaluating skeletal metabolism and identifying conditions such as osteoporosis, though the strict classification into formation versus resorption markers is limited, as some (e.g., osteocalcin) reflect both processes.

This study aims to analyze IRCCS San Raffaele database records of urinary and serum biomarkers related to bone, muscle, and energy metabolism, to assess their trends and associations according to age and sex, and to develop statistical models capable of explaining their interrelationships.

Study Overview

• Status: Recruiting
• Conditions: Bone Remodeling; Energy Metabolism

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Eleonora Sabetta, MD; Phone Number: 0226435288; Email: sabetta.eleonora@hsr.it

Study Locations

• Italy
  • Italy
    • Milan, Italy, Italy, 20132
      • Recruiting
      • IRCCS San Raffaele Hospital
      • Contact: Eleonora Sabetta, MD; Phone Number: +390226435288; Email: sabetta.eleonora@hsr.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Adults (age > 18 years), both male and female (n = 1000), undergoing routine blood sampling, whose biological specimens (blood and/or urine) were analyzed at the Laboratory Medicine Service of IRCCS San Raffaele Hospital, Milan, between January 1, 2006 and March 31, 2025.

Description

Inclusion Criteria:

• Age > 18 years.
• Blood sampling performed at the Laboratory Medicine Service of IRCCS San Raffaele Hospital, Milan, between January 1, 2006 and March 31, 2025.

Exclusion Criteria:

-Age < 18 years

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
OVAD cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate circulating levels of osteocalcin, the main non-collagenous protein bound to hydroxyapatite (HAP) and synthesized by osteoblasts-thus considered a biomarker of bone formation-in relation to circulating vitamin D, an endocrine factor involved	Osteocalcin data will be acquired, retrospectively, through the San Raffaele Hospital database from January 1st, 2016 to November 30th, 2023	As a retrospective study, data were obtained from the San Raffaele Hospital database for the period January 1, 2016, to November 30, 2023, regardless of patients' therapeutic paths.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
As a secondary outcomes biomarkers of bone formation and reabsorption as well as biomarkers of skeletal muscle and energy metabolism will be evaluated in order to gain insights on how different tissues can influence each other.	The circulating levels of the following analytes will be analyzed to identify statistically significant associations between different biomarkers. Such associations may provide insights into how various tissues influence each other in relation to bone metabolism. Due to character limits in this form, a more detailed description cannot be provided.; Cross Linked C-telopeptide of Type I Collagen (CTx-I); Alkaline phosphatase protein (ALP); Urinary and serum creatinine; Urinary Pyridinoline; Calcium; Ionized calcium; Estrogen; Creatin kinase (CK); Lactate dehydrogenase (LDH); Potassium; Glucose; Glucagon; Insulin; Triglycerides; Total cholesterol; Parathormone; Thyrotropin; Thyroglobulin; Cortisol The International Standard Unit of measurment (SI units) will be adopted fot the above analytes. Data will be acquired, retrospectively, through the San Raffaele Hospital database from January 1st, 2016 to November 30th, 2023	As a retrospective study, data were obtained from the San Raffaele Hospital database for the period January 1, 2016, to November 30, 2023, regardless of patients' therapeutic paths.

Collaborators and Investigators

• Sponsor: IRCCS San Raffaele

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2025
• Primary Completion (Actual): November 1, 2025
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: September 5, 2025
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Energy metabolism; Bone resorption markers (CTx-I, NTx-I, deoxypyridinoline/DPD); Bone turnover markers (BTMs); Statistical modeling of metabolic interactions
• Other Study ID Numbers: OVAD

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