Comparison of Bone Mineral Density in the Third Trimester Between Women in Singleton and Twin Pregnancies Using Questionnaires and REMS Densitometric Examination (TWINBONE)

Pregnancy-associated Reduction in Bone Mineral Density: a Comparative Study Using REMS Technology Between Singleton and Twin Pregnancies in the Third Trimester

This clinical study aims to monitor and evaluate bone mineral density and fracture risk in women with singleton and twin pregnancies through the combined use of:

• two specific questionnaires developed by the Fragility Fracture Observatory (OFF), and
• a bone densitometric examination using REMS technology, performed between the 35th and 41st week of gestation.

Primary objective:

• To identify, in the third trimester of pregnancy (between the 35th and 41st gestational week), any differences in bone mineral density (BMD) between women with singleton pregnancies and women with dichorionic and monochorionic twin pregnancies.

Secondary objectives:

• Evaluate the relationship between bone mineral density (BMD) values and maternal clinical and historical parameters, such as age, body mass index (BMI), and obstetric and medical history.
• Evaluate the association between BMD values and scores obtained from validated questionnaires administered to investigate fracture risk and bone health-related quality of life in women with singleton and twin pregnancies.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy; Osteoporosis; Twin Pregnancy
• Intervention / Treatment: Device: bone densitometric examination using REMS technology; Other: questionnaires

Detailed Description

Upon enrollment, gestational history, maternal clinical conditions, drug therapy, demographic and anthropometric parameters will be recorded, and specific questionnaires developed by the Fragility Fracture Observatory (OFF) will be administered. These questionnaires aim to assess all risk factors that could lead patients to have a fracture during pregnancy and to evaluate both dietary habits (specifying the type of food with high, medium and low calcium content with relative portions and frequencies) and adherence to the Mediterranean diet (determining, based on the total score, whether the dietary calcium intake is sufficient to support the physiological adaptation of the pregnant woman, who must provide adequate amounts of calcium for the development of the fetal skeleton and the correct growth of the newborn during breastfeeding).

The first questionnaire is divided into two sections: one specifically for "calcium intake" and the other dedicated to assessing the woman's eating habits (Predimed Questionnaire) during pregnancy, which measures portion sizes and the frequency of nutrient intake through food and beverages.

The second questionnaire, AFEF (Fracture Risk Algorithm for Women of Childbearing Age), specifically assesses fracture risk during pregnancy. It collects anthropometric information (weight and height), medical history and personal and family medical history, lifestyle (number of cigarettes smoked daily), and any therapies undertaken before and during pregnancy.

An assessment of bone health using ultrasound densitometry using REMS technology, integrated into the EchoStation device (Echolight Spa, Lecce, Italy), is performed during the third trimester checkup.

The importance of using REMS ultrasound lies in its complete absence of ionizing radiation, ease of use, and rapid scanning. Thanks to an innovative parameter called Fragility Score (FS), intrinsically correlated with bone quality and independent of BMD, REMS allows for the assessment of bone fragility and its resulting fracture risk, representing a useful diagnostic tool also in predicting the risk of fragility fractures. All of this makes this method absolutely compatible and optimal for routine monitoring of bone health and fracture risk in women during pregnancy.

The objectives of the REMS ultrasound technology are:

1. To obtain a quantitative and qualitative assessment of bone status at the proximal femur level in all patients enrolled in the study, stratifying them into two groups based on the BMD values obtained (normal and reduced).
2. To evaluate, using the REMS-based Fragility Score (FS), the risk factors associated with changes in bone fragility, and to identify the cut-off for the FS measured at the femoral neck specifically for pregnant women.

The EchoStation device (manufactured by Echolight Spa) consists of a medical-grade cart, which houses a panel PC, a medical-grade keyboard and mouse, a main unit, and a convex probe operating at a nominal frequency of 3.5 MHz. The EchoStudio software, integrated into the EchoStation device, dedicated to assessing bone health, allows for the automatic calculation of the same diagnostic parameters provided by a DEXA scan (Bone Mineral Density (BMD), T-score, and Z-score) from unfiltered ultrasound radiofrequency signals acquired during an ultrasound scan of a reference anatomical specimen (femoral neck). The ultrasound signals of the bone region in question are automatically processed and compared with reference spectral models previously derived from healthy and osteoporotic patients in order to assess the subject's bone mineral density; and with previously derived reference spectral models from patients with and without fractures to assess bone fragility and related fracture risk using the innovative FS parameter.

This approach, unlike conventional ultrasound, maximizes the information gathered from the acquired signals, while the reconstructed B-mode ultrasound images serve as a guide for the correct identification of the bone being examined. The simultaneous acquisition of multiple ultrasound signals for each frame is integrated with the ultrasound imaging, which also serves as a guide for identifying the region of interest (ROI) within the bone being examined, providing a solid and reliable statistical basis for subsequent analyses.

Women between the 35th and 41st week of gestation (inclusive) will undergo ultrasound examination of the proximal femur using an EchoStation ultrasound system (Echolight Spa, Lecce, Italy) with a convex probe operating at a nominal frequency of 3.5 MHz. Trained operators will follow a standard procedure. Specifically, a 40-second software-guided ultrasound scan will be performed with the ultrasound probe positioned at the head-neck axis of the femur. The probe will be positioned parallel to the long axis of the femur, and the transducer focus and scan depth will be appropriately set to place the femoral neck interface in the focal zone of the beam and in the central portion of the image. The software will then automatically analyze the unfiltered ultrasound signals, identifying the bone interface and ROI; the resulting signals will be processed and, after this automatic process, the diagnostic report will be produced.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tullio ghi; Phone Number: 0630155989; Email: tullio.ghi@policlinicogemelli.it

Study Locations

• Italy
  • RM
    • Roma, RM, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario A. Gemelli IRCCS
      • Contact: Tullio ghi; Phone Number: 0630155989; Email: tullio.ghi@policlinicogemelli.it
      • Contact: chiara Del prete; Phone Number: 3913187130; Email: chiara.delprete02@icatt.it

Participation Criteria

Eligibility Criteria

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

Description

INCLUSION CRITERIA

1. Signed informed consent
2. Willingness to participate in the study and ability to complete the study questionnaires
3. Women between 35 and 41 weeks of gestational age at the time of study inclusion
4. Singleton or twin pregnancy (dichorionic or monochorionic)
5. Age between 30 and 45 years at the time of study recruitment
6. No history of recent or previous bone fractures or traumatic fractures, and no motor disabilities (in the mother).
7. Absence of a diagnosis of osteopenia or osteoporosis according to the criteria of the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS).
8. No intake of vitamin D or other medications during pregnancy.
9. Absence of current or previous conditions that could potentially interfere with bone metabolism (e.g., thyroid, kidney, or liver disease).
10. Women of normal weight or with class I obesity (BMI between 18.5 and 34).

EXCLUSION CRITERIA

Patients will not be included in the study if at least one of the following exclusion criteria is met:

1. Failure to sign the informed consent form
2. Poor compliance and/or inability to complete the study questionnaires
3. Women with previous or newly diagnosed comorbidities during pregnancy
4. Age <30 and >45 years
5. Previous diagnosis of osteopenia or osteoporosis according to the criteria of the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS)
6. BMI <18.5 or >34

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: singleton pregnancy; Women in physiological pregnancy between the 35th and 41st week, with a single pregnancy	Device: bone densitometric examination using REMS technology; An assessment of bone health using ultrasound densitometry using REMS technology, integrated into the EchoStation device (Echolight Spa, Lecce, Italy), is performed during the third trimester check-up. Thanks to an innovative parameter called Fragility Score (FS), intrinsically correlated with bone quality and independent of BMD, REMS allows assessment of bone fragility and its resulting fracture risk, representing a useful diagnostic tool also in predicting the risk of fragility fractures.; Other: questionnaires; Specific questionnaires developed by the Fragility Fracture Observatory (OFF) will be administered. Their purpose is to assess all risk factors that could lead to fractures during pregnancy, as well as to evaluate both dietary habits and adherence to the Mediterranean diet
Experimental: Twin pregnancy; Women in physiological pregnancy between the 35th and 41st week, with a single pregnancy	Device: bone densitometric examination using REMS technology; An assessment of bone health using ultrasound densitometry using REMS technology, integrated into the EchoStation device (Echolight Spa, Lecce, Italy), is performed during the third trimester check-up. Thanks to an innovative parameter called Fragility Score (FS), intrinsically correlated with bone quality and independent of BMD, REMS allows assessment of bone fragility and its resulting fracture risk, representing a useful diagnostic tool also in predicting the risk of fragility fractures.; Other: questionnaires; Specific questionnaires developed by the Fragility Fracture Observatory (OFF) will be administered. Their purpose is to assess all risk factors that could lead to fractures during pregnancy, as well as to evaluate both dietary habits and adherence to the Mediterranean diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMD differences between singleton and twin pregnancies	To identify, in the third trimester of pregnancy (between the 35th and 41st gestational week), any differences in bone mineral density (BMD) between women with a singleton pregnancy and women with dichorionic and monochorionic twin pregnancies.	From enrollment through delivery, an average of six weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMD values and maternal clinical parameter	Evaluation of the correlation between bone mineral density (BMD), measured by dual-energy X-ray absorptiometry (DEXA) and expressed in g/cm², and the following maternal clinical parameters: body mass index (BMI, kg/m²) maternal age (years) weight gain during pregnancy (kg) The correlation will be analyzed using a correlation coefficient (Pearson or Spearman, depending on the data distribution).	From enrollment through delivery, an average of six weeks
Correlation between bone mineral density (DEXA, g/cm²) and validated questionnaire scores (calcium intake, PREDIMED, AFEF)	Evaluation of the correlation between bone mineral density (BMD) values, measured by dual-energy X-ray absorptiometry (DEXA) and expressed in g/cm², and: daily dietary calcium intake, assessed using a dedicated questionnaire and expressed in mg/day; adherence to the Mediterranean diet, assessed using the PREDIMED questionnaire and expressed as a total score; individual risk, assessed using the AFEF questionnaire and expressed as a total score The correlation will be analyzed using a correlation coefficient (Pearson or Spearman, depending on the data distribution)	From enrollment through delivery, an average of six weeks

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Tullio Ghi, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2025
• Primary Completion (Estimated): December 23, 2026
• Study Completion (Estimated): December 23, 2027

Study Registration Dates

• First Submitted: December 23, 2025
• First Submitted That Met QC Criteria: March 27, 2026
• First Posted (Actual): April 2, 2026

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: pregnancy; twin pregnancy; bone mineral density; ultrasound densitometry
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Nutritional and Metabolic Diseases; Osteoporosis; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Surveys and Questionnaires
• Other Study ID Numbers: 8084

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No