New Tools for Assessing Fracture Risk

The goal of this study is to determine whether two new, non-X-ray techniques can discriminate between high-energy fractures of normal bone (trauma) and low-energy fractures (fragility) of osteoporotic bone. The current gold-standard for assessing fracture risk areal bone mineral density (aBMD) by dual energy X-ray absorptiometry (DXA) is not particularly effective at identifying individuals who are at risk of suffering a fracture. Yet, there is a growing population of diabetics and elderly individuals prone to fractures. In effect, the age-related and diabetes-related increase in fracture risk is independent of a person's aBMD. These findings stress the urgency in developing diagnostic tools that can improve fracture risk prediction so that patients can be treated with the appropriate anti-fracture therapies.

Study Overview

• Status: Terminated
• Conditions: Osteoporosis; Fracture Risk Assessment
• Intervention / Treatment: Device: Osteoprobe-Reference Point Indentation (RPI); Radiation: Dual-energy X-ray absorptiometry (DXA) Scans; Radiation: MRI

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Univeristy Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion/exclusion criteria for patients with a high-energy or fragility fracture requiring operative fixation (Arm 1)

Number of patients in Arm#1= 60 patients

Inclusion criteria:

1. Patients who are 18 years of age or older. This age range accounts for 60% of all distal radius fractures seen at Vanderbilt University Medical Center.
2. Patients who have sustained a low or high energy distal radius fracture that involves the metaphysis and requires open reduction internal fixation using volar plating.
3. English speaking due to feasibility of employing study personnel to deliver and assess study intervention.

Exclusion criteria:

1. Patients who have known risk factors of pathologic fractures (e.g. bone metastasis)
2. Patients who have or are receiving treatment for osteoporosis (e.g. bisphosphonate) lasted longer than 5 years
3. Patients who have Type 1 diabetes
4. Patients who have other bone disease (e.g., osteogenesis imperfecta, Paget's disease, thyroid disease, Vitamin D deficiency, hyperparathyroidism)
5. Patients that have a history of cancer, abnormal serum calcium, or chronic steroid use
6. Patients that would not be able to have a DXA scan (weight >350lbs, hardware in hips, patients that have lap band device)
7. Patients who are pregnant or who think they may be pregnant
8. Patients that have a medical contraindication to MRI (if patients are undergoing a study MRI)
9. Patients who have concurrent, bilateral upper extremity fractures where hardware or casting may affect study scan measurements
10. Patients who have distal radial shaft fractures

Exclusion criteria 1-5 are included because the goal of the study is to demonstrate whether new bone measurements differentiate normal bone from fragile bone. These exclusion criteria eliminate confounding factors that affect fracture resistance of bone in ways that are independent of osteoporosis. Exclusion criteria 6-8 are practical since DXA/MRI scans cannot accommodate all people.

Inclusion/exclusion criteria for patients with no fracture (Arm 2)

Number of patients in Arm#2= 40 patients

Inclusion criteria:

1. Patients who are 18 years of age or older.
2. Patients who have no history of fracture or family history of pathologic fracture
3. English speaking due to feasibility of employing study personnel to deliver and assess study intervention.

Exclusion criteria:

1. Patients who are taking medication to treat osteoporosis (e.g. bisphosphonate)
2. Patients who have or are receiving treatment for osteoporosis (e.g. bisphosphonate) lasted longer than 5 years
3. Patients who have Type 1 diabetes
4. Patients who have other bone disease (e.g., osteogenesis imperfecta, Paget's disease, thyroid disease, Vitamin D deficiency, hyperparathyroidism).
5. Patients that have a history of cancer, abnormal serum calcium, or chronic steroid use.
6. Patients that would not be able to have a DXA scan (weight >350lbs, hardware in hips, patients that have lap band device)
7. Patients who are pregnant or who think they may be pregnant.
8. Patients that have a medical contraindication to MRI.

Exclusion criteria 1-5 are included because the goal of the study is to demonstrate whether new bone measurements differentiate normal bone from fragile bone. These exclusion criteria eliminate confounding factors that affect fracture resistance of bone in ways that are independent of osteoporosis. Exclusion criteria 6- 8 are practical since DXA/MRI scans cannot accommodate all people.

Inclusion/exclusion criteria for patients with a high-energy or fragility fracture requiring nonoperative treatment (Arm 3)

Number of patients in Arm#3= up to 10 patients

Inclusion criteria:

1. Patients who are 18 years of age or older. This age range accounts for 60% of all distal radius fractures seen at Vanderbilt University Medical Center.
2. Patients who have sustained a low or high energy distal radius fracture that requires nonoperative treatment
3. English speaking due to feasibility of employing study personnel to deliver and assess study intervention.

Exclusion criteria:

1. Patients who have known risk factors of pathologic fractures (e.g. bone metastasis)
2. Patients who have or are receiving treatment for osteoporosis (e.g. bisphosphonate) lasted longer than 5 years
3. Patients who have Type 1 diabetes
4. Patients who have other bone disease (e.g., osteogenesis imperfecta, Paget's disease, thyroid disease, Vitamin D deficiency, hyperparathyroidism)
5. Patients that have a history of cancer, abnormal serum calcium, or chronic steroid use
6. Patients that would not be able to have a DXA scan (weight >350lbs, hardware in hips, patients that have lap band device)
7. Patients who are pregnant or who think they may be pregnant
8. Patients that have a medical contraindication to MRI (if patients are undergoing a study MRI)
9. Patients who have concurrent, bilateral upper extremity fractures where hardware or casting may affect study scan measurements

Exclusion criteria 1-5 are included because the goal of the study is to demonstrate whether new bone measurements differentiate normal bone from fragile bone. These exclusion criteria eliminate confounding factors that affect fracture resistance of bone in ways that are independent of osteoporosis. Exclusion criteria 6-8 are practical since DXA/MRI scans cannot accommodate all people.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Distal Radius Fracture Operative Group; Fracture group patients will undergo DXA and MRI scans, along with Osteoprobe indentation.	Device: Osteoprobe-Reference Point Indentation (RPI); Diagnostic tool used for bone indentation to measure the ability of the tissue to resist microindentation (bone mineral strength).; Radiation: Dual-energy X-ray absorptiometry (DXA) Scans; Assessment of Fracture Risk; Radiation: MRI; Determines bound water and pore water of bone.
Active Comparator: Healthy Volunteers (Non Fracture Group); Healthy volunteers will undergo DXA and MRI scans.	Radiation: Dual-energy X-ray absorptiometry (DXA) Scans; Assessment of Fracture Risk; Radiation: MRI; Determines bound water and pore water of bone.
Active Comparator: Distal Radius Fracture Non-operative Group; Fracture group patients will undergo DXA and MRI scans, but will not undergo Osteoprobe indentation.	Radiation: Dual-energy X-ray absorptiometry (DXA) Scans; Assessment of Fracture Risk; Radiation: MRI; Determines bound water and pore water of bone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Osteoprobe Measurements	Bone Material Strength index (BMSi) By engaging the bone at 10 N and then delivering a single impact force of ~40 N, the OsteoProbe records the maximum penetration depth of conical-spherical tip into cortical bone. This indentation distance increase (IDI) is indexed to the IDI acquired from a reference material immediately after the bone IDI measurements, such that the OsteoProbe-based measurement known as bone material strength index (BMSi) is 100 times IDI of reference material divided by IDI of the patient's bone. A lower BMSi measurement is the result of a higher indentation distance into the bone. For statistical analysis, we used the mean of the 10 BMSi measurements per case.	Within a week before or after surgery to repair distal radius fracture
MRI Scan Measurements	Bound Water Fraction	Within a week before or after surgery to repair distal radius fracture
MRI Scan Measurements	Pore Water Fraction	Within a week before or after surgery to repair distal radius fracture
DXA Scan Measurements	Bone Mineral Density	Within a week before or after surgery to repair distal radius fracture
DXA Scan Measurements	Bone Mineral Content	Within a week before or after surgery to repair distal radius fracture
DXA Scan Measurements	A T-score is the number of standard deviations (SD) below (negative value) or above (positive value) the mean BMD (bone mineral density) for a healthy population. A person with T-score below -2.5 is considered to have osteoporosis.	Within a week before or after surgery to repair distal radius fracture

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported Measurements	DASH (Disabilities of the Arm, Shoulder, and Hand) is a 30-item self-report questionnaire designed to assess musculoskeletal disorders of the upper limbs. The score ranges from 0 (no disability) to 100 (most severe disability). A higher scores indicate a greater level of disability and severity, whereas, lower scores indicate a lower level of disability.	Baseline/One-Time Completion and Post-op/-treatment: 3, 6, and 12 weeks
Patient-reported Measurements	PRWE (Patient-rated wrist evaluation) is a 15-item survey designed to measure wrist pain and disability in activities of daily living. The PRWE consists of a pain subscale and a function subscale. The pain subscale contains 5 items, each rated 0 (no pain) to 10 (worst pain ever). The pain subscale is calculated by adding all 5 item scores together (minimum score: 0, maximum score: 50). A lower score indicates a lower pain level. The function subscale contains 10 items, each rated 0 (no difficulty) to 10 (unable to do). The function subscale is calculated by adding all 10 item scores together and dividing by 2 (minimum score: 0, maximum score: 100). A lower score indicates a lower disability level. The total PRWE score is calculated by adding the pain and function subscales together. The total PRWE score ranges from 0 (best score) to 100 (worst score). The lower the score the better the outcome.	Baseline and Post-op/-treatment: 3, 6, and 12 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Center for Advancing Translational Sciences (NCATS); ActiveLife Scientific
• Investigators: Principal Investigator: Jeffry S Nyman, PhD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2015
• Primary Completion (Actual): May 23, 2018
• Study Completion (Actual): November 8, 2018

Study Registration Dates

• First Submitted: April 24, 2015
• First Submitted That Met QC Criteria: May 1, 2015
• First Posted (Estimate): May 6, 2015

Study Record Updates

• Last Update Posted (Actual): November 2, 2020
• Last Update Submitted That Met QC Criteria: October 12, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Wounds and Injuries; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Fractures, Bone; Osteoporosis
• Other Study ID Numbers: 141125; UL1TR000445 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No current plant to share individual participant data.

Drug and device information, study documents

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