Skeletal Effects of Type 1 Diabetes on Low-Trauma Fracture Risk

NCT05701254 | Recruiting

• 1 other identifier: 1425624-3
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with Type 1 Diabetes Mellitus (T1DM) have a higher risk of low-trauma (osteoporotic) fracture that is 7-12 times higher than non-diabetics. The bone density of people with Type 1 Diabetes is higher at the time of fracture than in non-diabetics. This suggests the presence of underlying bone tissue mechanical defects. The potential benefits to participants would be knowledge gained about their bone density and the results of laboratory tests. On a wider scale, there may be general benefits to society because the knowledge gained from this study may help better understand the effects of diabetes on bone health

Conditions

Type 1 Diabetes; Osteopenia; Bone Loss; Fractures, Bone

Keywords

Bone; Cortical Bone; Mechanical Strength

Outcome Measures

Primary Outcomes (1)

• Compare cortical bone tissue levels of pentosidine (AGE), pyridinoline (normal enzymatic collagen crosslinks), and matrix-bound water between T1DM and controls.

  For different advance glycation endproducts (AGEs), a) pentosidine (PEN), b) pyrinoline (Pyd), and c) tissue water (TW), will be measured using Raman spectroscopy technique on bone biopsy tissue obtained from study participants. Raman spectra will be obtained from the embedded block surfaces using a confocal Raman spectrometer (Renishaw InVia Qontor, www.renishaw.de). These spectra will be collected at the interstitial, cement lines, and actively bone forming osteons with evident fluorescent labels. A continuous laser beam with an excitation of 785 nm and power of 10 mW will be focused through a Raman microscope (Leica DM2700M), using the 50x objective, down to a micrometer-sized spot on the sample. 1. Pentosidine (PEN) \[ratio\]. PEN (Pentosidine) from the integrated area ratio of bands 1495 (PEN) cm-1 / 1450 cm-1 (methylene side chains (CH2)). 2. Pyrinoline (Pyd) \[ratio\]. The pyridinoline (Pyd; enzymatic trivalent collagen cross-link) content is calculated as the absorbance height

  6-8 weeks

Secondary Outcomes (1)

• Compare cortical bone tissue heterogeneity in nanoindentation measures of modulus and hardness between T1DM and controls.

  6- 8 weeks

Study Arms (2)

Type 1 Diabetics

All participants will complete 4 visits over 6-8 weeks. Visit 1 is a screening visit which includes a physical exam, a bone mineral density scan, a blood draw and an EKG. Visit 2 consists of dispensing the Tetracycline antibiotic required for the bone biopsy. Visit 3 is the bone biopsy and includes a blood draw. Visit 4 is to remove the stitches.

Procedure: Transilial bone biopsy

Non-Type 1 Diabetics

All participants will complete 4 visits over 6-8 weeks. Visit 1 is a screening visit which includes a physical exam, a bone mineral density scan, a blood draw and an EKG. Visit 2 consists of dispensing the Tetracycline antibiotic required for the bone biopsy. Visit 3 is the bone biopsy and includes a blood draw. Visit 4 is to remove the stitches.

Procedure: Transilial bone biopsy

Interventions

Transilial bone biopsy PROCEDURE

The transiliac bone biopsy will be performed on each subject under local anesthesia, and conscious sedation. From one skin incision located \~2cm posterior and inferior to the anterior-superior pelvic spine on one side of the pelvis, the investigators will obtain two iliac bone specimens, each 7.5 mm in diameter, cylindrical in shape, and including both inner and outer cortices and the intervening trabecular bone.

Non-Type 1 Diabetics; Type 1 Diabetics

Eligibility Criteria

• Age: 50 Years+
• Gender Eligibility Details: Males will not be recruited in order to avoid gender-based confounding effects in the data analysis.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

40 female type 1 diabetics (both fracturing and non-fracturing) and 40 matched healthy female controls. The investigators will enroll an age-matched, healthy, non-diabetic, non-fracturing female control who is 5 years past the onset of menopause. All of our subjects, diabetics and controls, will be Caucasians, free of diagnoses other than diabetes, and all will have DXA T-scores at the femoral neck and/or total hip and/or lumbar spine between -1.0 and -2.5, (i.e. none will have T-scores in the DXA T-score range of osteoporosis).

You may qualify if:

• Criteria for enrollment of female diabetics
• No chronic disease diagnoses that may affect bone, as confirmed by the PI.
• Normal clinical history, physical, and clinical laboratory exam (except for usual complications of a 10+-year diabetic, i.e., \~minimal neuropathy or retinopathy, known, but asymptomatic mild vascular disease, etc.)
• Glomelular Filtration Rate (GFR) \>45 ml/min (Renal Association lower limit for "mild" kidney failure).
• Willingness to sign a consent form.
• Willingness to undergo a transilial bone biopsy incision that yields 2 bone specimens.
• No abnormalities in clinical blood chemistry measurements (small, age-related decreases in GFR, will be permitted).
• Caucasian
• Criteria for each non-diabetic subject, compared to their matched diabetic:
• Dual-energy x-ray absorptiometry (DXA) measures (BMD, gm/cm) must be within +/- 15% in total hip.
• Body mass index (BMI) must be within +/-10%.
• Age must be within +/- 5 years.
• Caucasian

You may not qualify if:

• Women who have had Type 1 diabetes for less than 10 years.
• Non-insulin dependent Type 1 diabetic.
• Less than 50 years old.
• Less than 5 years post menopausal.

Sponsors & Collaborators

• Creighton University: lead

Study Sites (1)

Creighton University Osteoporosis Research Center

Omaha, Nebraska, 68122, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Transilial bone biopsy samples will be retained and stored for possible future testing. Type 1 Diabetics will be matched to non-diabetics. All subjects undergo the bone biopsy.

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Bone Diseases, Metabolic; Fractures, Bone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Bone Diseases; Musculoskeletal Diseases; Wounds and Injuries

Study Officials

• Mohammed Akhter, PhD

  Creighton University Osteoporosis Research Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adam Hornig

CONTACT

402-559-9116; adam.hornig@unmc.edu

Laura Armas, M.D.

CONTACT

402-559-8700; laura.armas@unmc.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 27, 2023
• Study Start: June 18, 2019
• Primary Completion: December 1, 2024
• Study Completion: January 1, 2025
• Last Updated: September 25, 2024

Record last verified: 2024-09

Locations

US (1)