Clinical trial NCT05701254: Skeletal Effects of Type 1 Diabetes on Low-Trauma Fracture Risk
Official title: Skeletal Effects of Type 1 Diabetes on Low-Trauma Fracture Risk
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Type 1 Diabetes
Osteopenia
Bone Loss
Fractures, Bone
Keywords: Bone
Cortical Bone
Mechanical Strength
Lead sponsor: Creighton University
Sponsor class: OTHER
First posted: 2023-01-27
Enrollment: 80
Sex: FEMALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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).

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

Detailed description: The investigators will enroll 40 female, postmenopausal, patients with T1DM, fracturing or non-fracturing, who are age 50 and over, and have had diabetes for more than ten years. The investigators will perform 2 transiliac (hip bone) biopsies on each subject, one for mechanical testing, tissue analysis of AGEs, enzymatic crosslinks and bone tissue-bound water in cortical bone, and the other for histomorphometry and high-resolution 3D imaging in trabecular bone. A matched, non-diabetic, healthy control will be enrolled at the time each T1DM is enrolled.

Eligibility criteria: Inclusion Criteria:

Criteria for enrollment of female diabetics

1. No chronic disease diagnoses that may affect bone, as confirmed by the PI.
2. 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.)
3. Glomelular Filtration Rate (GFR) \&amp;gt;45 ml/min (Renal Association lower limit for "mild" kidney failure).
4. Willingness to sign a consent form.
5. Willingness to undergo a transilial bone biopsy incision that yields 2 bone specimens.
6. No abnormalities in clinical blood chemistry measurements (small, age-related decreases in GFR, will be permitted).
7. Caucasian

Criteria for each non-diabetic subject, compared to their matched diabetic:

1. Dual-energy x-ray absorptiometry (DXA) measures (BMD, gm/cm) must be within +/- 15% in total hip.
2. Body mass index (BMI) must be within +/-10%.
3. Age must be within +/- 5 years.
4. Caucasian

Exclusion Criteria:

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

Primary outcomes:
measure: Compare cortical bone tissue levels of pentosidine (AGE), pyridinoline (normal enzymatic collagen crosslinks), and matrix-bound water between T1DM and controls.
timeFrame: 6-8 weeks
Secondary outcomes:
measure: Compare cortical bone tissue heterogeneity in nanoindentation measures of modulus and hardness between T1DM and controls.
timeFrame: 6- 8 weeks
Other outcomes:
Locations:
city: Omaha
country: United States
facility: Creighton University Osteoporosis Research Center
state: Nebraska
Study officials:
affiliation: Creighton University Osteoporosis Research Center
name: Mohammed Akhter, PhD
role: PRINCIPAL_INVESTIGATOR
References: