Skeletal Effects of Type 1 Diabetes on Low-Trauma Fracture Risk
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexFemale
Age50+
SponsorCreighton University
About this trial
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
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial 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).
Trial design
Design model
Case-control
Time perspective
Cross-sectional
Treatments tested in this trial
Transilial bone biopsy
Procedure/SurgeryThe 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.
Treatment groups
80 Participants
are divided into 2 treatment groupsGroup A: Type 1 Diabetics1 intervention
Group B: Non-Type 1 Diabetics1 intervention
Trial outcomes
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
Time frame
6-8 weeksSecondary outcomes
1
Compare cortical bone tissue heterogeneity in nanoindentation measures of modulus and hardness between T1DM and controls.
Bone tissue's hardness and modulus will be quantified by using nanoindentation technique. The nanoindentation is a mechanical/material strength testing technique. The technique has been used in bone tissue from bone biopsies. 1. Hardness \[GPa-giga-pascal-N/m2\] 2. Modulus \[GPa-giga-pascal-N/m2\]
Time frame
6- 8 weeksSponsors and contacts
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Source ClinicalTrials.gov