Microarchitecture, Bone Strength and Fracture Risk in Long-term Type 1 Diabetes

Type 1 Diabetes Mellitus Clinical Trial

— BOLD-1  

Official title:

Microarchitecture, Bone Strength and Fracture Risk in Long-term Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03751839
• Other study ID #: EKNZ 2018-01517
• Status: Completed
• Phase: N/A
• Start date: October 1, 2018
• Est. completion date: July 1, 2021

Study information

• Verified date: July 2021
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This single center case control study will assess differences in bone structure between women and men with longstanding type 1 diabetes (diabetes duration>/= 25 years) and healthy controls.

Description:

Based on a cross-sectional approach the investigators aim to assess microstructural, biomechanical and densitometric bone characteristics in patients with longstanding type 1 diabetes and age- and sex-matches controls. The investigators examine whether the presence of microvascular disease and/or poor diabetic control is associated with an altered bone microarchitecture and whether any such effect is independent of bone mineral density. Furthermore, the investigators aim to look into the relationship between an altered bone microarchitecture and advanced glycation end product (AGE) formation as well as biochemical markers of bone formation and bone turnover. The study aims to identify type 1 diabetic patients with high fracture risk by assessing the discriminatory power of parameters of cortical and trabecular microstructure measured via high resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius and tibia and high resolution quantitative computed tomography (HR-QCT) of the proximal femur and tibia with and without adjustment for bone density.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 136
• Est. completion date: July 1, 2021
• Est. primary completion date: July 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• women and men with longstanding type 1 diabetes (age 40-80 years, BMI 18-37 kg/m2 and age- and sex matched non-diabetic controls

• presence of type 1 diabetes for at least 25 years (defined by history of Insulin treatment)

Exclusion Criteria:

• Patients unable to give written informed consent, e.g. with severe dementia or patients not understanding German (or other local language)

• Any medical or psychiatric condition which would preclude the participant from adhering to the protocol

• Idiopathic or premenopausal osteoporosis or coexisting metabolic bone disease (e.g. Paget´s disease, primary hyperparathyroidism)

• Previous treatment with osteoporosis medication (bisphosphonates, denosumab) or intake of medications that are known to affect bone metabolism (e.g. steroids, anticonvulsants) within 6 months prior to enrollment

• Patients with medical conditions known to affect bone health ( e.g. metastatic bone disease, celiac disease, inflammatory bone disease, hypogonadism, thyrotoxicosis, hypercortisolism, chronic kidney disease stage IV and V (KDIGO), liver dysfunction (serum aspartate amino transferase (ASAT) >3 times the upper limit of normal)

• Inability to keep the extremities still for a few minutes of an HR-pQCT examination (e.g. Parkinson disease, spastic syndrome)

• Pregnant or breastfeeding women

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Diagnostic Test:
• Biochemical Tests
The investigators will perform blood tests in every participant.
• Osteodensitometry
The investigators will perform an osteodensitometry in every participant.
• Clinical Tests
The investigators perform the following clinical tests: vibration threshold test, monofilament test, chair rise test and timed up and go test in every participant.
• HR-QCT
The investigators will perform HR-QCT measurements of the proximal femur and tibia in every participant.
• HR-pQCT
The investigators will perform HR-pQCT measurements of the distal radius and distal tibia in every participant.

Locations

Country	Name	City	State
Switzerland	Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel	Basel	Basel Stadt

Sponsors (4)

Lead Sponsor	Collaborator
Christian Meier	University Hospital Inselspital, Berne, University Hospital Schleswig-Holstein, University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	volumetric bone mineral density in mg hydroxyapatite (HA)/ccm	measured by HR-pQCT at the distal radius and tibia	through study completion, an average of 6 months
Primary	cortical porosity in %	measured by HR-pQCT at the distal radius and tibia	through study completion, an average of 6 months
Primary	bone stiffness in kilonewton (kN)/mm	a measure of bone strength, measured by HR-pQCT at the distal radius and tibia	through study completion, an average of 6 months
Primary	failure load in kN	a measure of bone strength, measured by HR-pQCT at the distal radius and tibia	through study completion, an average of 6 months
Secondary	areal bone mineral density of the spine in g/cm2	measured by osteodensitometry (DXA)	through study completion, an average of 6 months
Secondary	areal bone mineral density of the proximal femur in g/cm2	measured by osteodensitometry	through study completion, an average of 6 months
Secondary	areal bone mineral density of the distal radius in g/cm2	measured by osteodensitometry	through study completion, an average of 6 months
Secondary	trabecular bone score of the spine	a measure of bone texture, measured by osteodensitometry	through study completion, an average of 6 months
Secondary	cortical thickness at the mid tibia in cm	the cortical thickness will be measured by pulse-echo ultrasound and high resolution quantitative computed tomography (HR-QCT)	through study completion, an average of 6 months
Secondary	density weighed cortical thickness at the mid tibia in cm	the density weighed cortical thickness will be measured by pulse-echo ultrasound and HR- QCT	through study completion, an average of 6 months
Secondary	bone marrow adiposity in mg/cm3	measured by HR-pQCT	through study completion, an average of 6 months
Secondary	measurement of serum carboxy-terminal collagen crosslinks (CTX) in pg/ml	biochemical marker of bone resorption	through study completion, an average of 6 months
Secondary	measurement of serum n-terminal procollagen type 1 (P1NP) in mcg/l	biochemical marker of bone formation	through study completion, an average of 6 months
Secondary	measurement of serum pentosidine in pmol/m	biochemical marker associated with bone fragility	through study completion, an average of 6 months
Secondary	measurement of serum carboxymethyl-lysine (CML) in pmol/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months
Secondary	measurement of serum insulin in mU/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months
Secondary	measurement of serum sclerostin in pg/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months
Secondary	measurement of serum adiponectin in ng/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months
Secondary	measurement of serum insulin like growth factor -1 (IGF1) in nM	biochemical marker associated with bone fragility	through study completion, an average of 6 months
Secondary	measurement of serum ultrasensitive c-reactive protein (usCRP) in mg/l	biochemical marker associated with bone fragility	through study completion, an average of 6 months
Secondary	measurement of serum interleukin 6 (IL6) in pg/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months
Secondary	measurement of serum periostin in ng/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months