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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Diagnostic test: Biochemical Tests; Diagnostic test: Osteodensitometry; Diagnostic test: Clinical Tests; Diagnostic test: HR-QCT; Diagnostic test: HR-pQCT

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel Stadt
    • Basel, Basel Stadt, Switzerland, 4031
      • Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic; The investigators will examine all participants in the same way by performing biochemical tests, clinical tests, osteodensitometry, HRQCT and HRpQCT measurements.

Diagnostic test: Biochemical Tests; The investigators will perform blood tests in every participant.; Diagnostic test: Osteodensitometry; The investigators will perform an osteodensitometry in every participant.; Other Names: dual energy x-ray absorptiometry (DXA scan); Diagnostic test: 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.; Diagnostic test: HR-QCT; The investigators will perform HR-QCT measurements of the proximal femur and tibia in every participant.; Diagnostic test: HR-pQCT; The investigators will perform HR-pQCT measurements of the distal radius and distal tibia in every participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
cortical porosity in %	measured by HR-pQCT at the distal radius and tibia	through study completion, an average of 6 months
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
areal bone mineral density of the spine in g/cm2	measured by osteodensitometry (DXA)	through study completion, an average of 6 months
areal bone mineral density of the proximal femur in g/cm2	measured by osteodensitometry	through study completion, an average of 6 months
areal bone mineral density of the distal radius in g/cm2	measured by osteodensitometry	through study completion, an average of 6 months
trabecular bone score of the spine	a measure of bone texture, measured by osteodensitometry	through study completion, an average of 6 months
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
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
bone marrow adiposity in mg/cm3	measured by HR-pQCT	through study completion, an average of 6 months
measurement of serum carboxy-terminal collagen crosslinks (CTX) in pg/ml	biochemical marker of bone resorption	through study completion, an average of 6 months
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
measurement of serum pentosidine in pmol/m	biochemical marker associated with bone fragility	through study completion, an average of 6 months
measurement of serum carboxymethyl-lysine (CML) in pmol/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months
measurement of serum insulin in mU/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months
measurement of serum sclerostin in pg/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months
measurement of serum adiponectin in ng/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months
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
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
measurement of serum interleukin 6 (IL6) in pg/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months
measurement of serum periostin in ng/ml	biochemical marker associated with bone fragility	through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Christian Meier
• Collaborators: University Hospital Inselspital, Berne; University Hospital, Basel, Switzerland; University Hospital Schleswig-Holstein
• Investigators: Principal Investigator: Christian Meier, Prof., University Hospital, Basel, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: November 21, 2018
• First Posted (Actual): November 23, 2018

Study Record Updates

• Last Update Posted (Actual): July 27, 2021
• Last Update Submitted That Met QC Criteria: July 24, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: EKNZ 2018-01517

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: In the informed consent document participants can choose whether they agree to the further use of their coded data and biochemical material for future research purposes.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No