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Completed

NCT Number: NCT03751839

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

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.

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Key information

Age range

40 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel

Basel, Canton of Basel-City, 4031, Switzerland

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Biochemical Tests

Diagnostic Test

The investigators will perform blood tests in every participant.

Osteodensitometry

Diagnostic Test

The investigators will perform an osteodensitometry in every participant.

Other names: dual energy x-ray absorptiometry (DXA scan)

Clinical Tests

Diagnostic Test

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

Diagnostic Test

The investigators will perform HR-QCT measurements of the proximal femur and tibia in every participant.

HR-pQCT

Diagnostic Test

The investigators will perform HR-pQCT measurements of the distal radius and distal tibia in every participant.

Primary outcomes

  1. volumetric bone mineral density in mg hydroxyapatite (HA)/ccm

    Time frame: through study completion, an average of 6 months

    measured by HR-pQCT at the distal radius and tibia

  2. cortical porosity in %

    Time frame: through study completion, an average of 6 months

    measured by HR-pQCT at the distal radius and tibia

  3. bone stiffness in kilonewton (kN)/mm

    Time frame: through study completion, an average of 6 months

    a measure of bone strength, measured by HR-pQCT at the distal radius and tibia

  4. failure load in kN

    Time frame: through study completion, an average of 6 months

    a measure of bone strength, measured by HR-pQCT at the distal radius and tibia

Secondary outcomes

  1. areal bone mineral density of the spine in g/cm2

    Time frame: through study completion, an average of 6 months

    measured by osteodensitometry (DXA)

  2. areal bone mineral density of the proximal femur in g/cm2

    Time frame: through study completion, an average of 6 months

    measured by osteodensitometry

  3. areal bone mineral density of the distal radius in g/cm2

    Time frame: through study completion, an average of 6 months

    measured by osteodensitometry

  4. trabecular bone score of the spine

    Time frame: through study completion, an average of 6 months

    a measure of bone texture, measured by osteodensitometry

  5. cortical thickness at the mid tibia in cm

    Time frame: through study completion, an average of 6 months

    the cortical thickness will be measured by pulse-echo ultrasound and high resolution quantitative computed tomography (HR-QCT)

  6. density weighed cortical thickness at the mid tibia in cm

    Time frame: through study completion, an average of 6 months

    the density weighed cortical thickness will be measured by pulse-echo ultrasound and HR- QCT

  7. bone marrow adiposity in mg/cm3

    Time frame: through study completion, an average of 6 months

    measured by HR-pQCT

  8. measurement of serum carboxy-terminal collagen crosslinks (CTX) in pg/ml

    Time frame: through study completion, an average of 6 months

    biochemical marker of bone resorption

  9. measurement of serum n-terminal procollagen type 1 (P1NP) in mcg/l

    Time frame: through study completion, an average of 6 months

    biochemical marker of bone formation

  10. measurement of serum pentosidine in pmol/m

    Time frame: through study completion, an average of 6 months

    biochemical marker associated with bone fragility

  11. measurement of serum carboxymethyl-lysine (CML) in pmol/ml

    Time frame: through study completion, an average of 6 months

    biochemical marker associated with bone fragility

  12. measurement of serum insulin in mU/ml

    Time frame: through study completion, an average of 6 months

    biochemical marker associated with bone fragility

  13. measurement of serum sclerostin in pg/ml

    Time frame: through study completion, an average of 6 months

    biochemical marker associated with bone fragility

  14. measurement of serum adiponectin in ng/ml

    Time frame: through study completion, an average of 6 months

    biochemical marker associated with bone fragility

  15. measurement of serum insulin like growth factor -1 (IGF1) in nM

    Time frame: through study completion, an average of 6 months

    biochemical marker associated with bone fragility

  16. measurement of serum ultrasensitive c-reactive protein (usCRP) in mg/l

    Time frame: through study completion, an average of 6 months

    biochemical marker associated with bone fragility

  17. measurement of serum interleukin 6 (IL6) in pg/ml

    Time frame: through study completion, an average of 6 months

    biochemical marker associated with bone fragility

  18. measurement of serum periostin in ng/ml

    Time frame: through study completion, an average of 6 months

    biochemical marker associated with bone fragility

Sponsors and collaborators

Lead sponsor

Christian Meier

Other

Collaborators

  • Insel Gruppe AG, University Hospital Bern
  • University Hospital Schleswig-Holstein
  • University Hospital, Basel, Switzerland

Registry information

Acronym: BOLD-1

Important dates

Study start
2018
Primary completion
2021
Study completion
2021
First posted
Nov 23, 2018
Registry last updated
Jul 27, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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