Microarchitecture, Bone Strength and Fracture Risk in Long-term Type 1 Diabetes
- Conditions
- Type 1 Diabetes Mellitus
- Interventions
- Diagnostic Test: Biochemical TestsDiagnostic Test: OsteodensitometryDiagnostic Test: Clinical TestsDiagnostic Test: HR-QCTDiagnostic Test: HR-pQCT
- Registration Number
- NCT03751839
- Lead Sponsor
- Christian Meier
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 136
- 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)
- 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. PagetĀ“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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Diagnostic Osteodensitometry The investigators will examine all participants in the same way by performing biochemical tests, clinical tests, osteodensitometry, HRQCT and HRpQCT measurements. Diagnostic Clinical Tests The investigators will examine all participants in the same way by performing biochemical tests, clinical tests, osteodensitometry, HRQCT and HRpQCT measurements. Diagnostic HR-QCT The investigators will examine all participants in the same way by performing biochemical tests, clinical tests, osteodensitometry, HRQCT and HRpQCT measurements. Diagnostic Biochemical Tests The investigators will examine all participants in the same way by performing biochemical tests, clinical tests, osteodensitometry, HRQCT and HRpQCT measurements. Diagnostic HR-pQCT The investigators will examine all participants in the same way by performing biochemical tests, clinical tests, osteodensitometry, HRQCT and HRpQCT measurements.
- Primary Outcome Measures
Name Time Method volumetric bone mineral density in mg hydroxyapatite (HA)/ccm through study completion, an average of 6 months measured by HR-pQCT at the distal radius and tibia
cortical porosity in % through study completion, an average of 6 months measured by HR-pQCT at the distal radius and tibia
bone stiffness in kilonewton (kN)/mm through study completion, an average of 6 months a measure of bone strength, measured by HR-pQCT at the distal radius and tibia
failure load in kN through study completion, an average of 6 months a measure of bone strength, measured by HR-pQCT at the distal radius and tibia
- Secondary Outcome Measures
Name Time Method bone marrow adiposity in mg/cm3 through study completion, an average of 6 months measured by HR-pQCT
measurement of serum carboxy-terminal collagen crosslinks (CTX) in pg/ml through study completion, an average of 6 months biochemical marker of bone resorption
areal bone mineral density of the spine in g/cm2 through study completion, an average of 6 months measured by osteodensitometry (DXA)
areal bone mineral density of the proximal femur in g/cm2 through study completion, an average of 6 months measured by osteodensitometry
areal bone mineral density of the distal radius in g/cm2 through study completion, an average of 6 months measured by osteodensitometry
trabecular bone score of the spine through study completion, an average of 6 months a measure of bone texture, measured by osteodensitometry
cortical thickness at the mid tibia in cm 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)
density weighed cortical thickness at the mid tibia in cm through study completion, an average of 6 months the density weighed cortical thickness will be measured by pulse-echo ultrasound and HR- QCT
measurement of serum n-terminal procollagen type 1 (P1NP) in mcg/l through study completion, an average of 6 months biochemical marker of bone formation
measurement of serum pentosidine in pmol/m through study completion, an average of 6 months biochemical marker associated with bone fragility
measurement of serum carboxymethyl-lysine (CML) in pmol/ml through study completion, an average of 6 months biochemical marker associated with bone fragility
measurement of serum insulin in mU/ml through study completion, an average of 6 months biochemical marker associated with bone fragility
measurement of serum sclerostin in pg/ml through study completion, an average of 6 months biochemical marker associated with bone fragility
measurement of serum adiponectin in ng/ml through study completion, an average of 6 months biochemical marker associated with bone fragility
measurement of serum insulin like growth factor -1 (IGF1) in nM through study completion, an average of 6 months biochemical marker associated with bone fragility
measurement of serum ultrasensitive c-reactive protein (usCRP) in mg/l through study completion, an average of 6 months biochemical marker associated with bone fragility
measurement of serum interleukin 6 (IL6) in pg/ml through study completion, an average of 6 months biochemical marker associated with bone fragility
measurement of serum periostin in ng/ml through study completion, an average of 6 months biochemical marker associated with bone fragility
Trial Locations
- Locations (1)
Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel
šØšBasel, Basel Stadt, Switzerland