Prevalence of Vertebral Fractures in Patients With Type 1 Diabetes (DenSiFy)

Prevalence of Vertebral Fractures in Patients With Type 1 Diabetes (Diabetes Spine Fractures, DenSiFy)

Background : Type 1 diabetes is associated with an increased risk of fractures. The mechanisms accounting for this bone fragility are not yet fully understood. The lower bone mineral density (BMD) observed in individuals with type 1 diabetes cannot solely explain the higher fracture incidence. Bone microarchitecture defects significantly contribute to bone fragility. Few studies assessed spine fractures in type 1 diabetes.

This cross-sectional multicenter case-control study aims (1) to evaluate the prevalence of asymptomatic vertebral fractures in individuals with type 1 diabetes in comparison to age- and sex-matched healthy controls; (2) to compare individuals with diabetes with vertebral fractures and those without vertebral fracture using clinical, biochemical and radiological parameters.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1; Bone Health; Bone Fracture
• Intervention / Treatment: Diagnostic test: Clinical tests; Diagnostic test: Clinical tests; Diagnostic test: Biochemical tests; Diagnostic test: DXA scan; Diagnostic test: AGE Reader

• Study Type: Observational
• Enrollment (Actual): 192

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4G2
    • Centre de recherche du CHU de Québec - Université Laval
  • Quebec
    • Montréal, Quebec, Canada, H2W 1R7
      • Institut de recherches cliniques de Montréal (IRCM)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

127 individuals with type 1 diabetes and 64 healthy subjects

Description

Individuals with type 1 diabetes

Inclusion Criteria:

• Diagnosis of type 1 diabetes for at least 5 years;
• Age 20 years and older.

Exclusion Criteria:

• Pregnancy or breastfeeding;
• Conditions associated with bone disease (significant liver disease, intestinal malabsorption other than celiac disease, organ transplant, active cancer, rheumatoid arthritis, hyperthyroidism, hypothyroidism with abnormal thyroid-stimulating hormone (TSH), hyperparathyroidism, hypoparathyroidism, acromegaly, Cushing syndrome, adrenal insufficiency);
• Any of these medications in the past 6 months : glucocorticoids ≥ 7,5 mg prednisone/day or equivalency ≥ 3 months, aromatase inhibitors, antiandrogens, antiepileptic drugs, anticoagulants, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, thiazolidinediones;
• Past medical history of traumatic vertebral fracture;
• Inability to consent.

Healthy controls

Inclusion Criteria:

• Age 20 years and older.

Exclusion Criteria:

• As above (as individuals with diabetes), and :
• Diagnosis of diabetes or prediabetes;
• Celiac disease;
• Chronic kidney disease (CrCl < 60 mL/min);
• Any of theses medications in the past 6 months : biphosphonates, teriparatide, denosumab, calcitonin;
• Past medical history of fragility fracture.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy controls	Diagnostic test: Clinical tests; The investigators perform the following clinical tests: vibration threshold test, monofilament test, and height, weight and waist circumference measurement in every participant.; Diagnostic test: Clinical tests; The investigators perform the following clinical tests: height, weight and waist circumference measurement in every participant.; Diagnostic test: Biochemical tests; The investigators perform blood and urine tests in every participant.; Diagnostic test: DXA scan; The investigators perform a dual energy x-ray absorptiometry (DXA scan or osteodensitometry) in every participant.; Diagnostic test: AGE Reader; The investigators perform a skin advanced glycation end products (AGEs) measurement with the AGE Reader machine in every participant.
Individuals with type 1 diabetes	Diagnostic test: Clinical tests; The investigators perform the following clinical tests: vibration threshold test, monofilament test, and height, weight and waist circumference measurement in every participant.; Diagnostic test: Clinical tests; The investigators perform the following clinical tests: height, weight and waist circumference measurement in every participant.; Diagnostic test: Biochemical tests; The investigators perform blood and urine tests in every participant.; Diagnostic test: DXA scan; The investigators perform a dual energy x-ray absorptiometry (DXA scan or osteodensitometry) in every participant.; Diagnostic test: AGE Reader; The investigators perform a skin advanced glycation end products (AGEs) measurement with the AGE Reader machine in every participant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vertebral fracture detected with VFA	Vertebral Fracture Assessment (VFA) software of dual-energy X-ray absorptiometry (DXA scan) is used to identify vertebral fractures. If there is evidence of a vertebral fracture on VFA, a lateral and anteroposterior spine X-ray will be obtained to confirm the VFA results.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Areal bone mineral density of the spine in g/cm2	Measured by DXA scan	Baseline
Areal bone mineral density of the spine, T-score	Measured by DXA scan	Baseline
Areal bone mineral density of the spine, Z-score	Measured by DXA scan	Baseline
Areal bone mineral density of proximal femur in g/cm2	Measured by DXA scan	Baseline
Areal bone mineral density of proximal femur, T-score	Measured by DXA scan	Baseline
Areal bone mineral density of proximal femur, Z-score	Measured by DXA scan	Baseline
Areal bone mineral density of total hip in g/cm2	Measured by DXA scan	Baseline
Areal bone mineral density of total hip, T-score	Measured by DXA scan	Baseline
Areal bone mineral density of total hip, Z-score	Measured by DXA scan	Baseline
Areal bone mineral density of distal radius in g/cm2	Measured by DXA scan	Baseline
Areal bone mineral density of distal radius, T-score	Measured by DXA scan	Baseline
Areal bone mineral density of distal radius, Z-score	Measured by DXA scan	Baseline
Lean mass (arm, leg, trunk, android, gynoid and total)	Body composition measured by DXA scan	Baseline
Fat mass (arm, leg, trunk, android, gynoid and total)	Body composition measured by DXA scan	Baseline
Skin AGE measurement	Measured by AGE Reader	Baseline
C-telopeptide	Bone turnover marker (serum)	Baseline
Sclerostin	Bone turnover marker (serum)	Baseline
Osteocalcin	Bone turnover marker (serum)	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1C	Diabetes control marker	Baseline
Hemoglobin	Blood level measurement	Baseline
Creatinine	Blood level measurement	Baseline
Lipid panel	Blood level measurement	Baseline
Thyroid-stimulating hormone (TSH)	Blood level measurement	Baseline
Calcium	Blood level measurement	Baseline
Albumine	Blood level measurement	Baseline
Phosphate	Blood level measurement	Baseline
25-Hydroxyvitamin D	Blood level measurement	Baseline
Parathormone (PTH)	Blood level measurement	Baseline
Insulin like growth factor-1 (IGF-1)	Blood level measurement	Baseline
Antitransglutaminase antibodies	Blood level measurement	Baseline
Immunoglobulin A (IgA)	Blood level measurement	Baseline
Follicle stimulating hormone (FSH, women)	Blood level measurement	Baseline
Total testosterone (men)	Blood level measurement	Baseline
Sex hormone-binding globulin (SHBG, men)	Blood level measurement	Baseline
Microalbuminuria	Urine microalbuminuria / urine creatinine ratio measurement	Baseline

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Investigators: Principal Investigator: Claudia Gagnon, Dr, CHU de Québec - Université Laval

Publications and helpful links

General Publications

• Coll JC, Garceau E, Leslie WD, Genest M, Michou L, Weisnagel SJ, Mac-Way F, Albert C, Morin SN, Rabasa-Lhoret R, Gagnon C. Prevalence of Vertebral Fractures in Adults With Type 1 Diabetes: DenSiFy Study (Diabetes Spine Fractures). J Clin Endocrinol Metab. 2022 Apr 19;107(5):e1860-e1870. doi: 10.1210/clinem/dgac031.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2019
• Primary Completion (Actual): March 2, 2021
• Study Completion (Actual): March 2, 2021

Study Registration Dates

• First Submitted: August 17, 2019
• First Submitted That Met QC Criteria: August 20, 2019
• First Posted (Actual): August 21, 2019

Study Record Updates

• Last Update Posted (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Wounds and Injuries; Endocrine System Diseases; Spinal Injuries; Back Injuries; Diabetes Mellitus; Diabetes Mellitus, Type 1; Fractures, Bone; Spinal Fractures
• Other Study ID Numbers: 2019-4550

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No