Clinical trial NCT05171153: Analysis of Bone Quality in Adult Patients With Inflammatory Bowel Disease
Official title: Analysis of Bone Quality in Adult Patients With Inflammatory Bowel Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Inflammatory Bowel Diseases
Osteoporosis
Lead sponsor: Quironsalud
Sponsor class: OTHER
First posted: 2021-12-28
Enrollment: 100
Sex: ALL
Minimum age (years): 21
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients of the Endocrinology and Nutrition, Digestive System and Rheumatology departments of the Ruber Juan Bravo Hospital,

Brief summary: Inflammatory bowel disease (IBD) is considered a risk factor for the development of osteoporosis, which leads to an increased risk of fractures. There is no data on bone quality obtained with imaging techniques other than bone densitometry such as Trabecular Bone Score (TBS), 3D bone densitometry (DXA-3D) or quantitative bone ultrasound (QUS). The TBS study can provide information on bone microarchitecture in these patients, with TBS values expected to be lower than those of subjects without IBD, with a decrease of up to 50 points in this parameter.

Primary objective: to evaluate and compare TBS values in patients with IBD and in a control group of volunteers without IBD or known metabolic bone pathology, adjusted for age, sex and body mass index (BMI).

Secondary objectives: to evaluate and compare results in DEXA parameters, QUS, DEXA-3D, biochemical parameters and FRAX data between patients with IBD and controls. To evaluate the prevalence of vertebral fractures analyzed by VFA. As well as to evaluate the evolution in one year of all these parameters in patients with IBD.

Prospective observational study with a cohort of patients with IBD and another of volunteers without IBD or metabolic bone pathology, adjusted for age, sex and BMI. Baseline bone quality data will be analyzed by bone densitometry, TBS, DEXA-3D and QUS, fractures assessed by VFA and bone remodeling markers in both cohorts. Subsequently, a one-year analysis of the parameters of the IBD cohort will be performed.

Detailed description: Inflammatory bowel disease (IBD) is considered a risk factor for the development of osteoporosis, which leads to an increased risk of fractures. There is no data on bone quality obtained with imaging techniques other than bone densitometry such as Trabecular Bone Score (TBS), 3D bone densitometry (DXA-3D) or quantitative bone ultrasound (QUS).

HYPOTHESES OF THE STUDY Subjects with inflammatory bowel disease present an alteration in bone quality that can be assessed by TBS, with TBS values expected to be lower than those of subjects without IBD or known bone pathology, with a decrease of up to 50 points in this parameter.

Primary Objective : to evaluate and compare the values of the trabecular bone score (TBS), a surrogate marker of bone quality, in patients with inflammatory bowel disease (IBD) and in a control group of volunteers without IBD or known metabolic bone pathology, recruited in the consultations of the Endocrinology and Nutrition, Digestive System and Rheumatology departments of the Hospital Ruber Juan Bravo during routine health control visits, adjusted for age, sex and body mass index (BMI).

Secondary Objectives

1. To compare bone mineral density (BMD) values measured by dual energy X-ray absorptiometry (DXA) at the lumbar spine (anteroposterior and lateral) and proximal femur in patients with IBD with those of a control group of subjects adjusted for age, sex and BMI.
2. To compare the ultrasound velocity and attenuation parameters (BUA and SOS) obtained by quantitative ultrasound of the calcaneus (QUS) in patients with IBD with those of a control group of subjects adjusted for age, sex and BMI.
3. To analyse the prevalence and severity of vertebral fractures using the Vertebral Fracture Assessment (VFA) software of lateral DXA in patients with IBD compared to a control group adjusted for age, sex and BMI.
4. To correlate the TBS results with the ultrasound velocity and attenuation parameters (BUA and SOS) obtained with QUS.
5. To correlate TBS results with BMD parameters measured by DXA in the lumbar spine (anteroposterior and lateral) and in the proximal femur.
6. To compare biochemical markers of bone remodelling \[carboxy-terminal telopeptide of type I collagen (ß-CTx Crosslaps) and N-terminal propeptide of type I protocolagen (P1NP)\] in patients with IBD with a control group of subjects adjusted for age, sex and BMI.
7. To correlate baseline levels of biochemical markers of bone remodelling with the results of: a) BMD obtained with DXA in the lumbar spine (anteroposterior and lateral) and in the proximal femur, b) TBS values and c) parameters obtained with QUS.
8. To assess the absolute 10-year risk of major fractures and hip fractures using the FRAX tool, in subjects with IBD. To correlate the absolute risk of fractures with the TBS and QUS values.
9. To evaluate the effect of adjusting the FRAX tool by including TBS values for the calculation of the absolute risk of major and hip fractures.
10. To analyse the evolution of bone microarchitecture parameters measured by TBS, bone ultrasound parameters of ultrasound velocity and attenuation, BMD in the lumbar spine (anteroposterior and lateral) and in the proximal femur and biochemical markers of bone remodelling in patients with IBD after one year of follow-up.
11. To analyse the discriminative capacity for the diagnosis of vertebral fractures evaluated with VFA of the TBS and QUS values, compared with the BMD values obtained in lumbar DXA (anteroposterior and lateral) in patients with IBD.
12. To compare volumetric BMD parameters measured by 3D bone densitometry (DXA-3D) of the hip in patients with IBD with a control group of subjects adjusted for age, sex and BMI.
13. To correlate bone quality parameters measured by TBS and QUS with volumetric BMD measured by 3D DXA-3D in the hip.
14. To evaluate the effect of the different disease-modifying treatments (biologicals, corticoids, etc.) on TBS values, bone ultrasound parameters, BMD values by conventional DXA and DXA-3D in patients with IBD.

This study is organised into two sub-studies:

* Sub-study 1: observational, analytical, prospective, cross-sectional. Cohort-type study, with a cohort of patients with IBD and a cohort of volunteers without IBD or known metabolic bone pathology, recruited in the consultations of the Endocrinology and Nutrition, Digestive System and Rheumatology departments of the Ruber Juan Bravo Hospital during routine health control visits, adjusted for age, sex and body mass index (BMI). The baseline data on bone quality measured by: a) bone densitometry in the lumbar spine (anteroposterior and lateral), b) bone densitometry in the proximal femur, c) TBS, d) DEXA-3D, e) calcaneal ultrasound, e) fractures assessed by VFA and f) biochemical markers of bone remodelling in both cohorts will be analysed to respond to the primary objective, secondary objectives 2 to 9 and exploratory objectives 11 to 14.
* Sub-study 2: observational, analytical, prospective and longitudinal, with one-year follow-up of IBD patients only. Bone quality parameters measured by: a) bone densitometry in the lumbar spine (anteroposterior and lateral), b) bone densitometry in the proximal femur, c) TBS, d) DEXA-3D, e) calcaneal ultrasound, e) fractures assessed by VFA and f) biochemical markers of bone remodelling will be analysed to respond to secondary objective 10.

Eligibility criteria: Inclusion Criteria:

1. Subjects over 21 years old, with inflammatory bowel disease (both ulcerative colitis and Crohn's disease), diagnosed by clinical, biochemical, endoscopic and anatomo-pathological criteria.
2. Subjects over 21 years old, without IBD or known metabolic bone pathology, recruited voluntarily in the Endocrinology and Nutrition, Digestive System and Rheumatology departments of the Ruber Juan Bravo Hospital, during routine health control visits (control group).
3. Subjects without language barriers, who expressed their willingness to cooperate in the follow-up and who gave their informed consent before entering the study.

Exclusion Criteria:

1. Other concomitant causes of metabolic bone disease: Paget's disease, severe chronic renal insufficiency (estimated glomerular filtration rate \<30 ml/min/1.73m2), metastatic bone disease, multiple myeloma, Hypercalcemia \> 11 mg/dl, period of immobilisation for more than 3 months in the previous year.
2. Pregnant women or women planning pregnancy during the recruitment and testing process.
3. Anatomical alteration of the right foot that may interfere with calcaneal ultrasound, including moderate-severe edema.
4. Patients on active treatment with antiresorptive drugs, osteoformers, or pharmacological doses (\>50,000 units/month) of vitamin D3 (cholecalciferol).
5. Patients with a history of treatment with oral bisphosphonates, strontium ranelate or therapeutic doses of fluoride (\>20 mg/day) for more than 3 months in the two years prior to the baseline visit, or for more than two years at any time in their life.
6. Patients who have received an intravenous bisphosphonate in the three years prior to the baseline visit.
7. Patients who have received denosumab within 6 months prior to the baseline visit.
8. Patients who have received calcitonin or a selective oestrogen receptor modulator in the 3 months prior to the baseline visit.
9. Participation at the time of recruitment in a clinical trial with medicinal products for the prevention or treatment of osteoporosis and/or IBD.

   Additional exclusion criteria for the control group:
10. Chronic diseases affecting bone metabolism, for example, active hyperthyroidism within the last 6 months, Cushing's syndrome, anorexia nervosa, early menopause, type 1 diabetes mellitus, poorly controlled type 2 diabetes mellitus of more than 5 years' duration or with microvascular complications, or primary hyperparathyroidism.
11. Active treatment with drugs that affect bone quality such as corticoids, oral anticoagulants, anti-estrogens (aromatase inhibitors and/or GnRH analogues), anti-androgens and anti-retroviral

Primary outcomes:
measure: Trabecular Bone Score
timeFrame: 1 year
Secondary outcomes:
measure: BMD
timeFrame: 1 year
measure: BQI
timeFrame: 1 year
measure: VFA
timeFrame: 1 year
measure: ß-CTx
timeFrame: 1 year
measure: P1NP
timeFrame: 1 year
Other outcomes:
measure: Volumetric BMD
timeFrame: 1 year
Locations:
city: Madrid
country: Spain
facility: Hospital Ruber Juan Bravo
Study officials:
affiliation: Quironsalud
name: Maria Cortes
role: PRINCIPAL_INVESTIGATOR
References: