Effects of Lansoprazole on Bone Turnover Markers

Evaluation of the Effects of Lansoprazole Usage on Bone Turnover Markers in Children With Gastroesophageal Reflux or Gastroesophageal Reflux Disease

Use of proton pump inhibitors (PPI) has increased in recent years. There are concerns that PPIs have possible negative effects on bone metabolism. It has been suggested that PPIs may reduce the absorption of calcium from the small intestine and lead to bone resorption by affecting osteoclastic activity. In this study, it is planned to investigate the effects of lansoprazole, a proton pump inhibitor, on bone turnover markers in pediatric patients with gastroesophageal reflux or gastroesophageal reflux disease.

Study Overview

• Status: Completed
• Conditions: Calcium Metabolism Disorders; Bone Turnover Rate Disorder
• Intervention / Treatment: Diagnostic test: Blood and urine specimens

Detailed Description

This study is planned to be conducted with children who are diagnosed with gastroesophageal reflux or gastroesophageal reflux disease aged 2-18 years and healthy volunteers. The diagnosis of gastroesophageal reflux will be made in accordance with the guidelines of North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). Written and verbal consent will be obtained from patients/healthy volunteers and/or parents who want to participate in the study. Serum calcium, magnesium, alkaline phosphatase, parathormone, 25-OH vitamin D and osteocalcin and urine calcium, creatinine, deoxypyridinoline, C-terminal telopeptides type-1 collagen and N- terminal telopeptides type-1 collagen levels will be measured at baseline and second month in study group and once in control groups.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Turkey
  • Erzurum, Turkey, 25240
    • Ataturk University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with gastroesophageal reflux or gastroesophageal reflux disease aged 16 to18 years who were treated in Pediatric Gastroenterology Department of Ataturk University Hospital included to the study.

Description

Inclusion Criteria:

• Patients diagnosed with gastroesophageal reflux or gastroesophageal reflux disease aged 16 to18 years.

Exclusion Criteria:

• Patients with a malabsorptive disease.
• Patients with any chronic disease.
• Patients who use any medication that may affect calcium and bone metabolism.
• Patients who used proton pumps inhibitor within the last 3 months.
• Patients who do not use lansoprazole in the study group.
• Patients whose blood and urine samples are not taken in the eighth week of treatment.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; Patients with gastroesophageal reflux or gastroesophageal reflux disease who will use lansoprazole.	Diagnostic test: Blood and urine specimens; Blood and urine samples will be taken at baseline and at the end of the second month. For this purpose, 5 ml of blood samples will be taken to plain blood tubes for evaluation of calcium, magnesium, alkaline phosphatase, parathormone, 25-OH vitamin D and osteocalcin quantities. And 3 ml of urine for calcium, creatinine, deoxypyridinoline, C-terminal telopeptides type-1 collagen and N- terminal telopeptides type-1 collagen.
Control group; Healty volunteers who will not use lansoprazole.	Diagnostic test: Blood and urine specimens; Blood and urine samples will be taken at baseline and at the end of the second month. For this purpose, 5 ml of blood samples will be taken to plain blood tubes for evaluation of calcium, magnesium, alkaline phosphatase, parathormone, 25-OH vitamin D and osteocalcin quantities. And 3 ml of urine for calcium, creatinine, deoxypyridinoline, C-terminal telopeptides type-1 collagen and N- terminal telopeptides type-1 collagen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measuring serum calcium levels	Measuring serum calcium levels with spectrophotometric method (mg/dL).	First day
Measuring serum alkaline phosphatase levels	Measuring serum alkaline phosphatase levels with spectrophotometric method (U/L).	First day
Measuring serum magnesium levels	Measuring serum magnesium levels with spectrophotometric method (mg/dL).	First day
Measuring serum osteocalcin levels	Measuring serum osteocalcin levels with spectrophotometric method (mg/L).	First day
Measuring serum parathyroid hormone levels	Measuring serum parathyroid hormone levels with immunoassay method (pg/mL).	First day
Measuring serum vitamin D levels	Measuring serum vitamin D with immunoassay method (ng/mL).	First day
Measuring urine deoxypyridinoline levels	Measuring urine deoxypyridinoline levels with immunoassay method (nmol DPD/mmol creatinine).	First day
Measuring spot urine calcium levels	Measuring urine calcium levels with spectrophotometric method (mg/dL).	First day
Measuring urine creatinine levels	Measuring urine creatinine levels with spectrophotometric method (mg/dL).	First day
Measuring urine C-terminal telopeptides Type I collagen levels	Measuring urine C-terminal telopeptides Type I collagen levels with immunoassay method (ng/mL).	First day
Measuring urine N-terminal telopeptides Type I collagen levels	Measuring urine N-terminal telopeptides Type I collagen levels with immunoassay method (ng/mL).	First day

Collaborators and Investigators

• Sponsor: Ataturk University
• Investigators: Principal Investigator: Ali Islek, MD, Ataturk University School of Medicine

Publications and helpful links

General Publications

• Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27;296(24):2947-53. doi: 10.1001/jama.296.24.2947.
• Sheraly AR, Lickorish D, Sarraf F, Davies JE. Use of gastrointestinal proton pump inhibitors to regulate osteoclast-mediated resorption of calcium phosphate cements in vivo. Curr Drug Deliv. 2009 Apr;6(2):192-8. doi: 10.2174/156720109787846225.
• Targownik LE, Lix LM, Metge CJ, Prior HJ, Leung S, Leslie WD. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008 Aug 12;179(4):319-26. doi: 10.1503/cmaj.071330.
• Targownik LE, Lix LM, Leung S, Leslie WD. Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology. 2010 Mar;138(3):896-904. doi: 10.1053/j.gastro.2009.11.014. Epub 2009 Nov 18.
• Sharara AI, El-Halabi MM, Ghaith OA, Habib RH, Mansour NM, Malli A, El Hajj-Fuleihan G. Proton pump inhibitors have no measurable effect on calcium and bone metabolism in healthy young males: a prospective matched controlled study. Metabolism. 2013 Apr;62(4):518-26. doi: 10.1016/j.metabol.2012.09.011. Epub 2012 Oct 24.
• Kocsis I, Arato A, Bodanszky H, Szonyi L, Szabo A, Tulassay T, Vasarhelyi B. Short-term omeprazole treatment does not influence biochemical parameters of bone turnover in children. Calcif Tissue Int. 2002 Aug;71(2):129-32. doi: 10.1007/s00223-001-2068-9. Epub 2002 Jul 23.
• Qvist P, Christgau S, Pedersen BJ, Schlemmer A, Christiansen C. Circadian variation in the serum concentration of C-terminal telopeptide of type I collagen (serum CTx): effects of gender, age, menopausal status, posture, daylight, serum cortisol, and fasting. Bone. 2002 Jul;31(1):57-61. doi: 10.1016/s8756-3282(02)00791-3.

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2019
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 23, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Actual): January 25, 2022
• Last Update Submitted That Met QC Criteria: January 10, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Lansoprazole; Gastroesophageal reflux; Bone turnover
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Disease; Gastroesophageal Reflux; Metabolic Diseases; Calcium Metabolism Disorders
• Other Study ID Numbers: B.30.2.ATA.0.01.00/500

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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