Alterations of Inflammatory and Matrix Production Indices in Celiac Disease with Low Bone Mass on Long-term Gluten-free Diet

M. Di Stefano, M. Bergonzi, I. Benedetti, M. De Amici, C. Torre, N. Brondino, E. Miceli, E. Pagani, G.L. Marseglia, G.R. Corazza, A. Di Sabatino

Research output: Contribution to journalArticle

Abstract

Background:A clinically meaningful impairment of bone mass secondary to malabsorption is frequent in untreated celiac disease. In adult patients, a rigorous gluten-free diet (GFD) significantly improves, but does not always normalize, bone mineral density (BMD). The reason for this marginal response is unclear. Accordingly, we evaluated the role of both local and systemic factors for bone loss in celiac patients on long-term GFD.Study:In a prospective cohort, 22 patients with low lumbar and/or femoral BMD and 22 with normal BMD underwent bone and mineral metabolism evaluation: we tested calcium, phosphate, parathyroid hormone, and vitamin D; telopeptide of type I collagen, a bone resorption index; propeptide of type I procollagen, a bone neoformation index; receptor antagonist of NF-kB ligand, an osteoclast-stimulating factor; osteoprotegerin (OPG), a decoy receptor for RANKL. Sunlight exposure and physical exercise were measured.Results:Patients with bone loss showed prevalently osteopenia, severe osteoporosis was rare. In comparison with normal BMD patients, they showed higher serum OPG, telopeptide, and lower serum propeptide, suggesting an increased bone turnover. Lumbar T-score was negatively correlated with OPG, telopeptide and RANKL and positively with propeptide. Propeptide was negatively correlated with OPG and telopeptide. OPG was positively correlated with telopeptide.Conclusions:The persistent activation of inflammation should be considered the main pathophysiological mechanism for bone defect in celiac disease patients with bone loss on long-term GFD. High levels of OPG, an attempt at protective mechanism, and low levels of propeptide of type I procollagen, reflecting an insufficient matrix production, characterize this subgroup of patients. © 2019 Lippincott Williams and Wilkins. All rights reserved.
Original languageEnglish
Pages (from-to)E221-E226
JournalJournal of Clinical Gastroenterology
Volume53
Issue number6
DOIs
Publication statusPublished - 2019

Fingerprint

Gluten-Free Diet
Osteoprotegerin
Celiac Disease
Bone and Bones
Bone Density
Collagen Type I
NF-kappa B
Bone Remodeling
Metabolic Bone Diseases
Sunlight
Bone Resorption
Thigh
Parathyroid Hormone
Serum
Vitamin D
Abdomen
Osteoporosis
Minerals
Exercise
Ligands

Keywords

  • celiac disease
  • gluten-free diet
  • osteoporosis
  • osteoprotegerin
  • RANKL
  • 24,25 dihydroxyvitamin D
  • calcium
  • collagen
  • immunoglobulin enhancer binding protein
  • osteoclast differentiation factor
  • parathyroid hormone
  • phosphate
  • procollagen
  • procollagen type 1 propeptide
  • telopeptide
  • telopeptide of type I collagen
  • unclassified drug
  • vitamin D
  • adult
  • Article
  • bone density
  • bone mass
  • bone mineralization
  • bone turnover
  • calcium blood level
  • clinical article
  • cohort analysis
  • comparative study
  • controlled clinical trial
  • controlled study
  • disease severity
  • exercise
  • female
  • femur
  • gluten free diet
  • human
  • inflammation
  • long term care
  • lumbar spine
  • nutritional status
  • osteoclast
  • osteolysis
  • osteopenia
  • parathyroid hormone blood level
  • phosphate blood level
  • physical activity
  • prevalence
  • priority journal
  • protein blood level
  • vitamin blood level

Cite this

@article{b3857c556c7944e19bbdec2c08c1ec53,
title = "Alterations of Inflammatory and Matrix Production Indices in Celiac Disease with Low Bone Mass on Long-term Gluten-free Diet",
abstract = "Background:A clinically meaningful impairment of bone mass secondary to malabsorption is frequent in untreated celiac disease. In adult patients, a rigorous gluten-free diet (GFD) significantly improves, but does not always normalize, bone mineral density (BMD). The reason for this marginal response is unclear. Accordingly, we evaluated the role of both local and systemic factors for bone loss in celiac patients on long-term GFD.Study:In a prospective cohort, 22 patients with low lumbar and/or femoral BMD and 22 with normal BMD underwent bone and mineral metabolism evaluation: we tested calcium, phosphate, parathyroid hormone, and vitamin D; telopeptide of type I collagen, a bone resorption index; propeptide of type I procollagen, a bone neoformation index; receptor antagonist of NF-kB ligand, an osteoclast-stimulating factor; osteoprotegerin (OPG), a decoy receptor for RANKL. Sunlight exposure and physical exercise were measured.Results:Patients with bone loss showed prevalently osteopenia, severe osteoporosis was rare. In comparison with normal BMD patients, they showed higher serum OPG, telopeptide, and lower serum propeptide, suggesting an increased bone turnover. Lumbar T-score was negatively correlated with OPG, telopeptide and RANKL and positively with propeptide. Propeptide was negatively correlated with OPG and telopeptide. OPG was positively correlated with telopeptide.Conclusions:The persistent activation of inflammation should be considered the main pathophysiological mechanism for bone defect in celiac disease patients with bone loss on long-term GFD. High levels of OPG, an attempt at protective mechanism, and low levels of propeptide of type I procollagen, reflecting an insufficient matrix production, characterize this subgroup of patients. {\circledC} 2019 Lippincott Williams and Wilkins. All rights reserved.",
keywords = "celiac disease, gluten-free diet, osteoporosis, osteoprotegerin, RANKL, 24,25 dihydroxyvitamin D, calcium, collagen, immunoglobulin enhancer binding protein, osteoclast differentiation factor, parathyroid hormone, phosphate, procollagen, procollagen type 1 propeptide, telopeptide, telopeptide of type I collagen, unclassified drug, vitamin D, adult, Article, bone density, bone mass, bone mineralization, bone turnover, calcium blood level, clinical article, cohort analysis, comparative study, controlled clinical trial, controlled study, disease severity, exercise, female, femur, gluten free diet, human, inflammation, long term care, lumbar spine, nutritional status, osteoclast, osteolysis, osteopenia, parathyroid hormone blood level, phosphate blood level, physical activity, prevalence, priority journal, protein blood level, vitamin blood level",
author = "{Di Stefano}, M. and M. Bergonzi and I. Benedetti and {De Amici}, M. and C. Torre and N. Brondino and E. Miceli and E. Pagani and G.L. Marseglia and G.R. Corazza and {Di Sabatino}, A.",
note = "Export Date: 10 October 2019 CODEN: JCGAD Correspondence Address: Di Stefano, M.; Departments of Internal Medicine, IRCCS S. Matteo Hospital, P.le Golgi 5, Italy; email: m.distefano@unipv.it Chemicals/CAS: 24,25 dihydroxyvitamin D, 83931-84-4; calcium, 7440-70-2, 14092-94-5; collagen, 9007-34-5; osteoclast differentiation factor, 200145-93-3; osteoprotegerin, 205944-50-9; parathyroid hormone, 12584-96-2, 68893-82-3, 9002-64-6; phosphate, 14066-19-4, 14265-44-2 Funding details: 715, 08045901/12 Funding text 1: Received for publication December 4, 2017; accepted February 25, 2018. From the Departments of *Internal Medicine; †Pediatrics, IRCCS “S. Matteo” Hospital Foundation; and ‡Department of Psychiatry, University of Pavia, Pavia, Italy. Supported with a research grant from IRCCS S. Matteo Hospital Foundation: project number 715, project code 08045901/12. M.D.S.: planned and conducted the study, interpreted data, drafted the manuscript. M.B. and I.B.: conducted the study, collected and interpreted data, drafted the manuscript. M.D.A., C.T., N.B., E.M., and E.P.: conducted the study, collected data and drafted the manuscript. G.L.M., G.R.C., and A.D.S.: planned the study, interpreted data and drafted the manuscript. The authors declare that they have nothing to disclose. Address correspondence to: Michele Di Stefano, MD, I Department of Medicine, IRCCS “S. Matteo” Hospital, P.le Golgi 5, Pavia 27100, Italy (e-mail: m.distefano@unipv.it). Copyright {\circledC} 2018 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MCG.0000000000001032 References: Corazza, G.R., Di Stefano, M., Mauri{\~n}o, E., Bones in coeliac disease: Diagnosis and treatment (2005) Best Pract Res Clin Gastroenterol, 19, pp. 453-465; Di Stefano, M., Mengoli, C., Bergonzi, M., Bone mass and mineral metabolism alterations in adult celiac disease: Pathophysiology and clinical approach (2013) Nutrients, 5, pp. 4786-4799; Corazza, G.R., Di Sario, A., Cecchetti, A., Influence of pattern of clinical presentation and gluten-free diet on bone mass and metabolism in adult coeliac disease (1996) Bone, 18, pp. 525-530; Valdimarsson, T., L{\"o}fman, O., Toss, G., Reversal of osteopenia with diet in adult coeliac disease (1996) Gut, 38, pp. 322-327; Selby, P.L., Davies, M., Adams, J.E., Bone loss in celiac disease is related to secondary hyperparathyroidism (1999) J Bone Miner Res, 14, pp. 652-657; Bai, J.C., Gonzalez, D., Mautalen, C., Long-term effect of gluten restriction on bone mineral density of patients with coeliac disease (1997) Aliment Pharmacol Ther, 11, pp. 157-164; Ciacci, C., Cirillo, M., Mellone, M., Hypocalciuria in overt and subclinical celiac disease (1995) Am J Gastroenterol, 90, pp. 1480-1484; Molteni, N., Bardella, M.T., Vezzoli, G., Intestinal calcium absorption as shown by stable strontium test in celiac disease before and after gluten-free diet (1995) Am J Gastroenterol, 90, pp. 2025-2028; Keaveny, A.P., Freaney, R., McKenna, M.J., Remodeling indices and secondary hyperparathyroidism in celiac disease (1996) Am J Gastroenterol, 91, pp. 1226-1231; Pazianas, M., Butcher, G.P., Subhani, J.M., Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake (2005) Osteoporos Int, 16, pp. 56-63; Taranta, A., Fortunati, D., Longo, M., Imbalance of osteoclastogenesis-regulating factors in patients with celiac disease (2004) J Bone Miner Res J, 19, pp. 1112-1121; Goldbourt, U., Medalie, J.H., Weight-height indices (1974) Br J Prev Soc Med, 28, pp. 116-126; (2007) WHO Scientific Group on the Assessment of Osteoporosis at Primary Health Care Levels. Summary Meeting Report 2004, pp. 1-17. , Brussels, Belgium: World Health Organization; Villareal, D.T., Civitelli, R., Chines, A., Subclinical vitamin deficiency in postmenopausal women with low vertebral bone mass (1991) J Clin Endocrinol Metab, 72, pp. 628-634; Elders, P.J.M., Netelenbos, J.C., Lips, P., Perimenopausal bone mass and risk factors (1989) Bone Miner, 7, pp. 289-299; Faul, F., Erdfelder, E., Lang, A.G., G∗Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences (2007) Behav Res Methods, 39, pp. 175-191; Mora, S., Barera, G., Beccio, S., Prospective, longitudinal study of the long-term effect of treatment on bone density in children with celiac disease (2001) J Pediatr, 139, pp. 516-521; Mazure, R., Vazquez, H., Gonzalez, D., Bone mineral affection in asymptomatic adult patients with celiac disease (1994) Am J Gastroenterol, 89, pp. 2130-2134; Corazza, G.R., Di Sario, A., Cecchetti, A., Bone mass and mineral metabolism in patients with celiac disease (1995) Gastroenterology, 109, pp. 122-128; McFarlane, X.A., Bhalla, A.K., Robertson, D.A.F., Effect of gluten free diet on osteopenia in adults with newly diagnosed celiac disease (1996) Gut, 39, pp. 180-184; Mustalahti, K., Collin, P., Sievanen, H., Osteopenia in patients with clinically silent coeliac disease warrants screening (1999) Lancet, 354, pp. 744-745; Bod{\'e}, S., Hassager, C., Gudmand-H{\o}yer, E., Body composition and calcium metabolism in adult treated coeliac disease (1991) Gut, 32, pp. 1342-1345; Valdimarsson, T., Toss, G., L{\"o}fman, O., Three years' follow-up of bone density in adult celiac disease: Significance of secondary hyperparathyroidism (2000) Scand J Gastroenterol, 35, pp. 274-280; Walters, J.R., Banks, L.M., Butcher, G.P., Detection of low bone mineral density by dual energy X-ray absorptiometry in unsuspected suboptimally treated coeliac disease (1995) Gut, 37, pp. 220-224; McFarlane, X.A., Bhalla, A.K., Reeves, D.E., Osteoporosis in treated adult coeliac disease (1995) Gut, 36, pp. 710-714; Mora, S., Barera, G., Ricotti, A., Reversal of low bone density with a gluten-free diet in children and adolescents with celiac disease (1998) Am J Clin Nutr, 67, pp. 477-481; Hofbauer, L.C., Osteoprotegerin ligand and osteoprotegerin: Novel implications for osteoclast biology and bone metabolism (1999) Eur J Endocrinol, 141, pp. 195-210; Leslie, W.D., Lix, L.M., Langsetmo, L., Construction of a FRAX{\circledR} model for the assessment of fracture probability in Canada and implications for treatment (2011) Osteoporos Int, 22, pp. 817-827; Aubin, J.E., Bonnelye, E., Osteoprotegerin and its ligand: A new paradigm for regulation of osteoclastogenesis and bone resorption (2000) Osteoporos Int, 11, pp. 905-913; Fiore, C.E., Pennisi, P., Ferro, G., Altered osteoprotegerin/RANKL ratio and low bone mineral density in celiac patients on long-term treatment with gluten-free diet (2006) Horm Metab Res, 38, pp. 417-422; Ueland, T., Bollerslev, J., Godang, K., Increased serum osteoprotegerin in disorders characterised by persistent immune activation or glucocorticoid excess-possible role in bone homeostasis (2001) Eur J Endocrinol, 145, pp. 685-690; Szalay, F., Hegedus, D., Lakatos, P.L., High serum osteoprotegerin and low RANKL in primary biliary cirrhosis (2003) J Hepatol, 38, pp. 395-400; Maimoun, L., Couret, I., Mariano-Goulart, D., Changes in osteoprotegerin/RANKL system, bone mineral density, and bone biochemical markers in patients with recent spinal cord injury (2005) Calcif Tissue Int, 76, pp. 404-411; Corazza, G.R., Di Stefano, M., Jorizzo, R.A., Propeptide of type I procollagen is predictive of posttreatment bone mass gain in adult celiac disease (1997) Gastroenterology, 113, pp. 67-71",
year = "2019",
doi = "10.1097/MCG.0000000000001032",
language = "English",
volume = "53",
pages = "E221--E226",
journal = "Journal of Clinical Gastroenterology",
issn = "0192-0790",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Alterations of Inflammatory and Matrix Production Indices in Celiac Disease with Low Bone Mass on Long-term Gluten-free Diet

AU - Di Stefano, M.

AU - Bergonzi, M.

AU - Benedetti, I.

AU - De Amici, M.

AU - Torre, C.

AU - Brondino, N.

AU - Miceli, E.

AU - Pagani, E.

AU - Marseglia, G.L.

AU - Corazza, G.R.

AU - Di Sabatino, A.

N1 - Export Date: 10 October 2019 CODEN: JCGAD Correspondence Address: Di Stefano, M.; Departments of Internal Medicine, IRCCS S. Matteo Hospital, P.le Golgi 5, Italy; email: m.distefano@unipv.it Chemicals/CAS: 24,25 dihydroxyvitamin D, 83931-84-4; calcium, 7440-70-2, 14092-94-5; collagen, 9007-34-5; osteoclast differentiation factor, 200145-93-3; osteoprotegerin, 205944-50-9; parathyroid hormone, 12584-96-2, 68893-82-3, 9002-64-6; phosphate, 14066-19-4, 14265-44-2 Funding details: 715, 08045901/12 Funding text 1: Received for publication December 4, 2017; accepted February 25, 2018. From the Departments of *Internal Medicine; †Pediatrics, IRCCS “S. Matteo” Hospital Foundation; and ‡Department of Psychiatry, University of Pavia, Pavia, Italy. Supported with a research grant from IRCCS S. Matteo Hospital Foundation: project number 715, project code 08045901/12. M.D.S.: planned and conducted the study, interpreted data, drafted the manuscript. M.B. and I.B.: conducted the study, collected and interpreted data, drafted the manuscript. M.D.A., C.T., N.B., E.M., and E.P.: conducted the study, collected data and drafted the manuscript. G.L.M., G.R.C., and A.D.S.: planned the study, interpreted data and drafted the manuscript. The authors declare that they have nothing to disclose. Address correspondence to: Michele Di Stefano, MD, I Department of Medicine, IRCCS “S. Matteo” Hospital, P.le Golgi 5, Pavia 27100, Italy (e-mail: m.distefano@unipv.it). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MCG.0000000000001032 References: Corazza, G.R., Di Stefano, M., Mauriño, E., Bones in coeliac disease: Diagnosis and treatment (2005) Best Pract Res Clin Gastroenterol, 19, pp. 453-465; Di Stefano, M., Mengoli, C., Bergonzi, M., Bone mass and mineral metabolism alterations in adult celiac disease: Pathophysiology and clinical approach (2013) Nutrients, 5, pp. 4786-4799; Corazza, G.R., Di Sario, A., Cecchetti, A., Influence of pattern of clinical presentation and gluten-free diet on bone mass and metabolism in adult coeliac disease (1996) Bone, 18, pp. 525-530; Valdimarsson, T., Löfman, O., Toss, G., Reversal of osteopenia with diet in adult coeliac disease (1996) Gut, 38, pp. 322-327; Selby, P.L., Davies, M., Adams, J.E., Bone loss in celiac disease is related to secondary hyperparathyroidism (1999) J Bone Miner Res, 14, pp. 652-657; Bai, J.C., Gonzalez, D., Mautalen, C., Long-term effect of gluten restriction on bone mineral density of patients with coeliac disease (1997) Aliment Pharmacol Ther, 11, pp. 157-164; Ciacci, C., Cirillo, M., Mellone, M., Hypocalciuria in overt and subclinical celiac disease (1995) Am J Gastroenterol, 90, pp. 1480-1484; Molteni, N., Bardella, M.T., Vezzoli, G., Intestinal calcium absorption as shown by stable strontium test in celiac disease before and after gluten-free diet (1995) Am J Gastroenterol, 90, pp. 2025-2028; Keaveny, A.P., Freaney, R., McKenna, M.J., Remodeling indices and secondary hyperparathyroidism in celiac disease (1996) Am J Gastroenterol, 91, pp. 1226-1231; Pazianas, M., Butcher, G.P., Subhani, J.M., Calcium absorption and bone mineral density in celiacs after long term treatment with gluten-free diet and adequate calcium intake (2005) Osteoporos Int, 16, pp. 56-63; Taranta, A., Fortunati, D., Longo, M., Imbalance of osteoclastogenesis-regulating factors in patients with celiac disease (2004) J Bone Miner Res J, 19, pp. 1112-1121; Goldbourt, U., Medalie, J.H., Weight-height indices (1974) Br J Prev Soc Med, 28, pp. 116-126; (2007) WHO Scientific Group on the Assessment of Osteoporosis at Primary Health Care Levels. Summary Meeting Report 2004, pp. 1-17. , Brussels, Belgium: World Health Organization; Villareal, D.T., Civitelli, R., Chines, A., Subclinical vitamin deficiency in postmenopausal women with low vertebral bone mass (1991) J Clin Endocrinol Metab, 72, pp. 628-634; Elders, P.J.M., Netelenbos, J.C., Lips, P., Perimenopausal bone mass and risk factors (1989) Bone Miner, 7, pp. 289-299; Faul, F., Erdfelder, E., Lang, A.G., G∗Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences (2007) Behav Res Methods, 39, pp. 175-191; Mora, S., Barera, G., Beccio, S., Prospective, longitudinal study of the long-term effect of treatment on bone density in children with celiac disease (2001) J Pediatr, 139, pp. 516-521; Mazure, R., Vazquez, H., Gonzalez, D., Bone mineral affection in asymptomatic adult patients with celiac disease (1994) Am J Gastroenterol, 89, pp. 2130-2134; Corazza, G.R., Di Sario, A., Cecchetti, A., Bone mass and mineral metabolism in patients with celiac disease (1995) Gastroenterology, 109, pp. 122-128; McFarlane, X.A., Bhalla, A.K., Robertson, D.A.F., Effect of gluten free diet on osteopenia in adults with newly diagnosed celiac disease (1996) Gut, 39, pp. 180-184; Mustalahti, K., Collin, P., Sievanen, H., Osteopenia in patients with clinically silent coeliac disease warrants screening (1999) Lancet, 354, pp. 744-745; Bodé, S., Hassager, C., Gudmand-Høyer, E., Body composition and calcium metabolism in adult treated coeliac disease (1991) Gut, 32, pp. 1342-1345; Valdimarsson, T., Toss, G., Löfman, O., Three years' follow-up of bone density in adult celiac disease: Significance of secondary hyperparathyroidism (2000) Scand J Gastroenterol, 35, pp. 274-280; Walters, J.R., Banks, L.M., Butcher, G.P., Detection of low bone mineral density by dual energy X-ray absorptiometry in unsuspected suboptimally treated coeliac disease (1995) Gut, 37, pp. 220-224; McFarlane, X.A., Bhalla, A.K., Reeves, D.E., Osteoporosis in treated adult coeliac disease (1995) Gut, 36, pp. 710-714; Mora, S., Barera, G., Ricotti, A., Reversal of low bone density with a gluten-free diet in children and adolescents with celiac disease (1998) Am J Clin Nutr, 67, pp. 477-481; Hofbauer, L.C., Osteoprotegerin ligand and osteoprotegerin: Novel implications for osteoclast biology and bone metabolism (1999) Eur J Endocrinol, 141, pp. 195-210; Leslie, W.D., Lix, L.M., Langsetmo, L., Construction of a FRAX® model for the assessment of fracture probability in Canada and implications for treatment (2011) Osteoporos Int, 22, pp. 817-827; Aubin, J.E., Bonnelye, E., Osteoprotegerin and its ligand: A new paradigm for regulation of osteoclastogenesis and bone resorption (2000) Osteoporos Int, 11, pp. 905-913; Fiore, C.E., Pennisi, P., Ferro, G., Altered osteoprotegerin/RANKL ratio and low bone mineral density in celiac patients on long-term treatment with gluten-free diet (2006) Horm Metab Res, 38, pp. 417-422; Ueland, T., Bollerslev, J., Godang, K., Increased serum osteoprotegerin in disorders characterised by persistent immune activation or glucocorticoid excess-possible role in bone homeostasis (2001) Eur J Endocrinol, 145, pp. 685-690; Szalay, F., Hegedus, D., Lakatos, P.L., High serum osteoprotegerin and low RANKL in primary biliary cirrhosis (2003) J Hepatol, 38, pp. 395-400; Maimoun, L., Couret, I., Mariano-Goulart, D., Changes in osteoprotegerin/RANKL system, bone mineral density, and bone biochemical markers in patients with recent spinal cord injury (2005) Calcif Tissue Int, 76, pp. 404-411; Corazza, G.R., Di Stefano, M., Jorizzo, R.A., Propeptide of type I procollagen is predictive of posttreatment bone mass gain in adult celiac disease (1997) Gastroenterology, 113, pp. 67-71

PY - 2019

Y1 - 2019

N2 - Background:A clinically meaningful impairment of bone mass secondary to malabsorption is frequent in untreated celiac disease. In adult patients, a rigorous gluten-free diet (GFD) significantly improves, but does not always normalize, bone mineral density (BMD). The reason for this marginal response is unclear. Accordingly, we evaluated the role of both local and systemic factors for bone loss in celiac patients on long-term GFD.Study:In a prospective cohort, 22 patients with low lumbar and/or femoral BMD and 22 with normal BMD underwent bone and mineral metabolism evaluation: we tested calcium, phosphate, parathyroid hormone, and vitamin D; telopeptide of type I collagen, a bone resorption index; propeptide of type I procollagen, a bone neoformation index; receptor antagonist of NF-kB ligand, an osteoclast-stimulating factor; osteoprotegerin (OPG), a decoy receptor for RANKL. Sunlight exposure and physical exercise were measured.Results:Patients with bone loss showed prevalently osteopenia, severe osteoporosis was rare. In comparison with normal BMD patients, they showed higher serum OPG, telopeptide, and lower serum propeptide, suggesting an increased bone turnover. Lumbar T-score was negatively correlated with OPG, telopeptide and RANKL and positively with propeptide. Propeptide was negatively correlated with OPG and telopeptide. OPG was positively correlated with telopeptide.Conclusions:The persistent activation of inflammation should be considered the main pathophysiological mechanism for bone defect in celiac disease patients with bone loss on long-term GFD. High levels of OPG, an attempt at protective mechanism, and low levels of propeptide of type I procollagen, reflecting an insufficient matrix production, characterize this subgroup of patients. © 2019 Lippincott Williams and Wilkins. All rights reserved.

AB - Background:A clinically meaningful impairment of bone mass secondary to malabsorption is frequent in untreated celiac disease. In adult patients, a rigorous gluten-free diet (GFD) significantly improves, but does not always normalize, bone mineral density (BMD). The reason for this marginal response is unclear. Accordingly, we evaluated the role of both local and systemic factors for bone loss in celiac patients on long-term GFD.Study:In a prospective cohort, 22 patients with low lumbar and/or femoral BMD and 22 with normal BMD underwent bone and mineral metabolism evaluation: we tested calcium, phosphate, parathyroid hormone, and vitamin D; telopeptide of type I collagen, a bone resorption index; propeptide of type I procollagen, a bone neoformation index; receptor antagonist of NF-kB ligand, an osteoclast-stimulating factor; osteoprotegerin (OPG), a decoy receptor for RANKL. Sunlight exposure and physical exercise were measured.Results:Patients with bone loss showed prevalently osteopenia, severe osteoporosis was rare. In comparison with normal BMD patients, they showed higher serum OPG, telopeptide, and lower serum propeptide, suggesting an increased bone turnover. Lumbar T-score was negatively correlated with OPG, telopeptide and RANKL and positively with propeptide. Propeptide was negatively correlated with OPG and telopeptide. OPG was positively correlated with telopeptide.Conclusions:The persistent activation of inflammation should be considered the main pathophysiological mechanism for bone defect in celiac disease patients with bone loss on long-term GFD. High levels of OPG, an attempt at protective mechanism, and low levels of propeptide of type I procollagen, reflecting an insufficient matrix production, characterize this subgroup of patients. © 2019 Lippincott Williams and Wilkins. All rights reserved.

KW - celiac disease

KW - gluten-free diet

KW - osteoporosis

KW - osteoprotegerin

KW - RANKL

KW - 24,25 dihydroxyvitamin D

KW - calcium

KW - collagen

KW - immunoglobulin enhancer binding protein

KW - osteoclast differentiation factor

KW - parathyroid hormone

KW - phosphate

KW - procollagen

KW - procollagen type 1 propeptide

KW - telopeptide

KW - telopeptide of type I collagen

KW - unclassified drug

KW - vitamin D

KW - adult

KW - Article

KW - bone density

KW - bone mass

KW - bone mineralization

KW - bone turnover

KW - calcium blood level

KW - clinical article

KW - cohort analysis

KW - comparative study

KW - controlled clinical trial

KW - controlled study

KW - disease severity

KW - exercise

KW - female

KW - femur

KW - gluten free diet

KW - human

KW - inflammation

KW - long term care

KW - lumbar spine

KW - nutritional status

KW - osteoclast

KW - osteolysis

KW - osteopenia

KW - parathyroid hormone blood level

KW - phosphate blood level

KW - physical activity

KW - prevalence

KW - priority journal

KW - protein blood level

KW - vitamin blood level

U2 - 10.1097/MCG.0000000000001032

DO - 10.1097/MCG.0000000000001032

M3 - Article

VL - 53

SP - E221-E226

JO - Journal of Clinical Gastroenterology

JF - Journal of Clinical Gastroenterology

SN - 0192-0790

IS - 6

ER -