Identification of Bone Metabolism Disorders in Patients with Alström and Bardet-Biedl Syndromes Based on Markers of Bone Turnover and Mandibular Atrophy

Overview

Journal Bone Rep

Date 2022 Jul 12

PMID 35818441

Authors

Krzysztof Jeziorny

Ewa Zmyslowska-Polakowska

Krystyna Wyka

Aleksandra Pyziak-Skupien

Maciej Borowiec

Agnieszka Szadkowska

Agnieszka Zmyslowska

Affiliations

Soon will be listed here.

Abstract

Objectives: Causative variants in genes responsible for Alström syndrome (ALMS) and Bardet-Biedl syndrome (BBS) cause damage to primary cilia associated with correct functioning of cell signaling pathways in many tissues. Despite differences in genetic background, both syndromes affect multiple organs and numerous clinical manifestations are common including obesity, retinal degeneration, insulin resistance, type 2 diabetes and many others. The aim of the study was to evaluate bone metabolism abnormalities and their relation to metabolic disorders based on bone turnover markers and presence of mandibular atrophy in patients with ALMS and BBS syndromes.

Material And Methods: In 18 patients (11 with ALMS and 7 with BBS aged 5-29) and in 42 age-matched ( < 0.05) healthy subjects, the following markers of bone turnover were assessed: serum osteocalcin (OC), osteoprotegerin (OPG), s-RANKL and urinary deoxypyridinoline - DPD. In addition, a severity of alveolar atrophy using dental panoramic radiograms was evaluated.

Results: Lower serum OC ( = 0.0004) and urinary DPD levels ( = 0.0056) were observed in the study group compared to controls. In ALMS and BBS patients, serum OC and urinary DPD values negatively correlated with the HOMA-IR index, while a positive correlation between the OC and 25-OHD levels and a negative correlation between s-RANKL and fasting glucose concentrations were found. A significant difference in the incidence of low-grade mandibular atrophy between patients with ALMS and BBS and controls ( < 0.0001) was observed.

Conclusions: The identification of bone metabolism disorders in patients with ALMS and BBS syndromes indicates the necessity to provide them with appropriate diagnosis and treatment of these abnormalities.

Citing Articles

The "Burden" of Childhood Obesity on Bone Health: A Look at Prevention and Treatment.

Farella I, Chiarito M, Vitale R, DAmato G, Faienza M Nutrients. 2025; 17(3).

PMID: 39940349 PMC: 11821239. DOI: 10.3390/nu17030491.

Zhang Q, Huang Y, Gao S, Ding Y, Zhang H, Chang G Int J Mol Sci. 2024; 25(15).

PMID: 39126056 PMC: 11312664. DOI: 10.3390/ijms25158484.

Serum metabolomics identified specific lipid compounds which may serve as markers of disease progression in patients with Alström and Bardet-Biedl syndromes.

Jeziorny K, Pietrowska K, Sieminska J, Zmyslowska-Polakowska E, Kretowski A, Ciborowski M Front Mol Biosci. 2023; 10:1251905.

PMID: 38028552 PMC: 10657895. DOI: 10.3389/fmolb.2023.1251905.

Searching for Effective Methods of Diagnosing Nervous System Lesions in Patients with Alström and Bardet-Biedl Syndromes.

Waszczykowska A, Jeziorny K, Baranska D, Matera K, Pyziak-Skupien A, Ciborowski M Genes (Basel). 2023; 14(9).

PMID: 37761924 PMC: 10530666. DOI: 10.3390/genes14091784.

Bardet-Biedl Syndrome: Current Perspectives and Clinical Outlook.

Melluso A, Secondulfo F, Capolongo G, Capasso G, Zacchia M Ther Clin Risk Manag. 2023; 19:115-132.

PMID: 36741589 PMC: 9896974. DOI: 10.2147/TCRM.S338653.

References

Marshall J, Muller J, Collin G, Milan G, Kingsmore S, Dinwiddie D . Alström Syndrome: Mutation Spectrum of ALMS1. Hum Mutat. 2015; 36(7):660-8. PMC: 4475486. DOI: 10.1002/humu.22796. View

Tahani N, Choudhary S, Boivin C, Dawson C, Gittoes N, Geberhiwot T . Very high bone mineral density in a monogenic form of obesity-associated insulin resistance. Bone. 2020; 143:115756. DOI: 10.1016/j.bone.2020.115756. View

Montalvany-Antonucci C, Zicker M, Macari S, Pereira T, Diniz I, Andrade Jr I . High-refined carbohydrate diet promotes detrimental effects on alveolar bone and femur microarchitecture. Arch Oral Biol. 2017; 86:101-107. DOI: 10.1016/j.archoralbio.2017.11.013. View

Kim G, Jekal Y, Kim H, Im J, Park J, Chu S . Reduced serum total osteocalcin is associated with central obesity in Korean children. Obes Res Clin Pract. 2014; 8(3):e201-98. DOI: 10.1016/j.orcp.2012.12.003. View

Jeziorny K, Antosik K, Jakiel P, Mlynarski W, Borowiec M, Zmyslowska A . Next-Generation Sequencing in the Diagnosis of Patients with Bardet-Biedl Syndrome-New Variants and Relationship with Hyperglycemia and Insulin Resistance. Genes (Basel). 2020; 11(11). PMC: 7693916. DOI: 10.3390/genes11111283. View

Delmas P, Schlemmer A, Gineyts E, Riis B, Christiansen C . Urinary excretion of pyridinoline crosslinks correlates with bone turnover measured on iliac crest biopsy in patients with vertebral osteoporosis. J Bone Miner Res. 1991; 6(6):639-44. DOI: 10.1002/jbmr.5650060615. View

Majumdar U, Arya G, Singh S, Pillai A, Nair P . Oro-dental findings in Bardet-Biedl syndrome. BMJ Case Rep. 2012; 2012. PMC: 3339191. DOI: 10.1136/bcr.12.2011.5320. View

Cakatay U, Telci A, Kayali R, Akcay T, Sivas A, Aral F . Changes in bone turnover on deoxypyridinoline levels in diabetic patients. Diabetes Res Clin Pract. 1998; 40(2):75-9. DOI: 10.1016/s0168-8227(98)00025-4. View

Han J, Reyes-Capo D, Liu C, Reynolds J, Turkbey E, Turkbey I . Comprehensive Endocrine-Metabolic Evaluation of Patients With Alström Syndrome Compared With BMI-Matched Controls. J Clin Endocrinol Metab. 2018; 103(7):2707-2719. PMC: 6276679. DOI: 10.1210/jc.2018-00496. View

10.

Alvarez-Satta M, Castro-Sanchez S, Valverde D . Bardet-Biedl Syndrome as a Chaperonopathy: Dissecting the Major Role of Chaperonin-Like BBS Proteins (BBS6-BBS10-BBS12). Front Mol Biosci. 2017; 4:55. PMC: 5534436. DOI: 10.3389/fmolb.2017.00055. View

11.

Valentini A, Cianfarani M, Federici M, Tarantino U, Bertoli A . Osteoprotegerin in diabetic osteopathy. Nutr Metab Cardiovasc Dis. 2019; 30(1):49-55. DOI: 10.1016/j.numecd.2019.08.018. View

12.

Montalvany-Antonucci C, Zicker M, Ferreira A, Macari S, Ramos-Junior E, Gomez R . High-fat diet disrupts bone remodeling by inducing local and systemic alterations. J Nutr Biochem. 2018; 59:93-103. DOI: 10.1016/j.jnutbio.2018.06.006. View

13.

Gannage-Yared M, Yaghi C, Habre B, Khalife S, Noun R, Germanos-Haddad M . Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study. Eur J Endocrinol. 2008; 158(3):353-9. DOI: 10.1530/EJE-07-0797. View

14.

Starup-Linde J, Eriksen S, Lykkeboe S, Handberg A, Vestergaard P . Biochemical markers of bone turnover in diabetes patients--a meta-analysis, and a methodological study on the effects of glucose on bone markers. Osteoporos Int. 2014; 25(6):1697-708. DOI: 10.1007/s00198-014-2676-7. View

15.

Ugur-Altun B, Altun A, Gerenli M, Tugrul A . The relationship between insulin resistance assessed by HOMA-IR and serum osteoprotegerin levels in obesity. Diabetes Res Clin Pract. 2005; 68(3):217-22. DOI: 10.1016/j.diabres.2004.10.011. View

16.

Wical K, Swoope C . Studies of residual ridge resorption. I. Use of panoramic radiographs for evaluation and classification of mandibular resorption. J Prosthet Dent. 1974; 32(1):7-12. DOI: 10.1016/0022-3913(74)90093-6. View

17.

Ostrowska Z, Swietochowska E, Marek B, Kajdaniuk D, Tyrpien-Golder K, Wolkowska-Pokrywa K . Selected adipose tissue hormones, bone metabolism, osteoprotegerin and receptor activator of nuclear factor-kB ligand in postmenopausal obese women. Endokrynol Pol. 2015; 65(6):438-48. DOI: 10.5603/EP.2014.0061. View

18.

Bozic M, Ihan Hren N . Osteoporosis and mandibles. Dentomaxillofac Radiol. 2006; 35(3):178-84. DOI: 10.1259/dmfr/79749065. View

19.

El-Dorry G, Ashry H, Ibrahim T, Elias T, Alzaree F . Bone Density, Osteocalcin and Deoxypyridinoline for Early Detection of Osteoporosis in Obese Children. Open Access Maced J Med Sci. 2016; 3(3):413-9. PMC: 4877829. DOI: 10.3889/oamjms.2015.092. View

20.

Ortman L, Hausmann E, Dunford R . Skeletal osteopenia and residual ridge resorption. J Prosthet Dent. 1989; 61(3):321-5. DOI: 10.1016/0022-3913(89)90137-6. View