Multimodal Approaches to Diagnosing Metabolic Bone Diseases

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (31 May 2025) | Viewed by 2792

Special Issue Editors


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Guest Editor
Unit of Internal Medicine “Guido Baccelli”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy
Interests: metabolic bone diseases; inborn errors in metabolism; rare diseases; lysosomal diseases; diagnostics in metabolic diseases; biomarkers

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Guest Editor
Unit of Internal Medicine “Guido Baccelli”, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy
Interests: multiple myeloma; microenvironment; oncology; angiogenesis; hematology
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Guest Editor
Lysosomal Disorders Unit, Royal Free London NHS Foundation Trust, London NW3 2QG, UK
Interests: lysosomal storage disorders; paediatric familial hypercholesterolaemia; inherited metabolic disorders

Special Issue Information

Dear Colleagues,

Metabolic bone diseases encompass a diverse group of disorders, ranging from inherited to acquired conditions, which share a common disruption in the balance between bone formation and resorption and carry significant morbidity and mortality when misdiagnosed.

Due to their complex nature, metabolic bone diseases often require a multimodal and multidisciplinary approach to diagnosis and management that relies on close teamwork among clinicians, radiologists, pathologists, and geneticists. Recent advances in sensitive diagnostic and prediction methods, such as emerging biomarkers, new or integrated imaging techniques, machine learning, and computer-based diagnosis have been proven to represent a useful tool for supporting a physician during the diagnostic process. In this landscape, multimodal approaches that enable the deep phenotyping of patients are crucial to advance precision medicine and ensure early/accurate diagnosis, leading to better treatment and outcomes.

Metabolites is launching a Special Issue focused on multimodal approaches to diagnosing metabolic bone diseases. On behalf of the Editorial Office, we invite you to contribute your research papers, review articles, and interesting case reports on state-of-the-art diagnostic approaches to metabolic bone disorders from diverse perspectives for peer review and possible publication.

Dr. Simona D’Amore
Dr. Antonio G. Solimando
Dr. Uma Ramaswami
Guest Editors

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Keywords

  • bone disease
  • bone involvement in congenital and acquired conditions
  • artificial intelligence
  • bi-omarker discovery
  • clinical algorithm
  • integrated imaging approaches
  • omics-based approaches

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Published Papers (2 papers)

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Research

13 pages, 1044 KB  
Article
Quantitative Ultrasound for the Assessment of Bone Quality in Hyperphenylalaninemia/Phenylketonuria Patients: Vitamin D Supplementation Versus No Supplementation
by Albina Tummolo, Giada De Ruvo, Marta Di Nicola, Vito Di Tullio, Livio Melpignano, Donatella De Giovanni and Rosa Carella
Metabolites 2025, 15(11), 754; https://doi.org/10.3390/metabo15110754 - 20 Nov 2025
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Abstract
Background/Objectives: Skeletal impairment has been reported as a common finding in Hyperphenylalaninemia (HPA)/Phenylketonuria (PKU) patients regardless of age and method of diagnosis, both in children and adults. Quantitative Ultrasound (QUS) is a radiation-free and low-cost method for assessing bone quality, used in various [...] Read more.
Background/Objectives: Skeletal impairment has been reported as a common finding in Hyperphenylalaninemia (HPA)/Phenylketonuria (PKU) patients regardless of age and method of diagnosis, both in children and adults. Quantitative Ultrasound (QUS) is a radiation-free and low-cost method for assessing bone quality, used in various chronic conditions. Methods: Bone quality was evaluated using a calcaneal QUS device. Auxological parameters, nutritional intakes, and plasma levels of key bone biomarkers were also registered. The population was divided into four groups: PKU patients under diet therapy and HPA patients on a free diet, both divided into receiving or not receiving single vitamin D supplementation. Results: All HPA/PKU patients had median bone quality index (BQI) Z- and T-score values lower than −1, with slightly better values in HPA children and PKU-supplemented adults. Dietary vitamin D intake in PKU patients was significantly higher than in HPA subjects (p < 0.001), due to protein substitute supplementation. However, plasma 25(OH) vitamin D levels, although increased compared to baseline, were still overlapping among groups (p = 0.845) after supplementation. Approximately a quarter of both pediatric and adult non-supplemented PKU patients had Z-score and T-score levels below −2, and this percentage decreased with vitamin D supplementation in all groups. In PKU-supplemented patients, the Broadband Ultrasound Attenuation (BUA) was significantly higher than in the other groups (p = 0.040). Conclusions: The improvement in BUA may represent preliminary evidence of the effect of vitamin D on bone architecture, which could encourage this supplementation to prevent the worsening of bone structure and reduce the risk of fractures. Full article
(This article belongs to the Special Issue Multimodal Approaches to Diagnosing Metabolic Bone Diseases)
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20 pages, 13913 KB  
Article
Changes in Angiogenesis and Bone Turnover Markers in Patients with Gaucher Disease Developing Osteonecrosis
by Simona D’Amore, Kenneth Eric Poole, Uma Ramaswami, Derralynn Hughes, Kathleen Page, Antonio Giovanni Solimando, Angelo Vacca, Timothy Martin Cox and Patrick Deegan
Metabolites 2024, 14(11), 601; https://doi.org/10.3390/metabo14110601 - 7 Nov 2024
Cited by 2 | Viewed by 1547
Abstract
Background/Objectives: Patients with Gaucher disease have a high risk of bone disease, with osteonecrosis representing the most debilitating complication. The pathogenesis of osteonecrosis has not been fully elucidated yet, and there is an unmet need for predictive biomarkers of bone complications. We [...] Read more.
Background/Objectives: Patients with Gaucher disease have a high risk of bone disease, with osteonecrosis representing the most debilitating complication. The pathogenesis of osteonecrosis has not been fully elucidated yet, and there is an unmet need for predictive biomarkers of bone complications. We aimed to assess the utility of angiogenesis and bone turnover biomarkers as predictors of osteonecrosis in Gaucher disease. Methods: Angiogenesis and bone turnover biomarkers were measured in 146 Gaucher disease patients (70M:76F, median age 49.5 [IQR 36.7 to 61]) with/without osteonecrosis enrolled in the UK-based registry GAUCHERITE [enrolment 2015–2017]. Receiver-operating characteristic curve analysis was used to compare the osteonecrosis predictive value of angiogenesis and bone turnover biomarkers and determine the optimal cut-off values for each biomarker. Results: Sixty-two patients had osteonecrosis before study enrolment, 11 had osteonecrosis during follow-up, and 73 remained osteonecrosis-free. Patients with osteonecrosis showed increased osteopontin and matrix metalloproteinase (MMP)-2 levels and decreased MMP-9 and vascular endothelial growth factor (VEGF)-C compared with those free from osteonecrosis. MMP-9 predicted future osteonecrosis with higher sensitivity and specificity (area under the receiver operating characteristic curve [AUC] 0.84 [95% CI 0.84–0.99]; sensitivity/specificity 82%/75%; cutoff value ≤ 72,420 pg/mL) than osteopontin, MMP-2 and VEGF-C when taken alone. The combination of MMP-9 and VEGF-C further increased the discriminating accuracy. Conclusions: The osteopontin–MMPs–VEGF axis is dysregulated in Gaucher disease patients with osteonecrosis. The combination of MMP-9 and VEGF-C circulating levels may serve to identify Gaucher disease patients at risk of osteonecrosis. Full article
(This article belongs to the Special Issue Multimodal Approaches to Diagnosing Metabolic Bone Diseases)
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