An Explorative Study into the Aetiology of Developmental Dysplasia of the Hip Using Targeted Urine Metabolomics
-
Published:2023-02-21
Issue:3
Volume:12
Page:538
-
ISSN:2076-3921
-
Container-title:Antioxidants
-
language:en
-
Short-container-title:Antioxidants
Author:
Rhodes Amanda M. L.1, Ali Sehrish2ORCID, Minnion Magdalena2, Lee Ling H.3, Joseph Brijil M.3, Ndzo Judwin3, Clarke Nicholas M. P.4, Feelisch Martin2, Aarvold Alexander3
Affiliation:
1. Orthopaedic Surgery, University Hospital Southampton, Southampton SO16 6YD, UK 2. Clinical and Experimental Sciences, Faculty of Medicine, University Hospital Southampton, Southampton SO16 6YD, UK 3. Southampton Children’s Hospital, University Hospital Southampton, Southampton SO16 6YD, UK 4. Department of Paediatric Orthopaedics, University of Southampton, Southampton SO16 6YD, UK
Abstract
Developmental dysplasia of the hip (DDH) is the most prevalent congenital musculoskeletal disorder, yet its cause remains unknown. Adequate nutrient provision and coordinated electron exchange (redox) processes are critical for foetal growth and tissue development. This novel study sought to explore specific biochemical pathways in skeletal development for potential involvement in the aetiology of DDH. Spot urine samples were collected from infants, aged 13–61 days, with and without DDH. Ion chromatography-mass spectrometry was used to quantify thiosulphate, sulphate, nitrate, and phosphate, whilst nitrite was quantified using high-performance liquid chromato-graphy. Thiobarbituric acid reactive substances (TBARS) were measured as markers of lipid peroxidation. Creatinine and osmolality were determined by a 96-well plate assay and micro-osmometer to potentially normalise values for renal function, lean body mass, and hydration status. Urine samples were analysed from 99 babies: 30 with DDH and 69 age-matched non-DDH controls. Thiosulphate, TBARS, and creatinine concentrations differed between the DDH group and the controls (p = 0.025, 0.015, and 0.004 respectively). Urine osmolality was significantly lower in DDH compared to the controls (p = 0.036), indicative of the production of a more diluted urine in DDH infants. Following adjustment for osmolality, significant differences became apparent in urinary sulphate levels in DDH (p = 0.035) whereas all other parameters were similar between the groups. This is the first study to assess the potential role of these inorganic anions in DDH. The higher levels of sulphate found in infants with DDH suggests either enhanced intake from milk, increased endogenous formation, or impaired renal reabsorption. This investigation demonstrates the power of urine metabolomics and highlights the importance of normalisation for hydration status to disentangle developmental disorders. Our results strongly suggest that DDH is a systemic disease associated with altered uptake, formation, or handling of sulphate. There is potential for new opportunities in the prevention or treatment of DDH via nutritional intervention.
Funder
International Hip Dysplasia Institute Royal College of Surgeons of Edinburgh
Subject
Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology
Reference37 articles.
1. Epidemiology of developmental dysplasia of the hip within the UK: Refining the risk factors;Woodacre;J. Child. Orthop.,2016 2. Hip disease and the prognosis of total hip replacements. A review of 53,698 primary total hip replacements reported to the Norwegian arthroplasty register 1987–99;Furnes;J. Bone Joint Surg. Br.,2001 3. Harsanyi, S., Zamborsky, R., Krajciova, L., Kokavec, M., and Danisovic, L. (2020). Developmental Dysplasia of the Hip: A Review of Etiopathogenesis, Risk Factors, and Genetic Aspects Medicina (Kaunas). Medicina, 56. 4. What happens to the gluteus medius in young and middle-aged patients with hip dysplasia?;Chen;Int. Orthop.,2022 5. Developmental dysplasia of the hip: Update of management;Garay;EFORT Open Rev.,2019
|
|