title: The aetiology of rickets-like lower limb deformities in Malawian children.
abstract: Debilitating rickets-like lower limb deformities are common in children throughout the world, particularly in Malawi, Africa where the causes are unknown. We have identified that Blount disease and calcium deficiency rickets are the likely causes of these deformities and propose calcium supplementation as a potential treatment of Malawian rickets.
  
  
  
  Surgical correction of rickets-like lower limb deformities is the most common paediatric operation performed at Beit Cure Orthopaedic Hospital, Malawi. The aim of this study was to investigate the aetiology of these deformities.
  
  
  
  Children with a tibio-femoral angle of deformity >20° were enrolled (n = 42, 3.0-15.0 years). Anthropometric and early life and well-being data were collected. Early morning serum and urine samples were collected on the morning of the operation for markers of calcium and phosphate homeostasis. Knee radiographs were obtained, and the children were diagnosed with either Blount (BD, n = 22) or evidence of rickets disease (RD, n = 20). As BD is a mechanical rather than metabolic disease, BD were assumed to be biochemically representative of the local population and thus used as a local reference for RD.
  
  
  
  There were no differences in anthropometry or early life experiences between BD and RD. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, total alkaline phosphatase and urinary phosphate were significantly higher and serum phosphate, 25-hydroxyvitamin D (25OHD) and tubular maximal reabsorption of phosphate significantly lower in RD than BD. There was no difference in serum calcium, fibroblast growth factor 23 or markers of iron status between groups. All children had 25OHD > 25 nmol/L.
  
  
  
  Vitamin D deficiency is not implicated in the aetiology of RD or BD in Malawian children. The cause of RD in Malawi is likely to be dietary calcium deficiency leading to elevated PTH resulting in increased losses of phosphate from the bone and glomerular filtrate. The causes of BD remain unclear; there was no evidence in support of previously suggested risk factors such as being overweight or starting to walk early. Prior to surgical intervention, supplementation with calcium should be considered for children with RD.
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, UK. vickie.braithwaite@mrc-hnr.cam.ac.uk.
authors.forename: V S
authors.initials: VS
authors.lastname: Braithwaite
authors.affiliation: Department of Paediatric Orthopaedics, Robert Jones Agnes Hunt NHS Foundation Trust, Oswestry, Shropshire, UK.
authors.forename: R
authors.initials: R
authors.lastname: Freeman
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, UK.
authors.forename: C L
authors.initials: CL
authors.lastname: Greenwood
authors.affiliation: Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Summers
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, UK.
authors.forename: S
authors.initials: S
authors.lastname: Nigdikar
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, UK.
authors.forename: C B D
authors.initials: CBD
authors.lastname: Lavy
authors.affiliation: Department of Oncology and Metabolism, Academic Unit of Child Health, University of Sheffield, Sheffield, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Offiah
authors.affiliation: Department of Oncology and Metabolism, Academic Unit of Child Health, University of Sheffield, Sheffield, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Bishop
authors.affiliation: Beit Cure Orthopaedic Hospital, Blantyre, Malawi.
authors.forename: J
authors.initials: J
authors.lastname: Cashman
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge, UK.|MRC Keneba, Keneba, The Gambia.
authors.forename: A
authors.initials: A
authors.lastname: Prentice
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis; D001848:Bone Diseases, Developmental / Q000209:etiology*; D002118:Calcium / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D035002:Lower Extremity / Q000473:pathology*; D008295:Malawi / Q000453:epidemiology; D008297:Male; D055034:Osteochondrosis / Q000151:congenital* / Q000209:etiology; D010281:Parathyroid Hormone / Q000032:analysis; D010710:Phosphates / Q000032:analysis; D012279:Rickets / Q000209:etiology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C104450:25-hydroxyvitamin D; D000469:Alkaline Phosphatase; D002118:Calcium
keywords: Africa; Blount; Children; Genu valgum; Genu varum; Phosphate; Rickets