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Metabolic Bone Disease Dr Neil Hopper Metabolic Bone Disease in Children • Rickets • Osteogenesis Imperfecta • Other – Renal osteodystrophy – Non-OI osteoporosis e.g. Cerebral Palsy – Rarities Rickets • Wricken (OE) ‘to bend’ • Fully described by Glisson 1650 • Deficient mineralisation of growth plate • Adult equivalent is Osteomalacia Pathogenesis • Defective growth plate mineralisation • Inhibition of chondrocyte apoptosis, so transformation to bone inhibited. • Disordered cartilaginous growth plate extends laterally • Osteomalacia of bone • Bone strength compromised leading to bowing Skeletal Clinical Findings • Widened wrist and long bone bowing • Costochondral enlargement ‘rachetic rosary’ • Craniotabes • Frontal bossing • Harrison’s sulcus • Delayed closure of fontanelles Rickets Radiology Extraskeletal features • Hypocalcaemia and seizures – At times of rapid bone turnover • i.e. Infancy and puberty • Muscle hypotonia and delayed milestones • Infections • Cardiomyopathy Does this child have rickets? • Clinical suspicion • ALP usually elevated – note age specific reference ranges • X-Ray of wrist or knee should be abnormal Causes • Majority of cases are due to Vitamin D deficiency • Major differential is X-linked hypophosphataemic rickets • Rarer causes due to enzyme defects, receptor mutations and calcium deficiency Biochemical workup • • • • • Bone profile, LFTs PTH 25(OH) Vitamin D3 Save serum Urine Phosphate, Creatinine – to work out Tubular Resorption of Phosphate Expected findings (in Vitamin D Deficiency) • • • • High ALP Low 25(OH) Vitamin D3 Calcium may be low or normal Phosphate may be low When to suspect phosphopenic rickets (or rarities) • • • • • ALP high (may be subtle) PTH normal or marginal Phosphate low and TRP low Lack of response to Vitamin D therapy Family history! Treatment of Vitamin D deficient rickets • Pharmacological doses of Vitamin D (Ergo or Cholecalciferol) for 3 months – Under 6m age 3000 IU OD – Over 6m age 6000 IU OD • Stoss therapy • Then repeat biochemistry and Vit D level • Vit D 400 IU per day (Abidec 0.6ml OD) long term • Screen sibs and mother Prevention • Vitamin D deficiency common in northern England, especially in dark skinned people • No effective production from October to March at this lattitude • Can be prevented by – Education – Vitamin D supplementation in adult women – Especially during pregnancy and lactation • Screening for Vitamin D deficiency in at-risk populations • Screening in chronic disease Osteogenesis Imperfecta • Group of inherited connective tissue disorders leading to increased bone fragility • 1 in 20,000 • Mostly an AD mutation in COL1A1 or COL1A2 affecting type 1 collagen Sillence classification Type Description Gene I mild [Null COL1A1 allele] II severe and usually lethal in the perinatal period COL1A1, COL1A2, III considered progressive and deforming COL1A1, COL1A2 IV deforming, but with normal sclerae COL1A1, COL1A2 Types V-IX identified based on histological variants and new gene mutations Type II and severe type III are lethal, type I is common and mild and others share features between Clinical features • • • • • • • • • • Family history in 65% Excessive fractures Short stature Scoliosis Basilar skull invagination Blue sclerae Dentinogenesis Imperfecta Hearing Loss Wormian Bones Ligamentous and Cutaneous Laxity Radiology • Lethal forms are often detected antenatally on USS • Slender, gracile long bones • More than 10 Wormian bones • Multiple deformities Diagnosis • Can be difficult in early days • DD involves child abuse but OI much rarer – 5000 UK kids PA with unexplained #, 100 OI • • • • X ray long bones, skull AP and lateral Blue sclera can be normal in neonates Biochemistry unhelpful COL1A1 and COL1A2 genes can be sequenced • Skin biopsy allows collagen analysis in difficult cases OI - treatment • Physio • Orthopaedic care is difficult and specialised • Scoliosis surgery • Pain relief • Look for signs of basilar invagination – Headache, pseudoulnar palsy, paraesthesia below waist, CN palsy, nystagmus OI - Bisphosphonates • Widely used in all types except type VI and mild type 1 • Most experience with IV pamidronate • Oral agents e.g. Risedronate • Osteonecrosis of jaw never seen in paeds • Makes bone strong, but brittle, like chalk. • Long term effects unknown Questions