Transcript Metabolic Bone Disease

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