Metabolic Bone Disease

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Metabolic Bone Disease

• Amal Al Dabbagh, MD

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Rickets

• Amal AL Dabbagh, MD

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Classification of metabolic bone disease

• 1.Calcium deficiency disease.
• Any factor that impairs intestinal calcium
  absorption, including deficient dietary intake,
  results in calcium deficiency
• 2.Phosphate deficiency disease.
• On the other hand, except for dietary
  phosphate depletion, phosphate deficiency is the
  result of inappropriate excessive renal
  excretion of this ion.
• 3. If these deficiencies are severe enough, both
  osteomalacia and rickets will result
• 4. Rickets is the disorder wherein chondrocytes
  do not undergo mineralization, the provisional
  zone of calcification does not form.

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Hypocalcemic disorders of childhood

• Hypoparathyroidism ( post surgery, infiltration,
  idiopathic as congenital)
• Pseudohypoparathyroidism.
• Hypomagnesemia( impaired absorption, excess renal
  wasting, diarrhea).
• Vitamin D abnormalities( ?intake, ?sunlight
  exposure, ?absorption, hepatocellular disorders,
  that impair 25(OH)D synthesis, ? production of
  calcitriol- renal disease or AR vit D- dependant
  rickets, End-organ unresponsiveness to calcitriol
  with rickets).

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Hypophosphatemic disorders of childhood

• Primary hypophosphatemic rickets.
• Oncogenous rickets with phosphaturia (
  neurofibromatosis).
• Complex proximal tubulopathy ( Fanconi syndrome
  either 1ry or 2ry to Wilsons tyrosinosis,
  galactosemia, fructose intolerance).
• 2ry to ? iPTH secretion ( vit D ?rickets, vit D
  dependency rickets, rickets unresponsive to
  calcitriol with receptor defect, Fanconi with vit
  D ?).

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Introduction

• Normal bone growth mineralization require
  adequate availability of calcium phosphate.
• Deficient mineralization can result in rickets
  and/or osteomalacia.
• Rickets refers to the changes caused by deficient
  mineralization at the growth plate.
• Osteomalacia refers to impaired mineralization of
  the bone matrix.
• Rickets osteomalacia usually occur together as
  long as the growth plates are open only
  osteomalacia occurs after the growth plates have
  fused.

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Vitamin D metabolism
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Rickets , introduction

• Mineralization defect are classified according to
  the mineral deficiency.
• Calcipenic rickets ( vit D?, 1-alpha hydroxylase
  defect, vit D receptor dysfunction, dietary Ca ?,
  CRF) .
• Phosphopenic ricket Inadequate
  intake  (Premature infants (rickets of
  prematurity) , Aluminum-containing antacids).

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Rickets, Etiology

• Deficient Intake Ca, Ph, Vit D.
• Poor absorption vit D ?, pseudo vit D?, vit D
  resistance, high phytin content( soy formula),
  antacids, anticonvulsants, renal insufficiency,
  Fanconi syndrome, hepatic insufficiency, fat
  malabsorption (cystic fibrosis).
• Increased excretion furosemide, renal tubular
  dysfunction( phosphaturia, RTA with
  hypercalciuria), renal tubular damage e.g.
  cystinosis, tyrosinosis, galactosemia, fructose
  intolerance, wilson disease.
• Local effect on bone matrix hypophosphatasia(alp?
  )

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Causes of Rickets

• VITAMIN D DISORDERS Nutritional vitamin D
  deficiency Congenital vitamin D deficiency
  Secondary vitamin D deficiency  Malabsorption  I
  ncreased degradation Decreased liver
  25-hydroxylase Vitamin D-dependent rickets type
  1 Vitamin D-dependent rickets type 2 Chronic
  renal failure.
• CALCIUM DEFICIENCY Low intake  Diet  Premature
  infants (rickets of prematurity)
  Malabsorption  Primary disease  Dietary
  inhibitors of calcium absorption
• PHOSPHORUS DEFICIENCY Inadequate
  intake  Premature infants (rickets of
  prematurity)  Aluminum-containing antacids
• RENAL LOSSES X-linked hypophosphatemic rickets
  Autosomal dominant hypophosphatemic rickets
  Hereditary hypophosphatemic rickets with
  hypercalciuria Overproduction of
  phosphatonin ( Tumor-induced rickets,  McCune-Albr
  ight syndrome  Epidermal nevus
  syndrome,  Neurofibromatosis) ,Fanconi syndrome,
  Dent disease
• DISTAL RENAL TUBULAR ACIDOSIS

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Rickets, clinical manifestations

• Skeletal findings
• Delay in closure of the fontanelles.
• Parietal frontal bossing.
• Craniotabes ( soft skull bones).
• Enlargement of the costochondral junction
  (rachitic rosary).
• The development of Harrison sulcus ( caused by
  pull of the diaphragmatic attachments to the
  lower ribs).
• Enlargement of the wrist bowing of the distal
  radius ulna.
• Progressive lateral bowing of the femur tibia.

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Clinical features of Rickets

• GENERAL Failure to thrive Listlessness
  Protuding abdomen Muscle weakness (especially
  proximal) Fractures.
• HEAD Craniotabes Frontal bossing Delayed
  fontanelle closure Delayed dentition caries
  Craniosynostosis
• CHEST Rachitic rosary Harrison groove
  Respiratory infections and atelectasis
• BACK Scoliosis ,Kyphosis ,Lordosis
• EXTREMITIES Enlargement of wrists and ankles
  Valgus or varus deformities Windswept deformity
  (combination of valgus deformity of 1 leg with
  varus deformity of the other leg) Anterior
  bowing of the tibia and femur Coxa vara Leg
  pain.
• HYPOCALCEMIC SYMPTOMS Tetany Seizures Stridor
  due to laryngeal spasm

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Extra skeletal findings in Rickets

• Extraskeletal manifestation of rickets vary
  depending upon the 1ry mineral deficiency.
• Hypoplasia of the dental enamel is typical for
  hypocalcemic rickets, whereas abscesses of the
  teeth occur more often in phosphopenic rickets.
• Hypocalcemic seizures, decreased muscle tone
  leading to delayed motor milestones, recurrent
  infections, increased sweating.

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Biochemical findings in rickets

• Alkaline phosphatase usually is ?in all forms of
  rickets.
• Serum phosphorus concentrations usually are? in
  both hypocalcemic and hypophosphatemic rickets.
• Serum Ca is ?only in hypocalcemic rickets.
• Serum parathyroid hormone typically is ?in
  hypocalcemic rickets, in contrast it is N in
  hypophosphatemic rickets.
• 25-OH vitamin D reflect the amount of vitamin D
  stored in the body, and is ?in vit D deficiency.
• 1,25-OH2 vitamin D can be?, N or ?in hypocalcemic
  rickets and usually is N or slightly ?in
  hypophosphatemic rickets.

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Treatment of Rickets

• Vitamin D. stoss therapy 300,000-600,000 iu
  orally or IM in 2-4 divided doses over one day.
• High dose vit D 2000-5000 iu orally for 4-6wks
  followed by 400iu daily orally as maintenance.
• Adequate dietary Calcium phosphorus provided by
  milk, formula other dairy products.
• Symptomatic hypocalcaemia need IV cacl as 20mg/kg
  or ca gluconate as 100mg/kg as a bolus, followed
  by oral calcium tapered over 2-6 weeks.