Transcript Rickets & Metabolic Bone Diseases

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Calcium
Phosphate
PTH
Vitamin D
Calcitonin
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> 99% in bone
Muscle and nerve function
Clotting mechanisms
Free plasma Ca = Bound plasma Ca
Active transport absorption in the duodenum
and passive diffusion in the jejunum
98% reabsorption in the kidney
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600 mg/day in children
1300 mg/day in adolescents and young
adults
750 mg/day in adults
1500 mg/day in pregnant women
2000 mg/day in lactating women
1500 mg/day in postmenopausal women and
patients with fractures
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Key component of bone mineral
Enzyme systems and molecular interactions
85% in bone
Plasma Phosphate is mostly unbound
1000-1500 mg/day
Vitamin D metabolism
Secondary role
Other Hormones
- Estrogen
- Corticosteroids
- Thyroxin
Non-hormonal Factors
- Mechanical stress
- Prostaglandin E
- Acid-base balance
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Normal bone growth & mineralization require adequate
availability of calcium & phosphate.
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Deficient mineralization can result in rickets and/or
osteomalacia.
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Rickets refers to the changes caused by deficient
mineralization at the growth plate.
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Osteomalacia refers to impaired mineralization of the bone
matrix.
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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 disorders
◦ Nutritional vitamin D deficiency; Congenital vitamin D deficiency;
Secondary vitamin D deficiency; Malabsorption ; Increased
degradation; Decreased liver 25-hydroxylase; Vitamin D-dependent
rickets type 1; Vitamin D-dependent rickets type 2; Chronic renal
failure.
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Calcium deficiency
◦ Low intake, Calcium deficient Diet, Premature infants (rickets of
prematurity), Malabsorption, Dietary inhibitors of calcium absorption
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Phosphorus deficiency
◦ Inadequate intake, Premature infants (rickets of
prematurity), Aluminum-containing antacids
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RENAL LOSSES
◦ X-linked hypophosphatemic rickets; Autosomal dominant
hypophosphatemic rickets; Hereditary hypophosphatemic rickets
with hypercalciuria; Overproduction of phosphatonin (Tumorinduced rickets, McCune-Albright syndrome, Epidermal nevus
syndrome, Neurofibromatosis), Fanconi syndrome, Dent disease
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DISTAL RENAL TUBULAR ACIDOSIS
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GENERAL Failure to thrive; Listlessness; Protuding abdomen; Muscle
weakness (especially proximal); Fractures.
HEAD Craniotabes; Frontal bossing; Delayed fontanelle closure; Delayed
dentition; caries; Craniosynostosis
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CHEST Rachitic rosary; Harrison groove; Respiratory infections and atelectasis
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BACK Scoliosis ,Kyphosis ,Lordosis
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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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Extraskeletal manifestation of rickets vary depending upon
the 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.
Diagnostic approach to suspected rickets
Diagnostic approach to hypocalcimic rickets
Diagnostic approach to hypophosphatemic rickets
Biochemical findings in rickets
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Alkaline phosphatase usually is ↑in all forms of rickets.
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Serum phosphorus concentrations usually are↓ in both
hypocalcemic and hypophosphatemic rickets.
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Serum Ca is ↓only in hypocalcemic rickets.
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Serum parathyroid hormone typically is ↑in hypocalcemic
rickets, in contrast it is N in hypophosphatemic rickets.
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25-OH vitamin D reflect the amount of vitamin D stored in
the body, and is ↓in vit D deficiency.
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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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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
400 IU 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.
*Primary
hyperplasia - adenoma - carcinoma
*Secondary
persistent hypocalcaemia
*Tertiary
secondary leads to hyperplasia
Pathology
- PTH overproduction
- Increased renal tubular absorption , intestinal
absorption and bone resorption of Ca
- Hypercalcaemia and hypercalciuria
- Suppressed phosphate tubular reabsorption
- Hypophosphataemia and hyperphosphaturia
Pathology
*Hypercalcaemia
calcinosis , stone formation , recurrent
infection and soft tissue calcification
*Bone resorption
loss of bone substance , subperiosteal
erosion
osteitis fibrosa cystica and brown tumors
Symptoms & Signs
*Hypercalcaemia
anorexia , nausea , depression and polyuria
*Bone rarefaction
pain , pathological fractures and
deformities
*Biochemistry
hypercalcaemia , hypophosphataemia ,
high
alk. Phosphatase and serum PTH
X-rays
- Subperiosteal bone resorption
- Generalized decrease in bone density
- Brown tumors
- Chondrocalcinosis
knee , wrist and shoulder
Treatment
 Surgical excision of adenoma or
hyperplastic parathyroid tissue
 Hungry bone syndrome
◦ Treated by vitamin D
* Normal mineralization
* Decrease bone mass
(amount of bone per unit volume)
* Age related
* Associated or manifestation of other
conditions
Causes
* Idiopathic
* Nutritional
* Endocrine disorders
* Drug induced
* Malignant diseases
* Miscellaneous
- Idiopathic osteoporosis - normal investigations
- In old patients we have to role out malignancy
and multiple myeloma
- Younger patients must be fully investigated
- Several causes may be involved
- Osteoporosis can be associated with
osteomalacia
Symptoms & Signs
- Bony aches
- Easy fractures
spine - lower radius - femoral neck
- Rib fracture , chest pain
- Normal biochemistry
X-rays
- Decrease bone density
- Wedging or biconcave vertebrae
- Thin cortex and deformities
- Dexa Scan
- Biopsy
Treatment
- Treat underlying cause
- Idiopathic , extremely difficult
- Calcium and vitamin D
- Fluoride and triple therapy
- Calcitonin , Diphosphonate
- Treat fractures
Prevention
* Good diet
* Exercise
* Exposure to sun light
* Ca supplement
* Hormone therapy
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Diminished renal P excretion
Increased Ca excretion
Impaired synthesis of Vit D
Toxicity e.g. Aluminum and amyloidosis