RICKETS
• Rickets is the failure of mineralization of the cartilaginous matrix of the
growth plate of long bones leading to deformation and fractures
• Rickets refers to the changes caused by deficient mineralization at the
growth plate.
• Osteomalacia refers to impaired mineralization of the bone matrix.
• Rickets and osteomalacia usually occur together as long as the growth
plates are open; only osteomalacia occurs after the growth plates have
fused
• Deficiency of vitamin D, typically caused by dietary deficiency and
inadequate exposure to sunlight, is associated with hypocalcemia,
hypophosphatemia, and rickets in children and osteomalacia in adults
Classification
• Mineralization defects are classified according to the predominant
mineral deficiency.
• Calcipenic rickets is caused primarily by calcium deficiency
• Phosphopenic rickets is caused primarily by phosphate deficiency
•
Physiology
• 7-Dehydrocholesterol, stored in the epidermis, is converted to vitamin D
(cholecalciferol) by ultraviolet light (wavelengths 280–310 nm)
• Dietary vitamin D is absorbed in the small intestine as a fat soluble vitamin
incorporated into chylomicrons.
• Vitamin D formed in the skin is a lipophilic substance that is transported to the
liver bound to albumin and a specific vitamin D–binding protein (DBP).
• In the liver, vitamin D is hydroxylated to produce 25-hydroxyvitamin D (25-[OH]D)
• 25-(OH)D is still rather lipophilic, and it is transported by DBP in the serum to
target tissues
• The final metabolic processing step in the synthesis of the active hormone takes
place principally in the kidney.
• The conversion of 25-(OH)D to 1,25-(OH)2D by the 25-(OH)D1-
hydroxylase in the renal cortex is tightly regulated.
• The synthesis of 1,25-(OH)2D is increased by PTH, thus linking the
formation of 1,25-(OH)2D closely to PTH in the integrated control of
calcium homeostasis.
• The production of 1,25-(OH)2D is also stimulated by
hypophosphatemia and hypocalcemia.
• On the other hand, hypercalcemia, hyperphosphatemia, and
decreased PTH will reduce 1,25-(OH)2D production
• The primary target organs for 1,25-(OH)2D are intestine and bone.
• The most essential action of 1,25-(OH)2D is to stimulate the intestinal transport of
calcium.
• 1,25-(OH)2D also induces the active transport of phosphate, but passive absorption
dominates this process, and the net effect of 1,25-(OH)2D is small.
• In bone, 1,25-(OH)2D regulates a number of osteoblastic functions.
• Vitamin D deficiency leads to rickets, a defect in mineralization.
• However, the defect in mineralization results mainly from decreased delivery of
calcium and phosphate to sites of mineralization.
• 1,25-(OH)2D also stimulates osteoclasts to resorb bone, releasing calcium to
maintain the extracellular calcium concentration
Etiology
• Vitamin D deficiency or resistance is caused by one of four mechanisms
• Impaired availability of vitamin D, secondary to inadequate dietary vitamin
D, fat malabsorptive disorders, and/or lack of photoisomerization
• Impaired hydroxylation by the liver to produce 25-OH vitamin D
• Impaired kidney production of 1,25(OH)2-vitamin D
• End organ insensitivity to vitamin D metabolites (hereditary vitamin D
resistant rickets).
• Lack of vitamin D activity leads to reduced intestinal absorption of calcium
and phosphorus.
•
• Vitamin D deficiency
• Dietary
• UV light
• Malabsorption
• Liver disease
• Anticonvulsants
• Renal disease
• End organ resistance
• Receptor abnormalities
•
Pathogenesis
• Growth plate thickness is determined by two opposing processes:
chondrocyte proliferation and hypertrophy on the one hand and
vascular invasion of the growth plate followed by conversion into
primary bone spongiosa on the other
• Vascular invasion requires mineralization of the growth plate cartilage
and is delayed or prevented by deficiency of calcium or phosphorus
• In these circumstances, growth plate cartilage accumulates and the
growth plate thickens.
• In addition, the chondrocytes of the growth plate become
disorganized, losing their regular straight-columned orientation
• In the bone below the growth plate (metaphysis), the mineralization defect
leads to the accumulation of osteoid
• These abnormalities decrease the biomechanical resistance of the involved
skeletal sites, leading to a secondary increase in the diameters of the
growth plate and metaphysis.
• These changes may be regarded as an attempt to compensate for
decreased bone strength by increased bone size.
• Nonetheless, bone stability is compromised, and if the underlying condition
does not improve, bowing occurs.
• The deformation and fractures in rickets occur particularly at sites of stress
due to weight bearing or at muscle and ligament insertions
Clinical manifestations
• Hypocalcemic and hypophosphatemic rickets manifest initially at the
distal forearm, knee, and costochondral junctions.
• They are the sites of rapid bone growth, where large quantities of
calcium and phosphorus are required for mineralization.
• Skeletal findings: The skeletal findings are similar for hypocalcemic
and hypophosphatemic rickets.
The typical findings of advanced rickets include
• Enlargement and delayed closure of the anterior fontanelle
• Parietal and frontal bossing
• Craniotabes (soft skull bones), caused by thinning of the outer table of the skull
• Enlargement of the costochondral junction visible as beading along the
anterolateral aspects of the chest (the "rachitic rosary")
• The development of Harrison sulcus caused by the muscular pull of the
diaphragmatic attachments to the lower ribs
• Enlargement of the wrist and bowing of the distal radius and ulna
• Progressive lateral bowing of the femur and tibia
• Delayed eruption of the teeth and tooth enamel defects
• Scoliosis
• Exaggerated lordosis
• Bowlegs in older infants
• Greenstick fractures in the long bones.
• The site and type of deformity of the extremities depend upon the age of the
child and the weight-bearing patterns in the limbs.
• Thus, deformities of the forearms and posterior bowing of the distal tibia are
found more commonly in the infant, whereas an exaggeration of the normal
physiological bowing of the legs (genu varum) is a characteristic finding in the
toddler who has started to walk
Extraskeletal findings
• Hypoplasia of the dental enamel is a typical finding of hypocalcemic rickets,
whereas abscesses of the teeth occur more often in phosphophenic rickets.
• Hypocalcemic rickets can affect the musculoskeletal system with decreased
muscle tone, leading to delayed achievement of motor milestones
• Hypocalcemic seizures are a frequent presenting sign in the first year of life
• Children with hypocalcemic rickets also are particularly prone to acquiring
infectious diseases
• Increased sweating is a common finding in young infants with hypocalcemic
rickets and may be caused by bone pain
Investigations
• Laboratory findings: Alkaline phosphatase usually is increased markedly over
the age-specific reference range in both forms of rickets.
• Serum phosphorus concentrations usually are low in both hypocalcemic and
hypophosphatemic rickets, whereas serum calcium concentration is
decreased only in hypocalcemic rickets.
• The serum concentration of parathyroid hormone typically is elevated in
hypocalcemic rickets.
• Serum concentrations of 25-OH vitamin D reflect the amount of vitamin D
stored in the body and, consequently, are low in vitamin D deficiency.
• 1, 25-OH2 vitamin D can be low, normal, or increased in hypocalcemic rickets
and usually is normal or slightly increased in hypophosphatemic forms
Radiographic findings:
• Widening of the epiphyseal plate and loss of definition of the zone of
provisional calcification at the epiphyseal/metaphyseal interface are the
early signs of rickets
• As the disease progresses, disorganization of the growth plate becomes
more apparent, with cupping, splaying, formation of cortical spurs, and
stippling.
• The appearance of the epiphyseal bone centers may be delayed, or they
may be small, osteopenic, and ill-defined
• The shafts of the long bones are osteopenic, and the cortices become thin.
• The trabecular pattern is reduced and becomes coarse.
• Deformities of the shafts of the long bones typically are present, and,
in severe rickets, pathological fractures and looser zones may be
noted.
• Looser zones are pseudofractures, fissures, or narrow radiolucent
lines, 2 to 5 mm in width with sclerotic borders, and are the
characteristic radiologic finding in osteomalacia
