· deficiency of calcium and/or phosphorus for mineralisation of the skeleton
· leads to less mineralised bone per unit volume of bone
· rickets
· increased uncalcified osteoid in the immature skeleton (children)
· osteomalacia
· increased uncalcified osteoid in the mature skeleton (adults)
· vitamin D deficiency is classic form of disease
· now much less common
· most common cause now is hypophosphataemic rickets
· deficiency states
· vitamin D
· calcium
· phosphate
· gastrointestinal
· vitamin D resistance
· phosphaturic
· type-1 dependent
· type-II dependent
· renal tubular acidosis
· renal osteodystrophy
General
Calcium and vitamin D
· reduced vitamin D intake leads to
· decrease in calcium absorption from gut leads to
· decreased serum Ca++ leads to
· secondary hyperparathyroidism leads to
· increase of serum Ca++ to low normal and
· phosphate diuresis with decrease of serum phosphate
Calcium
· decrease in calcium intake leads to
· decreased serum Ca++ leads to
· secondary hyperparathyroidism leads to
· increase of serum Ca++ to low normal and
· phosphate diuresis with decrease of serum phosphate
Phosphate
· decrease in phosphate intake leads to
· decreased serum PO4-- leads to
· increased renal production of 1,25-vit D leads to
· increased bone resorption
Vitamin D deficiency
· classic form
· usually results from
· dietary deficiency of vitamin D (elderly, vegans)
· inadequate exposure to sunlight
· overcome by vitamin D and calcium supplements
Calcium deficiency
· decreased dietary intake
· seen where dairy products avoided
Chelators
· very uncommon
· seen with bizarre diet
· substances that can bind calcium and make it unabsorbable are
· phytate (cereals)
· oxalate (spinach)
· phosphate excess
Phosphorus deficiency
· dietary cause very unusual
· may be due to precipitation of insoluble phosphates by
· beryllium (industrial toxin)
· aluminium (in antacids)
Gastric
· seen previously with surgery for peptic ulcer disease
· result of Polya or Billroth II gastrectomy
· decreased absorption of calcium due to
· decreased acid content in stomach
· excessively rapid transit of contents through duodenum and proximal jejunum (‘dumping’)
Biliary
· reduced vitamin D absorption due to abnormal fat metabolism
· associated with
· failure of emulsifying action of bile salts
· presence of free fat in GIT
· may be reduced calcium absorption
· from production of insoluble calcium soaps with free fatty acids
Enteric
· decreased calcium absorption from diffuse injury to wall of small bowel
· inflammatory bowel disease
· shunts or fistulae
· rapid transit
Hypophosphataemic
· most prevalent cause of rickets
· due to genetic or aquired defect in handling of phosphate in proximal tubule
· no secondary hyperparathyroidism because serum calcium not affected
· thus no excessive resorption
· administration of vitamin D has little effect
· overcome by administration of phosphate
· congenital and acquired forms
X-linked hypophosphataemia
· Albright’s syndrome
· most common congenital form
· X-linked dominant disorder
· diminished tubular reabsorption of phosphate
· treated with administration of high doses of phosphate
· high doses of vitamin D added to offset secondary hyperparathyroidism
Vitamin D dependent
· rare disorders
· classical features of vitamin D deficiencies
· psuedodependence as no response to vitamin D replacement
· overcome by administration of high doses of 1,25-D and calcium
Type I
· failure of conversion of 25-D to 1,25-D
· may be due to abnormality of renal alpha-hydroxylase
Type II
· end-organ insensitivity to 1,25-D
· may be due to failure of gut and other cells to recognise 1,25-D
Renal tubular acidosis
· may be
· primary genetic syndrome
· acquired syndrome
· part of another disorder
· part of another renal tubular syndrome
· caused by inability for kidney to conserve bicarbonate
· leads to decreased serum bicarbonate and acidosis
· result is
· erosion of bone from metabolic acidosis
· release of calcium from bone as carbonate used as buffer
· calcium excretion in urine
· cannot be treated by vitamin D
· overcome by correction of metabolic acidosis with sodium bicarbonate
Fanconi’s syndrome
· generalised defect in renal proximal tubular transport
· impaired resorption of paphate, glucose, amino acids etc
· excessive excretion of calcium
· heterogenous group of causes
· due to
· inherited disorders
· metabolic or toxic injury to proximal tubule
· rickets and osteomalacia from
· phosphaturia
· hypercalcuria
· abnormal vitamin D metabolism
Hypophosphatasia
· rare inherited form
· due to generalised reduction in tissue non-specific alkaline phosphatase activity
· causes retardation of skeletal mineralisation
· often severe and fatal
Fibrous dysplasia or neurofibromatosis
· rickets or osteomalacia may be rare manifestations
Bone and soft tissue tumours
· most common in benign fibrous soft-tissue tumours
· due to production of humoral factors that affect renal tubule
· esp. phosphate handling
Chronic use of anticonvulsants
· with all anti-seizure drugs
· due to interference with hepatic handling of vitamin D
· vit D converted to inactive metabolites rather than 25-D
· cortices thin
· trabeculae thin and irregular
· osteoid seams
· layer of unmineralized bone
· surrounds a mineralized segment
· reserve and proliferative zones are essentially normal
· hypertrophic zone disordered
· greatly widened and increased in height
· orderly columnization lost
· tongues of hypertrophic cells extend down into metaphysis
· height increased because cells do not release calcium and remain alive
· metaphysis abnormal
· matrix does not calcify
· few spicules of bone that do form are poorly mineralized
· wide osteoid seams present
Growth
· stunting of height
· weight not affected
· may have enlarged abdomen (rachitic pot-belly)
Activity
· apathy and hypokinesis
· irritability
· weakness
· may be severe with inability to walk
Skull
· softening (craniotabes)
· prominence of sutures (hot-cross skull)
· prominence of frontal bones (frontal bossing)
Teeth
· defects of enamel
· extensive caries
Thorax
· prominence of costochondral junctions (rachitic rosary)
· pectus carinatum
· indenation of lower part of rib cage at insertion of diaphragm (Harrison’s groove)
Spine
· thoracic kyphosis (rachitic cat-back)
Extremities
· enlagement of wrists, elbows, ankles and knees
· bowing deformity of long bones
· esp. lower extremity - bow legs and knock knees
· pathological fractures
· few findings
· malaise and easy fatiguability
· bone pain and tenderness
· may present with back pain
· proximal muscle weakness
· Trendelenburg gait
· low or low-normal Ca++
· low PO4-
· calcium/phosphate index low
· Ca++ x PO4- < 2.4 (normal > 3)
· high ALP
· PTH normal or high
· low serum 25-D
General
· rickets
· primarily affects growth plate but also bones
· bones may show changes of secondary hyperparathyroidism
· osteomalacia
· affects only bones
· changes less evident because bones less active
· may also see changes of secondary hyperparathyroidism
· osseous changes
· thin cortices
· indistinct fuzzy trabeculae with ground-glass appearance
· may be
· bowing
· pathological fractures
· growth plate changes characteristic
Physis
· enormous increase in height of growth plate
· irregular cupping and flaring of metaphysis
· failure of mineralisation of metaphysis
Secondary hyperparathyroidism
· subperiosteal erosions
· in areas of maximal remodelling
· medial borders of
· proximal humerus
· femoral neck
· distal femur
· proximal tibia
· lateral borders of
· distal radius
· distal ulna
· three characteristic features
Looser's zones
· syn. Milkman's pseudofractures
· ribbon-like linear radiolucent lines
· transverse to long axis of bone
· often do not extend completely across bone
· are stress fractures that have healed with unmineralised callus
· occur on concave side of long bones
· medial femoral neck
· ischial and pubic rami
· ribs, clavicles
· axillary border of scapulae
· may propagate
Codfish vertebrae
· may be multiple vertebral compression fractures from disc pressure
· result is biconcave (codfish) vertebrae
Trefoil pelvis
· billateral indentation of acebulum
· gives appearance of champagne glass or trefoil
· patchy areas of increased uptake
· Looser’s zones are active
· much less common because of improved management of patients with renal failure
· rickets or osteomalacia plus secondary hyperparathyroidism as a result of glomerular failure
· glomerular failure leads to
· failure of filtration and retention of phosphate leads to
· hyperphosphataemia and
· decreased tubular mass leads to
· decreased synthesis of 1,25-D and
· increased phosphate level in GIT cells leads to
· decreased calcium absorption leads to
· decreased serum Ca++ leads to
· secondary hyperparathyroidism leads to
· defect in bone mineralisation leads to
· low-normal serum Ca++ leads to
· ectopic calcification and ossification and osteosclerosis
Aluminium toxicity
· in patients on prolonged haemodialysis, condition may not respond to 1,25-D
· may be due to aluminium intoxication
· aluminium-containing phosphate-binding antacids used in haemodialysis fluid to control phosphate accumulation
· features of rickets or osteomalacia
· features of hyperparathyroidism
· slipped upper femoral epiphysis
· patchy osteosclerosis
· vertebral sclerosis may be in upper and lower thirds of bodies (rugger jersey spine)
· ectopic calcification and ossification
· conjunctivae (red eyes)
· blood vessels (media and muscularis)
· skin (itching)
· periarticular (frozen joints)
· adoption of appropriate diets
· dietary supplements
· sun exposure
General
· agents
· vitamin D
· 1,25-D
· alpha-hydroxylase
· calcium
· phosphate
· dialysis
· subtotal parathyroidectomy
Orthopaedic
· establish diagnosis
· fixation of fractures
· bracing or osteotomy of deformity
· fixation of slipped epiphysis
· realignment or replacement of damaged joints