Definition
These conditions are characterized by defective mineralization of bone due to vitamin D deficiency, resistance to the effects of vitamin D or hypophosphatemia.
Osteomealacia is a syndrome in adults of defective bone mineralization, bone pain, increased bone fragility and fractures.
Rickets is the equivalent syndrome in children and is characterized by enlargement of a growth plate and bone deformity.
Epidemiology
The disease is prevalent in elderly people who have a poor diet and limited sunlight exposure.
Causes
1.
Vitamin D deficiency (classical or due to malabsorption)
2.
Failure of vitamin D of 1,25 synthesis (chronic renal failure or vitamin Dresistant rickets type I
3.
Vitamin D receptor defects (vitaminD-resistant rickets type II)
4.
Defects in phosphate and pyrophosphate metabolism (hypophosphatemic rickets, tumour-induced hypophosphatemic osteomalacia and hypophosphatasia)
5.
Iatrogenic (bisphosphonate therapy, aluminium and fluoride)
Causes:
Lack of sunlight exposure since maintenance of normal vitamin D depends on UV sunlight exposure to catalyse synthesis of cholecalceferol from 7dehydrocholesterol in the skin.
Dietary deficiency
Pathogenesis
Low cholecalceferol  low 25(OH)D by liver  low 1,25(OH)2D3 by kidney  low calcium absorption  low serum calcium  high PTH  phosphate wasting and increased bone resorption  progressive bone demineralization
Clinical features of rickets
Delayed development

Muscle hypotonia
Craniotabes
Bossing of the frontal and parietal bones
Delayed anterior fontanelle closure
Enlargement of epiphyses at the lower end of the radius
Swelling of the rib costochondral junction
Clinical features of osteomalacia
Asymptomatic or present with fractures if mild
Muscle and bone pain, malaise and fragility fractures
Proximal muscle weakness
Bone and muscle tenderness
Investigations
Raised serum alkaline phosphatase
Low 25(OH)D
Raised PTH
Low or normal serum calcium and phosphate
X-rays are normal, focal radiolucent areas (pseudofractures or Loozer's zones) in advanced disease, osteopenia, vertebral crush fractures
in children, thickening and widening of the epiphyseal plate
Management
Ergocalciferol (250-1000 microgram daily)for 3-4 months.
Maintenance dose of vitamin D reduced to 10-20 microgram daily.
Causes
 Inactivating mutations in the 25-hydroxyvitamin D-1-alpha-hydroxylase enzyme which converts 25(OH)D to the active metabolite 1,25(OH)2D3 (type
I VDRR)

Inactivating mutations in the vitamin D receptor which impair its ability to activate transcription (type II VDRR)
Clinical features
Clinical features are similar to those of infantile rickets.
Diagnosis is first suspected when the patient fails to respond to vitamin D supplementation.
There may be a positive family history (both conditions are autosomal recessive).

Investigations
In type I, all biochemical features are similar to vitamin D deficiency, except that levels of 25(OH)D are normal
In type II, 25(OH)D is normal but PTH and 1,25(OH)2D3 are raised.
Treatment
Type I – active vitamin D metabolites, 1-alpha hydroxyvitamin D (1-2 microgram daily) or 1,25(OH)2D (0.25-1.5 microgram daily orally), with or without calcium supplements
Type II – sometimes responds partially to very high doses of active vitamine D metabolites and calcium and phosphate supplements.
They occur in patients with chronic renal failure due to:
Defects in synthesis of 1,25(OH)2D3
Over treatment with oral phosphate binders.
Treatment
1-alpha hydroxylated vitamin D
Dietary restriction of foods with high phosphate content (milk, cheese, eggs)
Phosphate-binding drugs (calcium carbonate, aluminum hydroxide)
Causes
Inherited or acquired defects in renal tubular phosphate reabsorption
Tumours that secrete phosphaturic substance
Clinical features and diagnosis
Hereditary disorders present as rickets. The diagnosis is made on the basis of the presence of hypophosphatemia with renal phosphate wasting in the absence of vitamin D deficiency.
Tumour-induced disorder presents with severe , rapidly progressive symptoms in patients with no obvious predisposing factor for osteomalacia.
Management

Phosphate supplements (1-4g daily) + active metabolites of vitamin D (to promote intestinal calcium and phosphate absorption)
Tumour-induced osteomalacia is treated in the same way + surgical excision of the tumour.
It is an autosomal recessive disorder caused by inactivating mutations in the alkaline phosphatase gene resulting in accumulation of pyrophosphate and inhibition of bone mineralization.
Investigations
Low level of ALP
Normal calcium, phosphate, PTH and vitamin D metabolites
Treatment
No medical treatment
Bone marrow transplantation in severe cases
Definition
It is a condition characterized by focal areas of increased and disorganized bone remodeling. It is mostly affects the pelvis, femur, tibia, lumbar spine, skull and scapula.
Epidemiology
It is seldom diagnosed before age 40.
It affects up to 8% of the UK population by the age of 85.
The disease is common in Caucasians from Europe but rare Asians.
Genetic factors play an important role in its etiology.
Pathophysiology
Increased osteoblastic bone resorption.
Marrow fibrosis
Increased vascularity of bone
Increased osteoblast activity
Bone is abnormal and has reduced mechanical strength.
Clinical features

Bone pain
Bone deformity and expansion
Pathological fractures
Increased warmth over affected bones
Asymptomatic
Complications
Deafness
Cranial nerve defects
Nerve root pain
Spinal cord compression and spinal canal stenosis
High-output cardiac failure
Osteosarcoma
Investigations
Elevated serum ALP
X-ray: bone expansion with alternating areas of radiolucency and osteosclerosis
Radionuclide bone scanning
Management
Analgesics and NSAIDs
Bisphosphonates
Calcitonin
Definition
Neurological disease may result in rapidly destructive arthritis of joints, first described by Charcot in association with syphilis.
Pathogenesis
Repetitive microtrauma following sensory loss
Altered blood flow secondary to impaired sympathetic nervous system control
Predisposing diseases
 Diabetic neuropathy (hindfoot)

Syringomyelia (shoulder, elbow, wrist)

Leprosy (hands, feet)
 Tabes dorsalis (knees, spine)

Clinical features
Subacute or insidious monoarthritis or dislocation
Joint effusion, crepitus, instability and deformity
Complications
Peripheral nerve entrapment
Spinal canal compression
Investigations
X-ray:
Disorganization of normal joint architecture
Fragmentation
Sclerosis
Multiple loose bodies
Gross new bone formation
Soft tissue swelling
Treatment
Othoses
Arthrodesis