Dr. Nizar Abdulateef Assistant Professor & Consultant Rheumatologist OSTEOMALACIA AND RICKETS

Definition Vitamin D deficiency Vitamin D-resistant rickets (VDRR) Renal rickets and osteomalacia Hypophosphatemic rickets and osteomalacia Hypophosphatasia

Definition 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. The disease is prevalent in elderly people who have a poor diet and limited sunlight exposure.

Causes Vitamin D deficiency (classical or due to malabsorption) Failure of vitamin D of 1,25 synthesis (chronic renal failure or vitamin D-resistant rickets type I Vitamin D receptor defects (vitaminD-resistant rickets type II) Defects in phosphate & pyrophosphate metabolism (hypophosphatemic rickets, tumour-induced hypophosphatemic osteomalacia and hypophosphatasia) Iatrogenic (bisphosphonate therapy, aluminium & fluoride)

Vitamin D deficiency Causes: Lack of sunlight exposure since maintenance of normal vitamin D depends on UV sunlight exposure to catalyse synthesis of cholecalceferol from 7- dehydrocholesterol 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 & increased bone resorption  progressive bone demineralization

Clinical features of rickets Delayed development Muscle hypotonia Bossing of the frontal & 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 Proximal muscle weakness Bone and muscle tenderness

Investigations Raised serum alkaline phosphatase Low 25(OH)D Raised PTH Low or normal serum calcium & phosphate X-rays are normal, focal radiolucent areas (pseudofractures or Loozer's zones) in advanced disease, osteopenia, vertebral crush fractures in children, thickening & widening of the epiphyseal plate

Management Ergocalciferol ( microgram daily)for 3-4 months. Maintenance dose of vitamin D reduced to microgram daily.

Vitamin D-resistant rickets (VDRR) 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 & 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 ( microgram daily orally), with or without calcium supplements Type II – sometimes responds partially to very high doses of active vitamine D metabolites & calcium and phosphate supplements.

Renal rickets and osteomalacia 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)

Hypophosphatemic rickets and osteomalacia Causes Inherited or acquired defects in renal tubular phosphate reabsorption Tumours that secrete phosphaturic substance Clinical features & 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.

Hypophosphatasia 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

PAGET'S DISEASE OF BONE Definition Epidemiology Pathophysiology Clinical features Complications Investigations Management

Definition It is a condition characterized by focal areas of increased & disorganized bone remodeling. It is mostly affects the pelvis, femur, tibia, lumbar spine, skull & 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 & 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 & spinal canal stenosis High-output cardiac failure Osteosarcoma

Investigations Elevated serum ALP X-ray: bone expansion with alternating areas of radiolucency & osteosclerosis Radionuclide bone scanning Management Analgesics & NSAIDs Bisphosphonates Calcitonin

NEUROPATHIC (CHARCOAT) JOINTS Definition Pathogenesis Predisposing diseases Clinical features Complications Investigations Treatment

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

Quiz Q1. osteomalacia is prevalent in elderly people who have a poor diet and limited sunlight exposure. True False

Q2. All of the followings are clinical features of osteomalacia except: A. Muscle pain B. Bone pain C. Malaise D. Distal muscle weakness

Q3. Laboratory findings in osteomalacia include all of the followings except: A. Raised serum alkaline phosphatase B. Low 25(OH)D C. Low PTH D. Low or normal serum calcium E. Low or normal serum phosphate

Q4. Complication (s) of Paget’s disease of bone include (s) A. Cranial nerve defects B. Nerve root pain C. High-output cardiac failure D. Osteosarcoma E. All of the above

Q5. X-ray finding (s) in Charcot’s joints include (s): A. Fragmentation B. Sclerosis C. Multiple loose bodies D. Gross new bone formation E. All of the above