Metabolic Bone Disease

Question 1

RANK Ligand

Answer 1

Secreted by osteoblasts and binds to the RANK receptor on osteoclast precursor cells and causes them to mature into osteoclast cells. They are then stimulated and cause bone resorption.

Question 2

Factors which increase expression of RANKL

Answer 2

• TNF-alpha
• PTHrP
• IL-1
• IL-11
• Vit D
• Glucocorticoids
• PTH
• PGE2

Question 3

Vitamin D metabolism

Answer 3

Absorbed by the skin as (7DHC) which is then transported to the liver where it is further converted into 25(OH)VitD which is then transported to the kidneys where it is converted further into 1,25 (OH)2

Question 4

Relation of Vitamin D to calcium absorption

Answer 4

Vitamin D is required for the kidneys to create calcium for bone. IT also increases intestinal absorption of calcium

Question 5

Rickets and Osteomalacia

Answer 5

Severe nutritional Vitamin D or Calcium deficiency causes insufficient mineralisation and thus rickets in a growing child and osteomalacia in the adult when the epiphyseal lines are closed.

Question 6

Clinical Features of Rickets and Osteomalacia

Answer 6

The areas of bone affected are the metaphyses of long bones leading to a craniotabes of the skull, enlarged epiphyses of the wrists, “rickety rosary” of the osteochondral junctions, Harrisons sulcus in the rib cage, Bow legs, floppy baby, dental abnormalities and delayed growth.

Question 7

Symptoms of Osteomalacia

Answer 7

Bone pain, proximal myopathy with normal creatinine kinase, pathological fracture and polyarthralgia

Question 8

Signs of Osteomalacia

Answer 8

Bone tenderness, waddling gait, proximal weakness, tetany *hypocalcaemia

Question 9

Radiology signs of Osteomalacia

Answer 9

Looser’s zone, pathological fractures, demineralisation, features of hyperparathyroidism

Question 10

Biochemistry findings of Osteomalacia

Answer 10

Normal or low Calcium

Normal or low phosphate

Alkaline Phosphate increased or normal

25-hydroxyvitamin D low

PTH high

Question 11

Investigations Osteomalacia

Answer 11

X-ray, bone profile, U+E, serum ferritin

Question 12

Causes of Osteomalacia

Answer 12

Reduced sun exposure

Renal osteodystrophy (chronic renal failure causing bone disease)

Hyperparathyroidism

Malabsorption

Use of anticonvulsants

Question 13

Management of Osteomalacia

Answer 13

Vitamin D is abundant in oily fish

Oral Vitamin D supplements

Calcium supplementation (800mg/day)

Question 14

What is Pagets Disease

Answer 14

Localised disorder of bone turnover. There is increased bone resorption followed by increased bone formation leading to disorganised bone: bigger, less compact, more vascular and more susceptible to deformity and fracture.

Question 15

Aetiology of Pagets Disease

Answer 15

Genetic due to Loci of SQSTMI

Chronic viral infection within the osteoclast cells

Question 16

Clinical Features of Pagets Disease

Answer 16

Over 40 with bone pain and deformity

Bone Pain

Osteoarthritis

Pathology fractures

Bone deformity

Headhache

Nerve root compression

Hearing loss

Question 17

Complication of Pagets Disease

Answer 17

Osteosarcoma

Question 18

Bones most frequently affected by pagets disease

Answer 18

Pelvis
Lumbar Spine
Femur
thoracic Spine
Sacrum 
Skull
Tibia
Humerus

Question 19

Investigations of Pagets Disease

Answer 19

Raised bone specific Alkaline Phosphatase

Increased PINP, N-telopeptide type 1 collagen in urine

X-ray - typical appearances of thickened, coarse cortical bone

MRI and CT can help distinguish between carcinoma

Question 20

Treatment of Pagets Disease

Answer 20

Bisphosphonates (these inhibit osteoclast activity). A single infusion of 5mg zoledronate is sufficient to control disease only in symptomatic disease

Question 21

Osteogenesis Imperfecta

Answer 21

This is a genetic disorder of the connective tissue characterised by fragile bones

Question 22

Type 1 Osteogenesis Imperfecta

Answer 22

Nearly all cases of OI, mild or severe, are caused by a dominant genetic mutation that affects the body’s production of type 1 collagen. Midly affected by the disorder.

Question 23

Type 2 Osteogenesis Imperfecta

Answer 23

Lethal by age 1

Question 24

Type 3 Osteogenesis Imperfecta

Answer 24

This is progressive deformation with severe bone dysplasia and poor growth

Question 25

Type 4 Osteogenesis Imperfecta

Answer 25

Similar to type 1 but more severe

Question 26

Symptoms and signs of Osteogenesis Imperfecta

Answer 26

• Growth deficiency
• Defective tooth formation
• Hearing loss
• Blue sclera
• Scoliosis
• Barrel Chest
• Ligamentous Laxity
• Easy Bruising

Question 27

Treatment of Osteogenesis Imperfecta

Answer 27

Surgical treatment of fractures or Bisphosphonates to prevent fractures.