Metabolic Bone Disease Flashcards
RANK Ligand
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.
Factors which increase expression of RANKL
- TNF-alpha
- PTHrP
- IL-1
- IL-11
- Vit D
- Glucocorticoids
- PTH
- PGE2
Vitamin D metabolism
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
Relation of Vitamin D to calcium absorption
Vitamin D is required for the kidneys to create calcium for bone. IT also increases intestinal absorption of calcium
Rickets and Osteomalacia
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.
Clinical Features of Rickets and Osteomalacia
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.
Symptoms of Osteomalacia
Bone pain, proximal myopathy with normal creatinine kinase, pathological fracture and polyarthralgia
Signs of Osteomalacia
Bone tenderness, waddling gait, proximal weakness, tetany *hypocalcaemia
Radiology signs of Osteomalacia
Looser’s zone, pathological fractures, demineralisation, features of hyperparathyroidism
Biochemistry findings of Osteomalacia
Normal or low Calcium
Normal or low phosphate
Alkaline Phosphate increased or normal
25-hydroxyvitamin D low
PTH high
Investigations Osteomalacia
X-ray, bone profile, U+E, serum ferritin
Causes of Osteomalacia
Reduced sun exposure
Renal osteodystrophy (chronic renal failure causing bone disease)
Hyperparathyroidism
Malabsorption
Use of anticonvulsants
Management of Osteomalacia
Vitamin D is abundant in oily fish
Oral Vitamin D supplements
Calcium supplementation (800mg/day)
What is Pagets Disease
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.
Aetiology of Pagets Disease
Genetic due to Loci of SQSTMI
Chronic viral infection within the osteoclast cells
Clinical Features of Pagets Disease
Over 40 with bone pain and deformity
Bone Pain
Osteoarthritis
Pathology fractures
Bone deformity
Headhache
Nerve root compression
Hearing loss
Complication of Pagets Disease
Osteosarcoma
Bones most frequently affected by pagets disease
Pelvis Lumbar Spine Femur thoracic Spine Sacrum Skull Tibia Humerus
Investigations of Pagets Disease
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
Treatment of Pagets Disease
Bisphosphonates (these inhibit osteoclast activity). A single infusion of 5mg zoledronate is sufficient to control disease only in symptomatic disease
Osteogenesis Imperfecta
This is a genetic disorder of the connective tissue characterised by fragile bones
Type 1 Osteogenesis Imperfecta
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.
Type 2 Osteogenesis Imperfecta
Lethal by age 1
Type 3 Osteogenesis Imperfecta
This is progressive deformation with severe bone dysplasia and poor growth
Type 4 Osteogenesis Imperfecta
Similar to type 1 but more severe
Symptoms and signs of Osteogenesis Imperfecta
- Growth deficiency
- Defective tooth formation
- Hearing loss
- Blue sclera
- Scoliosis
- Barrel Chest
- Ligamentous Laxity
- Easy Bruising
Treatment of Osteogenesis Imperfecta
Surgical treatment of fractures or Bisphosphonates to prevent fractures.
