Metabolic bone disease Flashcards
Generally outline Paget’s Disease of Bone.
This is a localised disease of bone turnover. It results in increased bone resorption followed by increased bone formation. Leading to the formation of disorganised bone. Bones are bigger, less compact, more vascular and more susceptible to deformity and fracture. The most commonly affected areas are the pelvis, femur, and lumbar vertebrae, and skull.
Outline the genetic association of Paget’s Disease.
There is a strong genetic component in Paget’s Disease. 15-30% of the disease is familial. Two genes, SQSTM1 and RANK are associated with Paget’s disease of bone. Genetic causes may or may not involve a family history of Paget’s disease.
What is the suspected environmental trigger that causes Paget’s Disease?
One possible environmental trigger is potentially a chronic viral infection within Osteoclasts.
What are the symptoms seen in Paget’s Disease?
Presents in a patient >40 years. Bone pain is common. Bone deformity may be seen. Excessive heat may be felt over the affected (Pagetic) bone. There may be neurological complications seen, such as nerve deafness. Rarely the development of osteosarcoma in affected bone.
What are the investigations of choice in Paget’s Disease?
Increased serum alkaline phosphatase with normal serum calcium and phosphate reflects increased bone turnover. Levels may be normal with limited or monostotic Paget’s disease. Levels are reduced with treatment and increased during relapse.
Vitamin D should be measured, as deficiency is frequent in the age group affected by Paget’s disease and should be corrected to avoid hypocalcaemia following bisphosphonate treatment.
X-ray features are very variable in Paget’s, however X rays are used to investigate and view the extent of the disease.
Isotope bone scans are useful to determine the extent of skeletal involvement, but are unable to distinguish between Paget’s disease and sclerotic metastatic carcinoma (especially breast and prostate).
How is Paget’s Disease treated?
Intravenous Bisphosphonates (Zoledronate) are the mainstay of treatment. Usually it is IV but can also be given orally.
(The bisphosphonates inhibit the resorption of bone by osteoclasts and may have an effect on osteoblast.)
There is no evidence supporting the treatment of asymptomatic Paget’s, unless it is in the skull or in an area requiring surgical intervention.
What is Rickets/ Osteomalacia? What is the cause Rickets/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.
Vitamin D stimulates the absorption of calcium and phosphate from the gut and calcium and phosphate then become available for bone mineralisation. Muscle function is also impaired in Low vit. D states.
How does rickets look in a child?
- Stunted growth
- Large forehead
- Odd curve to spine
- Odd shaped ribs/ breast bone
- Large abdomen
- Wide joints at elbow and wrist
- Wide bones
- Odd shaped legs
- Wide ankles
Causes of Osteomalacia and Rickets?
There are various causes of Rickets and Osteomalacia, such as deficient intake or absorption of vitamin D, primary renal phosphate wasting, etc.
The most common cause of osteomalacia is hypophosphataemia due to hyperparathyroidism secondary to vitamin D deficiency. The most common cause of vitamin D deficiency worldwide is dietary deficiency.
What are the clinical features of Osteomalacia ?
Commonly seen symptoms include:
- Bone pain
- Muscle weakness
- Increased falls risk.
- Muscle weakness
- Waddling gait and Difficulty climbing stairs or getting out of chairs.
What are the investigations of choice in Osteomalacia and Rickets?
Serum alkaline phosphatase is elevated in 90% of cases.
Low serum calcium, low phosphate and elevated PTH are each present in approximately half of the cases.
Plain radiographs demonstrate decreased bone mineralization.
What is the management of Rickets/Osteomalacia?
Vitamin D replacement is the cornerstone of treatment.
What is Osteogenesis Imperfecta?
This is a genetic disorder of connective tissue characterised by fragile bones from mild trauma and even acts of daily life.
It is associated also with other non bone clincal features.
There is a broad clinical range, from those who are prenatally fatal to those only presenting in 40s with early ‘osteoporosis’.
What is the defect in Osteogenesis imperfecta?
What are the different types of Osteogenesis Imperfecta?
Defects in type 1 collagen - eight different types exist-first 4 most common
- Type 1: milder form-when child starts to walk and can present in adults
- Type 11: lethal by age 1
- Type 111: progressive deforming with severe bone dysplasia and poor growth
- Type 4 : similar to type 1 but more severe
What are the commonly seen features of Osteogenesis Imperfecta?
- Fragille bones.
- Growth deficiency
- Defective tooth formation (dentigenesis imperfecta)
- Hearing loss
- Blue sclera
- Scoliosis/Barrel Chest
- Ligamentous Laxity - cause of chronic body pain characterized by loose ligaments
- Easy bruising
