NON- NEOPLASTIC BONE DISEASES Flashcards
1
Q
Risk factor of osteoporosis
A
- Age:
- increases with age
- osteoblast from older individual have reduced proliferative and synthetic potential
- cellular response to growth factors become slow - Genetic factors
- Hormones:
- deficiency of oestrogen accelerates osteoporosis. - Nutritional status
- lack of calcium and vit. D - Physical activity
- reduced physical activity promotes osteoporosis (mechanical forces stimulate normal bone remodeling)
2
Q
Aetiology of osteoporosis
A
- Primary osteoporosis
- postmenopausal osteoporosis
- senile - Secondary osteoporosis
- Endocrine deficiencies: hypogonadism, anorexia nervosa, ovarian failure
- Endocrine hyperfunction: Hypercortisolism, hyperthyroidism, hyperparathyroidism
- GI: malnutrition, malabsorption, subtotal gastrectomy, hepatic insufficiency
- Bone marrow malignancies: multiple myeloma, lymphoma, metastatic tumor
- Drugs: corticosteroids, chemotherapy, anticonvulsant
- Others: alcohol, smoking, immobilisation
3
Q
Pathogenesis of osteoporosis
A
- Age related changes
- osteoblast from older individuals have reduce proliferative and biosynthetic potential
- Decreased replicative activity of osteoprogenitor cells
- Decreased synthetic activity of osteoblasts
- Diminished growth factor
- Reduced physical activity
- Osteoclast retain their youthful vigor
- The net result is diminished capacity to make bone
- Reduced physical activity - Hormonal influences
- Low oestrogen increase secretion of inflammatory cytokines by monocytes
- Stimulate osteoclast recruitment and activity
- Increase RANKL
- Diminish the expression of PG
- Increase osteoclast activity
- Prevent osteoclast apoptosis - Reduced physical activity
- Mechanical forces stimulate normal bone remodeling
- Increase the rate of bone loss
- Bone loss in immobilised and higher bone density in athletes exemplify the role of physical activity in preventing bone loss.
- The decreased physical act. contributes to senile osteoporosis. - Calcium nutritional state
- Contribute to peak bone mass
- This calcium deficiency occurs during a period of rapid growth, restricting the peak bone mass to be achieved
- Lack calcium, increased PTH level and reduce level of vit. D may play a role in the development of senile osteoporosis - Genetic factor
- Vit. D receptor polymorphisms appear to influence the peak bone mass early in life
- Polymorphism in other gene may account for the variation in the peak bone density within a populations
4
Q
Morphology of osteoporosis
A
Hallmark:
- Histologically normal bone
- Decreased in quantity
- The cortices are thinned and the trabeculae are reduced in thickness and lose their interconnections
- Once enough bone is lost, risk of fracture increases
5
Q
Clinical manifestations/ complications of osteoporosis
A
- Chronic back pain
- In osteoporosis, osteoclastic activity/ bone resorption exceeds osteoblastic activity/ bone formation - generalised/ nett decrease in bone density
- Osteoporosis weakens the bone and results in multiple vertebrae fracture - pain
- The fractures may cause impingement of the nerves - which may also result in pain - Kyphosis
- In osteoporosis, osteoclastic activity exceeds osteoblastic activity - generalised decrease in bone density
- Osteoporosis weakens the bone and results in multiple vertebrae fractures
- The fracture in osteoporosis is usually wedge shaped
- Without correction multiple wedge fracture invariably contributes to excessive curvature of the spine - Scoliosis
- Low trauma fracture
- Loss of height
- Pulmonary embolism and pneumonia - complications of fractures
6
Q
Ways to diagnose osteoporosis.
A
- X- ray
- DEXA scan - measure bone density
- Biopsy - rarely performed
- Bone resorption test - rate of bone loss
- Bone formation test - rate of bone production
7
Q
How to prevent and treat osteoporosis?
A
Prevention
- Discontinue alcohol and smoking
- Take calcium and vit. D supplement
Treatment
- Adequate analgesia
- Antiresorptive and osteoanabolic agents
Antiresorptive: bisphosphonates, calcitonin, oestrogen, denosumab
Anabolic agent: PTH
8
Q
Describe the aetiology of osteomalacia and rickets
A
- Osteomalacia is a disorder in which the bone is formed during remodeling is undermineralised and can lead to fracture.
- Osteomalacia is d/t inadequate mineralisation of osteoid.
- Osteoid is a protein mixture that is secreted by the osteoblast and forms the organic matrix of the bone.
- Osteomalacia is caused mainly by the deficiency of vit. D or its abnormal metabolism
- Rickets is a problem when the bone formed by a growth plate does not mineralised.
- Rickets can only be seen in children because adults does not have growth plate anymore.
- It is most likely affect the femoral neck and vertebral bodies.
- Rickets also d/t vit. D deficiency.
- Causes vitamin D deficiency:
1. Diet is insufficient
2. Limited exposure to sunlight
3. Malabsorption
4. Renal disorders causes phosphate depletion
5. Genetically variants of the vitamin D receptor - DIFFERENCE BETWEEN OSTEOMALACIA AND RICKETS
1. Osteomalacia - adults,, Rickets - children
2. Osteomalacia - mature bone,, Rickets - immature bone
9
Q
Describe the pathogenesis of osteomalacia and rickets
A
- When the amount of vit. D is defficient, the renal a-1-hydroxylase is reduced.
- This causes the conversion of inactive vit. D to active vit. D which is calcitriol decreases.
- Hence, the amount of Ca and P absorption in the gut is reduced.
- Thus the serum level of Ca and P also reduced.
- Parathyroid gland will secreted parathyroid hormone.
- The secretion of parathyroid hormone will lead to mobilisation of Ca and P.
- The renal excretion of Ca is low, but the renal excretion of P is high.
- This causes the serum level of calcium is restored to near normal but hypophosphatmia persist.
- Hence, mineralisation of bone is impaired or there is high bone turnover.
10
Q
Describe the morphology of osteomalacia and rickets
A
- Bone trabeculae are of normal thickness, BUT they are incompletely calcified.
- Central core of the bone is normally calsified.
- The red osteoid is too thick and covers most of the surface of the bone.
11
Q
Describe the clinical manifestations/ complications of osteomalacia and rickets
A
- OBSERVATION
- Craniotabes: flattened occipital bones
- Frontal bossing: Excess of osteoid produces square head
- Rachitic rosary: Overgrowth of osteoid tissue at the costochondral junction
- Pigeon breast deformity: Anterior protrusion of the sternum
- Harrison groove: inward pull at the margin of the diaphgragm
- Pelvis deformed
- Bowing of the leg - LAB INVESTIGATION
- Vit. D low
- Ca low
- P low
- Alkaline phosphatase high
- TRO renal failure - X RAY
- bowed leg
12
Q
Describe aetiology of Paget disease of the bone
A
- Pagetic is characterised by abnormal remodelling and thickening of the bones
- Structurally disorganised and can lead to deformities and fractures.
- Paget diseases start at late adulthood
- Greater in males and increases with age
13
Q
Desc the pathogenesis of Paget disease of the bone
A
- Can be due to genetic and environmental
- Can be mutation in the SQSTM1 gene
- Will lead to increase of NF- KB
- Increase osteoclast acitivity
14
Q
Desc the morphology of Paget disease of the bone
A
HALLMARK:
- Mosaic pattern of lamellar bone (sclerotic phase)
OTHER MORPHOLOGY
- Jigsaw puzzle: appearance is produce by unusually prominent cement lines, which join haphazardly oriented units of lamellar bone
- In the sclerotic phase, the bone is thickened but lacks structural stability making it vulnerable to deformation and fracture
- The initial lytic phase is characterised by numerous large osteoclast and resorption pits
- Osteoclast persists in the mixed phase, but many of the bone surfaces are also lined by prominent osteoblasts
15
Q
Desc the clinical menifestations/ complications of Paget disease of the bone
A
- Monostatic
- Polyostotic
- Localised pain
- Enlargement of the craniofacial skeleton may produce leontiasis ossea (lion face)
- Cranium is heavy that causes the person having difficulties to hold the head erect
- Lead to invagination of the skull base (platybasia) and compression of the posterior fossa
- Chalk stick-type fracture: occur in the long bones of the lower extremities
- Development of kyphosis: An increased front-to-back curve of the upper spine
- Elevated serum alkaline phosphatase levels but normal serum calcium and phosphorus
COMPLICATIONS:
- fracture; femoral shaft and subtrochanteric regions
- Neoplasms
- Hypervascularity of pagetic bone warms the overlying skin
- Increased blood flow - high output heart failure @ lead to heart disease
