Metabolic Bone Disease

Question 1

What are cells found in the bone?

Answer 1

• Osteoblasts
• Osteoclasts
• Osteocytes

Question 1

What are bone tissues?

Answer 1

• Cortical
• Trabecular(spongy )

Question 2

What is the extracellular matrix made up of?

Answer 2

• Organic (Osteoid): Type 1 collagen, Proteins, Proteoglycan
• Inorganic: Calcium, phosphorus

Question 3

What are steps for Bone Remodelling?

Answer 3

• Orgination
• Osteoclast Recruitment
• Resorption of bone
• Osteoblast recruitment
• Mineralization of bone
• Resting phase

Question 4

What is the definition of Osteoporosis?

Answer 4

Progressive systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture

Question 5

What are risk factors for osteoporosis?

Answer 5

• Steroid use of >5mg/day of prednisolone
• Hyperthyroidism; hyperparathyroidism; hypercalciuria
• Alcohol and tobacco use↑
• Thin (BMI <22)
• Testosterone↓ (e.g. anti-androgen ca prostate ℞)
• Early menopause
• Renal or liver failure
• Erosive/inflammatory bone disease (eg myeloma or rheumatoid arthritis)
• Dietary Ca2+↓/malabsorption; diabetes mellitus type 1

Question 6

What are scoring systems for osteoporosis?

Answer 6

• Fracture Risk Estimation

Question 7

What are signs and symptoms for osteoporosis?

Answer 7

• Loss of height
• Fracture from a fall
• Back or neck pain
• Stooped posture or compression fracture

Question 8

How is osteoporosis practically diagnosed?

Answer 8

• Bone Mineral Density(BMD) measurement
• The normal reference range is that derived from the NHANES survey for Caucasian women age 20-29 years

Question 9

What are the classifications based on the bone mineral density T-score?

Answer 9

• Normal: ≥ - 1.0
• Osteopaenia: between -1.0 and -2.5
• Osteoporosis: ≤ -2.5
• Severe osteoporosis: ≤ -2.5 and a fragility fracture

Question 10

What are routine investigations for Osteoporosis?

Answer 10

• History and Physical examination
• Blood cell count
• Sedimentation rate or C-reactive protein
• Serum Calcium
• Albumin
• Creatinine
• Phosphate
• Alkaline Phosphatase
• Liver Transaminases
• Thyroid function test
• Bone densitometry

Question 11

What is the management of Osteoporosis?

Answer 11

Lifestyle Measures

Calcium/vitamin D

• Calcium: 1200 mg daily ( postmenopausal women)
• Vitamin D: 800 international units daily

Diet
Exercise: At least 30 minutes three times per week.

Smoking cessation

Management of secondary causes

Question 12

What are the types pharmacological therapy for Osteoporosis?

Answer 12

• Anti- resorptive agents
• Anabolic agents

Question 13

What are anti-resorptive agents used in osteoporosis?

Answer 13

Bisphosphonates

• Inhibits bone resorption
• Action on osteoclasts
• Long skeletal retention time

Denosumab

• Human monoclonal antibody against RANKL
• Prevents osteoclast formation
• Reversible

Question 14

What are anabolic agents used in osteoporosis?

Answer 14

Teriparatide

• Recombinant human PTH 1-34
• Stimulates osteoblast function
• ↑Bone formation

Romosozumab

• Monoclonal anti-sclerostin antibody
• ↑Bone formation

Strontium ranelate: Dual mode of action and No longer available

Question 15

What is Osteomalacia?

Answer 15

Decreased mineralisation of bones

• Rickets: in children (open growth plate)
• Osteomalacia: in adults (fused growth plate)

Question 16

What are clinical manifestations of Osteomalacia?

Answer 16

• Bone pain
• Fractures
• Difficulty in walking and waddling gait

Question 17

How is osteomalacia diagnosed?

Answer 17

Biochemistry

• Reduced serum calcium
• Reduced serum phosphate
• Raised Alkaline phosphatase (ALP)
• Raised PTH (secondary hyperparathyroidism) • Low 25-OH vitamin D

Radiology Bone Biopsy

• Looser zones

Bone Biopsy

• Double tetracycline labelling
• Most accurate method of diagnosis (invasive and infrequently used)

Question 18

How is Osteomalacia treated?

Answer 18

• Treat the underlying disorder
• Cholecalciferol in cases of vitamin D deficiency

Question 19

What are clinical manifestations of Paget’s Disease?

Answer 19

Asymptomatic

Symptomatic

• Bone Pain
• Deformities in the affected area

Question 20

What is Paget’s Disease?

Answer 20

• Accelerated bone remodelling resulting in bone overgrowth. The new bone is laid out in highly disorganised fashion.
• Aetiology: Genteic, Viral

Question 21

What is the Biochemistry of Paget’s Disease?

Answer 21

Biochemistry:

• Raised ALP
• Normal serum calcium and phosphate

Radiology:

• Plain radiography: ‘woven bone’
• Bone scintigraphy show ‘Hot spots’ due to increased uptake in affected sites. It is more sensitive than plain radiograph

Question 22

What is the treatment for Paget’s Disease?

Answer 22

Bisphosphonates

• Intravenous (Zoledronic acid)
• Oral (Risedronate, Alendronate)

Question 23

How do Bone Disorders manifest in CKD?

Answer 23

Laboratory Abnormalities:

• Serum calcium
• Phosphorus
• Parathyroid hormone (PTH)
• Vitamin D metabolism

Bone Disease:

• Abnormalities in bone turnover, mineralization, volume linear growth, or strength

Calcifications:

• Vascular or other soft tissue

Question 24

What is osteogenesis imperfecta (Brittle bone)?

Answer 24

• Inherited osteoporosis
• Genetic defect affecting the production of Collagen type I

Question 25

What is the Diagnostic Criteria in Osteogenesis Imperfecta?

Answer 25

1. Three fragility fractures aged <20 years.
2. At least one of: blue sclerae, scoliosis, hearing loss, joint laxity, dentinogenesis imperfecta (abnormalities of the teeth), affected family member.
3. Osteoporosis

Analysis of collagen type 1 genes ( 90%)