Metabolic Bone Disease Flashcards
What are cells found in the bone?
- Osteoblasts
- Osteoclasts
- Osteocytes
What are bone tissues?
- Cortical
- Trabecular(spongy )
What is the extracellular matrix made up of?
- Organic (Osteoid): Type 1 collagen, Proteins, Proteoglycan
- Inorganic: Calcium, phosphorus
What are steps for Bone Remodelling?
- Orgination
- Osteoclast Recruitment
- Resorption of bone
- Osteoblast recruitment
- Mineralization of bone
- Resting phase
What is the definition of Osteoporosis?
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
What are risk factors for osteoporosis?
- 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
What are scoring systems for osteoporosis?
- Fracture Risk Estimation
What are signs and symptoms for osteoporosis?
- Loss of height
- Fracture from a fall
- Back or neck pain
- Stooped posture or compression fracture
How is osteoporosis practically diagnosed?
- Bone Mineral Density(BMD) measurement
- The normal reference range is that derived from the NHANES survey for Caucasian women age 20-29 years
What are the classifications based on the bone mineral density T-score?
- Normal: ≥ - 1.0
- Osteopaenia: between -1.0 and -2.5
- Osteoporosis: ≤ -2.5
- Severe osteoporosis: ≤ -2.5 and a fragility fracture
What are routine investigations for Osteoporosis?
- 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
What is the management of Osteoporosis?
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
What are the types pharmacological therapy for Osteoporosis?
- Anti- resorptive agents
- Anabolic agents
What are anti-resorptive agents used in osteoporosis?
Bisphosphonates
- Inhibits bone resorption
- Action on osteoclasts
- Long skeletal retention time
Denosumab
- Human monoclonal antibody against RANKL
- Prevents osteoclast formation
- Reversible
What are anabolic agents used in osteoporosis?
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
What is Osteomalacia?
Decreased mineralisation of bones
- Rickets: in children (open growth plate)
- Osteomalacia: in adults (fused growth plate)
What are clinical manifestations of Osteomalacia?
- Bone pain
- Fractures
- Difficulty in walking and waddling gait
How is osteomalacia diagnosed?
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)
How is Osteomalacia treated?
- Treat the underlying disorder
- Cholecalciferol in cases of vitamin D deficiency
What are clinical manifestations of Paget’s Disease?
Asymptomatic
Symptomatic
- Bone Pain
- Deformities in the affected area
What is Paget’s Disease?
- Accelerated bone remodelling resulting in bone overgrowth. The new bone is laid out in highly disorganised fashion.
- Aetiology: Genteic, Viral
What is the Biochemistry of Paget’s Disease?
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
What is the treatment for Paget’s Disease?
Bisphosphonates
- Intravenous (Zoledronic acid)
- Oral (Risedronate, Alendronate)
How do Bone Disorders manifest in CKD?
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
What is osteogenesis imperfecta (Brittle bone)?
- Inherited osteoporosis
- Genetic defect affecting the production of Collagen type I
What is the Diagnostic Criteria in Osteogenesis Imperfecta?
- Three fragility fractures aged <20 years.
- At least one of: blue sclerae, scoliosis, hearing loss, joint laxity, dentinogenesis imperfecta (abnormalities of the teeth), affected family member.
- Osteoporosis
Analysis of collagen type 1 genes ( 90%)
