Metabolic Disorders Of Bone - Altered Bone Turnover

Front 1

What is bone remodelling?

(inc average rates)

Back 1

• Coordinated osteoclastic resorption and osteoblastic
proliferation
• Maintains skeletal structure
• Annual rate of turnover
Cortical - 4%
Trabecular - 25%

Front 2

What are the six steps of the Bone Metabolic Unit as the basis of bone remodelling?

Back 2

1.Activation: Osteoclasts
2.Resorption: Bone matrix
3.Reversal: pre-osteoblasts
4.Formation: osteoid formation
5.Mineralization:
6.Quiescence

Front 3

How do bone grow?

Back 3

•Endochondral ossification - longitudinal
•Subperiosteal apposition - width
•At the same time endosteal bone resorption – medullary cavity expansion

Front 4

When does bone growth/remodelling stop and on what does it depend?

Back 4

It goes on throughout life and its rate depends upon
•Growth
•Hormones and growth/biochemical factors
•Mechanical stress

••During growth -- turnover high,
formation> resorption so net bone gain
••During adulthood -- turnover moderate, formation< resorption so net bone loss

Front 5

What is the chemical composition of bone?

Back 5

2/3 Inorganic - calcium hydroxyapatite

1/3 Organic -
•Type 1 collage (tensile)
•Proteoglycans (compressile)
•Osteocalcin – bone proteins
•Cytokines/IL

Front 6

What is woven bone?

Back 6

- Collagen fibres and cells – no specific arrangement
- Weak
- Temporary
- Forms on fibrous tissue

–Immature
–Healing

Front 7

What is lamellar bone?

Back 7

•Collagen fibres - parallel
•Osteocytes - in between and organised
- It is laid only on existing bone surface
Two forms
–Cortical
–Cancellous/trabecular – less mass, but more surface area

Front 8

What are the main bone cells?

Back 8

Osteoblast : bone formation
At the end of bone remodelling cycle they remain as resting osteocytes.

Osteocyte : dormant; sensitive to stimuli and communicate to osteoblasts

Osteoclast : bone resorption.
Derived from monocyte precursors in marrow

Front 9

What are the age-related changes in bone mass?

Back 9

•Puberty onwards 2-3% increase in bone mass upto peak 30yrs.
•Steady till about 35-40
•Then bone loss 0.3-0.5%/yr
•After menopause in women : rapid bone loss
2-3% per yr for the next 8-10 yrs (mainly trabecular)
•>60 rate of loss slows down to 0.5%/yr

Front 10

What main molecular factors determine bone turnover?

Back 10

•Calcium & Phosphates
•Parathyroid hormone (PTH).
•Cholecalciferol and Calcitriol (Vit.D3).
•Estrogen and other Sex hormones.
•? Calcitonin.

Front 11

What other factor affect bone turnover?

Back 11

•Local factors
•Insulin-Like Growth Factor I (somatomedin C)
–increased osteoblast proliferation,regulated by growth hormone
•TGF
–increased osteoblast activity, accounts for coupling and resorption
•IL-1/Osteoclast Activating Factor
–increases osteoclast activity
•PG’s
–increased bone turnover (in fractures & inflammn)
–Causes hypercalcaemia in metastatic bone disease
•BMP
–bone formation

Front 12

What are bone metabolic diseases?

Back 12

Abnormalities of formation ( bone morphology )
and
Metabolism of bone ( functions )

Front 13

What is the pathology of the major diseases of bone?

Back 13

Loss of MineralizationLoss Mineralization : osteomalacia/ricketsosteomalacia/rickets

Low bone mass: osteoporosis,Osteogenesis Imperfecta
High bone mass: osteopetrosis
High bone turnover: pagets, hyperparathyroidism, thyrotoxicosis
••Low bone turnover: adynamic disease, hypophosphatasia

Front 14

How are potential bone metabolism diseases assessed?

Back 14

•History
–duration
–drug Rx
–aetiological associations
•Exam: Features of underlying endocrine disorder
- moon face(hypercortisonism),
- hairless skin(testicular atrophy) ,
- physical underdevelopment (rickets)
•X-rays - plain and specialist
• - shows loss of horizontal trabeculae in osteoporosis
• - stress fractures (prox tibia and femur), compression fractures in vertbrae.
•Bone density (DEXA)
•Biochemical tests
•Rarely bone biopsy

Front 15

What biochemical tests are used?

Back 15

•Serum Ca/PO43- (rarely ionised calcium)
•Alkaline phosphatase (bone turnover)
•PTH
•Vit. D activity (measured by 25-HCC )
•Specific endocrine test
•Markers of bone turnover
•FGF-23

Front 16

What is osteomalacia/rickets?

3 points

Back 16

osteomalacia (adults)/rickets (children)

Poorly mineralised osteoid
Severe/long standing Vitamin D deficiency
Reduced availability of calcium and phosphate

Front 17

What is osteoporosis?

Back 17

•Reduced total bone mass
•Adequate mineralisation of present osteoid
•Many factors (inc Oestrogen deficiency)
•Relatively increased bone resorption

Front 18

What is Paget's disease?

Back 18

•Rapid bone turnover
•Both bone resorption and formation are increased
•Disorganised structure
•Reduced bone strength
•Risk of fracture
•Linked to osteosarcoma tumour suppressor gene

Front 19

What is corticosteroid-induced osteoporosis?

4 points

Back 19

•Increased osteoclastic activity
•Decreased osteoblastic activity
•Impaired collagen formation
•Increased bone turnover and poor bone formation and healing

Front 20

What is osteopetrosis?

Back 20

•‘Failure’ of remodelling – decreased turnover
•Unregulated osteoblastic activity, though not necessarily increased
•Impaired osteoclastic activity
•Dense but weak bones

Front 21

What is Fluorosis?

Back 21

Defective mineralisation
Fluoride replaces calcium in the matrix

Front 22

What is Primary hyperparathyroidism?

Back 22

•Unregulated PTH secretion
•Hypercalcaemia (low phosphate)
•Markedly increased bone turnover
•May retain bone mass, but in elderly or other risk factors, often osteoporosis

Front 23

More about rickets

Back 23

•Rickets
–Nutritional rickets
–Congenital rickets
–Rickets of prematurity
–Genetic rickets
–Neoplastic rickets
–Hypophosphataemic rickets
–Drug-induced rickets
•Renal causes - Renal osteodystrophy, Fanconi syndrome
•Tumor-induced osteomalacia
•Other causes
–Hypophosphatasia
–McCune-Albright syndrome
–Osteogenesis imperfecta with mineralization defect (syndrome resembling osteogenesis imperfecta)

Front 24

What is renal rickets(osteodystrophy)?

Back 24

•High Phosphate – only type of rickets
•Combines with Ca – hypocalcaemia
•Excess phosphate excreted into gut –combines with Ca in gut
•2° hyperPTH
•Aluminium excess – dialysis
•Types
- Adynamic (30%; ↓osteoblastic activity)
- Hyperdynamic (↑bone turnover).

Front 25

What is Osteogenesis imperfecta?

Back 25

•Genetic bone disorder
•Defect/deficiency Collagen I
•Various types – different severities
•Recurrent childhood fractures
•Deformities
•Ligamentous laxity; low muscle tone
•Bluish sclerae