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What is normal compositon of bone

90% type 1 collagen (contains glycoproteins and proteoglycans)

Osteoid (protein matrix of bone secreted by osteoblasts)

Hydroxyapatite (mineral component of calcium and phosphate)


State the properties of the two structural forms of bone

Woven bone: 
Rapid osteoid production
Collagen in an unorganised structure
Normally seen in growth and repair of bone

Lamellar bone: 
Parallel collagen fibres (lamellae)
Normal (adult) stable form of bone


What factors can cause disruption to the structure of bone?

Over active or underactive osteoblasts or osteoclasts (Change in bone turnover)

Renal disease


Loss of mineralisation (rickets due to lack of vitamin D)

Tumours (affect activity of osteoclasts and osteoblasts)




What biochemical tests can you do to assess bone structure?

Blood test and U+E analysis for biochemical markers. 

Calcium homeostasis (Ca2+, PO4-, vitamin D, PTH)

Bone turnover (Alk phos, osteocalcin, collagen breakdown)


What investigations could you do to assess bone structure?

Plain X-ray
Tc radionucleotide scans

Bone biopsy - histology

Bone density (diagnostic for osteoporosis)


What are osteochondrodysplasias?

group of conditions among the skeletal dysplasias characterised by abnormal growth or development,

e.g. osteogenesis imperfecta (OI)


What are the signs and symptoms associated with osteogenesis imperfecta?

'Brittle bone disease'

multiple fractures

deformed teeth (dentinogenesis imperfecta)

growth retardation

hearing loss

blue/grey sclera

Presentation varies because all areas of the body with type 1 collagen are affected


What investigations would you carry out in suspected OI?

Physical examination (blue sclera, hearing loss, dentition)

Genetic analysis


What are the main abnormalities seen in the four most common types of osteogenesis imperfecta?

type 1:  mild bony deformities, normal stature blue sclerae, defective dentine, early-onset deafness, hypermobility of joints, and heart valve disorders. 

type 2: lethal in the perinatal period

type 3: severe bone deformities, defective dentine, short stature, deformity at birth

type 4: mild/moderate deformity, short stature, tooth problems


What s the treatment given to patients with osteogensis imperfecta?


Inhibits osteoclast activity and increases the cortical thickness of bone


What are the common signs and symptoms associated with Paget's Disease?

Begins late in adulthood (70 years)


pain (microfractures of bone or bone overgrowth that compresses the nerves, localised to the affected bone)

deformities in bone (bowing, increased skull size, spinal curvature)





Describe the underlying pathology Paget's Disease

 Paget's disease is a disorder of bone remodelling.

The initial event of excessive resorption (osteolytic stage) followed by a compensatory increase in new bone formation by osteoblasts (mixed stage). 

Formation then exceeds resorption as osteoblastic activity predominates, however this progresses to a burnt-out osteosclerotic stage. The new lamellar bone is disordered, and has a mosaic pattern with coarse thick trabeculae and a soft, porous cortex that  lacks stability and is therefore prone to fractures under stress. 


How is Paget's disease diagnosed?

X-ray: Bone is typically enlarged with thick, coarsened cortices and cancellous bone. 

Isotopic bone scans can indicate areas of active bone formation

Many affected individuals have elevated serum alkaline phosphatase levels 


Describe the underlying pathology of osteogenesis imperfecta

OI is caused by deficiency in the synthesis of type 1 collagen, and primarily affects bone. 

Results from autosomal dominant mutations that involve the substitution of glycine residues in the alpha chains of collagen. This disrupts is secondary and tertiary structure  , making the triple helix unstable. The collagen produced is weaker and the resulting bone is brittle - therefore more likely to fracture. 


Describe the histological appearance of bone in a patient with Paget's disease

Mosaic pattern of lamellar bone

Bone is larger than normal

Has thick coarse trabeculae and porous cortex

More vascular


What is the treatment for Paget's disease?


Inhibits osteoclast activity


Describe the underlying pathology that occurs in rickets

Rickets/ osteomalacia are disorders caused by a defect in the mineralisation of the bone matrix, most commonly associated with a lack of vitamin D or metabolic disorder. 

Rickets: In children, failure or delay to mineralise the endochondral bone in the growth plate, which then becomes elongated and distorted. The skeleton becomes deformed due to the lack of structural rigidity in the developing bones 

Osteomalacia: In adults, lack of vitamin D means newly formed osteoid is inadequately mineralised. Bone is weak and vulnerable to fractures/microfractures


Describe the role of vitamin D in bone formation

Stimulates reabsorption of calcium from the intestine and the kidney, which is required for mineralisation of bone

Stimulates osteoblasts to synthesise osteocalcin - promotes calcium deposition during bone development

Stimulates differentiation into osteoclasts and osteoblasts



Causes of rickets/osteomalacia

Vitamin D deficiency

Calcium deficiency (low intake)

Lack of phospate

Genetic (rare) - X-linked hypophosphataemic rickets


What is the clinical presentation of rickets?

Weight bearing produces bowing of the lower limbs

Increase in fractures

Defects in teeth and enamel

Muscle weakness

Bone pain


How is osteoporosis diagnosed?

DEXA  to check the density of the bone

 Bone mineral density (T-score) of 2.5 standard deviations or more below the mean peak bone mass (average of young, healthy adults) 


Name 5 common causes of osteoporosis

Loss of oestrogen post-menopausal (oestrogen inhibits osteoclasts)

Steroids/immunosuppresive drugs

Reduced physical activity (mechanical forces stmulate bone remodelling)

Peak bone mass acheived (lower peak bone mass increases risk)

Pregnancy/breast feeding




What is the clinical presentation of osteoporosis?

Remains asymptomatic until skeletal there is advanced degeneration 

lordosis/kyphosis of the spine


Fractures of the wrist or hip

Loss of height

Compression fractures of the spine


Describe the pathophysiology of osteoporosis

As an individual ages, there is decreased replicative activity of osteoprogenitor cells and decreased activity of osteoblasts and growth factors. 

Reduced physical activity also reduces mechanical stress on the bone which encourages remodelling. 

In women, decrease in oestrogen also removes inhibiton of osteoclasts. 

Overall increase in osteoclast activity which promotes resportion of bone, particularly in bones with a large surface area e.g. vertebral bodies

Trabecular bone becomes thin and perforated, and cross-linking is lost. Bone becomes weak. 


Why is peak bone mass in important factor in the development of osteoporosis?

Peak bone is determined by gender, ethnicity and lifestyle factors (e.g. diet, exercise).

At the age of 25/30, bone mass reaches its maximum and is maintained for 10-20 years (consolidation) after which bone mass reduces with age. The rate of bone loss and the initial peak bone mass determines how quickly a patient will reach the 'threshold' where fractures are more common. 

Therefore patients with a lower peak bone mass are more likely to suffer from osteoporosis. 



What are the three classifications of bone tumours? Give examples

Bone forming 

Cartilage forming

Marrow tumor


What are the two presentations of metastasis in bone?

Blastic lesions: dense mass with very thick bone

Lytic lesion: mass where bone has disolved


Clinical presentation of bone tumours


Slow growing pass

Sudden pathologic fracture

Often involve joints 

Benign tumours are normally asymptomatic  


Name three benign and three malignant tumours of bone




What is osteoporosis?

Reduced bone mineral density and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility

Due to aging and increased osteoclast activity relative to OBs

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