Bone pathology Flashcards by Elizabeth McCabe

What are the basic functions of bone?

Mechanical support and movement
Protection of internal organs
Mineral homeostasis
Haematopoesis

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What is the main composition of bone?

35% osteoid and 65% minerals
Minerals are mainly hydroxyapatite -> vast majority of calcium and phosphorus
Osteoid is type 1 collagen and some glycosaminoglycans and other proteins

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What is cortical bone?

Arranged in haversian systems -> series of concentric lamellae of collagen fibres surrounding a central canal of blood vessels
Nutrients found in central interconnecting system of canaliculi between osteocytes and deep within bone matrix

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How does the presence of cortical and trabecula bone change over the course of a long bone?

Diaphysis -> has the thickest outer covering of cortical bone surrounding inner trabecular bone (which contains marrow)
In the metaphysics and epiphysis the cortical bone layer thins and the trabecular layer becomes predominant.

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What are the key histological features of cortical/compact/lamellar bone?

Thick, pink, mineralised with calcium
Smooth, organised almost glassy appearance.
Parallel collagen fibres provide structural integrity
May by areas of adipose tissue within

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What other layers may be visible on a histological slide of cortical bone?

Inner - trabecular bone
Outer - periosteum and skeletal muscle

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Where is medullary bone/spongy bone found?

Vertebral bodies and the ends of the long bones (epiphysisis)

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What is the organisation of lamellae in trabecular bone?

Runs parallel to the bone surface rather than concentrically as in cortical bone.

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What is the histological appearance of medullary bone?

Fine pink parallel lamellae
Interspaced by wide areas of adipose tissue/bone marrow
May contains areas of vast cell populations (purple nuclei that indicates haematopoesis)

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What are the key histological features of woven bone?

Produced rapidly such as during fetal development and fracture repair
Haphazard arrangement of collage fibres - less structural integrity.

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What is meant by the basic multicellular unit involved in bone reabsoprtion?

The different cell lineages that help recycle/remodel bone tissue -> includes osteoblasts, osteocytes and osteoclasts

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What are the different stages completed by the basic multicellular unit to resorption and deposition bone?

Resting bone - lining cell protect bone surface
Resorption - HSC differentiate into osteoclasts, lyse bone
Reversal - mononuclear cells clear debrie, mesenchymal stem cells being to differentiate into osteoblasts
Matrix deposition - by osteoblasts
Mineralisation - osteocytes

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What is the function of osteoblasts within the bone?

Found on the surface of the osteoid matrix - they make, transport and assemble matrix and regulate mineralisation. Bone builders
Quiescent osteoblasts remain on the trabecular surface or become embedded within the matrix as osteocytes

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What is the role of osteocytes?

Interconnected network of cells with dendritic extension through canaliculi in bone matrix.
Help regulate calcium and phosphate levels in microenvironment and regulate biological activity in response to mechanotransduction

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What is the role of osteoclasts?

Specialised multinucleated macrophages derived from monocytes
Attach to matrix via surface integrin proteins -> form sealed resorption pits -> secrete acid and proteases and MMPs -> dissolve inorganic and organic bone

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What are the key features of bone homeostasis?

Dynamic -> constant stress and damage at cellular level, hence undergoes constant remodelling

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What signalling pathways increase osteoclastic activity?

RANK ligand found on surface of stromal/blast cell bind to receptor on precursor

M-CSF secretion from stromal/blast cell regulated by PTH

Both cause expression of NFkB in osteoblast precursor triggering differentiation into osteoclast.

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What signalling pathways reduce osteoclast differentiation?

Wnt signalling -> stimulates osteoblasts to osteoprotegrin synthesis which blocks RANKL/R interaction

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What is the life cycle of bone?

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What is the function of PTH in bone regulation?

Major player
Receptors on Blasts
Intermittent PTH stimulates bone formation
Sustained high levels -> favours clast activity and bone resorption by causing blasts to express RANKL indirectly activating clasts

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What is the role of calcitriol in bone?

Stimulates bone resoprtion by upregulating RANKL expression in osteocytes.

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What is the role of growth hormone in bone?

Stimulates bone growth during childhood -> mediated by locally produced IGF-1 -> causes cartilage proliferation in epiphyseal plate -> endochondral ossification

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What is the role of sex steroids in bone function?

Oestrogens promote blast function and stimulate clast apoptosis, inc calcium uptake in gut -> promote bone formation

Androgen are locally converted to oestrogens so are anabolic

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What is the role of glucocorticoids in bone?

Catabolic
Promote osteoclast activity, inhibit calcium uptake in the gut
Long term glucocorticoid therapy has a risk of osteoporosis

What scan is used to calculate the T score in osteoporosis?

DEXA scan

What is the purpose of a Z-score in osteoporosis?

Compares bone density to people of the same age as the individual.

What are the key features of postmenopausal osteoporosis?

1st decade after menopause -> lose cancellous and cortical bone each year Oestrogen deficiency - inflammation cytokines such as IL_6 and TNF from innate immune cells -> increase RANKL and decrease OPG stimulating osteoclast activity. Leads to increased destruction

What is senile osteoporosis?

Reduced synthetic activity of osteoblasts Decreased activity of osteoprogenitor cells Decreased activity of matrix bound growth factors Reduced physical activity Leads to decreased formation

What are the key clinical features of osteoporosis?

Silent disease till fracture Vertebral fracture - pain, decrease in height, kyphoscoliosis Fractures - femoral neck, distal radius (colles) Significant mortality - complications such as PE and pneumonia

What are the key histological features of osteoporosis?

Thinning of the trabecular and cortical bone

What are the key treatments for osteoporosis?

Exercise (weight bearing) Calcium and vitamin D supplements Bisphosphonates - reduced osteoclastic activity, apoptosis Anti-RANKL antibody - denosumab Post-menopausal - HRT (consider risk of DVT and stroke)

Define fracture

Break in the structural continuity of the bone

What is mean by a comminuted fracture?

More than two fragments present

What is a complicated fracture?

Involvement of a nerve, artery or viscus

What is a hairline fracture?

Slowly developing fracture resulting from repetitive application of force e.g stress fracture

What is a greenstick fracture?

Usually seen in children Only one side of the bone is fractured, leaving it bent but intact

What is a crush/compression fracture?

Occurs in cancellous bone e.g vertebral body, heels, when excessive loading force is applied.

What are the four stages of fracture healing?

Haematoma Organisation Callus formation Consolidation Remodelling

What is the process of organisation in fracture healing?

Occurs within 24hrs - granulation tissue of inflammatory cells, fibrin and osteoprogenitor cells

What is the process of callus formation in fracture healing?

Woven bone Extrnay callus may contain cartilage (soft callus)

What is the process of consolidation in fracture healing?

Occurs by 3 weeks Bony callus forms by endochondral ossification Remodelling by osteoblasts and clasts -> woven bone replaced by compact lamellar bone This takes several months

What is the process of remodelling in fracture healing?

New lamellar bone orientated in the direction of loading stress and continuity of the medullary cavity restored.

What are some short term complications of a fracture?

Infection Neurological damage - laceration, compression, entrapment Vascular injury and haemorrhage Compartment syndrome Visceral injury

What are some longer term complications of a fracture?

Malunion - angulation or rotation Delayed union - norm 25% longer than average time Non-union -> within 1 year Joint stiffness/instability Avascular necrosis - NoF Myositis ossificancs - ossification within muscle or soft tissue Muscle contracture Complex regional pain syndrome

What is the key pathology of compartment syndrome?

Tissue wellbeing and bleeding leads to increased compartment pressure Decreased tissue perfusion due to vascular occlusion Ischaemia Cell death and release of myoglobin

What are the key signs and symptoms of compartment syndrome?

Intense pain (unrelieved by analgesics) Pain on stretching affected muscles Altered sensation - paraesthesia and decrease sensation Motor paralysis is a late sign

What are the treatments for compartment syndrome?

Fasciotomy and antibiotics

What are the links and signs of a fat embolism from a fracture?

Diaphyseal fat embolism as released from marrow into laceral venules Can cause acute respiratory distress, petechial haemorrhage, and cerebral hypoperfuson/volaemia which may present as confusion

What is the management of fat embolus from a fracture?

Supportive e.g oxygen

What are the common benign bone tumours?

Osteoid osteoma Osteoblastoma

What are the key features of osteoid osteoma?

<2cm More common in young men in teens and 20s Femur and tibia most common Presents as nocturnal bone pain relieved by NSAIDs

What is the treatment for osteoid osteoma?

Radiofrequency ablation

What are the features of osteoblastoma?

Benign >2cm Posterior spine Treated with currettage or an en block excision

What is the most common primary malignant tumour of bone?

Osteosarcoma

What are the key features of osteosarcoma presentation?

Bimodial - majority before 20yrs, smaller peaks in adults with predisposing factors Slightly more common in men Tumour usually in metaphyseal region of long bones - distal femur or proximal tibia Present as bone pain and pathological fractures

What are the key features shown in this x-ray?

Osteosarcoma Ill-defined mixed sclerotic/lytic lesions Periosteal reaction Cortical destruction Periosteal lifting - codmans triangle

What are the key microscopy features of osteosarcoma?

Lace like bone or bony trabecular Pleomorphism, large hyperchromatic nuclei, bizarre tumour giant cells and abundant mitoses

What is the treatment for osteosarcoma?

Presumed to have metastases at the time of diagnosis Neoadjuvant chemo + surgical reaction and post op adjuvant chemo Mets - lung, bone, brain Chemo - 5yrs survival of 70% without overt mets