- Terminally differentiated - Products of mesenchymal stem cells - Make osteoid, hormones, matrix proteins, alkaline phosphotase - Prerequisite for mineralisation

- Large - Multi nucleated - Ruffled resorption border - Break down bone - Found in bone pits (resorption bays) - Produce enzymes- tartrate resistant acid phosphatase & cathepsin K= breakdown ECM - Help enhance blood Ca levels - Regulated by hormones (PTH, Calcitonin, IL-6) - Help with osteoclastic maturation & activity

- Star shaped - Trapped/buried osteoblasts - Communicate via cytoplasmic extensions - Mechanosensory - Involved in regulating bone matrix turnover

- Synthesised by osteoblasts - Precursor molecule of type 1 collagen - Increases with increased osteoblast activity - Decreased by reduced osteoblast activity

bone Flashcards by Amy Spicer

What is bone composed of? Describe each layer

Cortical bone (hard, outer layer)
Trabecular bone (spongy, inner layer)
Cells (bone forming/resorbing cells)
Extracellular (organic matrix- collagen, inorganic compounds)

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Describe osteoblasts

Terminally differentiated
Products of mesenchymal stem cells
Make osteoid, hormones, matrix proteins, alkaline phosphotase
Prerequisite for mineralisation

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Describe osteoclasts

Large
Multi nucleated
Ruffled resorption border
Break down bone
Found in bone pits (resorption bays)
Produce enzymes- tartrate resistant acid phosphatase & cathepsin K= breakdown ECM
Help enhance blood Ca levels
Regulated by hormones (PTH, Calcitonin, IL-6)
Help with osteoclastic maturation & activity

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Describe osteocytes

Star shaped
Trapped/buried osteoblasts
Communicate via cytoplasmic extensions
Mechanosensory
Involved in regulating bone matrix turnover

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How is normal bone formed?

Resorption by osteoclasts

- Formation by osteoblasts

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What are the stages in bone formation?

Resting
Resorption
Osteoid formation
Mineralisation

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Give some examples of biochemical markers of bone turnover

Formation: Alkaline phosphatase, procollagen type 1 propeptides
Resorption: Crosslinked telopeptides of type 1 collagen
Osteoclast enzymes: tartrate resistant acid phosphatase, cathepsin K

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What is bone alkaline phosphatase?

Released by osteoblasts
Involved in mineralisation
Release stimulated by increased bone remodelling

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Describe P1NP

Synthesised by osteoblasts
Precursor molecule of type 1 collagen
Increases with increased osteoblast activity
Decreased by reduced osteoblast activity

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Why are bone markers used?

Evaluation of bone turnover & bone loss
Evaluation of treatment effect
Compliance with mediation

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How is bone mass investigated?

DEXA

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What are T scores and what do certain values mean?

Bone density
-1+ normal bone density
-2.5- -1 osteopenia
-4- -2.5 osteoporosis

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Name some bone disorders

Metastic disease
Paget’s disease
Osteoporosis
Osteomalacia/rickets
Hyperparathyroidism

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Describe osteoporosis

Dec bone mass & deranged bone micro architecture= failure of structural integrity
Loss of bone
Propensity to fractures- spine & hip
Diagnosis by DEXA/Xray

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What are common sites of fragility fractures?

Spine
Neck of femur
Wrist

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What are secondary causes of osteoporosis?

Endocrine: Early menopause, diabetes, Cushings,
GI: Coeliac, IBD, chronic liver disease
Haematological: myeloma, haemoglobinopathies
Respiratory: COPD, CF
Drugs: steroids, heparin, anti-convulsants, ciclosporin
Rheumatological: RA
Metabolic: homocysturia

What investigations can be carried out for secondary causes of osteoporosis?

Ca & bone profile
TFTs
FBC (U&Es- estimated GFR)
Vit D
PTH
Coeliac screen
Plasma viscosity

What are the types of treatments for osteoporosis?

Anabolic

- Antiresorptives: bisphosphonates

What is the mechanism of action for bisphosphonates?

Mimic pyrophosphate structure
Taken up by skeleton
Concentrated in newly mineralising bone under osteoclasts
Local release during bone resorption
Modulate signalling from osteoblasts to osteoclasts
Ingested by osteoclasts
Inhibit osteoclast formation, migration, activity, promote apoptosis

What are problems with using bisphosphonates?

Poor absorption
Cause oesophageal/ upper GI problems
Flu-like side effects
Osteonecrosis of jaw
Atypical femur fractures

What types of bone metastases are there?

Lytic: breast, lung, destruction of normal bone (osteoclasts)
Sclerotic/osteoblastic: deposition of new bone, prostate, lymphoma

What is the clinical presentation of bone metastasis?

Pain: worse at night, better with movement, constant
Broken bones: femur, humerus, vertebral, pathological
Numbness/paralysis/trouble urinating: spinal cord compression
Loss of appetite/nausea/thirst/fatigue/confusion: symptoms of hypercalcaemia
Anaemia: disruption of bone marrow

What are the symptom of hypercalcaemia?

Severe: abdo pain, vomiting, coma, pancreatitis, dehydration, arrhythmias
Mild: nausea, fatigue, constipation, anorexia, mood changes, polyuria/dipsia

Which cells secrete PTH?

Chief cells of parathyroid gland

What are the roles of PTH?

- Inc decomposition of bone releasing Ca - Inc absorption of Ca from food by intestines - Inc reabsorption of Ca from urine by kidneys - All lead to inc levels of blood Ca

What are the causes and signs of primary hyperparathyroidism?

- Sporadic or familial - Ca high - PTH high - Low phosphate - High alkaline phosphatase - Adenomas: encapsulated & consist of chief cells - Parathyroid carcinoma: aggressive, severe hypercalcaemia - Glandular hyperplasia: all 4 glands enlarged, sporadic or genetic MEN1, MEN2A - Ectopic adenomas: in mediastinum/thymus gland, migrate during embryogenesis

What are the causes and signs of secondary hyperparathyroidism?

- CKD, vit D deficiency - Normal/low Ca - PTH high - High phosphate if due to kidney problems

What are the causes and signs of tertiary hyperparathyroidism?

- prolonged secondary hyperparathyroidism, CKD - High Ca - High PTH - High or low phosphate

What are the classical symptoms of primary hyperparathyroidism?

- Hypercalcaemic symptoms - Renal disease/ CKD/ nephrolithiasis - Bone disease/ osteoporosis/osteitis/fibrosa cystica - Proximal muscle wasting

What are Calcimimetics used for and how do they work?

- Normalise Ca in sympotmatic patients/not fit for surgery | - Activates CaSR in PT gland leading to reduced PTH secretion

Describe Paget's disease of the bone

- Rapid bone turnover & formation - Abnormal bone remodelling - 50+ - Polyostotic or monostotic - Elevated alkaline phosphatase reflecting inc bone turnover

What are clinical features of Page's disease?

- Bone pain - Bone deformity - Fractures - Arthritis - Cranial nerve defects if skull affected (hearing/vision loss) - Risk of osteosarcoma

Which bones are most commonly affected by Paget's disease?

- Pelvis - Femur - Lower lumbar vertebrae

What is osteomalacia?

- Lack of mineralisation of bone due to it D deficiency/lack of Ca/phosphate - Widened osteoid seams - Childhood rickets: widened epiphyses & poor skeletal growth

What are the main causes of osteomalacia?

- Insufficient Ca absorption from intestines (diet or resistance) - Excessive renal phosphate excretion (genetic)

What are clinical features of osteomalacia?

- Muscle & bone weakness - Diffuse bone pains (symmetrical) - High alkaline phosphatase & PTH - Low vit D & Ca - Secondary hyperparathyroidism