bone Flashcards
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)
Describe osteoblasts
- Terminally differentiated
- Products of mesenchymal stem cells
- Make osteoid, hormones, matrix proteins, alkaline phosphotase
- Prerequisite for mineralisation
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
Describe osteocytes
- Star shaped
- Trapped/buried osteoblasts
- Communicate via cytoplasmic extensions
- Mechanosensory
- Involved in regulating bone matrix turnover
How is normal bone formed?
- Resorption by osteoclasts
- Formation by osteoblasts
What are the stages in bone formation?
- Resting
- Resorption
- Osteoid formation
- Mineralisation
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
What is bone alkaline phosphatase?
- Released by osteoblasts
- Involved in mineralisation
- Release stimulated by increased bone remodelling
Describe P1NP
- Synthesised by osteoblasts
- Precursor molecule of type 1 collagen
- Increases with increased osteoblast activity
- Decreased by reduced osteoblast activity
Why are bone markers used?
- Evaluation of bone turnover & bone loss
- Evaluation of treatment effect
- Compliance with mediation
How is bone mass investigated?
DEXA
What are T scores and what do certain values mean?
- Bone density
- -1+ normal bone density
- -2.5- -1 osteopenia
- -4- -2.5 osteoporosis
Name some bone disorders
- Metastic disease
- Paget’s disease
- Osteoporosis
- Osteomalacia/rickets
- Hyperparathyroidism
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
What are common sites of fragility fractures?
- Spine
- Neck of femur
- Wrist
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
