Musculoskeletal 1 - Metabolic Bone Disease - Histopathology Flashcards
What are 4 functions of bone
- Structure - gives structure and shape to body
- Mechanical - sites for muscle attachment
- Protective - vital organs and bone marrow
- Metabolic - Ca reserve and other minerals
Describe the composition of bone
65% Inorganic - calcium hydroxyapatite, stores 99% of Ca in body, and loads of P, Mg, Na
35% organic - bone cells and protein matrix
Describe bone geography
Split into Diaphysis (shaft part) and Epiphysis (articular part)
Diaphysis = medulla inside (bone marrow is in medullary cavity), then cortex, then periosteum
Epiphysis = articular cartilage, subchondral bone, epiphyseal line
Metaphysis = region between diaphysis and epiphysis
What are the 5 anatomical types of bone
- Flat - cranial bones, ribs, protective
- Long - tibia, femur, support weight and movement
- Short/cuboid - carpals/tarsals, stabilise and facilitate movement
- Irregular - vertebrae, pelvis, specific shape allowing to protect specific organ
- Sesamoid - patella, embedded in tendons, protective
Describe the macroscopic structure of bone
- Trabecular/spongy/cancellous bone
2. Cortical compact bone
Describe the microscopic structure of bone
- Woven bone (immature - low strength)
2. Lamellar bone (mature)
Describe the differences between cortical bone and cancellous(/trabecular/spongy) bone
Cortical = long bones, 80% of skeleton, appendicular, 80-90% calcified (as slow turnover so lots of time to get mineralised), structural, mechanical and protective function
Cancellous/Trabecular/Spongy - Vertebrae and pelvis, 20% skeleton, axial, 15-25% calcified (high turnover), mainly metabolic function (deposit minerals etc) and facilitated by large SA
Describe cortical bone microanatomy
Circular bones = osteons, consist of circular layers of lamellar bone. Centred around a Haversian canal with blood vessels.
Interstitial lamellae between circles
On the outside of bone - circumferential lamellae
Osteocytes with dendritic processes form a network
Do trabecular lamellae have a Haversian canal?
No, they form in layers instead
Mature lamellar bone has striations with lamellae. What about woven bone?
Has no lamellae, disorganised structure, collagen is disorganised - hence weaker
What are the 3 types of bone cells
- Osteoclasts - multinuclear cells part of macrophage family - they resorb bone
- Osteoblasts - produce osteoid which forms new bone
- Osteocytes - mechanosensory network embedded in mature bone
Explain the bone remodelling cycle
- Osteocyte apoptosis releases RANKL.
- RANKL binds to osteoclasts and stimulates resorption
- Reversal cells are put onto bone, signalling osteoblasts, and eventually osteoblasts lay down osteoid
Osteoblasts also produce RANKL and M-CSF which regulates/precurses osteoclasts.
Osteoblasts produce OPG - osteoprotegerin, which competitively binds RANKL and inhibits resorption
What do osteoblasts and osteocytes look like histologically
Osteoblasts = cuboid cells on lining of bone
Osteocytes = cells embedded in bone
What are the uses of bone biopsy
- Confirm diagnosis of bone disorder
- Find cause/evaluate ongoing bone pain/tenderness
- Investigate abnormality on Xray
- Bone tumour diagnosis
- Determine cause of unexplained infection
- Evaluate therapy performance
What are canaliculae
Channels that osteocytes use to communicate to bone surface
What is a Haversian canal
Channels in cortical canals that blood vessels travel through
What are the 2 types of bone biopsy
- Closed biopsy - using needle, core biopsy (e.g. Jamshidi needle)
- Open biopsy - for sclerotic/inaccessible lesions
What histological stains can be used?
- H & E stain
- Masson-Goldner trichrome stain - to tell between unmineralised and mineralised bone
- If you want to look at bone turnover, use tetracycline/calcein labelling
What is metabolic bone disease
Group of diseases that reduces bone mass and strength
Caused by imbalance of various chemicals in the body
Causes altered bone cell activity, rate of mineralisation, or changes in bone structure
Name 5 common metabolic bone diseases
- Osteoporosis
- Osteomalacia/Rickets
- Primary hyperparathyroidism
- Renal osteodystrophy
- Paget’s disease
What is osteoporosis and what are the risk factors
What are the 2 types of osteoporosis
Osteoporosis = bone mineral density T-score of -2.5 or lower (BMD is 2.5 SDs below mean peak BMD for their sex)
Primary RF = age, post menopause
Secondary RF = drugs, systemic disease
2 types = high turnover (high osteoclast relative to osteoblast) and low turnover (low osteoblast relative to osteoclast)
Which type of bone does osteoporosis affect most
Trabecular/cancellous/spongy bone - highly metabolic
What is osteomalacia
What are the 2 types
Defective mineralisation of normally synthesised bone matrix (aka rickets in children)
Type 1 - caused by Vit D deficiency
Type 2 - caused by PO4 (phosphate) deficiency
How does Vit D deficiency cause osteomalacia
Vit D acquired from sunlight or diet - activated in liver and kidney - causes Ca absorption in intestines and Ca reabsorption in kidney. Therefore a lack of it causes hypocalcaemia - causing osteomalacia
What are the symptoms of osteomalacia
- bone pain/tenderness
- fracture
- Proximal weakness
- Bone deformity
What are Loosers zone fractures?
Pseudo fractures that occur in areas of high tensile stress - typically at right angles to the cortex, occur partway into the bone and have symmetrical sclerotic margins
How can hyperparathyroidism be a cause of MBD
Excess PTH
This causes increased PO4 and Ca excretion in urine - leading to hypercalcaemia and hypophosphatemia —> this may lead to skeletal changes of osteitis fibres cystica
Which 4 organs are affected in hyperparathyroidism
- Parathyroid glands
2 Bones - Kidneys
- Proximal SI
What are the primary and secondary causes of hyperparathyroidism
Primary -
- Parathyroid adenoma
- Chief cell hyperplasia
Secondary
- Chronic renal deficiency
- Vit D deficiency
What is a useful mnemonic to remember the symptoms of hyperparathyroidism
- Stones - Ca oxalate renal stones
- Bones - osteitis fibrosa cystica, bone resorption
- Abdominal groans (acute pancreatitis)
- Psychic moans (psychosis and depression)
Stones, bones, groans and moans
How may hyperparathyroidism present on an x ray, histologically,
X ray - lesions in hand
Histologically -
- tunnelling erosion in trabeculae - centre of trabeculae have been eaten away
- Brown cell tumour, giant cells surrounding blood vessels - causes a pattern of giant cells, fibrous tissue and reactive bone outside it
What does renal osteodystrophy involve
All the skeletal changes resulting from chronic renal disease
Includes:
- Increased bone resorption
- Osteomalacia
- Osteosclerosis
- Growth retardation
- Osteoporosis
What is Paget’s Disease
Disorder of bone turnover - >40y/o usually
Sometimes it can be mono-osmotic (15%) but usually multiple bones affected
3 stages:
- Osteolytic
- Osteolytic-osteosclerotic
- Quiescent osteosclerotic
Which 2 genes may be affected that cause Paget’s disease
- RANK
- SQSTM1
Autosomal inheritance - incomplete penetrance
What are the clinical symptoms of Paget’s disease
- Pain
- Microfractures
- Nerve compression
- Skull changes - may put medulla at risk
- Deafness
- Haemodynamic changes/Cardiac failure
- Hypercalcaemia
- Rare but sarcoma development
What may Pagets disease look like x ray and histologically
X ray - thickened cortices, osteolytic black spots in medullary cavity
Histologically - usually see high turnover of bone with osteoclast resorbing bone. Later stages looks like disorganised bone with cement lines
