Musculoskeletal Flashcards
Describe the organic and inorganic structure of bone.
Inorganic (65%) mainly calcium hydroxyapatite. Contains 99% of the body’s calcium, 85% of its phosphorus, 65% of its sodium.
Organic (35%) is made up of cells and protein matrix (type 1 collagen).
Describe osteocytes
Osteocytes lie within lacunae and form a mechanosensory network (osteocyte canaliculi network) embedded in mature bone through cytoplasmic extensions which allow metabolic exchange. They never divide.
Osteocytes maintain the bone matrix and are involved in repair.
If a bone is damaged, osteocytes are freed from their lacunae and differentiate into osteoblasts or osteoprogenitor cells.
What are the 5 different classes of anatomical bones?
Flat, long, short/cuboid, irregular, sesamoid.
Contrast compact (cortical) and cancellous bones.
Cortical is 80-90% calcified and functions mainly as structural, mechanical and protective bone. Basic unit is the osteon. Osteocytes arranged in layers around a central Haversian canal. Each canal carries a blood and nerve supply to the osteon. The canals run parallel to the bone surface. Osteons arranged into lamellae - mostly concentric.
Cancellous is 15-25% calcified and has mainly metabolic functions. Lamellae not arranged into osteons. Matrix develops into an interlacing network of rods called trabeculae. Less heavy.
Briefly describe the process of remodelling.
Osteocytes sense new stress which requires remodelling - apoptose to release RANK-L. Binds to RANK-R on osteoclasts, resulting in resoprtion. Bone subsequently laid down by osteoblasts.
Remodelling 5% of skeleton at any given time, total skeleton replaced over 7 years.
What is woven bone?
Immature bone founding in the growing skeleton or after a fracture.
It is more random than lamellar bone, and is weaker or more flexible than lamellar bone.
What is lamellar bone?
Mature bone found in the normal skeleton. 2 types: cortical and cancellous bone.
What properties are afforded to bone by collagen and hydroxyapatite?
Collagen gives bone cable-like flexibility and resistance to tension.
Hydroxyapatite confers pillar-like stiffness and resistance to compression.
Describe osteoblasts
Osteoblasts produce osteoid, which is calcified to form bone matrix. Ultimately, the osteoblasts become osteocytes.
Describe osteoprogenitor cells
Stem cells which differentiate into osteoblasts. Only a small number present, actively involved in bone fracture repair.
Mostly located in periosteum, endosteum and the vascular canals in the bone matrix.
Describe osteoclasts
Also called giant cells, remove bone matrix (resorb bone). They are derived from monocytes and are of a different lineage from other bone cells.
What is the periosteum and what is the endosteum?
Periosteum = fibrous outer layer and cellular inner layer surrounding the superifical layer of compact bone. Endosteum = incomplete cellular layer lining the marrow cavity.
Describe intramembranous ossification.
Mesenchymal models of bones from embryonic development directly ossify into bone. Bones directly below skin ossify this way (skull, mandible, clavicle).
Mesenchymal cells produce the matrix (osteoid), which becomes calcified. Mesenchymal cells differentiate into osteoblasts to form an ossification centre. As ossification progresses, some osteoblasts are trapped in bony pockets (lacunae) and transform into osteocytes. Blood vessels grow into the area to maintain the metabolism of the bone. Initially cancellous bone, can subsequently be remodelled into compact bone. Periosteum forms around the bone and “traps” a surface layer of osteoblasts.
Describe endochondral ossification.
Mesenchyme differentiates into cartilage bone models. Most bones ossify this way.
Mesenchymal cells differentiate into chrondroblasts which form cartilage models of the bones. Cartilage bone model grows by expansion (interstitial growth) and new growth of cartilage at outer surface (appositional growth). In the middle of the bone, the cartilage calcifies and the chondroctyes die. Becomes primary ossification centre: grows in both directions replacing cartilage to form the diaphysis. Secondary ossification centres from in the epiphyses. The epiphyseal plate is the cartilagenous area between the diaphysis and epiphysis. The bone continues to grow until the epiphysis fuses with the diaphysis.
In endochondral ossification, how do short bones ossify and at what age do primary and secondary ossification centres tend to appear?
Short bones ossify via only one primary ossification centre.
Primary centres appear at around 2 months in utero; secondary centres appear about 2 years after birth.
Describe fracture repair.
Torn blood vessels bleed to produce a fracture haematoma. Osteoprogenitor cells and relatively inactive osteoblasts from the periosteum and endosteum differentiate into active osteoblasts and migrates towards the fracture. They form a provisional type of bone and cartilage called external callus, which bridges the end of the bones. Cartilage replaced by bone (initially woven bone) - then restructures to cancellous bone. Osteoblasts and osteoclasts remodel the cancellous bone to cortical bone.
What are the 2 types of bone biopsy?
Closed core biopsy - Jamshidi needle.
Open biopsy - for sclerotic/ inaccessible lesions.
If the reason for a bone biopsy is general, what biopsy would you perform?
A transiliac bone biopsy, since all types of bone can be seen in the one core.
What stains are used to look at bone?
H&E staining for decalcified samples
Masson-Goldner Trichrome staining looks at degree of mineralisation.
Tetracycline staining gives a fluorescent line at the frontier of osteoblasts to look at whether turnover is fast or slow.
What are metabolic bone diseases?
A group of diseases which cause reduced bone mass and strength due to imbalance of various chemicals in the body, causing altered bone activity.
What is osteoporosis?
Defined as a bone mineral density T-score of -2.5 or lower.
Primary causes include age and menopause.
Secondary causes include drugs and systemic disease.
Can be high turnover or low turnover osteoporosis (resorption > formation in both cases).
Thin trabeculae. Loss of cortical bone (thinning of cortex). Structurally normal, just reduced mass.
What is osteomalacia?
Defect of mineralisation of normally synthesised bone matrix. Leads to rickets in children. Use Masson-Goldner Trichrome stain.
2 types: deficiency of vitamin D, deficiency of PO43-
Pain/tenderness/ fractures/ proximal weakness.
Horizontal fractures in Looser’s zone (areas of high tensile stress). 90 degrees to bone.
What causes osteitis fibrosa cystica?
Hyperparathyroidism.
Characteristic “brown tumours” on X-ray. Fibrous tissue replaces bone. Also, chondrocalcinosis seen (calcification of articular cartilage).
Describe renal osteodystrophy.
Comprises all skeletal changes arising from renal deficiency. Increases resorption, osteomalacia, osteosclerosis, osteoporosis, growth retardation.
What is Paget’s disease?
A disorder of bone turnover. 3 stages: osteolytic, osteolytic-osteosclerotic, quiescent-osteosclerotic.
Onset >40yrs. M>F. Mono-ostotic 15%.
Thickened cortices (sclerosis) with irregular trabeculae.
Why might a bone biopsy be performed?
To confirm diagnosis, find cause, investigate abnormality on X-ray, diagnose bone tumour (benign vs malignant), determine cause of unexplained infection, evaluate therapy performance.
What is a radiological sign?
A change in imaging appearance, whether functional or structural, that may point towards a pathology.
What types of imaging are useful for investigating bones and what do they look at?
X-rays, CT, DEXA - look at density.
MRI - biochemical composition
Radionuclide bone studies - bone turnover.
What are insufficiency fractures?
Stress fractures due to normal stresses on bone, typically seen in osteoporosis.
How is the result of a DEXA scan interpreted?
Compare to normal population at peak (25 year olds).
T score
What does Paget’s disease look like on imaging.
Cortical thickening, bone expansion, coarsening of trabeculae, osteolytic, osteoslcerotic and mixed lesions.
Doesn’t cross joint.
What are codfish vertebrae?
Biconcave vertebrae seen on x-rays - a sign of osteoporosis and osteomalacia.
Give radiological signs of rickets
Indistinct/ frayed metaphyseal margin.
Widened growth plate without calcification
Osteopenia
Enlarged anterior ribs
Cupping/ splaying of metaphyses due to weight bearing.
What are looser zone fractures a radiological sign of?
Looser zone fractures = short fractures associated with sclerotic margin (which is whiter) - 90 degrees to bone.
Seen in osteomalacia.
What symptoms are associated with metabolic bone disease?
Metabolic symptoms - hyper/hypocalcaemia, hyper/hypophosphatemia.
Symptoms specific to bone - fractures and deformity.
How is primary hyperparathyroidism diagnosed?
Elevated total/ ionised calcium with PTH levels frankly elevated or in the upper half of the normal range.
Subjects with hypercalcemia and PTH in the upper half of the normal range are physiologically not normal.
What is the problem with CHRONICALLY elevated PTH?
Chronic PTH = catabolic (increased cortical bone resorption).
Pulsatile/ acute PTH = anabolic.
Give an overview of systemic lupus erythematosus (SLE).
One of a family of chronic overlapping autoimmune diseases.
M:F 1:9 (female preponderance)
Presentation 15-40 years old
Multiple genes implicated: complement deficiency
Principally affects joints and skin, lungs, kidney, bone marrow. Clinical features depend on organ affected.
Describe the presentation of systemic lupus erythematosus (SLE).
Malaise, fatigue, fever, weight loss.
Specific features: butterfly rash, alopecia, arthralgia, Raynaud’s phenomenon.
Other features: inflammation of kidney, CNS, heart, lungs, accelerated atherosclerosis, vasculitis.
Describe the aetiology of SLE (systemic lupus erythematosus).
Complex cause, involving genetic and environmental factors.
Abnormal clearance of apoptotic cell material.
Dendritic cell uptake of autoantigens - activation of B-cells.
IgG autoantibody production
Immune complexes
Complement activation, cytokine generation etc.
What is interesting about ESR and CRP in SLE?
ESR increases, but CRP remains the same.
How is systemic lupus erythematosus classified?
Mild = skin +/- joint involvement Moderate = inflammation of other organs Severe = severe inflammation of vital organs.
How do we treat mild SLE?
Paracetamol +/- NSAID.
Hydroxychloroquine (rash), topical corticosteroids (rash, not face).
