Metabolic Bone Disease – Histopathology Flashcards
What are the main functions of bones?
STRUCTURE give structure and shape to the body
MECHANICAL sites for muscle attachment
PROTECTIVE vital organs and bone marrow
METABOLIC reserve of calcium and other minerals
What are the two main components of bone and what are their relative proportions?
Inorganic (65%) – calcium hydroxyapatite (store of 99% of the body’s calcium, 85% of the phosphorous and 65% of Na and Mg) Organic (35%) – bone cells and protein matrix
Describe the classification of bone as cortical and cancellous.
Cortical
- Long bones
- 80% of skeleton
- Appendicular skeleton
- 80-90% calcified
- Mainly mechanical and protective role
Cancellous
- Vertebrae and pelvis
- 20% of skeleton
- Axial skeleton
- 15-25% calcified
- Mainly metabolic
- Large surface area
What are the uses of a bone biopsy?
Confirm diagnosis of bone disorder Evaluate bone pain or tenderness Investigate abnormality seen on X-ray For bone tumour diagnosis To determine the cause of unexplained infection To evaluate therapy
What are the types of bone biopsy?
Closed – needle – core biopsy with Jamshidi needle Open – for sclerotic or inaccessible lesions
What are the three types of bone cell?
Osteoblast – build bone by laying down osteoid Osteoclast – multinucleate cells of the macrophage family that resorb bone Osteocyte – osteoblast like cells, form connections to eachother to form a sesnory network
Where are osteocytes found?
Lacunae
What cytokine is important for stimulating the differentiation of osteoclast precursors into pre-osteoclasts?
M-CSF (this is produced by osteoblasts)
What stimulates bone resorption?
Pre-osteoblasts express RANK-L on their membrane which can bind to RANK expressed on pre-osteoclasts. Which then stimulates the maturation of osteoclasts
What do mature osteoblasts produce that blocks the RANK/RANKL binding?
Osteoprotegrin - competitvley binds RANKL
How are bones classified anatomically?
Flat Long Cuboid
What type of ossification leads to the formation of: a. Long Bones b. Flat Bones
a. Long bones Endochondral ossification exception is clavicle which is a long bone made by IM b. Flat bones Intramembranous ossification
Other than anatomically, how else can bone be classified?
Trabecular (cancellous) or compact (cortical) Woven (immature) or lamellar (mature)
What is metabolic bone disease?
Disordered bone turnover due to imbalance of various chemicals in the body (vitamins, hormones, minerals etc.) Group of diseases that causes reduced bone mass and bone strength Overall effect is reduced bone mass (osteopaenia) often resulting in fractures from little or no trauma
What are the three main categories of metabolic bone disease?
Related to endocrine abnormality (e.g. Vit D and PTH) Non-endocrine (e.g. age-related osteoporosis) Disuse osteopaenia
What are the primary causes of osteoporosis?
Age Post-menopause
What are the secondary causes of osteoporosis?
Drugs Systemic disease
Describe the histology of osteoporotic bone.
Weak trabecular bridging Holes and cysts
What is osteomalacia and what can it be caused by?
Condition of defective bone mineralisation that can be caused by: Vitamin D deficiency Phosphate deficiency (usually related to chronic renal disease)
What are the consequences of vitamin D deficiency?
Secondary hyperparathyroidism –> increased bone resorption Hypocalcaemia – neuronal excitability causing muscle twitching, spasms, tingling and numbness
Describe the histology of osteomalacia.
No calcification of bone
More uncalcified osteoid
Bones are very bendy and cannot carry musculature very easily
What are the clinical consequences of osteomalacia?
Bone pain/tenderness
Fracture (horizontal fractures at Looser’s zone in areas with high sheer stress e.g. at the neck of the femur)
Proximal weakness
Bone deformity - rickets in children
What is used to investigate mineralisation?
Fluorescent tetracycline labelling = stains the mineralising front green
Masson - Goldner technique = labels unmineralised bone orange and mineralised bone green
What are the endocrine and bone consequences of hyperparathyroidism?
Hypercalcaemia (increased Ca2+ reabsorption) Hypophosphataemia (increased phosphate excretion in the urine) Osteitis fibrosa cystica (due to increased osteoclast activity) - replacement of calcified matrix with fibrous deposits
List the four organs that are directly or indirectly affected by parathyroid hormone to control calcium metabolism.
Parathyroid glands Bones Kidneys Proximal small intestine
State some causes of primary hyperparathyroidism.
Parathyroid adenoma Chief cell hyperplasia
State some causes of secondary hyperparathyroidism.
Chronic renal insufficiency Vitamin D deficiency
What are the symptoms of hyperparathyroidism?
Stones, Bones, Abdominal Groans and Psychic Moans Stones – calcium oxalate renal stones Bones – osteitis fibrosa cystica Abdominal Groans – acute pancreatitis Psychic Moans – psychosis and depression
What is the most important investigation for hyperparathyroidism and what will it show in someone with hyperparathyroidism?
X-ray of the hand
Subperiosteal bone erosions
Brown cell tumours – small areas of resorption in the long bones of the fingers that are filled with osteoclasts
What are the five features of renal osteodystrophy?
Increased bone resorption (osteitis fibrosa cystica) Osteomalacia Osteoporosis Osteosclerosis Growth retardation
What are the consequences of renal osteodystrophy?
Hyperphosphataemia
Hypocalcaemia as a result of a decrease in vitamin D metabolism
Secondary hyperparathyroidism
Metabolic acidosis
Aluminium deposition
What is Paget’s disease?
Disorder of bone turnover (there is a lack of proper communication between the cells)
Describe the three stages of Paget’s disease
Osteolytic = Bone remodelling in disorganised fashion by osteoclasts
Osteolytic-osteosclerotic = holes + increased density from where osteoblasts are trying to build bone back up
Quiescent osteosclerotic = increased density
Describe the histology of Paget’s disease.
Prominent reversal lines Masses of osteoclasts in the same site as osteoblasts
In which ethnicities is Paget’s disease rare?
Asian African
Which sites does Paget’s disease most commonly affect?
in order most likely to least
- Spine
- Skull
- Pelvis
- Femur
- Tibia
- Sternum
- Humerus
List some clinical features of Paget’s disease.
Pain
Microfractures
Nerve compression
Skull changes
Deafness
Haemodynamic changes
Cardiac failure
Hypercalcaemias
Development of sarcoma in the area of involvement
What is a Haversian canal?
Channel that blood vessels run in within bone
What are Howship’s Lacunae?
Pits in the bone surface where osteoclasts are found (also called resorption bays)
Where are you likley to take a bone biospy from?
Illium
What is osteoperosis?
Bone mineral density (BMD) score of -2.5 or lower This means 2.5 SDs below peak bone mass for their gender
Describe the two types of osteoperosis
High turnover = increased resorption and deposition of bone but resorption is increased much more Low turnover = decreased resorption and deposition of bone but deposition is decreased much more
