Metabolic bone disease: Histopathology Flashcards
What is bone?
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
Describe the composition of bone?
Inorganic - 65%
- Calcium hydroxyapatite
- is storehouse for 99% of calcium in the body
- Store house for 85% of the phosphorus, 65% of sodium, of Magnesium
Organic - 35%
- Bone cell and protein matrix
Describe the bone structure?
See diagram
Epiphysis - end region of the bone
Metaphysis - epiphyseal line is where the growth plate would have been. Contains the bulk of cancellous bone.
Diaphysis - the main portion of the bone is called the. From superficial to deep - Periosteum, cortex and the medulla (trabecular bone found criss-crossing here).
Corticial compact bone
metaphysis
See digarams
Bone needs to be 50% mineralised to show up on an x ray
What are the different types of bone classification?
Anatomical bone
- Flat (protective; cranial bones)
- Long (support weight; femur and tibia)
- Short/cuboid (movement and stabilisation; tarsals and carpals)
- Irregular (specific shape protective; vertebrae/pelvis),
- Sesamoid (protective; patella)
Macroscopic structure
- trabecular/cancellous/spongy
- cortical/ thick compact bone
Microscopic structure
- Woven bone (immature): low strength, disorganised lamella, high bone turnover
- Lamellar bone (mature): Makes up most of your skeleton and is found in cortical and cancellous bone.
What the difference between cortical and cancellous bone?
CORTICAL (dense on the outside)
- long bones
- 80% of skeleton
- appendicular
- 80-90% calcified
- mainly structural,
- mechanical, and protective
CANCELLOUS/TRABECULAR (spongy)
- vertebrae & pelvis
- 20% of skeleton
- axial
- 15-25% calcified
- mainly metabolic
- large surface area
See diagram
Describe the strueture of cortical bone microantaomy
See diagram
Cortical bone is made up of parallel osteons. Osteons are structured circular layers of lamellae bone surrounding a central canal called the haversian canal which contains the blood vessels.
Circumferential lamellae - at the periosteum which goes around the whole bone.
Interstitial lamellae - which go between osteons.
Trabecullar lamellae - organised into layers
There are dendritic structures in the lacunae of the lamellae. These are osteocytes and the process form the canalicular network. (Mechanosensory network used to repair damaged bone or remodeling)
List the bone cells types?
Osteoclasts - multinuclear cells that resorb/remove bone
Osteoblasts - produce osteoid to form new bone
Osteocytes - Are the osteoblasts that have been embedded in osteoid. They make up the mechanosensoy network in mature bone - tell other bone cells what to do (remodelling).
What is the bone remodelling cycle?
Osteoclastic bone resorption and osteoblastic bone formation is balanced and coupled together
Typical bone remodelling occurs when osteocytes sense damage. The produce factors that promote the formation of mature osteoclasts.
1) RANKL
2) M-CSF
The osteoclasts resorb the bone and then die off. Osteoblasts are then recruited to the site and form new bone. Osteoblasts also produce factor.
1) OPG
OPG acts a decoy binding to the RANKL preventing it from binding to its receptor.
What are the types of bone biopsy?
Closed - core biopsy using a Jamshidi needle
Open - used for sclerotic or inaccessible lesions
Typical location would be a transiliac bone biopsy - in a small region you can get a sample of cortical bone on both sides and trabecular bone.
What are the indications for a bone biopsy?
- Investigation bone pain or tenderness
- Investigate abnormality seen on X-ray
- Bone tumour diagnosis
- Determine cause of an unexplained infection
- Evaluate effectiveness of therapy
What types of histological stains are used?
- H and E staining
- Masson - Goldener Trichrome. You can see unmineralised and mineralised bone.
- Tetracycline/Calcein labelling. Used to look at bone turnover.
Define metabolic bone disease?
A group of diseases that cause reduce bone mass and reduced bone strength.
Due to imbalance of various chemicals in the body (vitamins, hormones, minerals, etc)
It causes altered bone cell activity, rate of mineralisation of changes in bone structure
What are 5 common MBDs?
- Primary hyperparathyroidism
- Rickets/Osteomalacia
- Osteoporosis
- Paget’s diease
- Renal osteodystrophy
Define osteoporosis?
Defined as having a reduced bone density T score of -2.5 or lower.
Trabecular bone is absorbed away –> remaining trabeculae are thinner and less interconnected = weakened bone = fractures.
What causes osteoporosis?
Osteoporosis can be divided into:
- Primary osteoporosis:
- Secondary osteoporosis:
Causes
• Primary – the disease is age related or due to the rapid loss of bone mass that occurs in the 5 to 7 years following the menopause. No pathological cause
• Secondary – something has induced osteoporosis (drugs, systemic disease)
Imbalance in bone resorption and formation - more resorption than formation.
How do you diagnose osteoporosis?
Diagnosis
• IMPORTANT: serum biochemistry is NORMAL
• DEXA scans are used to assess bone mineral density (BMD)
• Alkaline Phosphatase (ALP) is used as a marker of bone turnover
• ALP is raised in: Paget’s, osteomalacia, bone metastases, hyperparathyroidism
Define osteomalacia
Defective mineralisation of normally synthesised bone matrix.
This is called rickets in children.
What causes osteomalacia?
Bone mineral is composed of both calcium and phosphorus, so loss of either will result in osteomalacia.
1) Vitamin D deficiency causing hypocalcaemia. Vit D deficiency causes increased PTH which increases bone resorption = osteomalacia.
2) Phosphate deficiency
Describe the histological features of osteomalcia?
Because osteomalacia is a problem with the mineralisation of bone this can be seen using a masson-trichrome stain (orange osteoid).
Not enough calcium available to form hydroxyapatite crystals necessary to mineralise bone.
What does hyperparathyroidism cause?
Excess PTH
- Increases posphate excretion in the urine
- Hypercalceamia = increased renal and gut Ca2+ absorption. Increases Ca2+ bone resorption
- Hyperhypophospahtemia
- Skeletal changes of osteitis fibrosa cystica: resorption of bone and replacement with fibrous tissue and the formation of cysts like ‘brown tumours.
What causes hyperparathyroidism?
Primary - parathyroid adenoma, chief cell hyperplasia
Secondary - chronic renal deficiency, Vit D deficiency
Symptoms of primary hyperparathyroidism –> hypercalcaemia
Stones (Ca oxalate renal stones)
Bones (osteitis fibrosa cystica, bone resorption
Abdominal moans (acute pancreatitis)
Physic moans (psychosis & depression)
Symptoms of hypercalcaemia
Define renal osteodystrophy?
Comprises all the skeletal changes resulting from chronic renal disease
- increased bone resorption (osteitis fibrosa cystica)
- osteomalacia
- osteoschleorosis
- growth retardation
- osteoporosis
Define pagets disease?
Disorder of bone turnover It is divided into 3 stages 1) Osteolytic 2) Osteolytic-osteoslcerotic 3) Quiescent osteosclerotic
Onset > 40 years
M > F
What causes pagets disease?
We don’t really know…
1) Genetic - autosomal (mutations of SQSTM1 or RANK)
2) Parvomyxovirus type particles
3) Overuse of previous bone injury
What are clinical symptoms of pagets disease?
Often asymptomatic
- pain
- microfractures
- nerve compression (incl. Spinal N and cord)
- skull changes may put medulla at risk
- deafness
- +/- haemodynamic changes, cardiac failure
- hypercalcaemia
- Development of sarcoma in area of involvement 1%
What is high turnover and low turnover osteoporosis
High turnover osteoporosis - both formation and resorption are increased but resorption is increased above the level of formation
Low turnover osteoporosis - - low turnover osteoporosis where both are decreased but formation is decreased to a greater extent than resorption
What is tetracycline labelling?
Tetracycline labelling allows us to monitor how much new bone is being formed. When administered it is incorporated into the mineralising front of any osteoid currently being mineralised. Administering it a second time allows us to determine much about the dynamic formation of bone in a patient. You can see here regions that have only one label or are double labelled. One label shows bone was only forming at the time of one of the tetracyline injection, two it was forming at both time points. The distance between the two labels tells us how much mineral accrued between the two injections of tetracycline. The mineral apposistion rate. The relationship between the mineral apposistion rate and the quantity of bone surface labelled tells us the bone formation rate, or how much bone in total formed in our sample between the two time points.
This can be useful for determining if bone turnover is fast, or slow, or if there is a defect in mineralisation
What does osteomalacia cause?
Bone pain/tenderness
Fracture - horizontal fracture in Looser’s Zone
Proximal weakness
Bone deformity
