Bone Pain Flashcards
What is osteopenia?
Decreased bone mass
1-2.5 SD of bone mass is below mean peak bone mass
What is osteoporosis?
It is osteopenia but the bone density is so little that it can increases the risk of a bone fracture
(>2.5 SD of bone mass is below mean peak bone mass)
Name the 2 types of primary osteoporosis and describe them
- Senile osteoporosis (when there is an imbalance between bone resorption and bone formation)
- Post- menopausal osteoporosis
Name the 3 types of secondary osteoporosis
- Endocrine disorders (hypothyroidism)
- Gastrointestinal disorders (Eating disorders/Malnutrition)
- Drugs (Corticosteroids)
What causes osteoporosis?
- Age related changes (adults osteoblasts do not respond to growth factors as much and can therefore not reform as much bone)
- Reduced physical activity (low magnitude influences bone density and weight exercises increased bone mass more than repetitive activities do (e.g cycling)
- Genetic factors (polymorphism has been linked to osteoporosis
- Adolescents that have low calcium intake and low vitamin D (reduces bone mass)
- Hormonal influences
What do WNT ligands do?
They stimulate bone growth
What are the main complications of osteoporotic fractures?
- Pulmonary embolism
- Pneumonia
Why do thromboembolisms form?
Due to the activation of the coagulation cascade which forms blood clots that can move to the heart
Why do patients that have hip fractures develop infections (Acute bronchopneumonia)
Because the patient is in pain which reduces their ability to cough and their mobility
What bacteria cause acute bronchopneumonia? Name 3
- staphylococcus aureus
- streptococcus pyogenes
- pseudomonas
What are the 2 vitamin D related disorders?
- Rickets disease
- Osteomalacia (result of unmineralized matrix)
Name some features of vitamin D
- Fat - soluble vitamin that is found in beef, cheese and salmon
- Maintains adequate plasma levels of calcium and phosphorus to support metabolic functions, bone mineralisation and neuromuscular transmissions
What is rickets disease caused by?
Deficiency of vitamin d and inadequate mineralization of children’s bone, where their epiphysis has not closed
What is osteomalacia?
Inadequate mineralization of the bone > causes softening of the bone
What is the major source of vitamin D for humans?
Synthesis in the skin
What are the main functions of vitamin D?
- In normal calcaemic states - it is required for calcium deposition
- Stimulates intestinal absorption of calcium in enterocytes and calcium reabsorption in distal renal tubules
- Upregulates Rank-ligand on osteoclasts which active rank receptors on osteoclast precursors causing differentiation into osteoclasts and bone resorption
- Promotes mineralisation of bone by stimulating osteoblasts to synthesise the calcium binding protein, osteocalcin, which promotes calcium deposition
What is vitamin D deficiency caused by?
- limited exposure to sunlight -by diets deficient in calcium and V.D
- malabsorption or renal disorders (can cause hypocalcaemia)
Vitamin D deficiency can cause bone fractures and bone loss in the elderly. TRUE OR FALSE
TRUE
In rickets ..(1).. unmineralised bone matrix causes ……(2)…
- Excess
2. Skeletal deformity
What does the inadequate calcification of the epiphyseal cartilage cause?
- causes overgrowth of the epiphyseal cartilage which causes irregular masses of cartilage which could project into the marrow cavity
- Deposition of osteoid matrix on inadequately mineralised cartilaginous remnants
- Can cause enlargement of the osteochondral junction
Name the clinical features of rickets
- Wide joints e.g hips, wrists and ankle
- Prominent forehead
- Bowing of limbs
- Rachitic rosary
- Enlarged epiphysis
What is most commonly affected by osteomalacia in the body?
The neck of femur and vertebral bodies
What other cells can produce vitamin D?
- macrophages, keratinocytes and tissues such as breast, prostate and colon can produce 1,25 - dihydroxyvitamin
Name some non skeletal effects of vitamin d
- immune cell differentiation and enhance inflammation
- inhibits tumour cell proliferation, induces differentiation and inhibits angiogenesis
What is the main action of parathyroid hormones?
Increase serum calcium
- activates osteoclasts by causing increased rank ligand expression on osteoblasts
- increases resorption of calcium by the renal tubules and increases urinary excretion of phosphate
- increases synthesis of vitamin D
What is the most common cause of asymptomatic hypercalcaemia?
- primary hyperparathyroidism
What is primary hyperparathyroidism usually caused by?
Sporadic parathyroid adenoma (benign tumours starting in the epithelial tissue of a gland or gland-like structure) and less commonly by a parathyroid hyperplasia and parathyroid carcinoma
How is hypercalcaemia detected?
By routine blood tests
What is secondary hyperparathyroidism caused by?
It is caused by hypercalcaemia secondary to renal failure and the parathyroid glands are hyperplastic
Is primary or secondary hyperparathyroidism more severe?
Primary
What is the most common cause of symptomatic hypercalcaemia
Malignancy
What are the clinical effects of parathyroid adenoma?
- Bone resorption - osteoporosis
- Brown tumour of hyperparathyroidism
- Osteitis fibrosa cystica (widespread resorption of bone leading to fibrosis and formation of cystic spaces)
- Nephrolithiasis - kidney stones
- Nephrocalcinosis - metastatic calcification of renal tubules
- GIT disturbances - constipation, peptic ulceration, acute pancreatitis
- CNS disturbance > depression and seizures
What are the clinical features of Paget’s disease?
- bone pain in pelvis, spine and femur
- Deformity
- Skull becomes so heavy that it becomes difficult to lift the head (Leontiasis ossea)
- Chalk stick fractures of legs, compression fractures of spine and kyphosis (hunchback)
- Elevated alkaline phosphatase
- Anterior bowing of femurs and tibiae (distorting femoral heads causing secondary osteoarthritis)
Paget’s disease is life threatening. TRUE or FALSE
FALSE
What is the pathogenesis of Paget’s disease?
- 50% of familial disease and 10% of sporadic(isolated) cases have a mutation in the SQTM1 gene which increases activity of nuclear factor kappa beta, which in turn increases osteoclast activity
- viral infections
- activation of mutations in RANK and inactivating mutations in OPG causes juvenile Paget’s disease
Why are bones affected by Paget’s disease more likely to be fractured?
Because the bones are denser meaning they cannot resist deformity as much and break
Who is renal osteodystrophy (mineralisation deficiency) seen in?
chronic renal disease - damaged kidney can not transport vitamin D in its active form (causes hypocalcaemia)
What does renal osteodystrophy cause?
- associated with osteomalacia
- can cause osteosclerosis
- growth retardation
- osteoporosis
- increases osteoclastic bone resorption
What is the treatment for osteomalacia and rickets?
- vitamin D replacement
What investigations should you take for osteomalacia?
- can be seen in laboratory investigations:
- low/normal calcium
- low/ normal phosphate
- raised serum alkaline phosphate
- low serum vitamin D
- raised parathyroid hormone levels
- low urinary calcium excretion
X-ray changes can also be seen e.g incomplete fractures
What are the clinical features of osteomalacia?
- bone pain
- lethargy (lack of energy)
- severe localized pain
- proximal myopathy (muscle disease/muscle weakening)
- skeletal deformity
- fracturing
Growth is impaired in children with rickets. TRUE OR FALSE
TRUE
What radiological changes are seen in patients with rickets?
- thin cortices
- widened growth plates
- delayed opacification of the epiphysis
What are the clinical features of osteoporosis
- deformity
- bone pain
- immobility due to fractures
- OSTEOPOROSIS IS USUALLY ASYMPTOMATIC AND THEREFORE THE IMPORTANCE OF TREATMENT TO PREVENT FRACTURES MUST BE EMPHASIZED TO PATIENTS
How is Paget’s disease investigated and diagnosed?
- serum alkaline phosphatase will be elevated
- plain radiographs show areas of disorganized bone with areas of lysis and sclerosis (cortex is usually thickened)
- isotope bone scans often show multiple areas of focal increased uptake and are most sensitive test for detecting pagetic lesions
What are lesions?
Damage to any tissue
What are the red flags in pagetic lesions?
Pagetic bone is highly vascular and bleeds a lot during surgery so patients are cross matched for blood in advance of planned surgery and blood is made available for emergency situations
How is paget’s disease treated?
- bisphosphonates are effective in inhibiting bone resorption and reducing the symptoms of Paget’s disea.se
- asymptomatic disease should only be monitored
- surgical treatment is used to manage complications
- e.g surgical stabilization, osteotomy( cutting and reshaping bone)
What are the main management techniques for osteoporosis/osteopenia?
- Modification of risk factors
- Drug therapies e.g bisphosphonates, denosumab, teriparatide etc.
- prevention of falls as most osteoporotic fractures are caused by falls
Why are elderly patients more predisposed to falls?
- aging process leads to slower reaction time
- poor mobility
- poor eyesight
- medical comorbidities e.g cardiac arrhythmia
- inadequate/unsafe housing environment
How is osteoporosis investigated/diagnosed?
- X-rays
- full examination and history
- full blood count to asses alkaline phosphatase, renal function, serum electrophoresis etc.
What are the causes of secondary osteoporosis?
- Hyperthyroidism
- Rheumatoid arthritis
- IBD
- Coeliac disease
- Renal failure
- Anorexia nervosa
- Crushing syndrome
Name 5 underlying causes of pathological fractures
- Tumours
- Paget’s disease
- Metabolic bone disease (e.g osteomalacia etc.)
- Lymphoma and Myeloma
- Rheumatoid arthritis
- Infection
A pathological fracture is one that requires (minimal/maximum) force to sustain
minimal
How is a pathological fracture usually identified?
By the past medical history and the radiograph
What is usually shown on a radiograph of a pathological fracture?
- lesions at the point of fracture
- Benign cystic lesion: purely lytic and margins are well defined
- Malignant lesion: rapidly growing benign lesion with infiltrative lesions
How do you manage pathological fractures?
- no fixation should be made before a definitive diagnosis is made (can be assumed in a child with radiographic features of benign bone cyst)
- biopsy (procedure where bone samples are removed) should be undertaken first
Most pathological fractures heal. TRUE OR FALSE
FALSE - Pathological fractures will not heal, therefore implants/screws are used which are designed to weight bear
What is a tumour?
Cells that keep dividing when new cells are not required - causes mass of tissue or tumour (unregulated and irreversible)
What is neoplasm?
It means new growth
Cells that keep dividing when new cells are not required - causes mass of tissue or tumour (unregulated and irreversible)
What is the difference between a benign and a malignant tumour?
A benign tumour does not spread to other parts of the body whereas a malignant one does
What is the name of benign vascular tumours in bones?
Haemangioma
What is the name of benign fibrous tissue tumours?
Fibroma
What is the name of benign cartilage tumours?
Chondroma, Osteochondroma
What is the name of benign bone tumours?
Osteoid osteoma
Malignant tumours are ……
cancer
What are the names of these malignant tumours
- Bone
- Cartilage
- Fibrous tissue
- Bone marrow
- Vascular
- Osteosarcoma
- Chondrosarcoma
- Fibrosarcoma
- Myeloma or Ewing’s sarcoma
- Angiosarcoma
What kind of bone tumour is most common in 40s?
Chondrosarcoma
What kind of bone tumour is most common and most common in 20s?
Osteosarcoma
What investigations should be carried out for bone tumours
Serum Biochemistry Plain Xrays :essential - show bone structure - lysis/sclerosis - must include a whole long bone Isotope Bone Scan: highlight areas of metabolic activity - no value in assessing structure - limited use in myeloma - beware sacral lesions CT: good for structure - good for pelvic and acetabular mets (3D) - screening of chest/abdomen and pelvis MRI: defines soft tissue involvement - essential in spinal disease - “skip lesions” in long bones - evaluation of suspected primary bone tumours
Bone biopsy
What is the difference between in - situ and invasive carcinoma
In - situ: epithelial neoplasm exhibiting the cellular features associated with malignancy but has not yet invaded through the epithelial basement membrane
Name the 4 histogenetic classifications of the human cells
- Epithelial cells
- Connective tissue/mesenchymal cells
- Lymphocytes
- Haematopoietic cells
Define an adenocarcinoma
Malignant tumour derived from glands
Define a squamous carcinoma
Malignant tumour derived from squamous epithelial cells
What is lipoma and liposarcoma
Lipoma - benign tumour of adipose tissue
Liposarcoma - malignant tumour of adipose tissue
What is leimyoma and leimyosarcoma?
Leimyoma - smooth muscle benign tumour
Leimyosarcoma - smooth muscle malignant tumour
State the names for a benign and malignant tumour of the skeletal muscle
Benign - rhabdomyoma
Malignant - rhabdosarcoma
What are the names of a malignancy of
- Lymphocytes
- Hemopoietic cells
- Leukemia or Lymphoma
2. Leukemia
What is tumour grading?
- How closely the tumour resembles the tissue from which it arises (differentiation)
- How aggressive the tumour is likely to be
What is usually used to grade or diagnose some types of cancer?
Immunohistochemistry
What are the factor which influence tumour invasion
- Decreased cell adhesion - malignant cells need to be able to separate
- Secretion of proteolytic enzymes
- Increased cell motility - cell migration
What is the first step of cellular invasion of tumours?
- Loosening of intercellular junctions - Cadherins (cell adhesive) is loosened
What is the second step of cellular invasion of tumours?
- Degradation of the extracellular matrix - tumour cells induce stroma or secrete lytic enzymes
What is the third step of cellular invasion of tumours?
- Migration and invasion
What is metastatic bone disease?
Cancer that begins in the organs e.g lungs and then spreads to the bone
What is the most common spinal fracture?
- Crush fractures in the lumbar vertebral bodies in older patients
Up to …….% of patients in their 80s have radiological evidence of a chronic vertebral fragility crush fracture
90
How do non pathological fractures usually occur?
By high energy trauma
Any patient suffering sufficient trauma should be assumed to have a spinal injury until proven otherwise. TRUE OR FALSE
TRUE
Name some features that would exclude a cervical spine injury without the need for a radiograph?
- Patient is alert and oriented
- no head injury
- no drugs or alcohol
- no neck pain
- no abnormal neurological signs
- no significant other injury that may distract the patient from complaining about the spine
- on examination: No bruising or deformity around the neck, no tenderness and a normal pain-free range of active movement
What are the investigations that should be carried out if a cervical spine injury is suspected?
- Cervical spine CT scan
- Fracture near the spine requires full spine imaging
- Thoracolumbar spine imaging is indicated if there is pain, bruising, swelling, deformity or abnormal neurological signs
What does damage to the spinal cord or peripheral nerves in the vertebral canal cause?
Catastrophic paralysis (can occur any moment of trauma and may be irreversible
What is spinal shock?
Period of altered distal function with loss of sphinceteric control and reflexes which may result from inadequate tissue perfusion secondary to the spinal injury interrupting autonomic control > leads to bradycardia and hypotension
How do you manage spinal shock?
- period of observation
- protection against pressure ulcers and urinary retention
Severe spinal cord injuries above C5 usually cause instant death. TRUE OR FALSE
True
What does the stability of the spine depend on?
The bony structure and the integrity of strong ligaments
How do you treat spinal injuries?
Stable fractures - mobilization
Unstable fractures - immobilization using bracing ,internal fixation etc.
Patients with spinal shock should receive iv fluids
The prognosis with people with spinal fractures is good. TRUE OR FALSE
FALSE
What are the clinical features of spinal injury?
- Tenderness
- Boggy swelling
- Bony step or gibbus
- Loss of sensation
- Rectal examination for anal tone
- Bradycardia and hypotension
Name some systematic features of metastatic bone disease
- weight loss
- anorexia
- acute pain
In what kind of patients is bone metastases a major clinical problem in?
In patients with
- Myeloma
- Breast/prostate cancer
- Thyroid
- Kidney
What are the clinical features of bone metastases
- bone pain
- pain worse at night and could be partially relieved by activity
- pathological fractures (usually occurs with metastatic breast/kidney/lung cancer)
How is metastatic bone cancer investigated?
- detections by isotope bone scan
- but preferred way is plain x-ray films as they pick up lesions
- in patients with a single lesion > perform biopsy
How is bone metastases managed?
- pain relief
- skeletal stabilisation
- preservation and restoration of function
- local tumour control
- surgical intervention (improves pain and reduces further skeletal related events)
- hormonal therapy is useful in prostate and breast cancer
- chemotherapy
- radiotherapy
What is the prognosis of bone metastases?
Bad prognosis
What are the genes called that promote normal cell growth
Proto-oncogenes
What are the genes called that promote abnormal cell growth
Oncogenes
What is the role of tumour suppressor genes?
Promote apoptosis
What is opioid dependency vs tolerance?
Tolerance: higher and/or more frequent doses of the drugs are needed to get the desired effects
Dependency; causes neurons to adapt so that they only function normally in the presence of the drug - absences of the drug can cause severe physiological reactions which can be life threatening
What is drug addiction characterised by?
Compulsive, uncontrollable drug seeking and use despite harmful consequences and long - lasting changes in the brain.
How do opioids work?
- reduces pain by acting on the central nervous system
- treats acute pain, palliative care, management of non- malignant chronic pain
- they bind to receptors in the CNS and other tissue
- the effect it has depends on which receptor they bind to
- opioids increase the tolerance to pain
Name some side effects of opiods
- euphoria
- constipation
-respiratory depression - sedation
- cough suppression
- nausea
-vomiting - ## comprises the immune system - decreases proliferation of macrophages
List the WHO pain relief ladder
- Non opioids medications (paracetamol)
- Adjuvant - NSAIDs (ibuprofen and diclofenac)
- Opioids (codeine, tramadol and dihydrocodeine)
- Mod-severe opioids (morphine)
Are analgesics more effective at preventing pain or providing relief of chronic pain?
PREVENTING PAIN
for chronic pain regular analgesia is the key
What are some signs of withdrawal
- irritability
- diarrhoea
- weight loss
- signs of aggression
Can you switch between opioids interchangeably?
NO
Methadone (OPIOIDS)
: Less sedating than morphine and lasts longer thus used to wean addicts off opiates (IV drug users). Avoid twice daily doses – risk of accumulation and overdose.
Remifentanil (OPIOIDS)
Used for sedation and anaesthesia. Rapid onset of action and recovery. Most opioids are metabolised by liver, this isn’t, it undergoes rapid metabolism via non-specific blood&tissue esterases, thus short duration of action, thus administer high doses over long periods without risk of accumulation
Naloxone
Antagonist
MORPHINE (OPIOIDS)
original opioid, non synthetic – benchmark gold standard drug
What effect does exercise have on our respiratory system?
- ventilation and oxygen consumption increases linearly with work load
Factors that play a role in regulating ventilation during exercise:
1. Rising core temperature
2. Increased venous return and cardiac output
3. Feedback from joint proprioceptors
4. Increased sensitivity of the peripheral chemoreceptors in oscillations in arterial pH and pCo2 - During heavy exercise, ventilation cannot supply enough 02 which produces lactic acid
What is the point called where anaerobic metabolism starts called?
- AEROBIC THRESHOLD (can be raised by physical training)
What are the main features of a cardiovascular response to exercise?
- increased cardiac output up to four or five times the resting cardiac output
- increased cardiac output is the result of increased heart rate than of increased stroke volume
- cardiovascular response to exercise mainly occurs in the CNS
What are the main drug treatments used in osteoporosis?
- Bisphosphates e.g alendronic acid, zoledronic acid
- Vitamin D and Calcium supplements
- Hormone replacement therapy
- Raloxifene (reduces post-menopausal osteoporosis)
- Teriparatide (form of parathyroid hormone)
- Denosumab (monoclonal antibody treatment)
What hormones are affected as you go through menopause?
Oestrogen and progesterone which is used to mineralize and lay done bone
