Bone pain - Clinical Medicine Flashcards
What is pagets disease?
A focal bone disease of remoedelling
a) Describe the predispositions of Paget’s disease
b) Describe the epidemiology
c) Descibre the genetic features of Paget’s
a)
- Genetics - 1st degree relatives of an affected person are 7x more likely
- Environment - viral infections e.g., paramyxoviralinfections, measles, RSV or canine distemper virus
b)
- More common in males
- Mostly seen in patients 40+
- 2nd most common metabolic disease
- Often asymptomatic
c)
- 10-20% have a family history
- Defects in the SQSTM1 gene - codes for a protein - affects RANK signally
- Incidence has declined rapidly in recent years
Explain the pathology of Paget’s disease
- Increases bone cell activity
- Osteoclasts are bigger than normal - they resorb bone at higher rate
- Osteoblasts lay down bone in a haphazard way to keep us with osetoclasts
- This leads to poor bone architecture leading to expansion of poor quality bone which is weak, irregular and woven
- Marrow replaced with fibrous tissue and blood vessels
a) What are the clinical features and complications of Paget’s related to?
b) How many bones can Paget’s disease affect?
a) Related to bone expansion
b) It ca be monostotic (one bone/portion) or polyostotic (2 or more bones)
Describe the clinical features of Paget’s disease
MSK
- Bone pain
- Bone deformity (bowing of legs)
- Fractures - bowing of bone secretes ares of weakness
- Acetabular protrusion
- Secondary OA (usually in pelvis)
Neurological
- Basilar invagination (top of spine pushes into base of skull)
- Cerebellar dysnfunction (inc. incoordination, imbalance and troubles with stabilizing eye movements)
- Obstructive hydrocephalus
- Cranial nerve palsies (Blood flow to cranials nerves are blocked leading to double vision or not being able to move eye a certain way)
- Spinal stenosis/cauda equina
- Deafness
- Tinnitus (ringng/other noise 1 or both ears)
- Para or quadripelgia (paralysis of lower limbs/all four limbs)
Cardiovascular
- Increased cardiac output
- Heart failure
- Aortic stenosis
- Endocardial calcification
- Atheroscelerosis
Metabolic
- Hypercalcaemia
- Hyperuricaemia
- Immobilisation hypercalciria
- Nephrolithiasis (kidney stones)
Neoplasia
- Osteosarcoma
- Chondrosarcoma
- Giant cell tumours
What are neurological symptoms of Pagets related to?
Related to bony symptoms and compression of neurological structures
a) Describe the diagnosis Paget’s disease?
b) What must you exclude?
a) Isolated alkaline phosphatase (reflects osteoblastic activity) and other markers of bone turnover are also high
b)
- Vit D deficiency
- Hyperparathyroidism
- Hyperthyroidism
- Renal osteodystrophy (constellation of MSK abnormalities that occur in patients with chronic renail failure)
- Malignany
What investigations must be undertaken to help diagnose Paget’s disease and include the findings
- Isolated alkaline phosphatase (from LFTs) - normal Ca and Phosphate
- Urine - increased hydroxyproline
- Plain radiographs - Bone expansion, cortical thickening, lysis and sclerosis, coarsened trabeculae
- Isotope bone scan - Areas of focal increased uptake, MOST SENSITIVE TEST
Desribe the radiological features of Paget’s disease
- Bones are typically expanded
- Show cortical thickening
- Coarsened trabeculae
- Mixture of lytic and sclerotic areas
Describe the treatment options for Paget’s disease
- Bisphosphonates
- Analgesia - relieve pain symptoms
- Ensure vit D levels adequate
- Physiotherapy
- Surgery- for fractures, joint replacement, spinal stenosis
List they 3 types of cancers you can get in bones and briefly describe them
- Tumour/neoplasm - cells keep dividing when new cells are not required and cause a mass of tissue or tumour
- Benign tumours - do not spread to other parts of the body - can be locally destructive
- Malignant tumour - cells are abnormal and divide out of control and can invade local and distant tissues
Bone malignancy can be primary or secondary. what is the name for a primary malignancy in:
a) Bone
b) Cartilage
c) Fibrous tissue
d) Bone marrow
e) Vascular
f) Uncertain
a) Osteosarcoma
b) Chondrosarcoma
c) Fibrosarcoma
d) Ewing’s sarcoma, myeloma
e) Angiosarcoma
f) Malignant giant cell tumour
a) Are primary bone tumours common?
b) What type of people are pirmary bone tumours seen in?
a) No
b) Young people
a) Which age group does osteosarcoma (osteoid) affect most?
b) Which type of bones does it affect?
c) Describe the radiological features
a) Usually under 20s
b) Affects long bones and growth plates
c) Sunburst appearance due to lifting of periosteum and Codman’s triangle
a) Which age groups does Chondrosarcoma usually affect
b) What are 2 clinical features?
c) What my it arise from?
a) Usually in 40s
b) Painful and progressive
c) May arise in underlying benign lesions
a) When is Ewing’s tumour most likely to occur
b) What part of the bone does it affect
c) Describe the radiological features
d) What may it present with?
a) Childhood (2nd most commnest in childhood)
b) From medullary (long bones) cavity
c) Onions on x-ray
d) Metastases
Bone cancer can be secondary. List the 5 most common types of cances that bone metastases originate from?
- Breast
- Prostate
- Lung
- Kidneys
- Thyroid
a) Which bones in the body can be affected by Paget’s?
b) What will you see and feel on examination of someone suspicious of Paget’s?
a) Any bone in the body
a) Warm, tender and deformities
What must you look for when examining for bone cancers
- Consitency with history and expected findings
- Beware of co-existing pathologies
- Scarring and skin changes
- Neurology and vascularity
- May not be any abnormalities - high index of suspicion
What investigations can be undertaken for bone cancers and describe their uses
Serum biohemistry
Plain X-rays
- Essential to shown bone structure
- Lysis/scelerosis
Isotope bone scan - highlights areas of metabolic activity
- No value is assessing structure
- Limited use in myeloma
- Beware sacral lesions (may not show up)
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
How should you initally treat bone tumours as?
Treat as primary bone tumour until proven otherwise
Describe the managment of metastases
- Pain - Analgesia
- Bisphosphonates
- Radiotherapy/Chemotherapy
- Surgery
What are the clinical features of osteoporosis?
There are no clinical features until fracture (usually from low energy injury)
a) List the risk factors to osteoporosis including modifiable and non-modifiable risk factors
b) List 5 secondary causes
- Age (> 50 for women and >65 for men)
- Female sex
SHATTERED FAMILY
- Steroid use
- Hyperthroidism, hyperparathyroidism
- Alcohol and smoking
- Thin (BMI < 22)
- Testesterone deficiency
- Early menopause
- Renal/liver failure
- Erosive/inflammatory bone disease
- Diabetes
- Family history
b)
- Drugs: corticosterioids/heparin
- Rheumatoid arthritis
- Coeliac disease
- Multiple myeloma
- Cushing syndrome
a) Describe the 3 types of verterbral fractures
b) Which is the most common?
a)
- Wedge fracture - several of these causes the person to become bent over
- Biconcave fracture - both sides of the vertebra collapse
- Crush fracture - whole vertebral body collapses in on itself
b) Wedge fracture
a) There are 3 types of vertebral compression fracture appearence. Fill out the box.
b) What are the signs of vertebral fractures
b)
- Thoracic pain after minor fall (sometimes no pain)
- If no pain, complain they’re ‘shrinking’, ‘kyphotic’ or ‘round shouldered’
Descibe how age related changes in bone mass varies between men and women
Men
- Peak bone mass peaks at late 20s
- Bone mass consolidated until mid/late 40s
- After mid/late 40s bone mass deteriorates gradually over time
Women
- Peak bone mass peaks at late 20s but less than men
- Bone mass cosolidated until mid/late 40s
- After mid/late 40s bone mass decreases rapidly due to menopause which mean less oestrogen around the bone health. This brings them much closer to the fracture threshold
Why do women lose bone mass quicker than men after the mid/late 40s
- This is due menopause where women have less oestrogen
- Oestrogen has a protective effect on bone
- So this means less oestrogen around the bone health
List the key determinants of peak bone mass and bone loss
- Genes
- Skeletal geometry
- Body weight
- Sex hormones
- Diet
- Excercise
- Racial factors (those with an african/caribbean root will have a stronger bone density than those who are descended from asian origins)
Describe the investigations to diagnose osteoporosis
- Dexa scan (gold standard)
- X-rays if fractures suspected
- MRI scan (to look for veterbral fractures)
List the 2 methods that can be used to calculate the risk of a fracture
- FRAX (Fracture risk assessment tool - gives a 10 year probability of a fracture)
- Qfracture
a) What do we use to radiologically measure bone?
b) List the 2 sites that are measured
c) When is it repeated? and ideally, why must the same machine be used?
a) Dual-energy X-ray absorptiometry (DEXA scan)
b) Lumbar spine and left hip (unless someone has had that replaced then the right hip)
c) Repeated only 18 months after and ideally, same machine should be used as results vary
What are the types of score a DEXA scan can give? Explain what the scores mean
T scores = the difference between mean bone density of a patient and a healthy young women
Z scores = the difference between mean bone density of patient and a healthy aged-matched woman
- What is the T score for:
a) Normal bone
b) Osteopenia
c) Osteoporosis
d) Severe osteoporosis - Describe the relation between the T scores and fracture risk
- What is the Z score for osteoporosis
1a) T > -1.0
b) T <1.0 to -2.5
c) T< -2.5
d) T < -2.5 plus one or more fractures
2. The more negative the T score is the higher the fractue risk
3. Less than -2
Describe the pathaphysiology of osteoporosis
Imbalance of osteoclastic and osteoblastic activity
List the investigations for osteoporosis to help find any underlying causes
- FBC
- ESR/CRP
- Serum calcium (albumin)
- Alkaline phosphatase (reflects osteoblastic activity)
- Liver function tests
- Thyroid
- Myeloma screen
- 25-hydroxyvitamin D levels
- PTH
- Endocrine: sex hormones/dibates/cortisol
- GI: coeliac disease antibodies
- Markers of bone turnover
- Urine Ca excretion
- Plain radiographs/MR/isotope bone scan/DEXA
a) When is a DEXA scan used to confirm osteoporosis in a patient?
b) If a patient over 70 sustains a fragility fracture is a DEXA scan needed?
a)
- Fragility fracture bteween the ages 50-70 years
- FRAX is >/= to 1%
b) No, you will assume they have osteoporosis
List the strategies for treatment and prevention of osteoporosis
- Patient education on having a balanced diet (high in calcium and vitamin D) weight bearing excercise, lifestyle - reduce/stop alcohol and/or smoking
- Treat underlying diseases
- Drug treatment - (bisphsphonates, Adcal, HRT etc)
- Falls interventions (OT to make sure home is safe, opticians to check eyesight, reduce amount of drugs)
a) Describe the anti-resportive drug treatments for osteoporosis
b) List anabolic drug treatments for osteoporosis
a)
- Bisphosphonates - used with Adcal (calcium + Vit D)
- Hormone replacement therapy (HRT)
- Raloxifene - Selective oestrogen receptor modulators, good for menopausal women
- Denosumab - monoconal antibody against RANKL, reducing osteoclastogenesis
- Calcitriol
b) Terparatide - Synthetic form of PTH (given for 2 years and no longer)
a) What is osteogenesis Imperfecta?
b) What type of genetic defect are most cases of OI (85-90%) caused by?
a) Syndrome of bone fragility due to mutations in type 1 collagen gene
b) Dominant genetic effect
There are 7 types of osteogenesis imperfecta from type I to type IIV
a) What is the most common type?
b) What is the mildest type?
c) What is the most severe type?
a) Type I
b) Type I
c) Type II
The clinical features of osteogenesis varies. List 10 variable clinical features
- Frequency of fractures
- Stature
- Coloured sclera
- Laxity of joints and muscles
- Bone deformity
- Scoliosis
- Brittle teeth
- Deafness
- Respiratory failure
- Collagen abnormalities
a) What is treatment of osteogenesis imperfecta directed towards?
b) List 4 treatment options
a)
- Preventing or controlling symptoms
- Maximising independant mobility
- Developing optimal bone mass and muscle strength
b)
- Care of fractures
- Extensive surgical and dental procedure
- Physical therapy
- Wheel chair and mobility aids ( severe OI)
What does the majority of osteomalacia cases arise from?
Disturbance of vitamin D and phosphate metabolism (Vit D and hosphate deficiency)
State the two forms of Vit D that exist. Describe where they’re derived from and how they enter the body
D2/ergocalciferol - plant derived and consumed in food
D3/cholecalciferol - formed from the effect of UV-B sunlight on 7-dehydrocholesterol in skin
There are 2 forms of vitamin D. D2/ergocalciferol and D3/cholecalciferol.
a) Where are they hydroxylated? and what are they hydroxylated into?
b) Describe what happends next to the product of this
a) Both forms are hydroxylated in the liver to form 250HD
b) .250HD is hydroxylated in the kidney to form 1,25(OH)2D - active vitamin D
An alternative pathway of metabolism of 250HD exists in many cells throughtout the body. What is the product of this called?
24,25(OH)2D
Describe 4 actions of 1,25(OH)2 Vit D
- Facilitates calcium (dueodenal) and phosphate (entiresmall intestine) absorption from the gut
- Triggers osteoblast RANKL which activates osteoclasts to resorb bone releasing calcium into the circulation
- Triggers osteoblast production of a number of mediators resulting in laying down bone osteoid
- Decreases PTH syntheseis and secretion
List 8 associations between Vit D deficiency and osteomalacia
- Low sun exposure
- Dark skinned immigrants and their breastfed babies
- Partial gastrectomy/intestinal malabsorption (coeliac disease)
- Chronic liver disease/chronic renal failure
- Rare hereditary causes (cystic fibrosis)
- Anticonvulsant medication (drugs affecting Vit D metabolism)
- Elderly
- strict diets e.g., lacto vegetarian
- Excessive high factor sunblock
What are the clinical features of osteomalacia in children?
Rickets - growth plate formation is abnormal and becomes wide and irregular
Describe clinical features of osteomalacia in adults
- Asymptomatic
- Bone and msucle pains - often non-specific, chronic and widespread
List 3 differential diagnosis of osteomalacia
- Fibromyalgia
- Chronic fatigue
- Depression
Describe the radiological features of osteomalacia
- Bone softening/defomity - hourglass thorax, bowing of long bones
- Increased fractures
- Biconcave vertebral bodies
- Pseudo fractures - small radiolucent lines through bone cortices (typically in femoralneck, pelvis and ribs)
- Osteopenia
Describe the investigations required to diagnose osteomalacia including the expected results
- Bone biochemistry
- Calcium - low
- Phospahte - low
- Vit D- low
- Calcium urine excrete - low
- ALP - raised
- PTH - raised
- Renal function - needs testing because low GFR is associated with phosphate retention
To exclude other mimics
- Liver function
- Folate
- Iron studies
- Coeliac
- Autoantibodies
- Autoimmne serology
a) Describe the treatments for osteomalacia
- Treat underlying conditions/causes of vt D deficiency
- Patient eductaion - dietary advice, encourage sunlight exposure
- Vitamin D supplements - drops for infants and young vhildren and cholecalciferol as a high loading dose (IM) and then loer maintenance dose in adults
a) What is HRT?
b) Describe the role it has in menopausal women?
c) List 3 problems with HRT
d) Which age range is HRT best for not and not best for?
a) HRT is hormone replacment therapy that can be either oestrgoen +/- progesterone
b) It delays the loss of bone seen in women at the time of menopause and is good for treating menopausal symptoms
c)
- Increased cardiovascular risk
- Increased risk of breast cancer
- Alzheimer’s?
d) HRT is best for younger patients with menopausal symptoms for 2 years and not a first line in those 50
a) How do bisphosphonates work? and provide 2 examples
b) How should they taken?
c) What are the side effect/problems associated with bisphosphonates
a) Work by reducing osteoclast action e.g., alendronate acid (oral) and zoledronic acid (IV)
b) Take it first thing in the morning (before breakfast as it is poorly absorbed so need to fast before) whilst sitting up and take a full glass of water with it and fast for a further 30 mins after
c) )
- General systemic effects - fatigue, fever, muscle pains and aches
- Itchy rashes or photosensivity
- GI side effects
- Bone pain
- Atypical fractures commonly spiral fracture of femur for long-term treatment
- Osteonecrosis of jaw - mostly seen in cancer patients (so all dental work must be done before are after you are put on bisphosphonates) for long-term treatment
- Increase in upper GI malignancy for long-term treatment
a) What is rolixfene
b) Is it used often?
a) Selective oestrogen receptor modulators, good for meopausal women
b) No
a) Describe the role of Strontium Ranelate (Protelos)
b) Describe 2 problems with Strontium Ranelate
a) It an osteoporosis medication that stimulates bone formation and reduces bone resorption
b)
- Increases bone mineral density so repeat DEXA can be hard to intepret
- Ofen poorly tolerated orally
a) What condition is PTH (Teriparatide) used to treat?
b) What is the effect of PTH?
c) According to the nice guildines what are the 3 situations where PTH (teriparatide) should be prescribed
a) Osteoporosis
b) Reduces risk of verebral and non-vertebral fragility fractures
c)
- Bisphosphonates ineffective
- T-score of -4 SD or below
- A T-score of-3 SD or below and 2+ fractures and at least one additional risk factors listed for bisphosphonates
a) Describe the role of Denosumab
b) Who is the treatment recommended for?
a) Denosumab is a monoclonal antibody that reduces osteoclast activity and so reduces bone resorption
b)
To prevent of osteoporotic fragility fractures in postmenopausal women a
- Who are unable to comply with instructions for bisphosphonates, have an intolerance or contradiction
- Combination of risk factors for a fracture: T-score, age, and independant clinical risk factors
How should you treat steriod induced osteoporosis in over 65s and under 65s?
If over 65 - treat
If under 65- treat if they’ve had a a fracture otherwise do a bone mineral density (BMD)
- If normal, repeat if high doses of prednisolone
- If osteopenic, repeat in 1-3 years
- If osteoporotic, treat
Describe how a GP distinguishes between bone pain and joint or mechanical pain
Bone pain
- Persistent - present whether you move or not
- More focused and lasts longer
Joint pain
- Painful on movemeent
- Generalized throughout body and tends to ease during the day
Mechanical pain
- Better with rest
- Worsens on activity
- Systemically well
- Tender around muscles
- History of back pain
a) What are features in the history that suggests bone pain
b) Red flag symptoms
c) How would you manage this?
d) Is he at risk of low viamin D? Explain your answer
e) What is your diagnosis?
a)
- Often poorly localised
- Deep, aching pain
- Persistent
- Not easily relieved by analgesia
- Often complain of night pain
b)
- Progressive
- Weight loss
- Aorexia
- Fevers
- Malaise etc
c)
- Red flag symptoms indicate a need to intervene quickly.
- Patients either need to be assessed and treated urgently or referred to secondary on a 2 week cancer wait
d) Yes, dietary intake decreases as you age, likelihood increases as he lives alone. May be possibly covered up when he goes on walks. Could be going out less due to the pain. He could be darker skinned
e) Metastatic bone malignany that spreadad to his pelvis
List some red flags of a MSK history
- Age > 55y
- History of cancer especially breast, prostate, lung, renal, thyroid and myeloma
- Unexplained weight loss
- Systemically unwell, symptoms of hypercalcaemia
- Constant pain
- Night pain
- Thoracic pain
- Progressive
- Lack of expected response to usual treatments
- Symptoms of cauda equina: urinary retention, faecal incontinence, saddle anaesthesia
- History of severe trauma
