Rheumatology Flashcards
1
Q
What is articular cartilage composed of?
A
High water content
Type II collagen and proteoglycans
2
Q
What condition is anti-citrullinated peptide antibodies (ACPA) highly specific for?
A
Rheumatoid arthritis
3
Q
What does the presence of serum anti-dsDNA indicate?
A
Systemic Lupus Erythematosus (SLE)
4
Q
What does the presence of serum anti-Ro indicate?
A
Primary scleroderma or systemic lupus erythematosus
5
Q
What does the presence of serum anti-La indicate?
A
Primary scleroderma or systemic lupus erythematosus
6
Q
What does the presence of serum anti-Smith indicate?
A
Systemic Lupus Erythematosus
7
Q
What does the presence of serum anti-Jo-1 indicate?
A
Polymyositis and dermatomyositis
8
Q
What does the presence of serum anti-phospholipid indicate?
A
Antiphospholipid syndrome
9
Q
Name the muscles of the rotator cuff muscles
A
Supraspinatus
Infraspinatus
Subscaularis
Teres minor
10
Q
What is meralgia paraesthetica?
A
Lateral cutaneous nerve of thigh compression
11
Q
What are the symptoms of meralgia paraesthetica?
A
Numbness and increased sensitivity to light touch over the anterolateral thigh - usually self-limiting
12
Q
What are the characteristics of mechanical back pain?
A
Sudden onset
Often unilateral and may be helped by rest
13
Q
Outline some causes of mechanical back pain
A
Lumbar disc prolapse Osteoarthritis Fractures Spondylolithiesis Spinal stenosis
14
Q
There a certain ‘red flag’ symptoms in the presentation of lumbar back pain. List them.
A
Aged <20 or >50 Constant pain without relief History of TB, HIV, steroid use or carcinoma Systemically unwell Localised bone tenderness Bilateral signs in legs Neurological deficit Bladder, bowel or sexual dysfunction
Any thoracic back pain is considered a ‘red flag’
15
Q
What course of action is indicated in the presence of ‘red flag’ symptoms for lower back pain?
A
Spinal X-ray
16
Q
In the presence of neurological symptoms with concurrent back pain, what imaging modality is of most value?
A
Spinal MRI
17
Q
How is mechanical back pain, in the absence of obvious pathology, managed?
A
Analgesia
Breif rest
Physiotherapy
18
Q
What is the pathophysiology of acute disc disease?
A
Prolapse of the intervertebral disc resulting in acute back pain with/without sciatica
19
Q
What demographic is acute intervertebral disease most common in?
A
Younger people
20
Q
What is the more common cause of sciatica in older patients?
A
The result of compression of the nerve root by osteophytes in the lateral recess of the spinal cord
21
Q
What is the typical presentation of acute vertebral prolapse?
A
Sudden onset of severe back pain (often following strenuous activity)
Pain is related to position and is aggrevated by movement
Muscle spasm leads to sideways tilt when standing
22
Q
How is acute vertebral prolapse managed?
A
Symptom control - analgesia, bed rest (on firm mattress)
In severe disease consider epidural corticosteroid injection or surgery
Physiotherapy in the recovery period
23
Q
What pathological process is chronic disc disease associated with?
A
Degenerative changes in the lower lumbar discs and facet joints. Pain is the mechanical type
24
Q
What area of pain may arise from an S1 lesion?
A
From buttock down the back of thigh and leg to the foot
25
What area of pain may arise from an L5 lesion?
Buttock to the lateral aspect of the leg and dorsum of the foot
26
What area of pain may arise from an L4 lesion?
Lateral aspect of the shin to the medial side of the calf
27
What area of sensory loss may arise from an S1 lesion?
Sole of foot and posterior calf
28
What area of sensory loss may arise from an L5 lesion?
Dorsum of the foot and anterolateral aspect of leg
29
What area of sensory loss may arise from an L4 lesion?
Medial aspect of the calf and shin
30
What area of motor weakness may arise from an S1 lesion?
Plantar flexion of ankle and toes
31
What area of motor weakness may arise from an L5 lesion?
Dorsiflexion of foot at toes
32
What area of motor weakness may arise from an L4 lesion?
Dorsiflexion and inversion of the ankle; extension of the knee
33
What reflex is associated with the S1 spinal level?
Ankle jerk
34
What reflex is associated with the L4 spinal level?
Knee jerk
35
What is spondylolithesis?
Slipping forward of one vertebra on another, most commonly L4/L5.
Arising from a defect in the pars interarticularis
36
How is spondylolisthesis managed?
Minor pathology is treated conservatively
| Major pathology is treated with spinal fusion
37
What is spinal stenosis?
Narrowing of the lower spinal canal compresses the cauda equina.
Typically coming on after a period of walking and resolving after rest
38
List some causes of spinal stenosis
Disc prolapse
Degenerative osteophytes formation
Tumour
Congenital narrowing
39
What position can a patient adopt that will open the spinal canal?
Bending forwards
40
What is the curative treatment for spinal stenosis?
Surgical decompression
41
What is the pathophysiology of osteoarthritis?
Arises from reparative processes characterised by progressive destruction and loss of articular cartilage
Attempts at repair produce cartilaginous growths at the margins of the joint which later calcify (osteophytes)
42
What is the typical presentation of osteoarthritis?
Joint pain made worse on movement and relieved by rest
Stiffness occurs after rest (called gelling)
Most common joints affected are distal interphalangeal joitns (DIPJs), first carpalmetacarpal, metatarsophalangeal and weight-bearing joints
43
What are some differential diagnoses of osteoarthritis?
Chondrocalcinosis
Chronic trophaeceous gout
Psoriatic arthritis
44
Outline the management of osteoarthritis
Focus on symptoms and disability:
Analgesia
Surgery
Physiotherapy
45
There are three main subgroups to inflammatory arthritis; what are they?
Rheumatoid arthritis
Seronegative Spondyloarthritis
Crystal arthritides
46
What is the pathophysiology of rheumatoid arthritis?
Chronic systemic autoimmune disorder characterised chiefly by synovitis (inflammation of the synovial lining of the joints, tendon sheathes and bursae)
47
What is the clinical presentation of rheumatoid arthritis?
Insidious onset of pain, early-morning stiffness (lasting 30mins or more) and symmetrical swelling in the proximal small joints of the hands and feet
Weakening of the joint capsule later occurs leading to instability, subluxation and deformity
48
Explosive and palindromic presentations of rheumatoid arthritis are much less common. Outline them.
Explosive - sudden onset of widespread arthritis
Palindromic - relapsing and remitting monoarthritis of different large joints
49
What pathology might you expect in a patient with disproportionate involvement of a single joint in the context of rheumatoid arthritis?
Must exclude septic arthritis
50
List some non-articular manifestations of rheumatoid arthritis (12)
```
Fever
Fatigue
Weight-loss
Sjögren's syndrome
Carpal tunnel syndrome
Cord compression
Anaemia
Pleural effusion
Thrombocytosis
Pericarditis
Nail fold infarcts
Amyloidosis
```
*Not exhastive list*
51
Outline the management of rheumatoid arthritis
NSAIDs and Coxibs
Corticosteroids
Disease-modifying antirheumatic drugs (DMARDs)
Biologics
52
What are the commonly used disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis?
(3)
Sulfasalazine
Methotrexate
Leflunomide
53
What characteristics are common across all the seronegative spondyloarthritides?
(5)
Predilection for axial (spinal and sacroiliac) inflammation
Asymmetrical peripheral arthritis
Absence of rheumatoid factor (seronegative)
Inflammation of the enthesis
Strong association with HLA-B27
54
List the common seronegative spondyloarthritides
Axial Spondyloarthritis
Psoriatic arthritis
Reactive arthritis
Enteropathic arthritis
55
What is axial spondyloarthritis?
Inflammatory disorder of the spine, affecting mainly young adults
56
What is the term used to describe axial spondyloarthritis with radiographic changes at the sacroiliac joints?
Ankylosing spondyloarthritis
57
What are the clinical features of axial spondyloarthritis?
Typically young male presenting with increasing pain and prolonged morning stiffness in the lower back which improves with exercise but not rest
58
What examination findings would be expected in the case of axial spondyloarthritis?
Loss of lumbar lordosis
Reduced spinal flexion (Schober test)
Reduction in chest expansion
Non-articular features (aortic incompetence, lung fibrosis)
59
Describe the radiographic changes associated with ankylosing spondyloarthritis
Sclerosis/ankylosis of sacroiliac joints
Progressive calcification of interspinous ligaments producing 'bamboo spine'
60
What is the management strategy for axial spondyloarthritis?
Morning exercises to maintain posture and spinal mobility
Slow release NSAIDs (usually taken at night)
Methotrexate (to help with peripheral disease)
TNF-alpha highly effective in both axial and peripheral disease
61
Psoriatic arthritis has several different subtypes. List them.
```
Distal interphalangeal arthritis
Mono- or oligoarthritis
Symmetrical seronegative polyarthritis
Arthritis mutilans
Sacroiliitis
```
62
What is the most common subtype of psoriatic arthritis?
Distal interphalangeal arthritis
63
Outline the treatment of psoriatic arthritis
Analgesia and NSAIDs
Local synovitis responds to intra-articular corticosteroid injections
In severe cases, methotrexate and TNF-alpha is effective
64
What is reactive arthritis?
Sterile synovitis following a gastrointestinal or sexually acquired infection.
65
The presence of what immunological marker increases the susceptibility to reactive arthritis?
HLA-B27 positivity
66
What bacteria are associated with reactive arthritis?
| 6
```
Shigella
Salmonella
Yersinia
Campylobacter
Chlamydia trachomatis
Ureaplasma urealyticum
```
67
What is the classical triad of Reiter's syndrome?
Urethritis
Reactive arthritis
Conjunctivitis
68
How is reactive arthritis managed?
NSAIDs and local corticosteroid injections
Persisting infection is treated with antibiotics
Relapsing cases can be treated with sulfasalazine, methotrexate and TNF-alpha inhibitors
69
What is enteropathic arthritis?
Large joint mono- or asymmetrical oligoarthritis occuring in 10-15% of patients with ulcerative colitis/Crohn's disease
70
What is the pathophysiology of gout?
Caused by hyperuracaemia and intra-articular sodium urate crystals
71
Hyperuracaemia and deposition of sodium urate crystals result in four clinical syndromes. What are they?
Acute sodium urate synovitis (acute gout)
Chronic interval gout
Chronic polyarticular gout
Chronic tophaceous gout
72
What are the two biological mechanisms leading to hyperuracaemia?
Imapired excretion of uric acid e.g. chronic kidney disease or hyerprtension
Production of uric acid e.g. HGPRT (Lesh-Nyan syndrome) or myeloproliferative disorder
73
How does acute gout present?
Sudden onset of severe pain, swelling, redness and warmth over the affected joint
Most typically the first metatarsophalangeal joint
74
What may precipitate an attack of acute gout?
Dietary or alcohol excess
| Dehydration (dietary or starting a diurectic)
75
How does chronic trophaecous gout present?
Large, white smooth white deposits (tophi) in the skin and around the joints (particularly the ears, fingers and on the Achilles tendon)
76
What investigations are indicated in a case of suspected gout?
Joint fluid microscopy - negatively bifringent under polarised light
Serum uric acid is raised
Serum urea and creatinine for signs of renal impairment
77
How is acute gout treated?
NSAIDs
Cochicine
Corticosteroids (intramuscular or intra-articular)
78
How is hyperuracaemia treated?
Allopurinol
79
When are uricosuric agents e.g. allopurinol contra-indicated?
In the immediate period (1 month) after an attack of acute gout as it has a risk to induce a further attack of acute gout
80
What is pseudogout?
Deposition of calcium pyrophosphate dihydrate in articular cartilage and peri-articular tissues producing the radiological appearence of chondrocalcinosis
81
How do pseudogout crystals appear under polarised light?
Positively bifringent
82
Delay in treatment of septic arthritis can lead to what complications?
Sepsis, irreversible joint destruction, long-term disability or death
83
What is the most common bacteria responsible for causing septic arthritis?
Staphylococcus aureus
84
In the elderly and immunosuppressed patients, what type of bacteria is the most common cause of septic arthritis?
Gram-negatives
85
What is the classic presentation of septic arthritis?
Hot, painful, swollen and red joint
86
Joint aspiration is necessary in the investigation of acute monoarthritis. How does it normally appear and what is the normal white cell count?
Straw coloured with <3000 WCC/mm^3
87
Joint aspiration is necessary in the investigation of acute monoarthritis. How does it appear and what is the normal white cell count during an inflammatory but not septic disease?
Cloudy and contains 3000 WCC/mm^3
88
Joint aspiration is necessary in the investigation of acute monoarthritis. How does it appear and what is the normal white cell count in septic disease?
Opaque and containing up to 75,000 WCC/mm^3 (mostly neutrophils)
89
What is the empirical treatment of acute non-gonococcal bacterial arthritis?
Flucloxacillin 1-2g hourly IV
Oral fusidic acid 500mg 8-hourly
Add gentamicin in immunosuppressed patients
90
What is the most common cause of septic arthritis in previously young and fit adults?
Gonnococcal arthritis
91
How is gonococcal septic arthritis treated?
Penecillin, ciprofloxacin or doxycyclin for two weeks and joint rest
92
What is meningococcal arthritis?
Complicates the clinical picture of meningococcal septicaemia and presents as a migratory polyarthritis
93
How is meningococcal arthritis treated?
Penecillin
94
What is tuberculosis arthritis?
Approx. 1% of tuberculosis patients have joint/bone involvement
Hip, knee and spine (intervertebral disc) are most commonly affected
95
What is the presentation of tuberculosis arthritis?
Insidous onset of pain, swelling and dysfunction.
Systemically the patient is febrile, has night sweats and loses weight.
96
How is tuberculosis arthritis treated?
Common tuberculosis treatment (rifampicin, isoniazid, ethambutol, pyrazinimide) but extended for nine months with intital joint rest and immobilisation
97
How can osteomyeltis develop?
Occurs due to haematogenous spread (e.g. from a boil) or due to local infection
98
What is the most common causative agents in osteomyelitis?
Staphylococcus aureus
Haemophilus influenzae
Salmonella
99
What are the symptoms of osteomyelitis?
Fever, pain and local eythema
| Sinus formation in chronic osteomyelitis
100
How is osteomyelitis diagnosed?
CT/MRI
Blood cultures
Bone biopsy and cultures
101
How is osteomyelitis treated?
Flucloxacillin and fusidic acid for at least of 4-6 weeks (IV initially with switch to oral therapy when tolerated)
102
What are autoimmune rheumatic diseases?
Autoimmune rheumatic diseases are a collection of diseases in which non-organ specific autoantibodies target joints among other sites
103
List the autoimmune rheumatic diseases
Systemic autoimmune erythematosus (SLE)
Antiphospholipid syndrome
Systemic sclerosis (scleroderma)
Polymyositis and dermatomyositis
Sjögren's syndrome
'Overlap' syndromes and undifferentiated autoimmune rheumatic disease
104
What is systemic lupus erythematosus (SLE)?
Inflammatory multisystem disease characterised by the presence of serum antibodies against nuclear components
105
Describe the epidemiology of systemic lupus erythematosus (SLE)
A disease mostly of young women with a peak age of onset between 20 and 40
106
What is the clinical presentation of systemic lupus erythematosus? List five features.
Any of the following:
Symmetrical small joint arthralgia
Skin manifestations (malar flush)
Non-specific features - fever, malaise and depression
Blood - anaemia, leucopenia, thrombocytopenia
Serositis (pleuritis and pericarditis)
Alopecia
Glomerulonephritis
107
Outline the managment of systemic lupus erythematosus (SLE)
NSAIDs useful for mild disease/arthralgia
Chloroquine and hydroxychloroquine when
NSAIDs are insufficient
Corticosteriods (mainstay of treatment)
Immunosuppressives
108
What is discoid lupus?
Benign variant of SLE which just manifests as skin disease - characterised by facial rash with erythematous plaque and scarring
109
What is antiphospholipid syndrome?
Syndrome characterised by thrombosis/recurrent miscarriages and persistently positive blood tests for antiphosophlipid antibodies (including anticardiolipin and lupus anticoagulant)
110
What are the clinincal features of antiphosphlipid syndrome?
Arterial: stroke, TIA, myocardial infarction
Venous: DVT
Placental: recurrent miscarriages
Other features: migrain, epilepsy, renal impairment, accelerated atheroma
111
What is the management of antiphosphlipid syndrome?
Long-term warfarin
Pregnant patients recieve aspirin and heparin
112
What is systemic sclerosis (scleroderma)?
A multi-system disease with involvement of the skin and Raynaud's phenomenon occuring early
113
What is the pathophysiology of scleroderma?
Uncontrolled and irreversible proliferation of connective tissue and thickening of vascular walls with narrowing of the lumen
114
What are the two clinical manifestations of scleroderma?
Limited cutaneous scleroderma (LcSSc, 70% of cases)
Diffuse cutaneous scleroderma (DcSSc, 30% of cases)
115
What is the disease course of limited cutaneous scleroderma?
Starting with Raynaud's phenomenon before skin disease
Skin of the lower legs, proximal arms and face is thickened and tethered
Sclerodactyly, microstomia, painful digital ulcers, calcinosis in the fingers
116
What was the term previosuly used to describe limited cutaneous scleroderma?
CREST syndrome
117
What does CREST syndrome stand for?
```
Calcinosis
Raynaud's phenomenon
Eosophageal involvement
Sclerodactyly
Telangiectasia
```
118
What is the difference between limited and diffuse cutaneous scleroderma?
Skin changes are more rapid and widespread with early involvement of other organs.
119
Outline the non-skin organ involvement of diffuse cutaneous scleroderma
Gastrointestinal - atony of oesophagus (headburn and dysphagia), small intestine (bacterial overgrowth, malabsorption), colon (pseudo-obstruction)
Renal - acute/chronic kidney disease, acute hypertensive crisis
Lung - fibrosis, pulmonary hypertension
Heart - myocardial fibrosis (causing arrythmias), hypertension
120
What investigations are indicated in scleroderma?
Blood count - anaemia, raised ESR
Urea/creatinine - increased in renal disease
Serum autoantibodies - anti-Ro/La, ANA, anticentromere
Radiology - showing calcinosis of hands
Barium swallow - oesophageal dysfunction
121
How is scleroderma treated?
Hypertension - ACEIs
Pulmonary hypertension - oral vasodilators, oxygen, warfarin
Pulomary fibrosis - cyclophosphamide/azothioprine with prednisolone
122
What is polymyositis/dermatomyositis?
Polymyositis is a rare muscle disorder of unknown aetiology in which there is inflammation and necrosis of skeletal muscle fibres
When skin is involved it becomes dermatomyositis
123
What are the clinical features of polymyositis?
Symmetrical progressive muscle weakness and wasting of proximal muscles of the shoulder and pelvic girdle
Involvement of respiratory muscles can lead to dystonia, dysphagia and respiratory failure
124
What are the characteristic skin changes of dermatomyositis?
Heliotrope rash (purple discolouration of the eyes)
Gottron's papules (scaly, erythematous plaques on the knuckles)
125
What investigations are relevant for the diagnosis of polymyositits/dermatomyositis?
Muscle biopsy is the definitive test
Serum muscle enzymes (creatine kinase, aminotransferases) are elevated
Anti-JO antibodies are positive
Electromyography show characteristic changes
126
What is the treatment of choice for polymyositis/dermatomyositis?
Oral prednisolone
Immunosuppressive therapy (azathioprine, methotrexate, ciclosporin) if the disease relapses
127
What is Sjögren's syndrome?
A disorder characterised by immunologically mediated destruction of epithelial exocrine glands, especially lacrimal and salivary glands
128
What are the symptoms of Sjögren's syndrome?
```
Keratoconjunctivitis sicca (dry eyes)
Xerostomia (dry mouth)
```
Other features: arthritis, Raynaud's phenomenon, renal tubular defects, pulmonary fibrosis
129
What investigations are indicated in Sjögren's syndrome?
Serum autoantibodies: anti-nuclear, anti-Ro and rheumatoid factors
Labial gland biopsy (shows lymphocytic infiltration and acinar destruction)
Positive Schirmer test
130
What is the Scirmer test?
A standrd strip of paper is placed on the inside of the lower eyelid; wetting of less than 10mm in 5 mins is positive
Confirms defective tear production
131
How is Sjögren's syndrome treated?
Symptomatic treatment with artificial tears and saliva replacement solutions
132
What is an 'overlap' autoimmune rheumatic syndrome?
A collection of symptoms the combines features of more than one autoimmune rheumatic disease
133
What is undifferentiated autoimmune rheumatic disease?
The term used to describe when patients have evidence of autoimmunity and some clinical features of autoimmune rheumatic diseases but not enough to make a diagnosis of any one specific condition
134
What are systemic vasculitides?
A term used to describe a group of multisystem diseases in which vasculitis is the main feature
135
What is polymyalgia rheumatica?
A condition characterised by abrupt onset of stiffness and intense pain in the hips and shoulder girdle pain.
136
What is giant cell arteritis?
Inflammation of the superficial temporal artery causing headache, tenderness of the scalp and claudication of the jaw when eating
137
What is the most devestating complication of giant cell arteritis?
Sudden loss of vision due to involvement of the ophthalmic artery.
138
What is the management strategy of both giant cell arteritis and polymyalgia rheumatica?
Corticosteroids to create a dramatic reduction in symptoms
139
What is polyangitis?
A condition involving the lungs and kidney.
Causing haemoptysis, haemturia, proteinuria and progressive renal failure
140
How is polyangitis diagnosed?
Renal biopsy
141
What is eosinophilic granulomatosis with polyangitis?
A rare disease characterised by the classic triad of asthma, eosinophilia and a systemic vasculitis affecting peripheral nerves and skin
142
What is the treatment for eosinophilic granulomatosis with polyangitis?
Corticosteroids and immunosuppressive
143
What is Henoch-Schönlein purpura?
A condition usually seen in children presenting as a purpuric rash of the lower legs and buttocks
Abdominal pain, arthritis and haematuria may also occur
144
What is the pathophysiology of Henoch-Schönlein purpura?
Vascular deposition of IgA-dominant immune complexes.
145
What cells secrete parathyroid hormone?
Secreted from chief cells in the parathyroid gland
146
What are the effects of parathyroid hormone?
Increase plasma calcium and decrease plasma phosphate
147
What is osteoporosis?
A reduction in bone mass density and micro-architectural deterioration of bone tissue; ultimately leading to fragility and increased fracture risk
148
What is the diagnostic criteria of osteoporosis?
Bone mineral density (BMD) more than 2.5 standard deviations below the young adult mean value (T score < -2.5)
149
What is the diagnostic criteria of osteopenia?
Bone mineral density (BMD) between than 1 and 2.5 standard deviations below the young adult mean value (T score < -2.5)
150
What are the most common sites of osteoporotic fractures?
Thoracic and lumbar vertebrae, proximal femur and distal radius
151
Recurrent vertebral fractures may lead to what deformity?
Kyphosis and loss of height ('Widow's stood')
152
What is the most important investigation for both the diagnosis and monitoring of osteoporosis?
Dual Energy X-ray Absorptiometry (DEXA) scan
153
Outline some of the pharmacological treatments of osteoporosis
(7)
```
Bisphosphonates - inhibit osteoclasts
Denosumab - anti-resorptive
Selective oestrogen-receptor modulators
Recombinant human parathyroid peptide
Oestrogen therapy
Testosterone
Strontium ranelate
```
154
What is Paget's disease?
Focal disorder of bone remodelling in which there is increased osteoclastic bone resorption followed by formation of weaker bone with increased vascularisation and fibrotic tissue
155
What are the clinical features of Paget's disease?
Pain in the bone/joints
Deformities: enlargement of the skull, bowing of tibia
Complications: nerve compression (deafness, paraperesis), pathological fractures, osteogenic sarcoma
156
What are the indicated investigations for Paget's disease?
- Serum alkaline phosphatase (raised)
- Urinary hydroxyproline
- X-rays (shows bony enlargement, deformity, osteolytic regions)
- Radionuclide bone scans
157
What is the mainstay of treatment for Paget's disease?
Bisphosphonates (mainly IV zoledronate)
158
What is osteomalacia?
Inadequate mineralisation of osteoid framework leading to soft bones
Causes Rickets disease in children and osteomalacia (after closure of epiphysium) in adults
The cause is profound vitamin D deficiency
159
What are the clinical features of osteomalacia?
Proximal muscle weakness and pain are the common symptoms (bone deformity in children with Rickets)
Severe vitamin D deficiency may present with hypocalcaemia, tetany and seizures
160
What investigations are relevant to osteomalacia?
Serum vitamin D levels
Serum alkaline phosphatase
Serum PTH levels
Radiology: Looser's pseudofractures (low density bands running perpendicular to the cortex)
161
What are the common side effects of bisphosphonates?
Gastrointestinal: dyspepsia, nausea, diarrhoea
Osteonecrosis of the jaw
Atypical femoral fractures
