OP; OA; OM; Pagets Flashcards
Describe the pathophysiology of primary osteoporosis [2]
As age increases, get increased bone breakdown by osteoclasts + decreased bone formation by osteoblast
Oestrogen is key to the activity of bone cells with receptors are found on osteoblasts, osteocytes, and osteoclasts. Following menopause, its deficiency leads to an increased rate of age-related bone loss. This affects both the cancellous (spongy) and cortical (compact) bone.
Prolonged use of glucocorticoids can result in a reduced turnover state (less bone breakdown) though even here synthesis (bone formation) is affected more leading to a loss of bone mass.
State causes of secondary osteoporosis [+]
Endocrine:
- DM
- Cushings
- Hyperparathyroidism
- Hyperthyroidism
- Low testosterone
Malabsorptive
- IBD
- Coeliac
COPD
CKD
Chronic liver disease
Clinical features of osteoporosis? [2]
Pathological or fragility fractures:
- Vertebral compression fractures
- Appendicular fractures - proximal femur or distal radius following a fall: Neck of femur and Colles fractures
Label A-D
Normal = < 1
Osteopenia = -1 to -2.5
Osteoporosis = < -2.5
Severe Osteoporosis = Osteoporosis with one or more fragility fractures
How would you differentiate osteoporosis and osteomalacia?
- presentation [2]
- investigations [1]
osteomalacia may cause generalised bone pain, tenderness and myopathy
- low Ca and PO4 serum; high ALP and PTH
Describe the treatment algorithm for osteoporosis [4]
First line: Bisphosphonates
- oral alendronate or risedronate weekly oral
- zoledronic acid - yearly infusion
- MOA: interfering with the way osteoclasts attach to bone, reducing their activity and the reabsorption of bone.
Second line: Denosumab:
- monoclonal antibody agaisnt RANK ligand, inhibits osteoclasts
- SC every 6 months
- can be used for osteoporosis in post-menopausal women or OP In men
- can be used for patients on steroids
Raloxifene
- Raloxifene is approved for the treatment and prevention of osteoporosis in postmenopausal women
- selective oestrogen receptor modulator (SERM)
HRT: unopposed oestrogen or O&P
- Prevention of fracture in women at high risk. It is normally reserved for use in younger women as the side effect profile is better.
Clinical scenarios
- if a patient is deemed high-risk based on a QFracture or FRAX score they should have a DEXA scan to assess bone mineral density (BMD): if T-score of - 2.5 SD or below start bisphosphinates
- A postmenopausal woman, or a man age ≥50 has a symptomatic osteoporotic vertebral fracture: above
start treatment straight away - oral bisphosphonates are used first-line e.g. alendronate or risedronate
- following a fragility fracture in women ≥ 75 years, a DEXA scan is not necessary to diagnose osteoporosis and hence commence a bisphosphonate
The following are all used to treat osteoporosis when bisphosphonates are not suitable.
Which of the following acts increases the risk of osteonecrosis of the jaw and atypical femoral fractures?
Denosumab
Romosozumab
Teriparatide
Hormone replacement therapy
Raloxifene
Strontium ranelate
The following are all used to treat osteoporosis when bisphosphonates are not suitable.
Which of the following acts increases the risk of osteonecrosis of the jaw and atypical femoral fractures?
Denosumab
Romosozumab
Teriparatide
Hormone replacement therapy
Raloxifene
Strontium ranelate
Describe which side effects can occur because of bisphosphinates and how you would safety net them? [4]
Oral bisphosphonates are taken on an empty stomach with a full glass of water.
Afterwards, the patient should sit upright for 30 minutes before moving or eating to reduce the risk of reflux and oesophageal erosions.
Osteonecrosis of the external auditory canal and jaw. Need good dental care so should see dentist before and after treatment
Atypical fractures - the patient should be aware to present if they develop pain in their hip or thigh.
Which groups are bisphosphinates CI in? [3]
Severe renal impairment (renally excreted)
Hypocalcaemia
Upper GI disorders
Smokers and dental disease should be cautioned because of jaw necrosis risk
The following are all used to treat osteoporosis when bisphosphonates are not suitable.
Which of the following increases the risk of VTE?
Denosumab
Romosozumab
Teriparatide
Hormone replacement therapy
Raloxifene
Strontium ranelate
The following are all used to treat osteoporosis when bisphosphonates are not suitable.
Which of the following increases the risk of VTE?
Denosumab
Romosozumab
Teriparatide
Hormone replacement therapy
Raloxifene
Strontium ranelate
The following are all used to treat osteoporosis when bisphosphonates are not suitable.
Which of the following acts as parathyroid hormone?
Denosumab
Romosozumab
Teriparatide
Hormone replacement therapy
Raloxifene
Strontium ranelate
The following are all used to treat osteoporosis when bisphosphonates are not suitable.
Which of the following acts as parathyroid hormone?
Denosumab
Romosozumab
Teriparatide
Hormone replacement therapy
Raloxifene
Strontium ranelate
In which patient groups is raloxifene CI In? [1]
history of venous thromboembolism or if a patient has prolonged immobilisation due to risk of VTE
Name three side effects of raloxifene [3]
Side effects include hot flushes, vaginal dryness and leg cramps.
NB: Raloxifene is a selective oestrogen receptor modulato
Name two side effects of denosumab [2]
In which patient populations is it CI In? [3]
Side effects include cellulitis and hypocalcaemia
CI in hypocalcaemia and hypersensitivity and avoided in pregnancy.
heparin
Normal serum calcium, normal serum phosphate, normal ALP and normal PTH
SERM
Describe what is meant by an acute phase response when giving bisphosphinates [1]
Sometimes get acute phase response: fever, myalgia and arthralgia following administration
Name the clinical presentation of the hand signs of OA [5]
Heberden’s nodes (in the DIP joints)
Bouchard’s nodes (in the PIP joints)
Squaring at the base of the thumb (CMC joint)
Weak grip
Reduced range of motion
Why is the CMC so likely to get OA? [1]
Where may pain from this joint present? [1]
The carpometacarpal joint at the base of the thumb is a saddle joint, with the metacarpal bone sitting on the trapezius bone, using it like a saddle. It gets a lot of use and is very prone to wear.
TOM TIP: Patients may present with referred pain, particularly in the adjacent joints. For example, consider osteoarthritis in the hip in patients presenting with lower back or knee pain.
Describe the pathophysiology of OA [3]
Pathology affects the whole unit of the synovial joint including the synovial fluid and adjacent bone.
As cartilage is lost, the joint space narrows, with areas of highest load affected the most.
Bone on bone interaction may occur causing large amounts of stress and reactive changes with subchondral sclerosis
Describe the clinical features of OA
Three common patterns are nodal, knee and hip osteoarthritis.
no morning stiffness or morning stiffness lasting < 30 minutes
Nodal OA:
- Most commonly affected joint is the first carpometacarpal (CMC, base of the thumb)
- DIPs (Heberdens)
- PIPs (Bouchards)
Knee OA
- Joint pain worse at night and with activity
- Mechanical locking
- Tenderness and effusion
Hip OA
- chronic groin ache following exercise; relieved by rest
- if advanced: trendelenburg gait
NICE CG 226: Osteoarthritis in over 16s: diagnosis and management (2022) advise a clinical diagnosis (without imaging) can be made when a patient: [3]
- Is 45 or over and
- Has activity-related joint pain and
- Has either no morning joint-related stiffness or morning stiffness that lasts no longer than 30 minutes.
Describe the medical management of OA
First line:
- NSAIDS (topical); w/ PPI. Hand: topical; Knee - topical; Hip - oral
Second line:
- oral NSAIDS
Third line - Intra-articular injections:
- corticosteroid injections for short-term pain relief in patients with moderate-to-severe knee OA and signs of local inflammation
- Hyaluronic acid (HA)
Surgery:
- Hip or knee replacement (Arthroplasty)
- Osteotomy (realignment)
NB: NICE guidance (NG 226) advise against hyaluronan injections (due to lack of evidence of efficacy), though some clinicians do use them, typically the patient must buy the medication privately.
Osteoarthritis patients typically have pain following use that improves with rest
NSAIDS can worsen which resp. pathology? [1]
Risk of exacerbating asthma
How do you investigate for OA? [2]
Serum 25-hydroxyvitamin D levels
- Less than 25 nmol/L = vitamin D deficiency
Other serology:
- Low Ca, PO4
- High ALP; PTH
Describe the treatment for osteomalacia [1]
Colecalciferol (vitamin D₃):
- Give a loading and maintenence dose
Describe the clinical presentation of osteomalacia [+]
Musculoskeletal Symptoms:
- Bone pain: Diffuse, poorly localized pain involving the lower back, hips, pelvis, and lower extremities is a common presenting symptom. Pain is typically exacerbated by weight-bearing activities and may be relieved with rest.
- Muscle weakness - especially proximal muscle weakness
- Joint pain
Hypocalcaemia:
- Paresthesia: Patients may complain of numbness or tingling sensations in their extremities due to hypocalcemia-induced neuromuscular excitability.
- Tetany: Severe hypocalcemia can cause carpopedal spasm, Chvostek’s sign (facial muscle twitching), or Trousseau’s sign (carpopedal spasm induced by inflating a blood pressure cuff).
Extra-skeletal Manifestations
* Dental abnormalities: Defective dentin formation may lead to dental caries, enamel hypoplasia, and periodontal disease.
* Nonspecific symptoms: Fatigue, anorexia, and weight loss may be present in patients with osteomalacia.
bone pain, muscle weakness, Asian female
Phenytoin
Type 2 renal tubular acidosis
Fanconi
Define Paget’s disease of the bone [1]
Describe the basic pathophysiology [3]
Paget’s disease is a disease of increased but uncontrolled bone turnover. The excessive turnover is not coordinated leading to areas of patchy sclerosis and lysis
Pathophysiology:
* Increased osteoclastic bone resorption (larger than normal osteoclasts)
* Increased osteoblastic response; but in an architecturally disorganised manner
* Get areas of alernating sclerotic and lytic phases
Clinical features of Pagets? [4]
Bone pain
Bone deformity
Fractures - bowing of tibia; bossing of skull
Hearing loss
Describe the investigations used to dx Paget’s [3]
Serology:
- Raised ALP
- Ca and P normal
Imaging:
- Osteolysis or mixed sclerosis / lytic lesions
- Skull: thickened vault and cotton wool appearance
- V-shaped osteolytic defects in the long bones
Management of Pagets? [+]
First line: Bisphosphinates
- Alendronic acid: This is often the first choice due to its favourable side effect profile and cost-effectiveness. It is typically given orally.
- Pamidronate and Zoledronic acid: These intravenous bisphosphonates may be used in patients who cannot tolerate oral bisphosphonates
Analgesics:
- Over-the-counter analgesics like paracetamol may be sufficient for some patients, but others may require stronger analgesics such as opioids.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) may be beneficial for those with associated inflammatory arthritis.
Surgery:
- Pathological fractures: These may require surgical fixation to allow for proper healing and to reduce pain.
- Severe osteoarthritis or joint destruction: Joint replacement surgery may be considered in patients with severe joint damage.
- Neurological complications: For patients with nerve compression syndromes, such as spinal stenosis, decompressive surgery may be required.
normal serum calcium, normal serum phosphate, raised ALP and normal PTH
An elderly man is investigated for ‘bone pains’. He is known to be deaf. Bloods show a raised ALP and a skull x-ray shows a thickened vault - Paget’s disease of the bone
For the following, state if you give oral or topical NSAIDs as first line treatment for OA [3]:
Hand
Knee
Hip
Hand: topical
Knee: topical
Hip: oral (& PPI)
How is zoledronate administered? [1]
Intravenously, once a year
What symptoms do patients with Paget’s disease first present with? [1]
Patients can present with bony deformities, such as enlargement in their skull leading to the classic textbook presentation of a patient whose hat no longer fits.
If symptomatic, patients may complain of a deep, boring, pain over the affected bones although this tends to be a late symptom. Patients can also present with pathological fractures
What are the non-musculoskeletal features of Paget’s disease? [3]
Skull enlargement can lead to complications such as hearing loss (most commonly), thought to be due to cochlear damage. They may also develop tinnitus because of nerve compression.
Rarely patients can develop osteosarcoma which might be suspected if their pain levels suddenly and significantly worsens.
From a cardiac perspective, patients are more likely to develop congestive heart failure, particularly if more than 40% of their skeleton is affected by the condition.
1.
What is the commonest clinical feature in Paget’s disease?
Asymptomatic in 90%
What is the typical fracture caused by Paget’s disease? [1]
Transverse fracture, perpendicular to the cortex
What is the rare malignant complication of Paget’s disease? [1]
Osteosarcoma
Which organ is mainly responsible for excretion of bisphosphonates?
Kidneys
