1: Metabolic Bone Disease Flashcards
What is osteoporosis
condition where there is a decrease bone density leading to decrease bone strength
Which age group is most likely to develop osteoporosis
Elderly
In which gender is osteoporosis more common
Females (4:1)
What is the typical demographic affected by osteoporosis
Post-menopausal females
How can the aetiology of osteoporosis be divided
Primary
Secondary
What is type I primary osteoporosis
Post-menopausal osteoporosis
Explain briefly the pathophysiology of type I osteoporosis
- Oestrogen activates osteoblasts and inhibits osteoclasts
- At menopause oestrogen decreases
- Drop in oestrogen increases osteoclast activity and decreases osteoblast activity
What is type II primary osteoporosis
Osteoporosis due to underlying disorder
How can the aetiology of secondary osteoporosis be divided
- Iatrogenic
- Endocrine
- Other
What are 3 iatrogenic causes of secondary osteoporosis
- PPI’s
- Corticosteroids
- Anti-epileptics
What 3 drugs can cause osteoporosis
- PPI’s
- Corticosteroids
- Anti-epileptics
What are the 5 endocrine causes of osteoporosis
- Hyperparathyroidism
- Renal osteodystrphy
- Hyperthyroidism
- Cushing’s disease
- Hypogonadism
Aside from endocrine and iatrogenic causes, what else may cause secondary osteoporosis
- Alcohol abuse
- Immobilisation
What is a mneumonic to remember risk factors for osteoporosis
SHATTERED
what are the risk factors for osteoporosis
Steroid use Hyperparathyroidism, hyperthyroidism, hypercalciuria Alcohol abuse Thin (BMI <18.5) Testosterone low Early menopause Renal or liver failure Erosive or inflammatory disease Diet malnutrition, T1DM
How will osteoporosis present clinically
asymptomatic. First presentation is typically with a fragility fracture
Order the following in most likely region to suffer from an osteoporotic fracture
Vertebral > Femoral neck > Colle’s fracture > long bone
how may vertebral fractures present
- Acute back pain
- If multiple fractures may present with progressive shortening and thoracic kyphosis
if trabecular bone is affected , what type of fracture is more common
Vertebral
in which gender are trabecular fractures more common and why
Females. As males trabecular bone remains stable in time, whereas females loose trabecular bone with age
if cortical bone is affected, what fractures are more likely
Long bone
what investigations may be performed following an osteoporotic fracture
- X-Ray
- Fracture assessment tool (FRAX, Q Fracture)
- DEXA scan
- Bone profile
what tool is used to assess risk of fracture
FRAX (fracture risk assessment tool)
who is a FRAX score calculated for
All women >65y
All men >75y
Younger patients in presence of risk factors
what does FRAX score calculate
Individuals risk of osteoporotic fragility fracture in 10y
what age range is FRAX score suitable for
40-90
if FRAX shows an intermediate score what should be done
Bone mineral density score
If FRAX shows a good score, what should be done
No treatment
If FRAX shows a poor score, what should be done
Treat
Aside from FRAX, what is another tool used to assess risk of osteoporotic fracture
QFracture
what age can QFracture be used for
30-99
If a individual had their FRAX score calculated with bone mineral density and scores the following what should be done
a. low risk
b. intermediate risk
c. high risk
a. do not treat
b. consider treatment
c. treat
when should the FRAX score be re-assessed
- After 2 years if individual was in ‘consider treatment’ but did not opt to
- Change in person’s risk factors
What is used to assess bone mineral density
DEXA scan
what are 6 indications for DEXA scan
- Women >65y with one or more risk factors of osteoporosis
- Women <65y with two or more RF for osteoporosis
- Low trauma fracture
- Fragility fracture
- Starting long-term prednisolone
- Bone remodelling disorder
What dose of prednisolone should individuals be DEXA scanned before giving
> 5mg/d for 3m
What group of patients do not need a DEXA scan before treating
> 75y with two or more of the following: rheumatoid arthritis, alcohol abuse, FHx
What does a DEXA scan provide
T score
What is the T score
Provides number standard deviations individual is away from average bone mineral density of a 30y male
what does T>0 indicate
Better than reference
What does T: 0 to -1 indicate
In top 84% (normal healthy bone)
What does T: -1 to -2.5 indicate
Osteopenia
What does T: less than -2.5 indicate
Osteoporosis
What is a Z score
Bone mineral density compared to individual the same age
Why may a bone profile be requested in osteoporosis
To identify hyperparathyroidism, or other diseases.
What is first-line management for osteoporosis
lifestyle management
What 6 pieces of lifestyle advice would you provide someone with osteoporosis
- Smoking cessation
- Limit alcohol to <2 units
- Tai chi
- Weight bearing exercises
- Falls prevention program
- Calcium and vitamin D supplementation
Why is tai chi offered
To improve balance and help reduce falls
when are calcium and vitamin D supplementation offered
If evidence of deficiency
what is second-line management for osteoporosis
Aledronate (bisphosphonate)
what dose of alendronate is offered
10mg/d
what is a contraindication to aledronate
eGFR <35
what other bisphosphonates may be used if the individual is intolerant to alendronate
risedrontate, etidronate
What is third-line for management of osteoporosis
strontium ranelate
why is strontium ranelate not first line
as it increases the risk of VTE and cardiovascular disease
what are the requirements for strontium ranelate
> 60Y and T score -3.5 or less
what is fourth-line for osteoporosis
Raloxifene
what is raloxifene
selective oestrogen receptor modulator
what is the benefit of raloxifene
it does not increase the risk of breast cancer
what is the main disadvantage of raloxifene
increases VTE risk
what is the criteria for raloxifene
Women >60y with a T score of less than -3.5
what is 5th line management for osteoporosis
denosumab
what is denosumab
RANKL monoclonal antibody
how is denosumab given
subcutaneous injection twice a year
what is the main complication of osteoporosis
fragility fractures
What are the 4 fat soluble vitamins
A,D,E,K
How can the causes of vitamin D deficiency be divided
- Poor intake
- Malabsorption
- Poor metabolism
What are 3 causes of vitamin D deficiency due to poor intake
- Dark skin (reduces UV absorption)
- Poor exposure to UVB
- Poor dietary intake
What are 3 causes of vitamin D deficiency due to malabsorption
Coeliac
Gastrectomy
Cystic fibrosis
Why does cystic fibrosis cause malabsorption of vitamin D
Due to reduced absorption of fat soluble vitamins
What are 4 causes of defective metabolism that lead to vitamin D deficiency
- CYP450 inducers
- Liver cirrhosis
- Anticonvulsants
- Renal disease
Define osteoporosis
decreased bone mineral density
Define osteopenia
decreased bone strength but less severe than osteoporosis
What is T score
compares individuals mean mineral bone density to mean peak mass of a healthy young adult
What T score indicates osteopenia
-1 to -2.5
What T score indicates osteoporosis
less than -2.5
What is the Z score
compares individuals mean mineral bone density to someone of the same age and gender
What are 4 ways osteoporosis may present
- Asymptomatic
- Fragility fracture
- Progressive shortening and thoracic kyphosis
- Acute back pain
What are 4 complications of osteoporosis
- Vertebral fracture
- Colle’s fracture
- NOF fracture
- Chronic pain syndrome
What are 3 structural consequences on bone in osteoporosis
- Fewer trabeculae
- Thinner cortical bone
- Widening of haversian canals
What is osteomalacia
insufficient mineralisation of bone
what is the difference between osteomalacia and ricket’s disease
it is termed osteomalacia if it occurs after epiphysis have fused. And, ricket’s if before.
how can the aetiology of osteomalacia be divided
vitamin D dependent and vitamin D independent
how can causes of vitamin D deficiency be divided
- Insufficient intake
- Malabsorption
- Decreased metabolism
how can vitamin D independent causes of osteomalacia be divided
- Phosphate deficiency
- Medication
- Defects in renal tubule
function
what are two defects in renal tubule function that may lead to osteomalacia
Fanconi’s syndrome
Renal tubule acidosis
What are 3 medications that could cause osteomalacia
Bisphosphonates
Aluminum
Fluoride
How will osteomalacia present
- Bone pain
- Pathological fracture
- Proximal myopathy
What does proximal muscle weakness cause in osteomalacia
Waddling gait
Explain how renal disease can lead to renal osteodystrophy
- Renal dysfunction causes an inability to hydroxylate vitamin D to it’s active form.
- Decreased vitamin D means insufficient absorption of calcium from the gut
- Calcium deficiency causes secondary hyperparathyroidism
- Increased PTH results in increased bone re-asborption
Explain how phosphate deficiency causes osteomalacia
Decreased phosphate in the blood stream and hence available to form bone matrix
What is first-line investigation of osteomalacia
Bone Profile
What may be seen on bone profile in osteomalacia
- Hypocalcaemia
- Hypophosphataemia
- Hyperparathyroidism
- Low vitamin D
- Raised ALP
What is second-line investigation of osteomalacia
X-ray
What finding on x-ray is pathognomic of osteomalacia
Looser’s pseudofractures
what are looser’s pseudo fractures
Sclerotic lines perpendicular to cortical margins
which 3 places are looser’s pseudo fractures most common
- Lateral border of scapula
- Inferior femoral neck
- Medial femoral shaft
what is first-line management for osteomalacia
Vitamin D and Calcium Supplementation
if individual is dietary vitamin D deficient what should they be offered
Vitamin D3
If individual has vitamin D deficiency due to hepatic disease, what form should they be offered
Ergocalciferol (Vitamin D2)
what is the dose of ergocalciferol offered in hepatic disease
40,000 IU (1mg/day)
if an individual has vitamin D deficiency due to renal disease what two forms can they be offered
- Alfacalcidiol (vitamin D2)
2. Calcitriol
what is alfacalcidiol
1a hydroxyvitamin D3 (it has been hydroxylated once, so therefore only relies on liver to hydroxylate it a second time)
what dose of alfacalcidiol is used
250mg/OD
what is calcitriol
1,25 (OH) hydroxy vitamin D
what dose of calcitriol is used
250mg/OD
what could be used to increase serum calcium concentration as a second line
Calcium carbonate (1-2g/day)
What is Paget’s disease also referred to
Osteitis deformans
What is Paget’s disease
Increase bone turnover in focal parts of the skeleton associated with increased osteoblast and osteoclast activity causing resultant remodelling, enlargement, deformity and weakness
What is a risk-factor for Paget’s Disease
Age. Typically onsets >55y
Male
What are two risk factors for Paget’s disease
FHx
Northern latitude
What % of patient’s with paget’s disease experience symptoms
10-30%
If symptoms, what is commonly experienced
Bone pain
If untreated, what are two severe presentations of Paget’s disease
Frontal Bossing
Bowing of the tibia
What is the stereotypical presentation of paget’s disease
Old male with isolated raised ALP
Explain pathology of Paget’s disease
Increased RANKL signalling increases NF-KB activity in osteoclasts. This increases osteoblast activity resulting in formation of dis-organised woven bone
What are the 3 phases of bone remodelling in Paget’s disease
- Lytic
- Lytic and plastic
- Sclerotic
What is the lytic phase
Increased osteoclast activity - increase bone reabsorption
What is the lytic and blastic phase
Increased osteoclast activity is associated with an increase in osteoblast activity
What is sclerotic phase
Decrease in both osteoblast and clast activity
What are 2 investigations of Paget’s disease
Bone profile
X-ray
What will be seen on bone profile in Paget’s disease
Isolated raised ALP
How will bone appear on x-ray in Paget’s disease
- Deformed bone with sclerotic and osteolytic lesions
- Thickened cortical bone
How is Paget’s disease managed
- Analgesia (NSAIDs)
2. Bisphosphonates
What bisphosphonates are offered for Paget’s disease
Oral riserdrontate
IV zoledronate
What are 4 complications of Paget’s disease
Deafness
Sarcoma
Fractures
High output cardiac failure
Why may Paget’s disease cause deafness
Due to enlargement of the skull trapping cranial nerve
What are 4 most common sites of Paget’s disease to assert
- Skull
- Vertebrae
- Pelvis
- Long bones
Why might paget’s disease cause high output cardiac failure
due to increased vascularity required by bone. (It is a rare complication)