Osteoporosis Flashcards
(190 cards)
1
Q
What is a fragility fracture?
A
A fracture caused by falling from standing height due to weakened bones
2
Q
What is the definition of osteoporosis?
A
A skeletal disorder characterised by compromised bone mineral density, quality and strength which predisposes an individual to increased risk of fracture
3
Q
What are the major risk factors for osteoporosis?
A
Age, sex, previous fracture
Long term steroid use, family history
4
Q
What populations are most and least likely to fracture their bones and why?
A
Most likely - Europeans/Caucasians; longer head of femur
Less likely - Asians/Africans; shorter neck of femur, physically larger bones
5
Q
Why do those at highest risk of osteoporosis need to be identified?
A
Bone loss is asymptomatic and therapy need to be targeted to those who will benefit most
6
Q
What is the approximate turnover of cortical and trabecular bone?
A
Cortical 4%
Trabecular 20%
7
Q
What is FRAX?
A
Fracture risk assessment tool which gives the 10 year probability of a fracture by combining several risk factors
8
Q
At what percentage risk of fracture would an individual be treated?
A
20%
9
Q
What are the limitations of FRAX?
A
Not all risk factors are covered
Lacks detail
Epidemiological data required
10
Q
Why must treatment options be balanced carefully with the patient’s age?
A
All therapy options have limitations on length of their use and there is no evidence that they have beneficial effects when used thereafter
11
Q
What are the mortality and morbidity statistics of a hip fracture in an elderly patient?
A
33% mortality
67% survival (70% independent, 30% dependent)
Large proportion of independent patients using walking aids
12
Q
What is the only drug used for osteoporosis which encourages bone growth?
A
Teriparatide (PTH)
13
Q
How can fracture risk be reduced?
A
Decrease bone turnover
Increase bone mineral density
Increase bone quality
14
Q
What are the modifiable risk factors for osteoporosis?
A
Smoking, weight, alcohol, exercise, diet
15
Q
What is the most common cause of iatrogenic osteoporosis?
A
Long term (>3 months) steroid use (>7.5mg prednisolone or equivalent)
16
Q
What iatrogenic causes of osteoporosis are there?
A
Phenytoin, heparin, immunosuppressants, depo-provera
17
Q
What are the common secondary causes of osteoporosis?
A
Rheumatoid arthritis, transplantation (immunosuppression), anorexia nervosa, chronic liver disease, coeliac disease, hyperparathyroidism, irritable bowel syndrome, steroids, male hypogonadism, renal disease, depo-provera, vitamin D deficiency, excess alcohol, smoking
18
Q
What factors are involved in peak bone mass?
A
Genetics, nutrition, hormones, lifestyle
19
Q
What are the problems with monitoring treatment of osteoporosis?
A
Slow response, low signal/noise ratio, increased bone mineral density may not be an adequate marker
20
Q
Why are vertebral fractures important to identify?
A
Often silent and unrecognised but increase risk x2
21
Q
What types of vertebral fractures are there?
A
Concave deformity, wedge fracture, compression fracture
22
Q
Which cancers can most commonly give rise to bone metastases?
A
Breast, prostatic, colonic
23
Q
What are the risk factors for falling?
A
Vision, balance, medication, dizziness, footwear, home, environmental
24
Q
What are the causes of osteoporosis in men?
A
Primary (idiopathic) - 50%
Secondary (glucocorticoids, alcoholism) - 50%
25
What are the treatment options for men with osteoporosis?
Same as women despite lack of evidence
| Androgens, limit glucocorticoids, thiazides
26
What do osteocytes secrete and what does it do?
Sclerostin to inhibit Wnt signalling
27
What is the role of magnesium in the kidneys?
Co-factor for parathyroid hormone
28
What body status affects calcium protein binding?
Acid-base balance
29
In what months is an appropriate wavelength of UVB available in the UK?
May - September
30
What are the biochemical changes in osteoporosis?
Everything normal, 25 OH vitamin D low
31
What are the biochemical changes in osteomalacia?
Calcium, phosphate, 25 OH vitamin D - low
| Alkaline phosphatase, PTH - high
32
What are the biochemical changes in primary hyperparathyroidism?
Phosphate, 25 OH vitamin D - low
| Calcium, alkaline phosphatase, PTH - high
33
What are the biochemical changes in secondary hyperparathyroidism?
Calcium - low
PTH - high
Phosphate - unchanged
34
What is the Scottish vitamin D deficiency reference amount?
<20 nmol/L
35
What must be considered alongside vitamin D for accurate measurement?
C-reactive protein
36
What are the risk factors for vitamin D deficiency?
Age (>65), decreased sun exposure, dark skin, pregnancy/breastfeeding
37
What is the normal vitamin D supplement concentration?
800-1000 IU/day
38
What are the main drugs used to treat osteoporosis?
Bisphosphonates, calcium and vitamin D, denusomab, HRT, raloxifene, teriparatide
39
What is the aim of osteoporosis treatment?
Reduce fracture risk by 50%
40
What is the mechanism of action of bisphosphonates?
Bind to calcium salts in the body/skeletal bone and is then taken up by osteoclasts which reduces their resorption
41
What is the difference between simple and nitrogenous bisphosphonates?
Simple - metabolised to cytotoxic ATP analogues to promote apoptosis
Nitrogenous - inhibit farnesyl diphosphate synthetase to prevent prenylation of small GTPases necessary for osteoclast function
42
What advice is given to patients before starting bisphosphonate therapy?
Complete dental work before starting and attend regular 6 monthly dental appointments while on therapy
43
Why are calcium and vitamin D supplements required alongside bisphosphonate therapy?
Decrease in bone resorption will decrease free calcium leading to paraesthesia/spasms
44
What is the mechanism of action of denusomab?
Binds and inhibits RANKL to prevent osteoclast resorption
45
What are the benefits and limitations of teriparatide?
Benefits - only anabolic treatment option, very effective for vertebral fractures
Limitations - not suitable for patients with history of malignancy, daily injections over 2 years, no hip fracture data
46
How long are the courses of alendronate and zolendronate?
Alendronate - 5 years (can be used for a further 5 years)
| Zolendronate - 3 years
47
How is alendronate administered?
```
Daily
Oral (tablets or solution)
10mg
With water
Upright position (maintained for 30 minutes)
Wait 4 hours before taking calcium
```
48
What are the contraindications of alendronate?
```
Pregnancy and breastfeeding
Kidney dysfunction (eGFR <35 ml/min)
Gastrointestinal problems (oesophageal abnormalities, ulcers)
```
49
What are the side effects of alendronate?
Oesophageal irritation, indigestion, abdominal pain
Atypical femoral stress fracture (persistent thigh pain)
Osteonecrosis of the jaw
50
Why are x-rays not used diagnostically in osteoporosis?
Only identifies depletion of bone >30%
51
What are x-rays used to investigate?
History of pain, height loss, acute bone pain, fracture investigation
52
How much bone loss does a T-score of -2.5 relate to?
15-20%
53
What x-ray features of osteoporosis can be seen on x-ray?
Decreased joint space, bony spurs (osteophytes)
54
What is the anterior/hunched curvature of the spine called?
Kyphosis
55
What wrist fracture is associated with osteoporosis/elderly patients?
Colles' wrist fracture
56
What conditions are isotope bone scans useful for?
Paget's, metastatic disease
57
What is multiple myeloma?
Malignancy of plasma B cells causing proliferation of a single clone which produces abnormal immunoglobulin (monoclonal paraproteins)
Plasma cells activate osteoclasts resulting in osteolytic bone lesions
58
At which stage of sample processing is there the highest percentage of error?
Pre-analytical phase - 68% human error
59
What is the difference between plasma and serum?
Plasma still has clotting factors present, serum does not
60
What substances can affect lab results and when might this happen?
Alkaline phosphatase - high in babies/children when growth is occurring
Cholesterol - increased in adolescence
Urate - increases with age and decreased renal function
61
What factors can affect lab tests?
```
Sex steroids and gonadotrophins
Body composition
Fasting
Time
Stress
Medication
```
62
What analytical and post-analytical errors can occur in sample testing?
Analytical - operator error, miscalibration
| Post - failure to communicate results, software error
63
What are the 2 main methods used to test samples?
Spectrophotometry - U&Es, LFTs; 2 minutes, small sample needed
Immunoassay - testosterone, cortisol; 20 minutes, large sample needed
64
What are the effects of oestrogen/androgen on bone and how do they act?
Slow bone remodelling and protect against bone loss
Increase osteoblast acitivty, decrease osteoclast activity
Sex steroid receptor and local biosynthesis on bone cells
65
What are the 3 forms of testosterone in the body?
Free (active)
Bound to steroid hormone binding globulin
Bound to albumin (active)
66
At what time of day does testosterone reach its peak?
Morning
67
What are the heavy and light chain options for immunoglobulins?
Heavy - IgM, IgA, IgD, IgG, IgE
| Light - kappa, lambda
68
What is a poor prognostic marker in multiple myeloma?
Free light chain proteins in urine
69
How are paraproteins in multiple myeloma identified?
Serum protein electrophoresis
70
How are paraproteins in multiple myeloma typed?
Serum immunofixation
71
What is the gold standard method of measuring bone turnover?
Radiotracer kinetic studies
72
How long do formation and resorption take?
Formation - 3-6 months
| Resorption - 10-20 days
73
What 2 types of bone markers can be measured?
Bone matrix components
| Enzymatic activity
74
What is the main bone marker for resorption?
Serum collagen type I telopeptides (CTx)
| Others - calcium, hydroxyproline, pyridinium
75
What is the main bone marker for formation?
Serum collagen type I propeptides (P1NP)
| Others - bone alkaline phosphatase, osteocalcin
76
What is tartrate resistant acid phosphatase?
Bone marker
Dissolves matrix
Type 5b in bone (5a in prostate)
Not affected by food intake
77
How are bone markers validated?
Must change in parallel manner with turnover - high in high turnover, low in low turnover
78
What factors affect bone markers?
Nutrients, lifestyle, medication, fasting, time, subject variability
79
What percentage difference is needed for changes in a bone mineral scan to be significant?
3-4%
80
What affect can suppression of CTx have on P1NP?
P1NP suppression
81
What are the potential applications of bone markers?
Identification of osteopenia
Monitoring disease of rapid bone loss (e.g. stroke, SCI, immobilisation)
Supplement to FRAX and BMD
Response monitoring
Compliance testing
Tailoring choice of treatment to degree of turnover (high = anti-resorptive, low = anabolic)
82
What are the limitations of using bone markers?
No quality control
Variability
Lack of reference ranges
83
Why do bones need to bear weight?
Weight bearing pulls on the muscle and periosteum which encourages bone growth (thickness)
84
What non-pharmacological treatments are there for osteoporosis?
Exercise
85
What type of exercise is required for osteoporosis therapy?
Low impact weight bearing
| On feet for 4 hours a day
86
Why is calcium supplementation best avoided if possible?
Risk of arrhythmia and renal stones
87
How frequently is a DEXA usually repeated?
Every 2 years
88
What is the result of steroid induced osteoporosis?
Increased osteoclast and decreased osteoblast activity
Decreased calcium absorption in gut
Impaired tissue healing
89
How can steroid induced osteoporosis be managed?
Decrease steroid dose
Alternative route of administration
Maintain good nutrition
90
When would a DEXA scan not be required to diagnose osteoporosis?
2 or more vertebral fractures
91
What is osteogenesis imperfecta?
Collagen I defect
| Prone to fracture, ligamentous laxity, blue tint sclera
92
What is pseudohypoparathyroidism?
Parathyroid hormone is present but not able to act
93
What is Looser's zone?
Pseudo fracture/non-mineralised cartilage in osteomalacia
94
What does DEXA stand for?
Dual-energy x-ray absorptiometry
95
How is single-energy x-ray absorptiometry carried out?
X-ray passed through wrist or heel while immersed in water to remove effects of soft tissue
96
How is dual-energy x-ray absorptiometry carried out?
2 x-ray beams of different energy levels (one reduced more by bone and the other by soft tissue) passed through hip and spine
97
What are the 3 images taken by the DEXA scan and what are they used for?
Hip - neck of femur density
Lumbar spine - T1-4 density
Lateral spine - vertebral fracture
98
What is the T-score range for osteopenia?
-1 to -2.5
99
What is the T-score range for osteoporosis?
Less than -2.5
100
What is a T-score?
Statistical value
Compares patient bone density to a standard group of young (25-29) white females
Amount of standard deviations from average gives T-score
101
What is the T-score a strong indicator of?
Fracture risk
102
What is a Z-score?
Compares patient bone density to people of the same age, sex and ethnicity
103
What factors are important to ensure repeatability of a DEXA scan?
```
Positioning of the patient
Using the same machine
Using the same operator
No repeat within 1 year
Artefacts
```
104
Why are DEXA scans not repeated within 1 year?
Errors in positioning and machine calibration exceed the maximum changes bones can achieve in this time
105
What are the limitations of DEXA scanning?
Not suitable for patients who cannot lie down
Affected by contrast agents etc from other scans
Results can be affected by artefacts/degenerative changes
Height and weight required - patient needs to stand
2 dimensional
Combines cortical and trabecular measurements
106
What are the benefits of DEXA scanning?
```
Low radiation dose
Quick
Precise
Scan speed/exposure can be adjusted
Cheap
Can monitor efficacy of treatment
```
107
How is zolendronate administered?
5mg over 15 minutes yearly for 3 years
| Patient should be well hydrated
108
What is the most common side effect of zolendronate?
Flu-like symptoms - mild fever, headache, muscle/joint/bone pain
109
What effect do bisphosphonates have on osteocytes?
Prevent osteocyte apoptosis; anti-fracture effect
110
What drugs are licensed for treatment of osteoporosis in men?
Alendronate, risedronate, zoledronate, denosumab, teriparatide
111
What factors affect compliance of osteoporosis drugs?
```
Silent disease
Failure to perceive benefits vs side-effects
Relative importance
Polypharmacy
Lack of understanding
Inconvenient dosing regimens
```
112
What new agent is under development to treat osteoporosis and how does it work?
Anti-sclerostin antibodies
E.g. romosozumab
Monoclonal antibody binds sclerostin to increase bone formation and decrease resorption - reduces vertebral fracture risk
113
How much does fracture risk increase with each T-score unit reduction?
2.5x
114
What are DEXA, QCT and QUS used for?
DEXA and QCT - diagnosis and monitoring
| QUS - risk assessment
115
What are the advantages of QCT?
Sensitive
Direct measurement of trabecular bone
3 dimensional volume measurement
116
What are the disadvantages of QCT?
Higher radiation
Less precision
More expensive
117
What are the advantages of QUS?
Inexpensive
Portable
No radiation
118
What are the disadvantages of QUS?
Unknown effectiveness of fracture risk prediction and osteoporosis diagnosis
119
What is scintigraphy?
Isotope bone scan
| Radioactive fluid injected and taken up by bones which are scanned after 3 hours for osteoblastic activity
120
What is the composition of bone?
70% inorganic hydroxyapatite
| 30% organic/water collagen I and non-collagenous proteins
121
Outline the bone remodelling cycle
Quiescence, resorption, reversal, formation
122
Which hormones increase osteoblast activity?
```
Growth hormone
Oestrogen
Growth factors
25 OH vitamin D
Calcitonin
```
123
Which hormones increase osteoclast activity?
Cytokines
Parathyroid hormone
1,25 OH vitamin D
124
What percentage of calcium is in the bones?
99%
125
How is calcium distributed in extracellular fluids?
41% bound to albumin
9% calcium salts
50% ionised/free
126
What hormones increase blood calcium?
Parathyroid hormone
| 1, 25 OH vitamin D
127
What hormones decrease blood calcium?
Calcitonin
| 25 OH vitamin D
128
What are the actions of parathyroid hormone?
Mobilises calcium from bone
Increase renal retention of calcium
Increase renal phosphate excretion
Increases renal production of 1, 25 OH vitamin D
129
Outline the vitamin D pathway
Sunlight → skin → 7-dehydrocholesterol → cholecalciferol → liver → 25 hydroxyvitamin D → kidney → 1, 25-dihydroxyvitamin D → calcium maintenance
130
Name sources of vitamin D2 and D3
D2 - plants
| D3 - fish, liver, milk, egg yolk
131
What are the gut and bone effects of vitamin D?
Gut - increases calcium and phosphate absorption
| Bone - increases resorption and formation
132
What are the effects of vitamin D deficiency on bones?
Decreased calcium absorption
Decreased bone mineral density
Induction of secondary hyperparathyroidism
Increased bone turnover/remodelling/loss/fracture
133
What are the effects of vitamin D deficiency on muscles?
Muscle weakness
| Abnormalities in contraction and relaxation
134
What are the classifications for vitamin D levels?
<20 nmol/L - deficient
20-49 - insufficient
50-70 - sufficient
>70 - optimal
135
How can breastfeeding lead to vitamin D deficiency in infants?
Vitamin D passes poorly into human milk
136
What are the common symptoms of vitamin D deficiency?
Bone pain, muscle pain, muscle weakness, irritability, rickets/osteomalacia, falls/fragility fractures, developmental delay
137
What are the severe symptoms of vitamin D deficiency?
Neonatal hypocalcaemia
| Infant cardiomyopathy
138
What are the symptoms of rickets?
Bone pain, poor growth, beaded ribs, bowed legs, knock knees, curvature of the spine, widening of ankles/wrists/knees, softening of bones including the skull (craniotabes), delayed closure of fontanelles, waddling gait, delayed walking, short stature, dental caries
Extreme cases -
hypocalcaemia (convulsions, irritability, tetany, breathing difficulties, cardiac arrest and heart failure)
139
What is the structure of CTx?
Two 8 amino acid stretches with various crosslinks (pyridinoline and deoxypyridinoline)
140
What are the 2 forms of TRACP?
TRACP 5a - macrophages
| TRACP 5b - osteoclasts
141
What are the advantages of TRACP 5b over CTx?
Does not accumulate in circulation in renal/hepatic failure
Diurnal variation is low
Not affected by feeding
142
What are the aims of pharmacological management of osteoporosis?
Target therapy to those with a high probability of fractures
Reduce incidence of fractures
Alleviate fracture related morbidity
143
How much calcium should postmenopausal women aim to ingest per day?
1000mg
144
What medications have been proven to reduce vertebral and non-vertebral fracture risk?
Alendronate, risendronate, HRT, zolendronate
145
When is teriparatide prescribed for osteoporosis?
>65 years old with T-score -3.5 and 2 previous vertebral fractures/>3 other, intolerant to bisphosphonates despite PPIs
Failure to respond to bisphosphonates, vertebral fracture/>2 other
146
List non-pharmacologic therapies for osteoporosis
```
Orthoses (spine brace, hip protector)
Exercise
Calcium and vitamin D supplement
Fall prevention
Kyphoplasty
Patient education and lifestyle measures
```
147
What are the advantages of exercise in osteoporosis?
Muscle strength, flexibility, balance, self-confidence, decreased risk of falling, increased bone mineral density
148
What types of exercise are useful in osteoporosis?
```
Spinal extension/flexion
Low impact weight bearing
Strength training
Tai chi
Physiotherapy classes
```
149
Why should calcium supplements be taken with food?
Calcium carbonate requires an acidic environment
150
How can falls be prevented in the elderly?
```
Gait analysis
Environment modification
Medication review
Exercise assessment
Provision of assistive devices
Identification of concomitant neuromuscular condition
```
151
What is vertebral kyphoplasty?
Minimally invasive spine procedure involving infiltration of bone cement into vertebral body after fracture
For relatively acute, painful compression to diminish pain and reduce kyphosis
152
How does bone grow?
In length by endochondral ossification
In width by subperiosteal opposition
Medullary cavity is expanded by endosteal bone resorption
153
Name a bone disease where there is loss of mineralisation
Osteomalacia/rickets
154
Name a bone disease where there is low bone mass
Osteoporosis
| Osteogenesis imperfecta
155
Name a bone disease where there is high bone mass
Osteopetrosis
156
Name a bone disease where there is high bone turnover
Pagets
Hyperparathyroidism
Thyrotoxicosis
157
Name a bone disease where there is low bone turnover
Adynamic disease
| Hypophosphatasia
158
What would be the biochemical findings in rickets?
Calcium - normal/low
Phosphate - normal/low
Alkaline phosphatase - high
159
What types of rickets are there?
```
Nutritional
Congenital
Premature
Genetic
Neoplatic
Hypophosphataemic
Drug-induced
```
160
What would be the biochemical findings in vitamin D deficiency?
```
25 OH vitamin D - low
1, 25 OH vitamin D - normal/low
Calcium - low
Parathyroid hormone - high
Alkaline phosphatase - high
Phosphate - low
```
161
What enzyme is needed for the first hydroxylation of vitamin D?
Alpha 1 hydroxylase
162
In what disease is alpha 1 hydroxylase mutated?
Vitamin D dependent rickets type 1
163
In what disease is the vitamin D receptor defective?
Vitamin D dependent rickets type 2
164
What is hypophosphataemic rickets?
Impaired renal tubular absorption of phosphate
FGF-23 mutation
Low phosphate, high alkaline phosphatase
165
What is osteodystrophy?
Renal rickets
Failure of kidney to excrete phosphate which binds to calcium and causes parathyroid hormone to be released which leaches calcium from bone
166
What are the biochemical findings in renal rickets?
Calcium - low
Phosphate - high
Alkaline phosphatase - high
Parathyroid hormone - high
167
How is renal rickets treated?
High dose vitamin D
168
What are the consequences of renal rickets?
Stunted growth, pasty face, rachitic deformity, myopathy
169
What is osteomalacia?
Reduced mineralisation of bone matrix due to calcium deficiency
170
What are the causes of hypercalcaemia?
Primary hyperparathyroidism, malignancy, excess vitamin D, calcium supplementation, granulomatous disease, thiazides
171
What are the clinical features of hypercalcaemia/primary hyperparathyroidism?
Bones (resorption, brown tumours), stones (kidney), groans (muscle pain), moans (depression)
172
What are the biochemical findings in hypercalcaemia?
Calcium - high
Phosphate - low
Alkaline phosphatase - high
Parathyroid hormone - high
173
What is measured in hypercalcaemia to determine the cause?
Parathyroid hormone
Undetectable - malignancy
Detectable - adenoma
174
What are the causes of hypocalcaemia?
Hypoparathyroidism, vitamin D deficiency, renal disease, magnesium deficiency, anticonvulsant treatment, citrated blood transfusion
175
What are the clinical features of hypocalcaemia?
Tingling, numbness, muscle cramps, tetany, convulsions, behavioural disturbance, cataracts, coagulation defects
176
What is measured in hypocalcaemia to determine the cause?
Check for renal disease and then parathyroid hormone
Low - post-surgical, magnesium deficiency, idiopathic
High - vitamin D deficiency, pseudohypoparathyroidism
177
What endocrine disorders can cause osteoporosis?
Cushings
| Hyperthyroidism
178
What happens to bones in menopausal/oestrogen deficiency osteoporosis?
Reduced bone mineral mass but normal mineral to matrix ratio
Higher resorption rates than formation
179
What is Paget's disease?
Increased rate of bone turnover with development of disorganised woven bone
180
What are the symptoms/complications of Paget's disease?
Leg bowing, fractures, enlarged teeth, pain
Hypervascularity causing high output heart failure
Deafness, arthritis, osteosarcoma, stroke, paralysis
181
How is Paget's disease treated?
Bisphosphonates
182
How is osteogenesis imperfecta treated?
Bisphosphonates
| Surgery for fractures/deformities
183
What is osteopetrosis?
Failure of osteoclast and chondroclast resorption = remodelling failure
Genetic disorder
184
What is fluorosis?
Abnormal matrix mineralisation
| Fluoride replaced calcium in hydroxyapatite
185
What are the side-effects of teriparatide therapy?
Common - anaemia, depression, dizziness, dyspnoea, fatigue, GI disorders, haemorrhoids, headache, muscle cramps, nausea, palpitation
Uncommon - hypercalcaemia, injection-site reactions, urinary disorders
Rare - hypersensitivity reactions
186
What are the contraindications of teriparatide therapy?
Pregnancy/breastfeeding, renal impairment, metastatic disease
187
What is OPG?
Osteoproteregin
| Decoy receptor which binds RANKL to inhibit resorption
188
What is RANK?
Receptor for RANKL which activates resorption
189
When is peak bone mass reached in men and women?
Men - 15/16
| Women - 13/14
190
Outline bone acquisition and loss with age
From puberty until 30 - 2-3% annual increase
30-40 years - steady
After 40 - 0.3-0.3% loss (2-3% in menopause)
