Disease of the Bone Flashcards
Osteoporosis is a disorder affecting the skeletal system characterised by
loss of bone mass.
Bone mineral density decreases with age
true
World Health Organisation define osteoporosis as
presence of bone mineral density (BMD) of less than 2.5 standard deviations (SD) below the young adult mean density.
Around?% of post-menopausal women will suffer an osteoporotic fracture at some point.
Around 50% of post-menopausal women will suffer an osteoporotic fracture at some point.
The major risk factors for osteoporosis are age and female gender.
true
Guidelines recommend using a screening tool such as
FRAX or QFracture to assess the 10-year risk of a patient developing a fragility fracture. A patient who has sustained a fragility fracture (e.g. following a Colles’ wrist fracture) should also be assessed for osteoporosis.
To assess the actual bone mineral density what is used?
dual-energy X-ray absorptiometry (DEXA) scan is used. The DEXA scan looks at the hip and lumbar spine. If either have a T score of < -2.5 then treatment is recommended.
The first-line treatment for osteoporosis is
oral bisphosphonate such as alendronate. Other treatments are available but the vast majority of patients are managed with this therapy.
Osteoporosis the first list we should order the following bloods as a minimum for all patients:
full blood count urea and electrolytes liver function tests bone profile CRP thyroid function tests
risk factors that are used by major risk assessment tools such as FRAX:
history of glucocorticoid use rheumatoid arthritis alcohol excess history of parental hip fracture low body mass index current smoking
Medications that may worsen osteoporosis (other than glucocorticoids):
SSRIs antiepileptics proton pump inhibitors glitazones long term heparin therapy aromatase inhibitors e.g. anastrozole
In terms of body systems - what can be a risk for osteoporosis
endocrine disorders: hyperthyroidism, hypogonadism (e.g. Turner’s, testosterone deficiency), growth hormone deficiency, hyperparathyroidism, diabetes mellitus
multiple myeloma, lymphoma
gastrointestinal disorders: inflammatory bowel disease, malabsorption (e.g. Coeliac’s), gastrectomy, liver disease
chronic kidney disease
osteogenesis imperfecta, homocystinuria
Which ethnicity higher risk OP
Caucasians and Asians
If a patient is diagnosed with osteoporosis or has a fragility fracture further investigations may be warranted. NOGG recommend testing for the following reasons:
exclude diseases that mimic osteoporosis (e.g. osteomalacia, myeloma);
identify the cause of osteoporosis and contributory factors;
assess the risk of subsequent fractures;
select the most appropriate form of treatment
The risk of osteoporosis is thought to rise significantly once a patient is taking the equivalent of
prednisolone 7.5mg a day for 3 or more months
if it likely that the patient will have to take steroids for at least 3 months then we should start bone protection straight away, rather than waiting until 3 months has elapsed.
true
a patient with newly diagnosed polymyalgia rheumatica. As it is very likely they will be on a significant dose of prednisolone for greater than 3 months what should be commenced immediately.
bone protection
Management of patients at risk of corticosteroid-induced osteoporosis
The RCP guidelines essentially divide patients into two groups:
- Patients over the age of 65 years or those who’ve previously had a fragility fracture should be offered bone protection.
- Patients under the age of 65 years should be offered a bone density scan, with further management dependent
Management of patients at risk of corticosteroid-induced osteoporosis &
Patients under the age of 65 years
bone scan results & management???
Greater than 0: Reassure
Between 0 and -1.5: Repeat bone density scan in 1-3 years
Less than -1.5: Offer bone protection
The first-line treatment is alendronate. Patients should also be calcium and vitamin D replete.
Osteoporosis: assessing risk
all women aged ? years and all men aged ? years should be assessed
all women aged >= 65 years and all men aged >= 75 years should be assessed
Osteoporosis: assessing risk when should younger patients be assessed?
previous fragility fracture, history of falls, family history of hip fracture
current use or frequent recent use of oral or systemic glucocorticoid
low body mass index (BMI) (less than 18.5 kg/m²)
smoking
alcohol intake of more than 14 units per week for women and more than 14 units per week for men.
NICE recommend using a clinical prediction tool such as ? to assess a patients 10 year risk of developing a fracture
FRAX or QFracture
Describe FRAX
estimates the 10-year risk of fragility fracture
valid for patients aged 40-90 years
based on international data so use not limited to UK patients
assesses the following factors: age, sex, weight, height, previous fracture, parental fracture, current smoking, glucocorticoids, rheumatoid arthritis, secondary osteoporosis, alcohol intake
bone mineral density (BMD) is optional, but clearly improves the accuracy of the results.
NICE recommend arranging a DEXA scan if FRAX (without BMD) shows an intermediate result
Describe Qfracture
estimates the 10-year risk of fragility fracture
developed in 2009 based on UK primary care dataset
can be used for patients aged 30-99 years (this is stated on the QFracture website, but other sources give a figure of 30-85 years)
includes a larger group of risk factors e.g. cardiovascular disease, history of falls, chronic liver disease, rheumatoid arthritis, type 2 diabetes and tricyclic antidepressants
There are some situations where NICE recommend arranging BMD assessment (i.e. a DEXA scan) rather than using one of the clinical prediction tools for assessing osteoporosis risk
these are?
before starting treatments that may have a rapid adverse effect on bone density (for example, sex hormone deprivation for treatment for breast or prostate cancer).
in people aged under 40 years who have a major risk factor
, such as history of multiple fragility fracture, major osteoporotic fracture, or current or recent use of high-dose oral or high-dose systemic glucocorticoids (more than 7.5 mg prednisolone or equivalent per day for 3 months or longer).
If the FRAX assessment was done without a bone mineral density (BMD) measurement the results (10-year risk of a fragility fracture) will be given and categorised automatically into one of the following:
low risk: reassure and give lifestyle advice
intermediate risk: offer BMD test
high risk: offer bone protection treatment
If the FRAX assessment was done witha bone mineral density (BMD) measurement the results (10-year risk of a fragility fracture) will be given and categorised automatically into one of the following:
reassure
consider treatment
strongly recommend treatment
If you use QFracture instead patients are not automatically categorised into low, intermediate or high risk. Instead the ‘raw data’ relating to the 10-year risk of any sustaining an osteoporotic fracture. This data then needs to be interpreted alongside either local or national guidelines, taking into account certain factors such as the patient’s age.
true
NICE recommend that we recalculate a patient’s risk (i.e. repeat the FRAX/QFracture):
if the original calculated risk was in the region of the intervention threshold for a proposed treatment and only after a minimum of 2 years, or
when there has been a change in the person’s risk factors
Describe DEXA scan - what does each score mean
T score: based on bone mass of young reference population
T score of -1.0 means bone mass of one standard deviation below that of young reference population
Z score is adjusted for age, gender and ethnic factors
Describe T score results
> -1.0 = normal
-1.0 to -2.5 = osteopaenia
< -2.5 = osteoporosis
In women aged 75 years or older, a DEXA scan may not be required ‘if
the responsible clinician considers it to be clinically inappropriate or unfeasible’
treatment is indicated following osteoporotic fragility fractures in postmenopausal women who are confirmed to have osteoporosis
true
What should be offered to all women undergoing osteoporisis tx
vitamin D and calcium supplementation
unless the clinician is confident they have adequate calcium intake and are vitamin D replete
around ?% of patients cannot tolerate alendronate
why?
around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems
Patients who cannot tolerate alendronate - what next
These patients should be offered risedronate or etidronate
Patients who cannot tolerate bisphosphonates - what next
strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates
treatment cut-off tables have been produced in the latest guidelines for patients who do not tolerate alendronate
These take into account
patients age, theire T-score and the number of risk factors they have from the following list:
parental history of hip fracture
alcohol intake of 4 or more units per day
rheumatoid arthritis
the T-score criteria for risedronate or etidronate are more/less than the others implying that these are the second line drugs
less
if alendronate, risedronate or etidronate cannot be taken then strontium ranelate or raloxifene may be given based on quite strict T-scores
true
alendronate, risedronate may be superior to etidronate in preventing
hip fractures
What is raloxifene?
Side effects?
selective oestrogen receptor modulator (SERM)
may worsen menopausal symptoms
increased risk of thromboembolic events
raloxifene can cause breast cancer
false
may decrease risk of breast cancer
What is Strontium ranelate?
Side effects?
‘dual action bone agent’ - increases deposition of new bone by osteoblasts (promotes differentiation of pre-osteoblast to osteoblast) and reduces the resorption of bone by inhibiting osteoclasts
due to these concerns the European Medicines Agency in 2014 said it should only be used by people for whom there are no other treatments for osteoporosis
increased risk of cardiovascular events: any history of cardiovascular disease or significant risk of cardiovascular disease is a contraindication
increased risk of thromboembolic events: a Drug Safety Update in 2012 recommended it is not used in patients with a history of venous thromboembolism
may cause serious skin reactions such as Stevens Johnson syndrome
Bisphosphonates are
analogues of pyrophosphate, a molecule which decreases demineralisation in bone. They inhibit osteoclasts by reducing recruitment and promoting apoptosis.
Bisphosphonates clinical uses?
prevention and treatment of osteoporosis
hypercalcaemia
Paget’s disease
pain from bone metatases
Bisphosphonates adverse effects?
oesophageal reactions: oesophagitis, oesophageal ulcers (especially alendronate)
osteonecrosis of the jaw
increased risk of atypical stress fractures of the proximal femoral shaft in patients taking alendronate
acute phase response: fever, myalgia and arthralgia may occur following administration
hypocalcaemia: due to reduced calcium efflux from bone. Usually clinically unimportant
The BNF suggests the following counselling for patients taking oral bisphosphonates
‘Tablets should be swallowed whole with plenty of water while sitting or standing; to be given on an empty stomach at least 30 minutes before breakfast (or another oral medication); patient should stand or sit upright for at least 30 minutes after taking tablet’
The duration of bisphosphonate treatment varies according to the level of risk. Some authorities recommend stopping bisphosphonates at 5 years if the following apply:
patient is < 75-years-old
femoral neck T-score of > -2.5
low risk according to FRAX/NOGG
Oral bisphosphonates are still given first-line, with oral alendronate being the first-line treatment. If alendronate is not tolerated then NICE recommend using an alternative bisphosphonate - either risedronate or etidronate. Following this the advice becomes more complicated with the next-line medications only being started if certain T score and other risk factor criteria being met. Raloxifene and strontium ranelate were recommended as next-line drugs in the NICE criteria but following recent safety concerns regarding strontium ranelate it is likely there will be an increasing role for denosumab.
true
Bone disorders: lab values
Osteoporosis
Calcium Normal
Phosphate Normal
ALP Normal
PTH Normal
Bone disorders: lab values
Osteomalacia
Calcium Decreased
Phosphate Decreased
ALP Increased
PTH Increased
Bone disorders: lab values Primary hyperparathyroidism (→ osteitis fibrosa cystica)
Calcium Increased
Phosphate Decreased
ALP Increased
PTH Increased
Bone disorders: lab values
Chronic kidney disease (→ secondary hyperparathyroidism)
Calcium Decreased
Phosphate Increased
ALP Increased
PTH Increased
Bone disorders: lab values
Paget’s disease
Calcium Normal
Phosphate Normal
ALP Increased
PTH Normal
Bone disorders: lab values
Osteopetrosis
Calcium Normal
Phosphate Normal
ALP Normal
PTH Normal
What is osteomalacia
normal bony tissue but decreased mineral content
Osteomalacia in kids
rickets
osteomalacia types
vitamin D deficiency e.g. malabsorption, lack of sunlight, diet renal failure drug induced e.g. anticonvulsants vitamin D resistant; inherited liver disease, e.g. cirrhosis
osteomalacia features
rickets: knock-knee, bow leg, features of hypocalcaemia
osteomalacia: bone pain, fractures, muscle tenderness, proximal myopathy
osteomalacia ix
low 25(OH) vitamin D (in 100% of patients, by definition) raised alkaline phosphatase (in 95-100% of patients) low calcium, phosphate (in around 30%) x-ray: children - cupped, ragged metaphyseal surfaces; adults - translucent bands (Looser's zones or pseudofractures)
Osteomalacia tx
calcium with vitamin D tablets
Paget’s disease is
disease of increased but uncontrolled bone turnover. It is thought to be primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity
Bones most affected in Paget’s
The skull, spine/pelvis, and long bones of the lower extremities are most commonly affected.
Paget’s disease is common and symptomatic in all patients
false
Paget’s disease is common (UK prevalence 5%) but symptomatic in only 1 in 20 patients
Paget’s disease risk factors
increasing age
male sex
northern latitude
family history
Pagets only ?% of patients are symptomatic
5%
the stereotypical presentation of pagets
an older male with bone pain and an isolated raised ALP classical, untreated features: bowing of tibia, bossing of skull bone pain (e.g. pelvis, lumbar spine, femur)
pagets skull x ray
thickened vault, osteoporosis circumscripta
Pagets bloods
raised alkaline phosphatase (ALP) - calcium* and phosphate are typically normal
other markers of bone turnover include: procollagen type I N-terminal propeptide (PINP), serum C-telopeptide (CTx), urinary N-telopeptide (NTx), and urinary hydroxyproline
Pagets Indications for treatment
bone pain, skull or long bone deformity, fracture, periarticular Paget’s
Pagets tx
bisphosphonate (either oral risedronate or IV zoledronate)
calcitonin is less commonly used now
Pagets complications
deafness (cranial nerve entrapment) bone sarcoma (1% if affected for > 10 years) fractures skull thickening high-output cardiac failure
What is Osteogenesis imperfecta
Osteogenesis imperfecta (more commonly known as brittle bone disease) is a group of disorders of collagen metabolism resulting in bone fragility and fractures. The most common, and milder, form of osteogenesis imperfecta is type 1
Inheritance pattern of Osteogenesis imperfecta
Pathophysiology?
autosomal dominant
abnormality in type 1 collagen due to decreased synthesis of pro-alpha 1 or pro-alpha 2 collagen polypeptides
Sx Osteogenesis imperfecta
presents in childhood fractures following minor trauma blue sclera deafness secondary to otosclerosis dental imperfections are common
Ix Osteogenesis imperfecta
adjusted calcium, phosphate, parathyroid hormone and ALP results are usually normal in osteogenesis imperfecta
