Diseases of the Bone Flashcards
Paget’s Disease of the Bone
Paget’s disease is a 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. Paget’s disease is common (UK prevalence 5%) but symptomatic in only 1 in 20 patients
Paget’s Disease of the Bone - Predisposing Factors
Predisposing factors increasing age male sex northern latitude family history
Paget’s Disease of the Bone - Clinical Features
Clinical features - only 5% of patients are symptomatic
bone pain (e.g. pelvis, lumbar spine, femur)
classical, untreated features: bowing of tibia, bossing of skull
raised alkaline phosphatase (ALP) - calcium* and phosphate are typically normal
skull x-ray: thickened vault, osteoporosis circumscripta
*usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation
NB: you should always think Paget’s disease if shown a skull x-ray in an exam.
Paget’s Disease of the Bone - Mx
Indications for treatment include bone pain, skull or long bone deformity, fracture, periarticular Paget’s
bisphosphonate (either oral risedronate or IV zoledronate)
2nd line = calcitonin but is less commonly used now
Unless CI all patients on bisphosphonates should be on supplements of Ca2+ and Vit D to avoid symptomatic hypocalcaemia
Paget’s Disease of the Bone - Cx
Complications deafness (cranial nerve entrapment) bone sarcoma (1% if affected for > 10 years) fractures skull thickening high-output cardiac failure
Osteoporosis - Glucocorticoid-induced
We know that one of the most important risk factors for osteoporosis is the use of corticosteroids. As these drugs are so widely used in clinical practice it is important we manage this risk appropriately.
The most widely followed guidelines are based around the 2002 Royal College of Physicians (RCP) ‘Glucocorticoid-induced osteoporosis: A concise guide to prevention and 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. It is important to note that we should manage patients in an anticipatory, i.e. 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. A good example is 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 bone protection should be commenced immediately.
Glucocorticoid-induced Osteoporosis: Example Question
A 51-year-old man presents to the emergency department with a 2-week history of lumbar back pain. He has a background of asthma, hypertension and benign prostatic hypertrophy (BPH). He has no history of trauma. Apart from a recent exacerbation of asthma, he is otherwise well.
On examination, you find a man of large body habitus. He is able to mobilise with some discomfort. He is afebrile, with a heart rate of 75 beats per minute and blood pressure 120/82mmHg. He has some spinal tenderness at L4, and discomfort on extension of the spine. On neurological examination he has no muscle wasting or fasciculations. He has full power in all limbs and normal tone. Reflexes are symmetrical and plantars downgoing. Sensation is intact and he has normal rectal tone, with no saddle anaesthesia.
Blood tests show:
Hb 14.1 g/dl
Platelets 245 * 109/l
WBC 8.0 * 109/l
Na+ 137 mmol/l
K+ 4.0 mmol/l
Urea 5.1 mmol/l
Creatinine 82 µmol/l
Bilirubin 14 µmol/l ALP 42 u/l ALT 17 u/l CRP 3 mg/L PSA 3.1ng/mL
What is the most likely diagnosis?
Paget's disease Infective discitis Spinal metastases > Vertebral compression fracture Lumbar radiculopathy
This man has a crush fracture of the lumbar spine. He has had repeated courses of steroid treatment for his asthma, which has led to the development of osteoporosis. A plain X-ray would reveal the diagnosis. Paget’s disease is unlikely given the normal ALP. Back pain due to metastases can be a presenting feature of prostate carcinoma. Although this man has BPH, his normal PSA and ALP make metastatic prostate cancer unlikely. He does not have neurological signs or symptoms suggestive of lumbar radiculopathy. Raised inflammatory markers would be expected in infective discitis.
Other side effects of prolonged corticosteroid use include: Peptic ulcer Skin thinning Mood and sleep disturbance Central obesity Myopathy Avascular necrosis of bone Cataracts
Glucocorticoid-induced Osteoporosis - Mx
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:
T Score greater than 0 = Reassure
T Score between 0 and -1.5 = Repeat bone density scan in 1-3 years
T Score less than -1.5 = Offer bone protection
The first-line treatment is alendronate. Patients should also be calcium and vitamin D replete.
Osteopenia - Diagnosis: Example Question
A 58-year-old woman of Indian ethnic origin presents with pain in her hands. These pains have been present for the past few months and are getting gradually worse. The hand pains are also associated with generalised aches which are worst around the shoulders, lower back and feet/ankles. On the review of systems she describes lethargy and polydipsia.
She has a past medical history of depression and hypertension which is well controlled with lisinopril.
A hand x-ray is requested:
SEE PASSMED HAND XR OSTEOPENIA
What is the most likely underlying diagnosis?
Osteomalacia Tuberculosis > Hyperparathyroidism Psoriatic arthritis Osteoarthritis
The x-rays demonstrate generalised osteopenia, erosion of the terminal phalyngeal tufts (acro-osteolysis) and sub-periosteal resorption of bone particularly the radial aspects of the 2nd and 3rd middle phalanges. These changes are consistent with hyperparathyroidism.
Generalised aches and pain, polydipsia and lethargy are also common symptoms of having a raised calcium level.
Osteoporosis - Mx: NICE Updates
NICE guidelines were updated in 2008 on the secondary prevention of osteoporotic fractures in postmenopausal women.
Key points include
- treatment is indicated following osteoporotic fragility fractures in postmenopausal women who are confirmed to have osteoporosis (a T-score of - 2.5 SD or below). 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’
- vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete
- alendronate is first-line
- around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate (see treatment criteria below)
- strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates (see treatment criteria below)
Osteoporosis - Mx: Treatment Criteria for patients not taking Alendronate
Treatment criteria for patients not taking alendronate
Unfortunately, a number of complicated treatment cut-off tables have been produced in the latest guidelines for patients who do not tolerate alendronate
These take into account a 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
It is very unlikely that examiners would expect you to have memorised these risk tables so we’ve not included them in the revision notes but they may be found by following the NICE link. The most important thing to remember is:
- the T-score criteria for risedronate or etidronate are less than the others implying that these are the second line drugs
- if alendronate, risedronate or etidronate cannot be taken then strontium ranelate or raloxifene may be given based on quite strict T-scores (e.g. a 60-year-old woman would need a T-score < -3.5)
- the strictest criteria are for denosumab
Osteoporosis Mx - Bisphosphonates
Bisphosphonates
- alendronate, risedronate and etidronate are all licensed for the prevention and treatment of post-menopausal and glucocorticoid-induced osteoporosis
- all three have been shown to reduce the risk of both vertebral and non-vertebral fractures although alendronate, risedronate may be superior to etidronate in preventing hip fractures
- ibandronate is a once-monthly oral bisphosphonate
Osteoporosis - Mx: Vitamin D and Calcium
Vitamin D and calcium
poor evidence base to suggest reduced fracture rates in the general population at risk of osteoporotic fractures - may reduce rates in frail, housebound patients
Osteoporosis - Mx: Raloxifene
Raloxifene - selective oestrogen receptor modulator (SERM)
- has been shown to prevent bone loss and to reduce the risk of vertebral fractures, but has not yet been shown to reduce the risk of non-vertebral fractures
- has been shown to increase bone density in the spine and proximal femur
- may worsen menopausal symptoms
- increased risk of thromboembolic events
- may decrease risk of breast cancer
Osteoporosis - Mx: Strontium Ranelate
Strontium ranelate
- ‘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
- concerns regarding the safety profile of strontium have been raised recently. It should only be prescribed by a specialist in secondary care
- 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
Osteoporosis - Mx: Denosumab
Denosumab
- human monoclonal antibody that inhibits RANK ligand, which in turn inhibits the maturation of osteoclasts
- given as a single subcutaneous injection every 6 months
- initial trial data suggests that it is effective and well tolerated
Osteoporosis-Mx: Teriparatide
Teriparatide
- recombinant form of parathyroid hormone
- very effective at increasing bone mineral density but role in the management of osteoporosis yet to be clearly defined
Osteoporosis Mx: HRT
Hormone replacement therapy
has been shown to reduce the incidence of vertebral fracture and non-vertebral fractures
due to concerns about increased rates of cardiovascular disease and breast cancer it is no longer recommended for primary or secondary prevention of osteoporosis unless the woman is suffering from vasomotor symptoms
Osteoporosis - Mx: Hip Protectors
Hip protectors
evidence to suggest significantly reduce hip fractures in nursing home patients
compliance is a problem
Osteoporosis- Mx: Falls Risk Assessment
Falls risk assessment
no evidence to suggest reduced fracture rates
however, do reduce rate of falls and should be considered in management of high risk patients
Diffuse Idiopathic Skeletal Hyperostosis (DISH)
Diffuse idiopathic skeletal hyperostosis (DISH) describes the relatively common finding of ossification at sites of tendinous and ligamentous insertion of the spine. It tends to be seen in elderly patients.
DISH is generally asymptomatic.
Glucocorticoid-induced Osteoporosis - Prophylaxis: Example Question
A 68-year-old man presents for review to the rheumatology clinic following a clinical suspicion of polymyalgia rheumatica. He developed increasing tiredness and shoulder ache over two weeks, but following treatment with oral prednisolone he feels that he is feeling better than he has been for years. He has a past medical history of hypertension, ischaemic heart disease, gout and depression. He normally takes amlodipine, ramipril, aspirin and atorvastatin. He is a smoker, smoking a pack every week, and drinks one glass of whisky every Saturday. He has been assessed by the dietician who thinks that he has a relatively poor diet consisting largely of ready-meals. This has been the case since his wife died two years ago. Apart from continued corticosteroids, what further medications should be prescribed?
> Alendronate, calcium carbonate with cholecalciferol (e.g. Adcal-D3) and ompeprazole Alendronate and omeprazole Calcium carbonate with cholecalciferol and omeprazole Permidronate Calcium carbonate with cholecalciferol and omeprazole
The correct answer is alendronate, calcium carbonate and cholecalciferol and omeprazole. This is a patient who is being treated with long-term corticosteroid treatment and is therefore at risk of complications. The dose of steroids is likely to be greater than 7.5mg for more than three months and he is over 65 years old he should be started on bone protection in the form of alendronate. As his diet is poor, he should also be supplemented with calcium carbonate and cholecalciferol, and as he is at risk of peptic ulceration, especially with combining long-term steroids with aspirin, he should also have a proton pump inhibitor.
Alkaptonuria
Alkaptonuria
Alkaptonuria (ochronosis) is a rare autosomal recessive disorder of phenylalanine and tyrosine metabolism caused by a lack of the enzyme homogentisic dioxygenase (HGD) which results in a build-up of toxic homogentisic acid. The kidneys filter the homogentisic acid (hence black urine) but eventually it accumulates in cartilage and other tissues.
Alkaptonuria is generally a benign and often asymptomatic condition. Possible features include:
pigmented sclera
urine turns black if left exposed to the air
intervertebral disc calcification may result in back pain
renal stones
Treatment
high-dose vitamin C
dietary restriction of phenylalanine and tyrosine (cheese, soy, meat, seeds and nuts)
Perthes’ Disease
Perthes’ disease is a degenerative condition affecting the hip joints of children, typically between the ages of 4-8 years. It is due to avascular necrosis of the femoral head, specifically the femoral epiphysis. Impaired blood supply to the femoral head causes bone infarction.
Perthes’ disease is 5 times more common in boys. Around 10% of cases are bilateral
Features
hip pain: develops progressively over a few weeks
limp
stiffness and reduced range of hip movement
x-ray: early changes include widening of joint space, later changes include decreased femoral head size/flattening
Eg presentation
‘A 8-year-old boy is complains of progressively worsening pain in both groin areas. He has no past medical history of note and his immunisations are up-to-date. There is no recent history of trauma. On examination he walks with a limp.’
Diagnosis
plain x-ray
technetium bone scan or magnetic resonance imaging if normal x-ray and symptoms persist
Complications
osteoarthritis
premature fusion of the growth plates
Stage 1 = Clinical and histological features only
Stage 2 = Sclerosis with or without cystic changes and preservation of the articular surface
Stage 3 = Loss of structural integrity of the femoral head
Stage 4 = Loss of acetabular integrity
Management
To keep the femoral head within the acetabulum: cast, braces
If less than 6 years: observation
Older: surgical management with moderate results
Operate on severe deformities
Prognosis
Most cases will resolve with conservative management. Early diagnosis improves outcomes.
Paget’s Disease of the Bone - Refractory Case: Example Question
A 62-year-old man with a diagnosis of Paget’s disease is seen in clinic with a two month history of worsening bone pain, mainly in his left leg. His medications include paracetamol, ibuprofen, and alendronate.
Examination reveals marked deformity of the long bones, particularly the left tibia.
Blood tests:
Calcium 2.40 mmol/L (2.25-2.5) Albumin 37g/L (34-54) Corrected calcium 2.50 mmol/L (2.25-2.5) Alkaline phosphatase 484 U/L (45-105) Alanine transaminase 27 U/L (5-35)
What is the next stage in the treatment of this patient?
Cholecalciferol Surgery > Calcitonin Hearing aid Prednisolone
Paget’s disease is characterised by abnormal bone remodelling, particularly in the skull and long bones. The characteristic blood test results include an elevated alkaline phosphatase, with otherwise normal liver function tests (as alkaline phosphatase is also found in bone). A raised calcium may only be seen if there is associated immobility.
Analgesics and non-steroidal inflammatory drugs are initially used to manage pain, with treatment escalated to bisphosphonates and calcitonin in refractory cases.
Bisphosphonate Treatment Failure in Osteoporosis
Bisphosphonate treatment failure is defined as two or more fractures on treatment, or one fracture with a reduction in bone density
Cx of Long term Bisphosphonate Use in Osteoporosis
Due to increasing awareness of complications associated with long-term bisphosphonate treatment, treatment breaks (or ‘drug holidays’) can be considered for some patient’s after five years treatment. Guidelines recommend consideration of treatment breaks for patients less than 75 years old with a femoral neck T-score greater than -2.5 and who are defined as low risk by WHO Fracture Risk Assessment Tool (FRAX) and National Osteoporosis Guideline Group (NOGG) guidelines. When a drug holiday is agreed, advice is to repeat DEXA scan after two years, or sooner in the event of a fracture. Treatment breaks are never recommended if a patient has ever suffered from a vertebral insufficiency fracture.
Osteoporosis and Bisphosphonate Treatment Failure - Example Question:
A 73-year-old woman attends rheumatology clinic for review of her osteoporosis treatment. The patient had been diagnosed with osteoporosis five years previously on a DEXA scan performed after she had sustained a fractured right neck of femur. Since the time of diagnosis, the patient had been receiving treatment with alendronic acid (70 mg weekly).
During clinic review, the patient reported taking her alendronic acid as prescribed without any associated side effects. A review of her past medical history revealed that the patient had sustained a left distal radius fracture the previous year following a trip at home. In addition, the patient had suffered from a deep vein thrombosis in her right leg three years before precipitated by a trans-continental flight and had been anti-coagulated with warfarin for six months.
The patient was a smoker (10 cigarettes per day) and also consumed around 20 units of alcohol per week. Her mother had suffered a fractured neck of femur at the age of 80. The patient had never been diagnosed with rheumatoid arthritis and had no significant exposure to corticosteroid treatment.
Clinical examination of the patient demonstrated no loss of height since previous measurement five years previously. There was no tenderness on palpation of the thoracic or lumbar spine.
Height 175 cm
Weight 95 kg
Femoral neck BMD (5 years previously) T - 2.7
Femoral neck BMD (present day) T - 2.9
FRAX 10-year probability of major osteoporotic fracture 60 %
FRAX 10-year probability of hip fracture 50 %
What is the appropriate management of the patient’s osteoporosis?
>
Stop treatment with alendronic acid and start treatment with denosumab Stop treatment with alendronic acid and start treatment with strontium ranelate Continue treatment with alendronic acid with repeat DEXA scan in five years Continue treatment with alendronic acid with repeat DEXA scan in two years Stop treatment with alendronic acid with repeat DEXA scan in two years
Due to her extensive risk factors, the patient is at an extremely high risk of suffering from further fragility fractures and it is essential that she continues with osteoporosis treatment. Bisphosphonate treatment failure is defined as two or more fractures on treatment, or one fracture with a reduction in bone density (as in this patient). Therefore, continuing treatment with alendronic acid is not advisable. Of the alternative treatments listed as possible answers, strontium ranelate is contra-indicated in this patient due to her history of deep vein thrombosis, leading to treatment with denosumab as the most appropriate treatment option.
Prevention of Osteoporosis in patients >75
Start alendronate in patients >= 75 years following a fragility fracture, without waiting for a DEXA scan
Example Question:
A 79-year-old woman falls over on to an outstretched hand and sustains a Colles’ fracture (fracture of the distal radius). She has no past medical history of note other than depression and osteoarthritis. What is the most appropriate next course of action with regards to her risk of sustaining a further fracture?
Arrange a DEXA scan Perform a FRAX (without bone mineral density) assessment > Start alendronate 70mg once weekly No further action is required Arrange a myeloma screen
Patients who sustain fragility fractures over the age of 75 are presumed to have osteoporosis and therefore started on oral alendronate 70mg once weekly. A DEXA scan does not need to be arranged.
Osteoporosis: Assessing patients following a fragility fracture
Patients >= 75 years of age
Patients >= 75 years of age
Patients who’ve had a fragility fracture and are >= 75 years of age are presumed to have underlying osteoporosis and should be started on first-line therapy (an oral bisphosphonate), without the need for a DEXA scan.
It should be noted that the 2014 NOGG guidelines have a different threshold, suggesting treatment is started in all women over the age of 50 years who’ve had a fragility fracture - ‘although BMD measurement may sometimes be appropriate, particularly in younger postmenopausal women.’
Osteoporosis: Assessing patients following a fragility fracture
Patients <75 years of age
Patients < 75 years of age
If a patient is under the age of 75 years a DEXA scan should be arranged. These results can then be entered into a FRAX assessment (along with the fact that they’ve had a fracture) to determine the patients ongoing fracture risk.
Pott’s Disease - Diagnosis: Example Question:
A 34-year-old man presents with back pain and leg weakness. This has been getting worse for the past two months and he now complains that he is ‘bent over’. Over the past three months he describes feeling generally unwell, with a poor appetite and night sweats.
His past medical history includes hypothyroidism. He emigrated from Bangladesh around 6 months ago.
On examination he has a kyphosis. He is most tender over the lower part of the thoracic spine. Neurological examination of his lower limbs demonstrates reduced power in both legs.
SEE PASSMED POTT’S DISEASE IMAGES
Osteoporosis secondary to hypogonadism > Pott's disease Actinomycosis Sarcoma Hodgkin's lymphoma
Osteoporosis - Assessing Risk: Example Question
A 55-year-old woman presents for review. Her mother has just been discharged after suffering a hip fracture. She is concerned that she may have ‘inherited’ osteoporosis and is asking what she should do. She has no significant past medical history of note, takes no regular medication and has never sustained any fractures. She smokes around 20 cigarettes per day and drinks about 3-4 units of alcohol per day.
What is the most appropriate course of action?
Arrange bone mineral density measurement (DEXA scan) Reassure her that assessment of fragility fracture risk does not need to be done until 65 years Refer her to the genetics team for a risk assessment Start first-line bone protection (i.e. ensure calcium/vitamin D replete + oral bisphosphonate) > Use the FRAX tool
This lady has a number of risk factors for developing osteoporosis:
positive family history
smoking
excess alcohol intake
She should therefore have an immediate FRAX assessment, rather than waiting until 65 years as we would for women without any relevant risk factors
Osteoporosis: Assessing Risk - NICE Guidelines
We worry about osteoporosis because of the increased risk of fragility fractures. So how do we assess which patients are at risk and need further investigation?
NICE produced guidelines in 2012: Osteoporosis: assessing the risk of fragility fracture. The following is based on those guidelines.
They advise that all women aged >= 65 years and all men aged >= 75 years should be assessed. Younger patients should be assessed in the presence of risk factors, such as:
previous fragility fracture
current use or frequent recent use of oral or systemic glucocorticoid
history of falls
family history of hip fracture
other causes of secondary osteoporosis
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 21 units per week for men.
Osteoporosis - Methods of Risk Assessment
Methods of risk assessment
NICE recommend using a clinical prediction tool such as FRAX or QFracture to assess a patients 10 year risk of developing a fracture. This is analogous to the cardiovascular risk tools such as QRISK.
Osteoporosis - FRAX
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
Osteoporosis - Risk Assessment: QFracture
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
Osteoporosis -Risk Assessment: DEXA Scan
There are some situations where NICE recommend arranging BMD assessment (i.e. a DEXA scan) rather than using one of the clinical prediction tools:
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).
Osteoporosis - Risk Assessment: Interpreting the results of FRAX
Interpreting the results of FRAX
Once we’ve decided that we need to do a risk assessment using FRAX and have entered all the data we are left with results to interpret.
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
Therefore, with intermediate risk results FRAX will recommend that you arrange a BMD test to enable you to more accurately determine whether the patient needs 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.
Osteoporosis - When should we reassess a patient’s risk?
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
Paget’s Disease of the Bone - Isotope Bone Scan
SEE PASSMED IMAGE
‘The bone scan demonstrates intense uptake involving several lower thoracic vertebrae, L3, right hemipelvis, sacrum, left proximal femur and right knee. There is expansion and bowing of the involved femur. These changes are typical of Paget’s disease.’
NB: Isotope bone scans are not useful for asssessing multiple myeloma or osteoporosis.
Osteoporosis - Bisphosphonate Treatment Break Mx: Example Question
A 72-year-old man attends rheumatology clinic for review of his osteoporosis treatment after being referred by the orthopaedic team. The patient had been diagnosed with osteoporosis six years previously after a DEXA scan had been arranged by his General Practitioner. Treatment with alendronic acid (70 mg weekly) had been initiated immediately after the diagnosis. After five years of bisphosphonate treatment, a repeat DEXA scan had been arranged and following review in rheumatology clinic, a treatment break had been agreed with the patient. Unfortunately, one year after stopping alendronic acid, the patient had tripped and fractured his right neck of femur, subsequently undergoing hemiarthroplasty.
Other past-medical history was significant for an episode of giant cell arteritis 10 years previously that had necessitated a prolonged course of corticosteroids. However, patient was now successfully weaned from corticosteroid treatment and remained in remission. The patient had never been diagnosed with rheumatoid arthritis and did not smoke cigarettes or drink alcohol. There was no family history of fragility fractures that the patient could recall.
On questioning, the patient reported that he had never had any adverse effects from alendronic acid treatment and would be happy to take this medication again if recommended.
Height 185 cm
Weight 90 kg
Femoral neck BMD (6 years previously) T - 2.7
Femoral neck BMD (1 year previously) T - 2.3
What is the most appropriate next step in the management of the patient’s osteoporosis?
Repeat DEXA scan not required, start treatment with zoledronic acid Repeat DEXA scan not required, restart treatment with alendronic acid Repeat DEXA scan in one year Repeat DEXA scan not required, start treatment with denosumab > Repeat DEXA scan immediately
Due to an increased awareness of the potential harms of long-term bisphosphonate treatment, treatment breaks are considered after five years of bisphosphonate treatment when a patient is aged under 75 years, has a femoral neck T-score greater than - 2.5 and is assessed as being below the treatment threshold based on the WHO Fracture Risk Assessment Tool (FRAX) and National Osteoporosis Guideline Group (NOGG) guidelines.
At the point in time when alendronic acid treatment was held one year previously, the above patient met these criteria with a 10-year probability of major osteoporotic fracture of 8.9 %.
Current recommendation is for an individual on a treatment break to have a repeat DEXA scan after two years or sooner in the event of a fragility fracture. Therefore, the correct answer is to repeat the DEXA scan immediately to allow re-calculation of the patient’s osteoporosis risk to inform future treatment decision.
If it is decided to restart treatment then it would be appropriate to return to alendronic acid as this had been well tolerated by the patient and had led to an improvement in bone density. Parenteral treatments such as zoledronic acid or denosumab are employed if oral treatments are not tolerated or in the event of bisphosphonate treatment failure.
Osteoporosis - Bisphosphonate Treatment Breaks
At the present time it is uncertain how long patients should take bisphosphonates. Recent concerns about side effects of long-term bisphosphonate treatment (for example, atypical femur fractures) have led to recommendations about the use of treatment breaks (‘drug holidays’) in certain patients.
Due to increased awareness of the potential complications of long-term bisphosphonate treatment, treatment breaks (or ‘drug holidays’) are now employed for some patients. Specifically, a treatment break should be considered for patients less than 75 years old, with femoral neck T score > - 2.5, no history of osteoporotic vertebral fracture and deemed low risk following assessment by WHO Fracture Risk Assessment Tool (FRAX) and National Osteoporosis Guideline Group (NOGG) guidance. For such a patient, treatment would typically be suspended for two years with repeat DEXA scan at the end of that period, or sooner in the event of fragility fracture.
Parenteral osteroporosis treatments such as zoledronic acid or denosumab should be considered if patient is intolerant of oral bisphosphonates or in the event of treatment failure (defined as two or more fractures on treatment, or one fracture and a fall in bone mineral density).
Osteoporosis - Bisphosphonate Treatment Breaks - Example Question
A 72-year-old woman attends rheumatology clinic for review of her osteoporosis treatment. She had been diagnosed with osteoporosis five years previously on the basis of a DEXA scan (see results below). At that time, the DEXA scan had been arranged by her GP due to a strong family history of osteoporosis (maternal hip fracture) and the patient having received multiple courses of corticosteroids as treatment for asthma. The patient has never sustained a fracture of her hip, wrist or vertebrae. Following the initial diagnosis, the patient had been treated with alendronic acid 70 mg weekly. She had not experienced any adverse effects from this medication although reported finding the need to drink copious water with her dose onerous.
The patient’s past medical history was significant for asthma, although the patient reported that this was now much better controlled than previously and she had not required any corticosteroid treatment in several years. She denied any history of thyroid disease or rheumatoid arthritis. The patient had never smoked and very rarely consumed any alcohol.
Details from the patient examination in clinic and selected results from her DEXA scans are given below.
Height 160 cm
Weight 65 kg
Femoral neck BMD (5 years previously) T -2.6 g / cm2
Femoral neck BMD (present day) T -1.9 g / cm2
FRAX 10-year probability of major osteoporotic fracture 18 %
FRAX 10-year probability of hip fracture 6.8 %
What is the most appropriate management of the patient’s osteoporosis?
Discontinue alendronic acid and initiate treatment with denosumab > Hold further osteoporosis treatment with repeat DEXA scan in two years Continue treatment with alendronic acid with repeat DEXA scan in five years Continue treatment with alendronic acid with repeat DEXA scan in two years Hold further osteoporosis treatment with repeat DEXA scan in five years
At the present time it is uncertain how long patients should take bisphosphonates. Recent concerns about side effects of long-term bisphosphonate treatment (for example, atypical femur fractures) have led to recommendations about the use of treatment breaks (‘drug holidays’) in certain patients.
The patient in this example meets the recommended criteria for a treatment break. In particular, her age (< 75 years), femoral neck bone mineral density > -2.5 and lack of history of fragility fracture are all favourable. A repeat DEXA scan is recommended after two years or in the event of fragility fracture to review need for further treatment.
It is recommended to use the WHO Fracture Risk Assessment Tool (FRAX) to estimate a patient’s 10-year risk of fragility fracture. This can be combined National Osteoporosis Guideline Group (NOGG) guidance to inform treatment decisions. In this example, the patient’s FRAX score would place her below the treatment threshold of NOGG guidance. It should be noted, that despite the recommendation to use FRAX score and NOGG guidance in this situation, neither tools are validated for patients taking bisphosphonates.
Parenteral treatments for osteoporosis such as denosumab should be reserved for individuals in whom bisphosphonate treatment has failure, or who are intolerant of bisphosphonates.
OA - X-ray Changes
Osteoarthritis: X-ray changes
X-ray changes of osteoarthritis
- decrease of joint space
- subchondral sclerosis
- subchondral cysts
- osteophytes forming at joint margins
Osteoporosis - Mx: Example Question
A 74-year-old woman attends rheumatology clinic for a review of her osteoporosis treatment. The patient had been diagnosed with osteoporosis on a DEXA scan five years previously after she fell and sustained a Colles fracture on the left side. Following this diagnosis, the patient had been initiated on treatment with alendronic acid.
In clinic, the patient reported that she had recently been suffering from nagging back pain over the past few weeks. She denied any history of recent falls or other trauma.
Past medical history was significant for rheumatoid arthritis, diagnosed when the patient was 28 years old. Following this diagnosis, she had received prolonged treatment with corticosteroids in association with a variety of disease modifying drugs. Ultimately, good control of her arthritis had been achieved using methotrexate (10 mg weekly) and the patient had not required corticosteroid treatment for many years. The patient reported no family history of osteoporosis or fragility fractures. She did not smoke or drink any alcohol.
The patient reported no concerns or side effects associated with taking her weekly alendronic acid (70 mg weekly).
Examination of the patients spine demonstrated mid-line point tenderness around the T12 - L1 level. Neurological examination of the lower limbs was unremarkable.
Thoracolumbar spine x-ray: anterior height loss of T12 vertebrae, otherwise unremarkable
Height 150 cm
Weight 55 kg
Femoral neck BMD (5 years previously) T - 3.2
Femoral neck BMD (present day) T - 2.4
FRAX 10-year probability of major osteoporotic fracture 27 %
FRAX 10-year probability of hip fracture 8.7 %
What is the most appropriate management of the patient’s osteoporosis?
Hold further osteoporosis treatment with repeat DEXA scan in two years Hold further osteoporosis treatment with repeat DEXA scan in five years Discontinue alendronic acid and initiate treatment with denosumab Discontinue alendronic acid and initiate treatment with zoledronic acid > Continue treatment with alendronic acid with repeat DEXA scan in five years
The patient’s bone mineral density has improved secondary to her treatment with alendronic acid. However, her recent back pain and abnormal thoracolumbar x-ray suggest she has suffered from a osteoporotic vertebral fracture. In one study, continuing alendronic acid from five to ten years treatment reduced the incidence of clinical vertebral fractures in all patients regardless of T score. Therefore, continuing alendronic acid treatment would be recommended for this patient.
Osteomalacia
Osteomalacia
Basics
normal bony tissue but decreased mineral content
rickets if when growing
osteomalacia if after epiphysis fusion
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
Features
rickets: knock-knee, bow leg, features of hypocalcaemia
osteomalacia: bone pain, fractures, muscle tenderness, proximal myopathy
Investigation
low calcium, phosphate, 25(OH) vitamin D
raised alkaline phosphatase
x-ray: children - cupped, ragged metaphyseal surfaces; adults - translucent bands (Looser’s zones or pseudofractures)
Treatment
calcium with vitamin D tablets
Osteomyelitis
Osteomyelitis
Osteomyelitis describes an infection of the bone.
Staph. aureus is the most common cause except in patients with sickle-cell anaemia where Salmonella species predominate.
Predisposing conditions diabetes mellitus sickle cell anaemia intravenous drug user immunosuppression due to either medication or HIV alcohol excess
Investigations
MRI is the imaging modality of choice, with a sensitivity of 90-100%
Management
flucloxacillin for 6 weeks
clindamycin if penicillin-allergic
Osteomyelitis - Example Question
A 58-year-old man who has no fixed abode comes to the Emergency department because he is unable to walk. He has a history of alcoholism and type 2 diabetes. His main complaint is that his shoes have worn out and because of loss of sensation he didn’t notice that he had stepped on a nail. In total the lesion on his right foot has been present for approximately 3 weeks.
Which of the following is the next step in evaluating his foot injury?
Inflammatory markers MRI foot > Plain x-ray foot USS foot Wound swab
The key next step here is to gather useful information about the extent of any foot infection. By 3 weeks post injury, changes consistent with osteomyelitis should be visible on plain x-ray. These may include soft tissue swelling, bone demineralisation, cortical irregularity, and an elevated periosteum.
Many patients progress from a plain x-ray on to MRI imaging of the foot for further evaluation of the extent of infection and to guide potential operative approaches for debridement. Inflammatory markers are a very non-specific marker of infection and ultrasound of the foot is only useful to visualise soft tissue swelling or collection of pus / fluid. A wound swab is likely to show a range of bacteria, this is what drives selection of a broader spectrum antibiotic such as co-amoxiclav in the diabetic population.
Paget’s Disease Mx: Example Question
A 67-year-old Caucasian man presents with progressive deafness and difficulty chewing. He also states that his father and paternal uncles suffered from similar symptoms that required medication. On examination, it is noted that there is frontal bossing. Further investigations find an elevated alkaline phosphatase and a serum calcium at the upper end of the normal range. His other investigations are normal. What is the best first line treatment for this man?
Calcium supplementation > Bisphosphonates Calcium and Vitamin D supplementation Calcitonin Surgery
This gentleman has findings consistent with Paget’s disease of the bone given his clinical symptoms, ethnic background, family history and biochemical results. The NICE guidelines recommend bisphosphonates as first line treatment in symptomatic patients. In asymptomatic patients, watchful waiting may be sufficient initially.
Supplementation is insufficient in this patient given that he is symptomatic. Calcitonin is used when there is hypocalcaemia and taking bisphosphonates may lower levels further. Surgery may be required if there are complications such as fractures or severe osteoarthritis but not at this stage.
Paget’s Disease of the Bone - Diagnosis: Example Question
A 56 year old male presents with progressive bilateral tinnitus of gradual onset over the past 3 months. He also reports worsening hearing during the same time period, intermittent headache and increasing lower limb oedema. He denies diplopia, vertiginous symptoms, dysphagia or dysarthria. He denies any urinary symptoms or weight loss. There is a past medical history of hypertension and insulin-dependent diabetes. The patient also reports a family history of prostate carcinoma, with both his father and uncle previously undergoing resections. On examination, cranial nerves are unremarkable except bilateral hearing loss. You note no limb weakness but significant spinal kyphosis. Heart sounds I and II are heard and no added sounds. Bibasal crackles are auscultated. His abdomen is soft and non-tender. His initial serum markers are as follow:
Platelets 264 * 109/l
WBC 9 * 109/l
Neuts 5.4 * 109/l
Na+ 142 mmol/l
K+ 4.3 mmol/l
Urea 7.8 mmol/l
Creatinine 90 µmol/l
Bilirubin 6 µmol/l
ALP 902 u/l
ALT 28 u/l
CRP 16 mg/l
Parathyroid hormone and vitamin D normal range. Which other biochemical marker will be abnormal?
Corrected calcium Gamma glutamyltransferase (GGT) Phosphate > C-telopeptide (CTx) Prostate specific antigen (PSA)
The patient describes a combination of hearing loss with tinnitus, signs of heart failure and associated skeletal deformities, associated with elevated alkaline phosphatase in the absence of other liver function test abnormalities. This is consistent with a diagnosis of Pagets disease, with skull complications (possible cochlear involvement or skull enlargement) resulting in hearing loss; high output heart failure and long bone deformities. Serum non-isomerised C telopeptide (CTx) is an extremely sensitive marker of increased bone turnover observed in Pagets disease and is useful in monitoring disease progression or treatment efficacy1. Diagnosis is often made on clinical features, radiological imaging and raised bone specific ALP, with exclusion of other causes of bone pathology. CTx has largely superseded old tests of urinary hydroxyproline classically used.
- Alexandersen P, Peris P, Guanabens N, et al; Non-isomerized C-telopeptide fragments are highly sensitive markers for monitoring disease activity and treatment efficacy in Paget’s disease of bone. J Bone Miner Res. 2005 Apr;20(4):588-95
Phenytoin and Osteomalacia - Example Question
A 52-year-old lady was seen in the general medicine clinic with aches and pains. The pains were present in her arms and legs, and not associated with her joints. They have been present for several months, and she was unable to identify any precipitating factors. She also felt that on occasion she felt generally weak and tired, though denied the presence of any specific weakness. Her past medical history comprised of epilepsy which was well controlled with phenytoin 500mg BD for several years, as well as hypertension and asthma. In addition to phenytoin 500mg BD she was prescribed ramipril 5mg OD, Clenil modulite 200mcg BD, salmeterol 100mcg BD and Elleste duo for the last six months. Upon specific questioning, she stated that she ate a nutritionally balanced diet, and that she had not suffered a previous fracture. Her mother was diagnosed with osteoporosis when she was 64-years-old, and she did not smoke. She drank 10 units of alcohol per week.
On examination, she was systemically well, with a blood pressure of 132/68 mmHg, heart rate 84, respiratory rate 16/min and body mass index of 23. Examination of her cardiovascular system revealed the presence of normal heart sounds and was unremarkable. Examination of the respiratory and gastrointestinal systems was likewise unremarkable except for the presence of gingival hypertrophy. Examination of the musculoskeletal system revealed the presence of Heberden’s nodes but was also otherwise unremarkable with a full range of movement in all joints. Examination of the neurological system was normal with a power of 5/5 in all muscle groups and normal sensation, tone and coordination. Cranial nerve and fundoscopy examinations were unremarkable. Examination of the thyroid gland was unremarkable.
Investigations revealed the following results:
Bilirubin 22 µmol/l ALP 262 u/l ALT 23 u/l Albumin 42 g/l Protein 76 g/l Globulin 34 g/l Adjusted calcium 2.06 mmol/l Phosphate 0.78 mmol/l Vitamin D level pending result Parathyroid hormone 88 (NR 11-54 pg/ml) IgG 11.2 g/L (NR 7.0 18.0) IgA 3.2 g/L(NR 0.8 4.0) IgM 2.1 g/L (NR 0.4 2.5)
Urinary Bence Jones Protein: negative
What is the most likely underlying diagnosis?
Fibromyalgia Paget's disease Primary hyperparathyroidism Osteoporosis > Osteomalacia
Phenytoin is known to affect the metabolism of vitamin D, and over prolonged periods of time may result in osteomalacia. This patient is also likely suffering other sequelae of prolonged phenytoin use as manifested by the presence of gingival hypertrophy. She has a raised parathyroid hormone level secondary to the low vitamin D level, and there is no evidence of osteoporosis.
Osteoporosis in a man
Check testosterone!
Whilst thyrotoxicosis is a known cause of osteoporosis, testosterone deficiency is much more likely in a middle aged man
Bone pain + Unilateral hearing loss + Isolated raised ALP =?
PAGET’S
NB Calcium and Phosphate Normal!
Avascular Necrosis
AVN = Defined as death of bone tissue 2dry to loss of blood supply
> bone destruction and loss of joint function
Features = initially asymptomatic > gradually INCREASING PAIN
Most commonly affects the epiphysis of long bones e.g. femur
Causes:
- Long term steroid use
- Chemo
- ETOH
- Trauma
Causes gradually increasing pain in joint affected e.g. hip
Ix =
- Plain x-ray may be normal initially
- MRI is the Ix of choice - more sensitive than radionucleotide bone scanning
Osteogenesis Imperfecta
More commonly known as BRITTLE BONE DISEASE
= a group of disorders of collagen metabolism > bone fragility and fractures
The most common and milder form of Osteogenesis Imperfecta = Type 1
- autosomal dominant
- abnormality in type 1 collagen due to decreased synthesis of pro-alpha 1 or pro-alpha 2 collagen polypeptides
Features:
- presents in childhood
- fractures following minor trauma
- blue sclera
- deafness 2dry to otosclerosis
- dental imperfections are common
Osteoporosis - Dexa Scan
Basics:
- 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
T-score: >-1.0 = normal -1.0 to -2.5 = Osteopenia < -1.5 = Risk of osteoporosis < -2.5 = Osteoporosis
Osteomalacia ALP , Ca2+ and Phosphate
ALP RAISED
Calcium + Phosphate LOW
Osteopetrosis
= Defective OSTEOCLAST function
Also known as Marble Bone Disease
- rare disorder of defective osteoclast function resulting in failure of Normal bone resorption
Results in dense, thick bones prone to fracture
Bone pain and neuropathies common
Calcium, phosphate and ALP are normal
Mx:
- Stem cell transplant and interferon-gamma have been used for treatment
Osteoporosis - Risk Factors
Important RFs: (DECREASED OESTROGEN)
- Hx of Glucocorticoid use
- RA
- ETOH
- Hx of parental hip fracture
- Low BMI
- Current smoker
Other RFs:
- Sedentary lifestyle
- Premature menopause
- Caucasians and Asians
- Endocrine disorders (Hyperthyroidism, Hypogonadism, DM, GH deficiency)
- Multiple Myeloma
- Lymphoma
- GI disorders (IBD, Coeliac, Gastrectomy, Liver disease)
- CKD (decreased calcium, decreased vit D)
- Osteogenesis imperfecta
- Homocystinuria
NB Obesity is NOT a RF for osteoporosis
Osteoporosis - Investigating Secondary Causes
If a patient is diagnosed with osteoporosis or has a fragility fracture, further Ix are warranted in order to:
- exclude diseases that mimic osteoporosis (e.g. osteomalacia, myeloma)
- identity causes and contributory factors
- assess risk of subsequent fractures
- select most appropriate form of treatment
Investigations recommended by NOGG: - Hx and Examn - FBC, Sedimentation rate, CRP, Ca2+, Albumin, U&Es, Phosphate, LFTs, TFTs, Bone profile - Bone densitometry (DEXA) Above = Minimum
Other procedures if indicated:
- lateral x-rays of lumber and thoracic spine/DEXA based vertebral imaging
- protein immunoelectrophoresis and Bence Jones
- PTH, serum testosterone, FSH, LH, Serum prolactin
- 24 hour urinary cortisol
- isotope bone scan
- markers of bony turnover
- urinary Ca2+ excretion
- endomysial and/or tissue transglutaminase antibodies (coeliac)
Osteomyelitis - Changes on plain XR
Osteomyelitis should be visible on plain x-ray after a prolonged period of time e.g. 2-3w
These may include soft tissue swelling, bone demineralisation, cortical irregularity, and an elevated periosteum.
Pagets and Serum C-telopeptide
Serum non-isomerised C telopeptide (CTx) is an extremely sensitive marker of increased bone turnover observed in Pagets disease and is useful in monitoring disease progression or treatment efficacy1. Diagnosis is often made on clinical features, radiological imaging and raised bone specific ALP, with exclusion of other causes of bone pathology. CTx has largely superseded old tests of urinary hydroxyproline classically used.
