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.
