39. Bone Disease TBL

Question 1

Which term denotes that 4 or less joints are affected when a patient complains of joint pain?

Answer 1

Oligoarthritis

Monoarthritis means one joint is involved, rheumatoid arthritis and osteoarthritis are diseases and polyarthritis means 5 or more joints are involved.

Question 2

Which joint or area is commonly affected by rheumatoid arthritis?

Distal interphalangeal (DIP) joints

Lumbar spine

Proximal interphalangeal (PIP) joints

Sacro-iliac joints

Temporomandibular joints (TMJ)

Answer 2

DIP joints are involved in OA mainly, TMJ and lumber spine are not commonly involved in rheumatoid arthritis. PIP joints are commonly involved in rheumatoid arthritis.

Question 3

Which muscle specific enzyme is elevated in myositis?

Amylase

Creatine kinase

Lipase

Maltase

Protease

Answer 3

Amylase, lipase and maltase are found in saliva, while protease and maltase are pancreatic enzymes.

Creatine kinase is the enzyme classically elevated in myositis.

Question 4

Elevated urate >300µmol/L and polyarticular arthritis are associated with which condition?

Gout

Osteoporosis

Paget’s disease

Rheumatoid arthritis

Vitamin D deficiency

Answer 4

Gout is caused when urate crystals form due the elevated serum levels and form in articular joints resulting in inflammation and arthritis. The serum levels of >300 µmol/L are often reported when evaluating serum results. Osteoporosis is the breakdown of bone and not articular cartilage. Paget’s disease is excessive bone production and is usually observed with elevated ALP. Vitamin D deficiency results in osteomalacia and rickets in children and is reported by decreased vitamin D levels in the serum.

Question 5

Elevated ALP, bone pain, bone enlargement and presence of deformity, degenerative joint disease, fractures and auditory complications can be associated with which condition?

Gout

Osteoporosis

Paget’s disease

Rheumatoid arthritis

Vitamin D deficiency

Answer 5

Paget’s disease is excessive bone production and is usually observed with elevated ALP levels. Vitamin D deficiency results in osteomalacia and rickets in children and is reported by decreased Vitamin D levels in the serum. Osteoporosis describes the breakdown of bone. In gout, serum levels of >300 µmol/L are often reported. Rheumatoid arthritis is associated wit the presence of anti-CCP, presence of rheumatoid factor and elevated CRP.

Question 6

Which of the following tests is best utilised to identify bone formation?

Anti-CCP

Creatine kinase

C-telopeptide of collagen cross-link (CTX)

N-telopeptide of collagen cross-link (NTX)

Procollagen 1 amino-terminal extension peptide (P1NP)

Answer 6

PINP is a marker of bone formation. CTX and NTX are indicators of collagen breakdown. Creatine kinase is utilised to measure muscle damage and anti-CCP is a marker specific to rheumatoid arthritis.

Question 7

When is peak bone mass achieved during our lifespan?

12-15 years

15-20 years

25-30 years

35-40 years

45-50 years

Answer 7

Peak bone mass is achieved in the late 20s. Bone accrual is maximal during puberty and adolescence. By aged 18 years, approximately 90% of bone mass has been achieved. Nutritional status and exercise levels are therefore important in the first two decades of life in determining peak bone mass. ‘Osteoporosis is a paediatric disease with geriatric consequences’.

Question 8

Rheumatoid arthritis increases the risk of osteoporotic fracture. How is this mediated?

By causing impaired absorption of dietary calcium and protein

By causing impaired hepatic and renal activation of Vitamin D3

By causing reduced BMI resulting in hypogonadotrophic hypogonadism

By increasing RANK Ligand expression resulting in increased bone resorption

By increasing serum parathyroid hormone levels and increasing bone resorption

Answer 8

In rheumatoid arthritis, pro-inflammatory cytokines (IL-1, IL-6, TNFa) increase osteoblastic expression of RANK Ligand. This binds osteoclastic RANK, increasing osteoclastic differentiation, and increased bone resorption.
Patients with rheumatoid disease are also more likely to be receiving corticosteroids, to do less exercise and to fall, thus further increasing their risk of osteoporosis, falls and fractures.

Question 9

How do anabolic osteotherapies exert their effects?

By increasing 1,25 dihydroxylation of Vitamin D3

By inhibiting osteocytes to reduce bone resorption

By suppressing IL-1 and TNFa expression, to promote osteoblast proliferation

By stimulating osteoblasts to promote new bone formation

By stimulation osteocytic mechanotransduction to promote bone strength

Answer 9

The anabolic osteotherapies promote new bone formation, whilst the anti-resorptive osteotherapies inhibit bone resorption. New bone formation is mediated by increased osteoblast differentiation, to secrete osteoid bone matrix in lamellar bone. Osteoclasts are responsible for mediating bone resorption in bone remodelling units.

Question 10

What factors can contribute to increased risk of falls and fractures? Explain why

Answer 10

• Age – independent risk factor for fragility fracture
• Inadequate vitamin D levels:
  o Darker skin of South Asian ethnicity makes dermal synthesis of vitamin D less efficacious
  o Reduced sunlight in northern hemisphere and reduced time spent outdoors due to loss of confidence and reduced exercise tolerance.
  o Vegetarian diet so will not eat oily fish or liver etc thus reliant on dermal synthesis alone.
  o Chronic kidney disease reducing 1a hydroxylation of 2,5 hydroxy vitamin D, therefore impaired Vitamin D activation.
• Sedentary lifestyle – reduced core muscle strength, reduced balance, making falling more likely
• BMI – 17.1. BMI <19 is a risk factor for:
  o osteoporosis (reduced peripheral aromatisation of estrogen, reduced skeletal load bearing, nutritional impairment (calcium, protein, micronutrients)
  o fracturing following a fall (reduced mechanical protection)
• Visual acuity – known cataracts, likely to have been exacerbated by corticosteroid exposure.
• Disease comorbidity:
  o Diabetes
   Peripheral neuropathy – how well controlled is the diabetes. Does she have good sensation in her feet, presence of ulcers etc.
   Diabetic retinopathy – again impacting upon visual acuity
  o Polymyalgia Rheumatica:
   Inflammatory disease
   Requiring Corticosteroid therapy – directly impacting upon bone quality and bone density. Also associated with steroid myopathy, reduced proximal muscle strength will further increase falling risk. Also, will have exacerbated cataract formation and destabilised glycaemic control in a diabetic patient.

 Musculoskeletal compromise due to shoulder/ hip girdle pain and stiffness, increasing risk of falls.
* Polypharmacy (especially in older patients) – associated with an increased fall risk. Drugs which may be exacerbating fall risk in Mrs Patel include:
o Anti-hypertensives (Ramipril, amlodipine) – postural hypotension
o Oral hypoglycaemic (Gliclazide) - hypoglycaemia
o Analgesics (co-codamol) – drowsiness, confusion
o Tricyclic antidepressant (amitriptyline) – drowsiness, confusion

Question 11

How can you minimise falls risks?

Answer 11

A Community Occupational Therapy home visit to consider how modifications within the home can reduce falls risk (e.g. hand rails, elevated toilet seat, removal of trip hazards, ramp provision).
Physiotherapy assessment and advice: strengthening/ balance/ postural exercises and assessment for a walking aid.
Assessment of vision/ hearing.
Measurement of postural BP
Medication review
Diabetic and PMR review
Footwear review
Correction of vitamin D3 deficiency
Advise on reducing alcohol consumption

Question 12

How can you minimise falls risks?

Answer 12

A Community Occupational Therapy home visit to consider how modifications within the home can reduce falls risk (e.g. hand rails, elevated toilet seat, removal of trip hazards, ramp provision).
Physiotherapy assessment and advice: strengthening/ balance/ postural exercises and assessment for a walking aid.
Assessment of vision/ hearing.
Measurement of postural BP
Medication review
Diabetic and PMR review
Footwear review
Correction of vitamin D3 deficiency
Advise on reducing alcohol consumption

Question 13

How do you define a fragility fracture?

Answer 13

A fracture that results from a fall from standing height or lower.
Often this is a bony injury which is disproportionate to the causative force or mechanism of injury.

Question 14

What symptoms of osteoporosis can you get?

Answer 14

osteoporosis is asymptomatic until first fracture.
* If previously undiagnosed vertebral fracture (present in >50% of patients who attend with a hip fracture) then she might have experienced:
o thoracic/ lumbar back pain (not necessarily post trauma)
o postural change
o height loss

Question 15

How can osteoporosis be diagnosed?

Answer 15

By measuring her bone density using a DEXA scan (Dual Energy Xray Absorptiometry). This will measure her BMD (bone mineral density) at the lumbar spine and left hip.

Question 16

7) Mrs Patel and her daughter feel particularly concerned about alendronic acid as the doctors told them a lot of information about it. What specific advice should you give regarding this medication:

a) Don’t stop the treatment suddenly as it will put her at greater risk of multiple vertebral fractures.
b) Increased risk of venous thromboembolism so report any leg pain or swelling as well as chest pain or breathlessness.
c) It is important to maintain good oral hygiene, visit the dentist regularly and report any oral symptoms.
d) That the medication needs to be given as an injection once every 6 months and that the nurse will do this.
e) The dose of alendronic acid may need to be halved depending on the results of her next kidney function.

Answer 16

c) It is important to maintain good oral hygiene, visit the dentist regularly and report any oral symptoms.

a) Cessation of denosumab is associated with increased vertebral fracture risk.
b) Increased venous thromboembolism (VTE) risk is seen with HRT/ SERM (e.g. raloxifene) usage but not bisphosphonates.
c) This is to prevent osteonecrosis of the jaw. It is seen more commonly in patients taking parenteral antiresorptive osteotherapies (e.g. Zoledronic acid/ Denosumab) but can still occur with oral preparations.
d) Denosumab is administered every 6 months as S/C injection
e) Alendronic acid should only be used if eGFR >35. If below this, you wouldn’t adjust the dose but seek alternative therapy.

Question 17

7) Mrs Patel and her daughter feel particularly concerned about alendronic acid as the doctors told them a lot of information about it. What specific advice should you give regarding this medication:

a) Don’t stop the treatment suddenly as it will put her at greater risk of multiple vertebral fractures.
b) Increased risk of venous thromboembolism so report any leg pain or swelling as well as chest pain or breathlessness.
c) It is important to maintain good oral hygiene, visit the dentist regularly and report any oral symptoms.
d) That the medication needs to be given as an injection once every 6 months and that the nurse will do this.
e) The dose of alendronic acid may need to be halved depending on the results of her next kidney function.

Answer 17

c) It is important to maintain good oral hygiene, visit the dentist regularly and report any oral symptoms.

a) Cessation of denosumab is associated with increased vertebral fracture risk.
b) Increased venous thromboembolism (VTE) risk is seen with HRT/ SERM (e.g. raloxifene) usage but not bisphosphonates.
c) This is to prevent osteonecrosis of the jaw. It is seen more commonly in patients taking parenteral antiresorptive osteotherapies (e.g. Zoledronic acid/ Denosumab) but can still occur with oral preparations.
d) Denosumab is administered every 6 months as S/C injection
e) Alendronic acid should only be used if eGFR >35. If below this, you wouldn’t adjust the dose but seek alternative therapy.

Question 18

8) Mrs Patel informs you that her neighbour, incidentally another patient of yours, is currently on a “drug holiday” which sounds wonderful to her and wonders whether she can have one as well. How would you manage this situation?

Answer 18

Would need to define what a drug holiday is – a period of time in which specific medicine(s) are stopped. The time period can vary from days to months or even years. It is an agreed decision between the patient and healthcare provider and done in the patient’s best interest. This time period requires close supervision.
Generic reasons why drug holidays might be considered; reduce tolerance and increase effectiveness. If there is little quality evidence on long-term efficacy of the drug. To reduce unpleasant side-effects. As part of a weaning process with a view to stopping the drug completely.

In the case of bisphosphonates (alendronic acid) a holiday may be considered after around 5 years to prevent prolonged bone turnover suppression and reduce the risk of atypical femoral fractures and osteonecrosis of the jaw.

In this case, there is ongoing high risk of further fracture, so it is likely she would benefit from continued treatment.

Question 19

8) Mrs Patel informs you that her neighbour, incidentally another patient of yours, is currently on a “drug holiday” which sounds wonderful to her and wonders whether she can have one as well. How would you manage this situation?

Answer 19

Would need to define what a drug holiday is – a period of time in which specific medicine(s) are stopped. The time period can vary from days to months or even years. It is an agreed decision between the patient and healthcare provider and done in the patient’s best interest. This time period requires close supervision.
Generic reasons why drug holidays might be considered; reduce tolerance and increase effectiveness. If there is little quality evidence on long-term efficacy of the drug. To reduce unpleasant side-effects. As part of a weaning process with a view to stopping the drug completely.

In the case of bisphosphonates (alendronic acid) a holiday may be considered after around 5 years to prevent prolonged bone turnover suppression and reduce the risk of atypical femoral fractures and osteonecrosis of the jaw.

In this case, there is ongoing high risk of further fracture, so it is likely she would benefit from continued treatment.

Question 20

9) How should you recommend that Mrs Patel takes her weekly alendronic acid and why?

Answer 20

This advice is important because of concerns with oral bisphosphonate dosing:
Significant risk of oesophagitis/ gastritis AND poor absorption.

Therefore, advise her to:
* Take the medication on an empty stomach, once a week, with a full glass of water, but no other food/fluids.
* Stay upright/ standing/ sitting up/ walking around etc for at least 30-45 minutes subsequently.
* Do not eat or drink anything until after 30-45 minutes of taking the medication.

Question 21

A few weeks later her daughter phones the surgery requesting an appointment with you to discuss her risk of osteoporosis. She is concerned about her risk of breaking a bone and would like to talk about her options. What is the next appropriate step?

a) Advise strength, balance and postural exercises
b) Prescribe calcium and vitamin D supplementation
c) Prescribe a suitable bisphosphonate
d) Request a DEXA scan
e) Use a fracture risk assessment tool

Answer 21

e) Use a fracture risk assessment tool

a) Whilst useful advice it doesn’t address her concerns.
b) You don’t know what her calcium intake is so would be inappropriate to prescribe supplementation.
c) In certain cases where it’s not practical to perform a DEXA scan and the clinician is sure about the diagnosis then a bisphosphonate can be prescribed without a risk assessment or DEXA scan, but that is not the case here.
d) DEXA scan may be indicated following the risk assessment but should not precede the risk assessment.
e) Below the age of 65 a formal fracture risk assessment is advised if patients have risk factors for falls or osteoporosis. Supriya has a positive family history of a maternal hip fracture. This would be an appropriate first step and should be followed by discussion around non-pharmacological optimisation of bone health in the first instance. It would also be appropriate to discuss preventative pharmacological interventions such as vitamin D3 and HRT.