Introduction

• Osteoporosis means literally porous bone
• Refers to decreased bone density, which leads to an increase in fracture risk
• Risk factors
  • Bone density declines with age
  • Highest risk is in post-menopausal women
  • Use of corticosteroids
• In women over 65, fracture risk (of any bone) is 3-5x that of men
  • Hip fracture risk is 2x that of men
  • 30% of women aged 90 will have suffered a hip fracture
• Incidence has declined due to effective treatments, but since the acknowledged association between HRT and breast cancer, rates have crept up again
• May not present until it is complicated by fracture
  • Vertebral crush fractures / loss of height
  • Hip fracture (femoral neck)
  • Colles fracture
• Can be prevented with lifestyle factors:
  • Regular exercise
  • Sufficient dietary calcium
  • Sufficient vitamin D
• Usually a primary disorder – due to increased osteoclast activity
• Rarely can be secondary – e.g. endocrine disease, malabsorption, malignancy
• The primary aim of treatment is to reduce the risk of fracture – not just to increase bone density

Epidemiology and Aetiology

• Very common in elderly populations
  • Approx 50% of women over 80
  • Approx 20% of men over 80
  • Lifetime risk of osteoporotic fracture – 60% for women and 30% for men
• All low trauma fractures are associated with increased mortality
• Massively under-treated
  • <30% of women with post-menopausal fractures receive pharmacological treatment
  • <10% of men with osteoporosis receive pharmacological treatment

Risk Factors

• Age
• Female gender
• Post-menopausal
• Frequent falls
• Glucocorticoids
  • 30-50% of patients on long-term glucocorticoids will have a fracture
• Low body weight
• Diabetes
• Vit D deficiency
• Low physical activity
• Hypothyroidism
• CKD
• Chronic liver disease
• Organ transplant
• Coeliac disease or other cause of malabsorption
• Myeloma
• HIV
• Depression
• Drugs
  • SSRI
  • Anti-psychotics
  • PPI
  • Anti-epileptics
  • Glucocorticoids (as above)

Diagnosis

Diagnosis is confirmed by either:

• Low bone density on densiometry (T score <-2.5) OR
• A fragility fracture – a low impact fracture from standing height that would otherwise not be expected to cause a fracture – e.g. hip fracture, or spine fracture

Investigations

Only bone densiometry is diagnostic. Other investigations such as x-ray can help to support a diagnosis and address risk factors.

X-ray

• Osteoporosis only be detected on x-ray once >40% of bone has been lost
• Osteoporosis can be suspected incidentally on x-rays performed for another reason
• Not often useful, except to detect wedge fractures of the spine. Do spinal series x-rays if:
  • Loss of height >3cm
  • Kyphosis
  • Unexplained back pain
  • If this confirms a wedge fracture – then move on to DEXA scan to confirm diagnosis

Bloods

• Vitamin D
  • Often low
• Calcium, phosphate, Alkaline phosphatase and parathyroid hormone
  • Often normal
• TFTs

DEXA scan (bone densitometry)

• DEXA – Dual-energy X-ray absorptiomety
• Measures bone density in multiple locations – usually the spine and femoral neck
• Femoral neck density is the most useful diagnostic measurement – this is the gold standard test
• T score
  • This is the number of standard deviations from the mean bone density of a 30 year old adult
  • E.g. -2.5 represents 2.5 SD below the young adult mean
  • Treat if T score <-2.5
  • >1.0 – NORMAL
  • -1 to -2.5 – OSTEOPENIA
  • <-2.5 – OSTEOPOROSIS
  • <-2.5 + # – SEVERE OSTEOPOROSIS
• Z score
  • This is the number of SD from the mean bone density of and age and gender matched control
  • Frequently reported on DEXA scan results, but often not useful clinically
  • Useful when suspecting osteoporosis in younger patients
  • Score of <-2 should prompt urgent further investigation

When to perform a bone density scan

• Any patient age >70
• Age >50 in women (or age >60 in men) and any of
  • On glucocorticoids
  • Postmenopausal
  • Fracture after age 40 with minimal trauma
  • FHx osteoporosis
  • Smoker
  • BMI <18
  • Consider in other patients with minor risk factors (see risk factors in Epidemiology and Aetiology above)
  • After diagnosis – repeat every 2 years
• OR age >45 with low trauma fracture
• Post menopausal women or men over 50 with a vertebral fracture (e.g. “wedge fracture”)

Consider using a fracture risk assessment tool – such as FRAX to assess risk in all patients over 50, and postmenopausal women over 45, even if you don’t think they require a DEXA scan

• DEXA scan can be performed about every 2 years after diagnosis of osteoporosis – or every 12 months if there are major changes to treatment
  • In patients on long term glucocorticoids – consider DEXA annually
• In osteopenia or pre-osteopenia, there is no defined time at which to repeat the scan. You should try to estimate when the patient will need another scan based off their original T score. The average loss of bone density, without treatment, is equivalent to a decline in T score of about 0.1 per year in the absence of any other underlying bone disease. For example:
  • A 70 year old lady, with no risk factors for accelerated bone loss, has a T score of -1.5. You could consider repeating in 5 years, knowing then that on average, her T score would be -2.0 at that point

Treatment

The main aim of treatment is to reduce the risk of fracture by preventing further bone loss.

When to treat

Initiate treatment in any of the following scenarios

• Minimal trauma hip or vertebral fracture
• Minimal trauma fracture at any other site AND T-score of <-1.5
• Risk assessed and DEXA scan performed based on risk-assessment:
  • T score <-2.5
  • T score <-1.5 AND hip fracture risk score >3% OR any fracture risk score >20%, based on risk fracture assessment tools such as FRAX

No agents have been shown to effectively increase bone density. Treatment duration is not well defined. Consider continuing treatment for all patients whose T score remains less than -2.5, OR if they have any recent fractures. Consider cessation of treatment if bone density is greater than -2.5 and there are no recent fractures. Recent US guidelines suggested there was no benefit to treatment after 3-5 years, and treatment could be safely stopped after this period. There is no specific recommendation in UK or Australian guidelines for when to stop treatment.

Hormone Replacement Therapy

• The most effective osteoporosis treatment – but also carries largest side effect burden
• Weigh up risks vs benefits
• Long-term use is not usually recommended

Bisphosphonates

• Decrease bone absorption
• Proven to reduce fracture rates
• Can be used in combination with other agents
• Traditionally the mainstay of treatment but are being challenged by denosumab (Prolia®)
• Side effects
  • Risk of osteonecrosis of the jaw – sometimes called MRONJ – Medication related osteonecoris of the jaw
    • Thankfully, very rare – less than 10 cases per 10 000
    • Can be very debilitating
    • Risk is reduced with good oral hygiene and increased when dental surgery occurs whilst on treatment – try to treat any dental disease before starting treatment
    • There is not enough evidence to suggest cessation of treatment for minor dental procedures
  • Oesophagitis
• Contraindications
  • Hypocalcaemia
  • Uveitis
  • Disorders which delay oesophageal emptying (oral agents)
• Agents
  • Alendronate
    • 10mg daily OR
    • 70mg weekly
  • Risedronate
    • 5mg daily OR
    • 35mg weekly OR
    • 150mg monthly
    • +/- vitamin D and calcium
  • Zoledrone acid
    • Annual IV injection
• IV agents are easy to administer. Oral agents can be difficult, because they require:
  • To be taken first thing in the morning
  • To be taken on an empty stomach
  • Not to eat for 30 minutes afterwards
  • To remain sitting upright or standing for 2 hours after taking (to prevent oesophageal irritation from reflux)

Denosumab

• Monoclonal antibody
  • Binds to “RANKL” – a signaller released by osteoblasts and taken up by osteoclasts. By binding to it – osteoclast activity is reduced.
• 60mg SC every 6 months
• ONLY give when calcium and vitamin D levels are adequate
• Also carries risk of osteonecoris of the jaw
• Treatment usually recommended for 3 years – but many patients remain on it indefinitely
  • The guidelines are unclear as to the pros and cons of continuing after 3 years – however – beware of the rebound effect
  • Rebound effect – it has been shown that after denosumab is stopped (or a dose is missed) – there is a a very large increase in osteoclast activity which reduces bone density below pre-treatment levels. One study(1) showed that the medium number of vertebral fractures at 7-11 months post cessation of denosumab was 5 (!).

It is very important to remind patients of this rebound effect. In my own clinical practice I tend to keep patients on denosumab indefinitely and advise them to be careful about not missing or being late for a dose – and I use clinical software to send SMS reminders to the patient to attend for the next dose when it is due – Dr Tom Leach.

Strontium

• Dissociates bone reabsorption and bone formation
• 2g (powder) daily – usually taken before bed and at least 2 hours after eating
• Can cause vascular complications – use with caution in vascular disease and renal impairment
• Also associated with VTE, serious skin reactions, including Stephens-Johnson Syndrome
• Strontium binds to bone, and absorbs x-rays – and so may artificially increase bone mineral density scores

Teriparatide

• A synthetic parathyroid hormone
• Increases bonce formation
• 20mg SC once daily

Prevention

• Calcium intake 1200 – 1300mg daily
  • Low fat dairy products recommended
  • 500mls of milk contains 1000mg
  • Fish – particularly tinned fish
  • Citrus fruit
  • Sesame and sunflower seeds
  • Supplementation is recommended in all post-menopausal women
    • Calcium citrate is better absorbed than carbonate
    • Doses are equivalent to 500mg elemental calcium
    • 38g of calcium citrate OR
    • 5g calcium carbonate (with food)
• Vitamin D
  • Maintain serum levels >75nmol/L
  • Recommended sunlight exposure (regional guidelines vary)
  • Supplementation – cholecalciferol
    • 1000 – 2000 IU daily (25 – 50 mcg)
• Exercise
  • Low intensity, ‘leisurely’ exercise such as walking, swimming or cycling do NOT improve bone density
  • Prescribed, regular, varied and high-intensity exercise, including balance training is strongly recommended
    • In postmenopausal women with osteoporosis there is good evidence that exercise increases bone density
  • Walking / jogging or similar sports may prevent bone loss, but are unlikely to increase bone density
• Smoking cessation
• Limit alcohol to safe drinking limits
  • <2 standard drinks per day, x2 alcohol free days per week
• Weight – keep BMI >18 Kg/m2
• In elderly patients at risk of falls
  • Falls prevention
  • Hip protectors – unsurprisingly compliance is poor!

Flashcard

References

• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Osteoporosis – RACGP Red Book
• Osteoporosis risk assessment, diagnosis and management – RACGP
• Osteoporosis – afp

1. How to manage the rebound effect at denosumab discontinuation and avoid multiple vertebral fractures? – Rev Med Suisse. 2019 Apr 17;15(647):831-835.

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