Dr Jamie Fraser summarises the recent SIGN guideline on the management of osteoporosis and explains how lifestyle measures and treatments can help prevent secondary fractures

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Read this article to learn more about:

  • validated tools for assessing fracture risk
  • general lifestyle advice for people at risk of fracture
  • use pharmacological treatment in postmenopausal women.

Key points

GP commissioning messages

Osteoporosis is a common bone disease characterised by low bone mass, which is associated with an increased risk of low-trauma fractures such as hip, clinical vertebral, forearm, and shoulder fractures (termed 'major fractures').

While all fractures cause serious morbidity, people who experience hip and vertebral fractures have a reduced life expectancy compared with population controls. 1,2 The incidence of hip fracture in the UK is 89,000 per year and low-trauma hip fractures are forecast to increase as the general population lives longer. 3

Remit of the guideline

The SIGN guideline on Management of osteoporosis and the prevention of fragility fractures (SIGN 142), published in March 2015, provides recommendations based on current evidence.4 The guidance does not include risk from falls as a separate NICE Clinical Guideline, Falls: assessment and prevention of falls in older people, covers this specialty,5 but it is important to note that the assessment of falls is also a key component for preventing fractures.

Risk factors for fracture

SIGN 142 details multiple risk factors for fracture that should alert clinicians to consider further assessment of risk (see Table 1, below). Some of these risk factors are modifiable (e.g. smoking), others are associated with disease (e.g. epilepsy or diabetes) or drug therapies (e.g. steroids), while some are non-modifiable (e.g. parental history of osteoporosis).

Table 1: Risk factors associated with fragility fracture that should prompt consideration of fracture-risk assessment4
Risk categoryCausative factor
Non-modifiable risk factors previous fracture
parental history of osteoporosis
history of early menopause (below age of 45)
Modifiable risk factors low BMI (<20 kg/m2)
smoking
low bone mineral density
alcohol intake
Coexisting diseases diabetes
inflammatory rheumatic diseases (RA or SLE)
inflammatory bowel disease and malabsorption
institutionalised patients with epilepsy
primary hyperparathyroidism and endocrine diseases
chronic liver disease
neurological diseases (including Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke)
moderate to severe chronic kidney disease
asthma
Drug therapy long-term antidepressants
antiepileptics
aromatase inhibitors
long-term DMPA
GnRH agonists (in men with prostate cancer)
PPIs
oral glucocorticoids
TZDs
  • BMI=body mass index; RA=rheumatoid arthritis; SLE=systemic lupus erythematosus; DMPA=depot medroxyprogesterone acetate; GnRH=gonadotropin-releasing hormone; PPI=proton pump inhibitor; TZD= thiazolidinediones.
  • SIGN website. SIGN 142. Management of osteoporosis and the prevention of fragility fractures. SIGN, 2015. Available at: www.sign.ac.uk/guidelines/fulltext/142
  • Reproduced with permission.

A meta-analysis of 11 cohort studies ( n =60,161 men and women), included in the NICE guideline on Osteoporosis: assessing the risk of fragility fracture, found that previous fracture was associated with approximately a two-fold increased risk of further fracture.6

SIGN 142 recommends that patients over the age of 50 who have experienced a fragility fracture should be managed within a formal integrated system of care that incorporates a fracture liaison service (FLS). 7 Patients often do not recognise the need for assessment and no particular clinician has overall responsibility for ensuring assessment. Systems of care provide a way of ensuring patients at risk of fracture are identified, assessed, and ultimately offered treatment.

Assessing risk

SIGN 142 recommends that the presence of risk factors should prompt an individual assessment of risk using a validated tool such as QFracture®, or FRAX,® prior to dual energy X-ray absorptiometry (DXA).4,6,8,9 Both risk tools compute a 10-year absolute risk of fracture. See Box 1, below for more information.

Box 1: Sources of further information

National Osteoporosis Society

This is a UK-wide charity dedicated to ending the pain and suffering caused by osteoporosis:

FRAX®

The FRAX® tool has been developed by the World Health Organization to evaluate fracture risk of patients:

QFracture®

This calculator has been designed to work out your risk of developing any osteoporotic (i.e. hip, wrist, shoulder, or spine) fracture or hip fracture alone by answering some simple questions.

Calcium calculator

The International Osteoporosis Foundation (IOF) is a registered not-for-profit, non-governmental foundation based in Switzerland. Its simple calcium calculator enables you to find out whether you are getting enough of the important mineral in your daily diet.

The QFracture tool is particularly appealing to primary care practitioners as it was developed using UK GP populations, was validated in over 1.5 million patients, and the associated algorithm has been published and peer reviewed. 9

Lifestyle advice

SIGN 142 gives recommendations for general lifestyle advice for individuals at risk of fracture (see Box 2, below).

Box 2: General lifestyle advice for people at risk of fracture4

  • Smokers should be advised to stop smoking
  • People who consume more than 3.5 units of alcohol per day should be advised to reduce their alcohol intake to nationally recommended levels (<14 units per week in women; <21 units per week in men)
  • Adults with a low BMI (<20 kg/m2) are at increased risk of fracture and should be encouraged to achieve and maintain a BMI level of 20–25 kg/m2
  • Combinations of exercise types including balance training, flexibility or stretching exercises, endurance exercise, and progressive strengthening exercises should be considered to reduce risk of fractures caused by falls
  • Calcium and vitamin D supplements may be considered to reduce the risk of non-vertebral fractures in patients who are at risk of deficiency due to insufficient dietary intake or limited sunlight exposure:
    • adequate dietary calcium consumption is recommended to meet reference intake levels of 700 mg/day in adults
    • in individuals who have inadequate sunlight exposure, supplementation with 10 micrograms/day of vitamin D (400 IU) should be considered to avoid deficiency
  • A balanced diet is recommended for bone health but there is no evidence that specific diets reduce fracture risk.

Targeting treatment

The algorithm shown in Figure 1 (below), details a pathway from risk factors to pharmacological treatment selection in postmenopausal women. When the 10-year risk of major fracture is 10% or more, or after low-trauma fracture, the recommendation is to refer patients for DXA.

Figure 1: Pathway from risk factors to pharmacological treatment selection in postmenopausal women
Pathway from risk factors to pharmacological treatment selection in post-menopausal treatment

Anti-osteoporosis therapies are effective in treating postmenopausal women with a bone mineral density (BMD) T-score of −2.5 or less (which is also the World Health Organization's definition of osteoporosis). 10–12 There is no evidence from randomised control trials of evidence to prove that such therapies given to patients purely on the basis of high risk defined by FRAX or QFracture (i.e. regardless of BMD) confer any benefit.

The presence of vertebral fractures suggests fracture risk independently of BMD, and treatments have been shown to be effective without necessarily requiring DXA, although it can be helpful as a baseline.10–14 Likewise, following hip fracture, zoledronic acid was shown to be effective in men and women to reduce the risk of non-vertebral and vertebral fractures after 3 years versus placebo. 15

Management of postmenopausal women with osteoporosis

There is good evidence for alendronate or risedronate (oral bisphosphonates) as first-line therapies among postmenopausal women.10–12 These agents are beneficial in preventing hip, non-vertebral, and vertebral fractures versus placebo, whereas ibandronate was shown only to prevent vertebral, and nonvertebral fractures. 11

Strontium ranelate has been shown to prevent vertebral and non-vertebral fractures compared with placebo,11 but has been associated with cardiovascular harms, therefore its use is now contraindicated in patients with a history of venous thromboembolism,16 cardiovascular or cerebrovascular disease, peripheral vascular disease, or uncontrolled hypertension.17

Zoledronic acid and denosumab are both parenteral therapies, which have been shown to reduce hip, non-vertebral, and vertebral fracture risk in postmenopausal women compared with placebo.18,19

In primary care, it is feasible to use denosumab as a second-line therapy when first-line agents are either unsuitable or not tolerated. It is important that patients are replete in vitamin D at baseline, and to monitor serum calcium, to attenuate the risk of hypocalcaemia.20

All anti-osteoporosis therapies require adequate calcium and vitamin D, which tends to be given in the form of supplementation. Alternatively, calcium intake can be from dietary sources, with intake assessed using a calcium calculator (see Box 1, above) in which case only vitamin D supplementation may be required.

Long-term harm associated with bisphosphonates and denosumab

Osteonecrosis of the jaw (ONJ) is a rare event associated with bisphosphonates21 and denosumab. It is defined as exposed bone in the oral cavity persisting for more than 8 weeks and not due to radiotherapy among patients exposed to bisphosphonates.22 As this is often associated with a trigger event such as tooth extraction, a pre-treatment dental check is suggested.

Atypical femoral fractures have been reported rarely with bisphosphonate therapy and with denosumab. The risk of atypical fracture increases with longer duration of exposure to bisphosphonates. 23,24 The overall benefits of treatment with bisphosphonates and denosumab for preventing hip fracture, however, exceed the risk for causing atypical fracture.

Optimal duration of treatment

All anti-osteoporosis therapies modify bone remodeling and have a long duration of effect that at times can persist for months or years after cessation, and this may lead to detrimental effects. There is no definitive study designed to quantify long-term benefits versus harms to clearly define optimal duration.4

The efficacy of alendronate has been evaluated in a trial among postmenopausal women. When given for 10 years, alendronate reduced the clinical vertebral fracture rate compared with women who switched to placebo after 5 years of alendronate exposure (HR: 0.45; 95% CI: 0.24–0.85).25 SIGN 142 recommends that alendronate may be continued for up to 10 years in women with osteoporosis, especially those who are at high risk of vertebral fracture.4

The optimal duration of bisphosphonate treatment is likely to be determined individually by weighing up the benefits against the harms after 5 years.

Monitoring therapy

Various methods including repeat BMD measurements have the potential to aid clinicians in monitoring the effectiveness of anti-osteoporosis drug therapies. Changes in BMD in response to treatment have been shown to correlate with efficacy in reducing fractures after 3 years to a variable extent with: alendronic acid,26 ibandronic acid,27 zoledronic acid,28 and denosumab.29 Repeat BMD measurements after 3 years of exposure to these therapies may be considered to monitor response according to the SIGN 142 recommendation.

Adherence and compliance

Patients may feel no tangible symptomatic benefit from preventative therapy, so educational interventions may help reinforce the benefits for preventing fractures and aid compliance. 30–32 SIGN 142 recommends interventions by healthcare professionals aimed at improving adherence in patients who are being given drug treatments for osteoporosis.

Osteoporosis in men

In postmenopausal women, there is a robust evidence base to demonstrate the efficacy of treatments, however, comparable studies have not yet been performed in men. Studies have shown that similar BMD responses occur in men as in women, in response to oral bisphosphonates. 11,33 The assumption is that fracture risk will be similarly reduced in men although this has not been demonstrated with alendronate or risedronate in methodologically robust studies.

Zoledronic acid15,34 and denosumab (in a prostate cancer population that is androgen deprived)35 have demonstrated fracture-risk reduction in men versus placebo.

Glucocorticoid-induced osteoporosis

Glucocorticoids increase fracture risk after 3 months of long-term use and this risk is dose dependent. Fracturerisk assessment and prevention of fractures is therefore recommended, but there is limited evidence to form recommendations. 36–39

SIGN 142 recommends that alendronate, risedronate, and zoledronic acid (second line) are all suitable options to prevent vertebral fractures associated with prednisolone 7.5 mg daily or greater (or equivalent alternative glucocorticoid). In clinical practice, the Royal College of Physicians glucocorticoid guidelines still tend to be followed.40

Challenges in primary care

Osteoporosis services vary around the UK,7 leaving some GPs poorly supported. Forty-two percent of health economies in the UK do not offer any form of FLS.7,41,42 The DXA scan report received by GPs regarding their patient may also depart from the recommended standard. 43,44

Some services have specialist osteoporosis nurses who offer patients initial management advice after DXA, while others do not. The pathway to treatment (see Figure 1, above) outlined by SIGN 142 may especially help GPs who lack service support.

The QFracture algorithm is integrated into primary care electronic records, allowing quick and easy assessment of fracture risk during a consultation. Most of the risk factors used in the algorithm will already be captured in the electronic patient records, but some may not (e.g. family history of osteoporosis, hip fracture, history of falls).

Many patients do not tolerate treatment with oral bisphosphonates, and of those, fewer than 70% may persist with this at 1 year.45 A medication review after the first 3–4 months of treatment can identify patients who have stopped taking treatments and allow intervention, for example, by offering an alternative agent to people intolerant of therapy.

Prior vertebral fracture was shown to be the strongest predictor of incident vertebral and hip fractures in a large study involving 60,393 women over age 55 years.46 There are opportunities for GPs to be alert to the presence of vertebral fracture and treatment can be started prior to referral for DXA.

Conclusion

SIGN 142 provides a systematic review of current evidence, offering clinicians recommendations in the management of osteoporosis. By clearly defining risk factors for fragility fracture and proposing the use of tools that can be easily implemented in routine clinical practice to assess this risk, the guideline will help to ensure that patients are identified and appropriately referred for DXA. By using the cohesive pathway (see Figure 1, above) in routine clinical practice, practitioners can offer evidence-based therapeutic interventions, with the ultimate aim of reducing the burden of clinical fragility fractures.

Key points

  • Patients aged over 50 years with a history of fragility fracture should be offered DXA scanning to evaluate the need for anti-osteoporosis treatment
  • Fracture-risk assessment should be carried out, preferably using QFracture, prior to DXA scanning in patients with clinical risk factors for osteoporosis, in whom anti-osteoporosis treatment is being considered
  • Advice on general lifestyle measures is recommended for those who are at risk of fracture (see Box 2, above)
  • Treatment of postmenopausal women is indicated in the presence of DXA by BMD −2.5 or less, or vertebral or hip fractures
  • Patients treated with anti-osteoporosis therapy require adequate calcium and vitamin D. If this cannot be achieved through diet and lifestyle alone, supplementation may be required
  • Alendronate or risedronate remain first-line treatment options for postmenopausal women:
    • if these agents are not tolerated or are unsuitable, denosumab or zoledronic acid are second-line options
  • Interventions by healthcare professionals aimed at improving adherence are recommended in patients who are being given drug treatments for osteoporosis
  • Bisphosphonates should be assessed after 5 years to consider the benefits versus risks
  • Repeat BMD measurements by DXA at 3-year intervals may be considered to assess response to treatment in postmenopausal women on alendronate, ibandronate, zoledronate, or denosumab therapy
  • Patients aged over 50 years who have experienced a fragility fracture should be managed within a formal integrated system of care that incorporates a fracture liaison service.

DXA=dual-energy X-ray absorptiometry; BMD=bone mineral density

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GP commissioning messages

written by Dr David Jenner, NHS Alliance GMS contract/PBC Lead

  • Osteoporosis carries the potential for major morbidity and premature mortality from subsequent fragility fractures, making it an important issue for commissioners
  • The evidence for secondary prevention of fractures following a first fragility fracture suggests that a focus on assessment of all those individuals with previous fragility fracture is likely to be cost efficient
  • Secondary prevention is currently incentivised through the QOF (indicators OST002, OST004, and OST005)—audits of practice achievement against these indicators can give a measure of performance
  • It is likely that many fragility fractures are not accurately coded. An FLS that follows patients from hospital to primary care and ensures they have the correct assessment (DXA) and treatment has the potential to boost numbers on the register who are receiving bone protection therapy:
    • these services can usually be effectively run by community employed nurses linking closely with secondary care
  • Local formularies should identify cost-effective agents and detail responsibility for who prescribes more specialised drugs like denosumab.

QOF=Quality and Outcomes Framework; FLS=fracture liaison service; DXA=dual-energy X-ray absorptiometry

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References

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