Key Learning Points: Management of Patients at Risk of Fragility Fractures

Dr David Stephens Presents 10 Key Learning Points from the National Osteoporosis Guideline Group’s Updated Guidance on the Prevention and Treatment of Osteoporosis

The National Osteoporosis Guideline Group (NOGG) Clinical guideline for the prevention and treatment of osteoporosis was reviewed in September 2021 and the update was published in April 2022,¹ in conjunction with the launch of the group’s new website: nogg.org.uk. This update to the NOGG guideline arose in part because of changes to the risk-stratification tool, FRAX®,² to introduce the concept of ‘very high risk’ of a fragility fracture.^1,3 Other key updates concern vertebral fracture detection, steroid treatment options, denosumab cessation, and the use of intravenous zoledronate as a first-line anti-osteoporosis therapy.³

Established in 2007, NOGG is a multidisciplinary group of healthcare professionals and patient representatives who review the latest evidence on the assessment, diagnosis, treatment, and prevention of fragility fractures in postmenopausal women and men aged 50 years and older in order to develop this clinical guideline.⁴ NOGG currently has 20 members, including professors of bone medicine, general practitioners, specialist nurses, and patient representatives.^4,5 The NOGG guideline has been accredited for use in the UK by NICE, and is endorsed by (among others) the International Osteoporosis Foundation and the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases;¹ however, it is not endorsed by the Royal College of General Practitioners.

Defining Osteoporosis

The World Health Organization (WHO) definition of osteoporosis, which is used by the NOGG guideline, states that it is a ‘progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture’.^1,6 In practical terms, the WHO definition recognises osteoporosis in anyone with a bone mineral density (BMD) T-score of less than or equal to −2.5.¹ This T-score has become a clinical definition for osteoporosis; however, NOGG emphasises that it is just one factor to consider when assessing fragility fracture risk.¹

The Burden of Osteoporosis

Why should GPs prioritise osteoporosis? There are three key reasons. Firstly, to reduce the estimated 549,000 new fragility fractures, 105,000 of which are hip fractures, that occur in the UK each year.¹ Hip fractures have a mortality rate of 15–36% in the first year after they arise,^1,7,8 as well as causing significant morbidity—approximately 50% of hip fractures cause permanent disability,⁸ and fragility fractures are estimated to account for over 500,000 disability-adjusted life years (DALYs) lost, comparable to the DALYs lost from dementia.¹ Secondly, with consistent, systematic screening, up to 25% of hip fractures (equating to more than 20,000 per year) could be prevented.⁹ Thirdly, the cost of osteoporosis to the NHS of almost £5 billion per year—2.4% of the NHS budget, an estimated £2.6 billion of which is due to fragility fractures—could be significantly reduced through effective diagnosis and treatment in primary care.¹

The updated guideline provides 32 key recommendations on the identification and management of osteoporosis;¹ this article offers 10 key learning points for primary care.

1. Undertake a Risk Assessment in People with a Clinical Risk Factor

FRAX®, the fragility fracture risk calculator used in the NOGG guideline, is a computerised calculation of the probability that a patient will develop a hip fracture or one of the other major fragility fractures (spine, shoulder, or forearm) in the next 10 years.² There are other fragility fracture risk calculators, such as the Garvan Institute of Medical Research’s Bone Fracture Risk Calculator¹⁰ and QFracture®,¹¹ but these are not used by NOGG and do not distinguish the patients whom FRAX® designates as at ‘very high risk’.

Various risk factors have been identified for osteoporosis, many of which are considered in a FRAX® assessment. The guideline highlights the following: low BMD, age, low body mass index, previous fracture, parental history of hip fracture, smoking, alcohol consumption (three units or more per day), and steroid use.¹ There are also secondary causes of osteoporosis, which include inflammatory bowel disease, endocrine disorders, rheumatoid arthritis, and diabetes.¹ Numerous medications—such as glucocorticoids, aromatase inhibitors, thiazolidinediones, antidepressants, antiparkinsonians, antipsychotics, anxiolytics, benzodiazepines, sedatives, H2 receptor antagonists, and proton-pump inhibitors—are also risk factors, as are other considerations that make patients less amenable to particular treatments, such as susceptibility to falls.¹

NOGG recommends undertaking a FRAX® assessment in all postmenopausal women and men aged 50 years and older with a clinical risk factor for fragility fracture, in order to guide further assessment and treatment where indicated.¹ This is a very large proportion of the population—there are approximately 25.5 million people in the UK aged over 50 years,¹²  many of whom will have risk factors for osteoporosis—so this recommendation may be unreasonable to implement face to face given the current pressures facing the NHS. However, it could be undertaken digitally—for example, by building a search for patients who are unknown and at risk of fragility fracture that is available on clinical software systems such as EMIS, SystmOne, and Vision.

2. Measure BMD in Relevant Populations

To make a diagnosis of osteoporosis, it is necessary to measure BMD. FRAX® can incorporate BMD measurements into its calculations, so NOGG advises that clinicians should refer patients who are initially assessed as being at very high, high, or intermediate risk of fragility fractures for dual-energy X-ray absorptiometry (DXA) scans, and then re-evaluate their fracture risk with FRAX® after the scan to refine the estimate of 10-year risk.^1,2 In addition, those at very high or high risk should have a DXA scan if a baseline measurement is needed against which to compare future BMD measurements.¹ BMD measurement can be targeted towards those close to thresholds—that is, from intermediate to high risk, or from high to very high risk—if necessary.¹

A DXA scan uses low radiation to measure bone density, and is usually used to make a diagnosis of osteoporosis.^1,13 However, if BMD measurement is not practical—for example, because of fragility or the patient’s inability to lie flat on a DXA table—clinicians can still use the NOGG intervention thresholds (Figures 1 and 2) based on FRAX® to guide treatment decisions.¹ It is recommended that fracture risk is categorised using the higher of the two risk assessments (for major osteoporotic or hip fracture).¹

3. Prioritise Treating Patients at Very High Risk

Fracture risk, as determined using FRAX®, was previously designated as low, intermediate, or high, and was used to create intervention thresholds to inform clinicians when to initiate (usually antiresorptive) medication.^14–16 The new concept of ‘very high risk’ enables clinicians to identify those patients who would benefit from immediate treatment, and stratifying those who would benefit from referral for anabolic treatment.¹ This is an important development because of the high mortality rate for individuals within the first year of a hip fracture,^1,7,8 and much higher mortality if combined with COVID-19 infection.¹⁷

The NOGG guideline emphasises that clinicians should prioritise, identify, and arrange treatment for very high-risk patients, as this group is at much higher risk of a further fragility fracture.¹ In some cases, this will require treatment in primary care; in others, urgent referral or re-referral to secondary care. NOGG recommends considering anabolic therapy for first-line treatment in postmenopausal women (teriparatide, romosozumab) and men aged 50 years and over (teriparatide) at very high risk of fracture.¹ This requires secondary care referral. Urgent treatment with oral bisphosphonates would also reduce fracture risk in these patients, and this is recommended if any delay in secondary care referral is anticipated.¹

Beyond this, NOGG recommends that treatment with alendronate, zoledronate, or denosumab is started without delay after the initial anabolic therapy.¹ Raloxifene can also be considered for follow-on treatment after anabolic therapy in women.¹

The approach recommended for decision making is based on fracture probabilities derived from FRAX®, and is underpinned by cost-effectiveness analyses.¹ This approach can be applied to men and women, and is centred around the FRAX® assessment thresholds for the 10-year probability of a major osteoporotic fracture, as shown in Figure 2.¹ Primary care clinicians can also redesignate patients in the high-risk category into the very high-risk category by considering additional clinical risk factors not taken into account in the FRAX® assessment, such as frequent falls or very low spine BMD.

4. Refer Patients with More Complex Conditions to Secondary Care

The NOGG guideline is directed at care for postmenopausal women and men aged 50 years or over. There are some complex patients who do develop osteoporosis outside of these two groups, but they are outside of the scope of the NOGG guideline; it is likely that they will need to be given specialist referral.¹ These more complex cases may include younger patients with eating disorders¹⁸ and conditions associated with severe malabsorption,¹ as well as patients being treated with long-term steroids.¹

5. Check for Vertebral Fractures

Consider imaging to check for vertebral fractures, particularly in people with acute-onset back pain who have risk factors for osteoporosis, as the majority of vertebral fractures currently go undiagnosed despite being a significant risk factor for future fractures.¹ Other groups that may benefit from imaging include postmenopausal women and men aged over 50 years who have:¹

• a history of 4 cm or more of height loss
• kyphosis
• recent or current long-term oral glucocorticoid therapy
• a BMD T-score of –2.5 or less at either the spine or the hip.

Vertebral fractures can also be identified opportunistically when computed tomography scans are being taken for other clinical reasons.¹

6. Treat Patients at High Risk of Fracture

As outlined in Figure 3, primary care clinicians should start drug treatment for patients who are classified as being at high or very high risk of fracture (see Figure 3 for more details on treatment at different risk levels).¹ Drug treatment may also be offered to those patients at intermediate risk who cannot have their BMD measured and have a history of fragility fracture, or whose FRAX® score exceeds the intervention threshold (see Figure 2).¹ When making decisions about drug treatment, it is important that clinicians take into account patient choice, the patient’s level of fracture risk, additional clinical risk factors, and the cost-effectiveness of different treatments.¹

Most first-line treatment will involve using oral alendronate (the more commonly prescribed oral treatment) or risedronate,¹ then reviewing the treatment at 3–4 months and considering a review of adherence to treatment after a year. Intravenous zoledronate is an alternative to these treatments, and its inclusion as a potential first-line treatment option is a significant development in this 2022 update.^1,3 Ibandronate, denosumab, hormone-replacement therapy, raloxifene, and strontium ranelate are all viable alternatives as well, and further details of their relative benefits, risks, and costs can be found in the guideline.¹

7. Think About Treatment in the Long Term

Following treatment with teriparatide or romosozumab, NOGG recommends starting alendronate, zoledronate, or denosumab without delay.¹ Before starting denosumab, it is recommended that clinicians have established a long-term, personalised osteoporosis management plan with the patient.¹ This is because cessation of denosumab can cause an increased risk of vertebral fractures, so denosumab treatment should not be stopped without a plan for subsequent antiresorptive therapy, where renal function permits.¹

Treatment for osteoporosis is long term, which means that oral bisphosphonates tend to be prescribed for at least 5 years and intravenous bisphosphonates for at least 3 years; the guideline suggests planning to prescribe treatments for this long before reassessing fracture risk.¹ In particular, longer-term treatment should be considered for patients who are aged over 70 years, have had hip or vertebral fragility fractures, or are on long-term, high-dose steroids.¹ Patients who have a further fragility fracture should also continue longer-term treatment.¹ As NOGG notes, cessation of antiresorptive therapy for osteoporosis is associated with an increase in patients’ risk of fragility fracture, so it is not supported by the evidence.^1,19 Once these terms of bisphosphonates are completed, however, doctors can consider a temporary treatment pause of 18–36 months in low-risk patients, in line with the patient’s wishes.¹

8. Don’t Underestimate Nonpharmacological Interventions

It is important to take a holistic view of patients with osteoporosis; hence, the updated guideline also emphasises the importance of lifestyle and dietary measures in the management and prevention of osteoporosis, particularly in those at low fracture risk.¹ When advising on nonpharmacological interventions, clinicians should recommend:¹

• a healthy, balanced diet
• moderation of alcohol consumption, ideally to less than two units per day
• avoidance of smoking
• sufficient dietary calcium (at least 700 mg daily) and vitamin D intake (at least 800 IU daily), supplementing these where necessary
• regular weight-bearing and muscle-strengthening exercise.

Consider a falls assessment for all patients who have experienced fragility fractures.¹ Exercise programmes may help these at-risk patients to improve their balance.¹

9. Reassess Fracture Risk at Appropriate Times

Any new fracture should prompt a reassessment of fracture risk, regardless of when this new fracture occurs.¹ Fracture risk should also be reassessed 18 months–3 years after pausing drug treatment if no new fracture has occurred.¹ In patients who are receiving drug treatment, this reassessment should be performed using FRAX® and BMD measurement, with adjustments for additional clinical risk factors.¹ The new risk category will inform future drug treatment and interventions.¹

10. Consider Bone-protective Treatment in Patients Taking Glucocorticoids

If a postmenopausal woman or man aged over 50 years starts taking glucocorticoids equivalent to 3 months of 7.5 mg prednisolone or more, it is recommended that clinicians should start bone-protective treatment and possibly anabolic treatment for those at very high risk of vertebral fracture at the same time (without waiting for a DXA scan).¹ Anabolic treatment requires secondary-care referral, particularly as high-dose glucocorticoids are considered an important clinical risk factor in the guideline.¹ Denosumab can also be considered as an alternative treatment option.¹

Summary

This guideline is an excellent compilation of the latest evidence and guidance on the assessment, management, and treatment of osteoporosis. It is probably the easiest-to-read guidance on osteoporosis to be published. However, osteoporosis is a condition that involves multiple specialities, including practitioners in emergency care, orthopaedics, and general medicine, as well as endocrinologists, metabolic bone specialists, geriatricians, fracture liaison specialist nurses, and GPs.¹ Although the guideline is excellent for guiding clinical decision making by specialists, it may be difficult to use as a quick reference by a GP managing a patient with osteoporosis (however, NOGG has published a summary of its main recommendations for ease of use). This is especially true when patients bring osteoporosis to primary care clinicians as part of an already-full 10-minute consultation. However, bone health leads are emerging in practices who will find this guideline useful.

Other guidance that can be consulted includes NICE guidance on assessing risk and preventing osteoporosis,^20,21 as well as SIGN Guideline 142, Management of osteoporosis and the prevention of fragility fractures.²² The NOGG guideline is perhaps more comprehensive than these alternatives, and gives more consideration to the different levels of osteoporosis care that can be provided to patients. The use of this guideline by GPs, in conjunction with previous NICE and SIGN guidelines, will help to reduce the more than half a million fragility fractures that occur in the UK each year.

Dr David Stephens FRCGP FRNZCGP

GP, Scotland