Dr Alun Cooper considers the impact fragility fractures have on individuals and UK health services and summarises recent NOGG recommendations on osteoporosis prevention and treatment
Read this article to learn more about:
- the profound impact of fragility fractures on patients and the health service
- assessing fracture probability
- intervention thresholds, pharmacological treatments, and lifestyle measures.
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NICE Accreditation Mark
NOGG 2017: clinical guideline for the prevention and treatment of osteoporosis has been awarded the NICE Accreditation Mark.
More than 1 in 3 women and 1 in 5 men will experience at least one fragility fracture in their lifetime.1 Most major osteoporotic fractures are associated with reduced relative survival that persists for more than 5 years after the event.2–4 In Europe, osteoporotic fractures contribute a significant disease burden to society, accounting for more disability-adjusted life years than rheumatoid arthritis, Parkinson’s disease, breast and prostate cancers.2,5
Background and impact
In the UK approximately 536,000 new fractures occur each year, of which 79,000 are hip fractures, 66,000 clinically diagnosed vertebral fractures, 69,000 forearm fractures, and 322,000 others (pelvis, rib, humerus, tibia, fibula, clavicle, scapula, sternum, other femoral fractures).6 At any one time, people with hip fractures occupy more than 4000 hospital beds in England, Wales, and Northern Ireland with an average length of stay of 20 days.7 About 53% of patients who experience hip fracture can no longer live independently and nearly 30% die within 12 months.2 Only 54% of individuals admitted from home with a hip fracture return there within 30 days.2
Hip fractures account for around half the total cost of fractures within the UK.2 The annual cost of fragility fractures to the NHS is over £4.4 billion (estimated for 2010). The first-year costs amount to £3.2 billion, subsequent year costs £1.1 billion, and pharmacological fracture prevention costs £84 million.2,6
In the UK, fracture rates vary by geographic location, socioeconomic status, and ethnicity.8,9 In recent decades there have been changes in age- and sex-adjusted fracture rates, with increases in hip fracture in men and vertebral fractures in women.2,10 If changes are not made to current practice the ageing of the UK population will result in a doubling in the number of osteoporotic fractures over the next 50 years.6,11
NOGG 2017 guideline update
Against this background, a major update to the UK National Osteoporosis Guideline Group (NOGG) UK clinical guideline for the prevention and treatment of osteoporosis was published in April 2017.1,2 The update and a patient information leaflet are available as PDFs2,12 and the full guideline was also published online.1 A summary of the main recommendations is also available. A summary of the scope and main recommendations in the guideline are given below.
Background and scope
The NOGG updated guideline was prepared with the support of stakeholders including the Royal College of General Practitioners, Primary Care Rheumatology Society, National Osteoporosis Society, British Geriatrics Society, British Orthopaedic Association, Royal Pharmaceutical Society, Arthritis Research, International Osteoporosis Foundation, and Royal College of Physicians.
Available systematic reviews, meta‑analyses, and randomised control trials were used to provide the evidence base.1,2 Conclusions and recommendations were systematically graded according to the strength of evidence available. The guideline has received 5-year accreditation from NICE.
The scope of the guidance is to ‘… review the assessment and diagnosis of osteoporosis, the therapeutic interventions available, and the manner in which these can be used to develop management strategies for the prevention of fragility fractures in postmenopausal women and in men aged 50 years or over.’1
Assessment of fracture risk
See Box 1 for a summary of NOGG recommendations for the assessment of fracture risk.1
Box 1: Assessment of fracture risk1
- Fracture probability should be assessed in postmenopausal women, and men aged 50 years or more, who have risk factors for fracture, using FRAX®. In individuals at intermediate risk, bone mineral density (BMD) measurement should be performed using dual-energy X-ray absorptiometry (DXA) and fracture probability re‑estimated using FRAX®
- Vertebral fracture assessment should be considered in postmenopausal women and men aged over 50 years if there is a history of height loss of 4 cm or more, kyphosis, recent or current long-term oral glucocorticoid therapy, or a BMD T-score of –2.5 or less.
Compston J, Cooper A, Cooper C et al, the National Osteoporosis Guideline Group (NOGG). UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 2017; 12 (1): 43
Fracture risk assessment tools
FRAX®13 calculates the 10‑year probability of hip or major osteoporotic fracture (i.e. clinical spine, hip, forearm, or shoulder fracture) in people aged 30–90 years with or without the addition of femoral neck bone mineral density (BMD) and has been extensively validated in independent cohorts.13,14
QFracture® is based on a prospective open cohort study of data from UK primary care populations and estimates the 1–10 year cumulative incidence of hip or major osteoporotic fracture in people aged 30–99 years.15
NICE has recommended the use of fracture risk assessment tools (FRAX® and QFracture®) in the assessment of patients including the proposal that their use should be considered in all women 65 years or older and men aged 75 years and older, and that people above the upper age limits for the both tools should be considered to be at high risk.16 As FRAX® and QFracture® yield different outputs, they cannot be used interchangeably. Furthermore, bone mineral density (BMD) values cannot be incorporated into QFracture® estimations. As the NOGG intervention thresholds are based on FRAX® probability, they cannot be used with fracture risk derived from QFracture®. The use of FRAX® is therefore recommended in NOGG 2017.1
However, it is not possible to model all clinical scenarios with the FRAX® algorithm. FRAX® does not take into account prior treatment or dose responses for several risk factors, e.g. two previous fractures carry a much higher risk than a single previous fracture, and dose responses for glucocorticoids are only partially addressed by NOGG. Practitioners need to be aware of these limitations and use their clinical judgment alongside the algorithm results.1
Dual-energy X-ray absorptiometry
The femoral neck is considered to be the preferred site for dual-energy X-ray absorptiometry (DXA) because of its high predictive value for fracture risk.1,17,18 The spine is not a suitable site in older people because degenerative changes can erroneously increase BMD values in these patients. However, the spine is the preferred site for assessing response to treatment.1
There is currently no accepted policy for population-based screening for osteoporosis so NOGG recommends a case-finding approach whereby patients are identified when they have a fragility fracture or because of risk factors. Fracture risk should be assessed in postmenopausal women and men aged 50 years or more with risk factors, where this assessment would influence management. See Box 2 for the risk factors that FRAX® takes into account.1 Other risk factors not currently taken into account by FRAX are shown in Box 3.1 Assessment of individuals with osteoporosis should include routine investigation for secondary causes (see Table 1).1
Box 2: Clinical risk factors considered in the FRAX® assessment of fracture probability1
- Low body mass index (19 kg/m2 or less)
- Previous fragility fracture, including morphometric vertebral fracture
- Parental history of hip fracture
- Current glucocorticoid treatment (any dose, by mouth for 3 months or more)
- Current smoking
- Alcohol intake three or more units daily
- Secondary causes of osteoporosis including:
- rheumatoid arthritis
- type 1 diabetes
- osteogenesis imperfecta in adults
- long-standing untreated hyperthyroidism
- hypogonadism/premature menopause (below 45 years)
- chronic malnutrition
- chronic malabsorption
- chronic liver disease.
Compston J, Cooper A, Cooper C et al, the National Osteoporosis Guideline Group (NOGG). UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 2017; 12 (1): 43
|Routine||Other procedures, if indicated|
|Compston J, Cooper A, Cooper C et al, the National Osteoporosis Guideline Group (NOGG). UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 2017; 12 (1): 43|
Box 3: Risk factors for osteoporosis/fractures not presently accommodated in FRAX®1
- Thoracic kyphosis
- Height loss (>4 cm)
- Type 2 diabetes
- Inflammatory disease—ankylosing spondylitis, other inflammatory arthritides, connective tissue diseases
- Endocrine disease—hyperthyroidism, hyperparathyroidism, Cushing’s disease
- Haematological disorders/malignancy
- Muscle disease—myositis, myopathies, and dystrophies
- Asthma, chronic obstructive pulmonary disease
- HIV infection
- Neurological/psychiatric disease, e.g. Parkinson’s disease, multiple sclerosis, epilepsy, stroke, depression, dementia
- Nutritional deficiencies—calcium, vitamin D, magnesium, protein (note that vitamin D deficiency may contribute to fracture risk through undermineralisation of bone [osteomalacia] rather than osteoporosis)
- some immunosuppressants (calmodulin/calcineurine phosphatase inhibitors)
- (excess) thyroid hormone treatment (levothyroxine and/or liothyronine). Patients with thyroid cancer with suppressed TSH are at particular risk
- drugs affecting gonadal hormone production (aromatase inhibitors, androgen-deprivation therapy, medroxyprogesterone acetate, gonadotrophin hormone releasing agonists)
- some anti-diabetic drugs
- some antipsychotics
- some anticonvulsants
- proton-pump inhibitors.
Intervention thresholds for pharmacological treatment
Recommended thresholds for decision making in the NOGG guideline are based on probabilities of hip and major osteoporotic fracture as evidenced by FRAX® and can be applied to men and women.1
Women who have had a previous fragility fracture can be considered for treatment without further assessment, although BMD measurements may be appropriate, especially in younger, postmenopausal women.1 Therefore greater accuracy of diagnosis of some fractures (e.g. rib and vertebral) is needed as the existence of a prior fracture determines whether treatment is aimed at primary or secondary fracture prevention. X-rays may now be indicated where previously it may have been thought that the results would not alter management plans.
Up to the age of 70 years the fracture probability thresholds are set at the values equivalent to a postmenopausal woman of that age with a prior fracture. Despite the apparently higher threshold the proportion of women eligible for treatment increases with age. The threshold flattens from 70 years upwards to ensure equity of risk for those identified with or without a fracture, as the latter were slightly disenfranchised by the previous thresholds;19 see Figure 1.
Pharmacological intervention in postmenopausal women
Alendronate or risedronate are still recommended as first-line treatment in most cases. In women who are intolerant of oral bisphosphonates, or in whom they are contraindicated, intravenous bisphosphonates or denosumab are the best alternatives. Raloxifene or hormone replacement therapy are options. The high cost of teriparatide restricts its use to those at very high risk, especially for vertebral fractures. Major treatments for osteoporosis are based on high levels of evidence and the grades of these recommendations are shown in Table 2.1
|Intervention||Vertebral fracture||Non-vertebral fracture||Hip fracture|
|A=grade A recommendation; NAE=not adequately evaluated; HRT=hormone replacement therapy
*in subsets of patients only (post-hoc analysis)
Treatment should be reviewed after 5 years of oral bisphosphonates or 3 years of the more powerful intravenous zoledronic acid. Treatment with bisphosphonates beyond this period can generally be recommended in those at high risk, that is individuals aged 75 years or more, those with a history of a hip or vertebral fracture, those who sustain a fracture while on treatment, and those taking oral glucocorticoids (7.5 mg prednisolone or more daily). Reassessment of fracture risk in treated individuals can be performed using FRAX® with femoral neck BMD.20 The NOGG intervention thresholds can then be used to guide whether or not the treatment can be interrupted (see Figure 2 for an algorithm on monitoring long-term treatment).1
If treatment is discontinued, fracture risk should be reviewed again after 18–36 months. If a fracture occurs while off treatment, the need for treatment should be reviewed at this time.1
There is no evidence to guide decisions on treatment and management beyond 10 years and these patients should be considered on an individual basis.1
Osteoporosis in men
Alendronate and risedronate are the first-line treatments in men. If these are contraindicated or not tolerated, zoledronic acid or denosumab provide the best alternatives.1
For estimation of fracture probability in men using the online version of FRAX®, femoral neck BMD values (g/cm2) should be entered and the manufacturer of the densitometer specified.1
Secondary causes of osteoporosis in men are common so thorough investigation and consideration of referral to specialist centres, especially in younger men or those with severe disease, are recommended.1
Women and men aged 70 years or older, with a previous fragility fracture, or those taking a high dose of glucocorticoids (prednisolone 7.5 mg or more a day) should be considered for bone protective therapy.1
Fracture probability in other individuals should be estimated using FRAX®, adjusting for steroid dosage.1
Bone protective treatment should be initiated at the onset of glucocorticoid therapy in people at high risk of fracture.1 Alendronate or risedronate are the first-line options.1
Lifestyle and dietary measures
Daily calcium intake of 700–1200 mg is advised, through normal dietary intake if possible.1 A simple dietary calcium intake calculator is available.
In postmenopausal women and men aged 50 years or older at increased risk of fracture, a daily dose of 800 IU colecalciferol (vitamin D3) is advised.1
In postmenopausal women and older men on bone protective therapy, calcium supplementation should be given if dietary intake is below 700 mg a day and vitamin D supplementation considered in those at high risk of, or who have evidence of, vitamin D insufficiency.1
Regular weight-bearing exercise is recommended, tailored to the individual.
A history of falls should be taken from those at increased risk of fracture and appropriate measures taken.1
Systems of care
Collaboration should be encouraged between all the medical and non-medical disciplines involved with a patient’s fragility fracture management—good communication between primary and secondary care (including orthopaedic/trauma surgeons, physicians, and geriatricians) is essential. The Department of Health advises that fracture liaison services (FLS), whether based in primary or secondary care, should be available to all patients sustaining a fragility fracture. Fracture Liaison Services are coordinated, intensive models of care providing, at a minimum, assessment and treatment options for patients who have suffered a fragility fracture (i.e. secondary fracture prevention). They are cost-saving and more effective in improving patient outcomes than care strategies that just involve GPs, patient alerts, and patient education. The ideal service would include identification, assessment and treatment and the use of an integrated electronic healthcare network, overseen by a co-ordinator who also monitors performance.1,21–23
As patients who suffer fragility fractures are often frail and elderly it is often difficult for them to attend even a local hospital for care. A service based in primary care, where the patient is seen at their own GP premises, can offer a valuable alternative.
The NOGG 2017 guideline provides a framework for the local management, treatment, and prevention of osteoporosis. A patient who has sustained a fragility fracture should at least be assessed for treatment to prevent further fractures. The recommendations in the NOGG guideline are intended to aid management decisions and not replace clinical judgment. It is unlikely that an individual GP will see enough new fractures per year to gain significant experience in managing these patients and therefore the service needs to be organised on a practice or CCG basis—this can be provided through FLS. Any minor changes to the NOGG guideline will be made on the NOGG website when appropriate until the next full update is published.2
- Fragility fractures impose a considerable burden on the lives of individuals and on health services:
- hip fractures account for around half the total cost of fractures in the UK and are associated with disability, decreased life expectancy, and loss of independence
- Hip fractures in men and vertebral fractures in women have increased in recent decades and numbers of osteoporotic fractures are predicted to rise steeply unless current practice is changed
- The 2017 NOGG guideline on prevention and treatment of osteoporosis has been approved after consultation with a large number of professional stakeholders and accredited by NICE
- NOGG intervention thresholds are based on FRAX® probability and so FRAX® is the recommended fracture risk assessment tool for NOGG guidance:
- FRAX® and QFracture® cannot be used interchangeably
- clinical judgment needs to be used to allow for risk factors not covered by FRAX®
- FRAX® fracture probability thresholds flatten from age 70 years onwards to allow equity of risk for people with and without previous fractures
- Treatment should be reviewed after 5 years for oral bisphosphonates or 3 years for zoledronic acid:
- treatment with bisphosphonates beyond this period can generally be recommended in people at high risk
- FRAX® and femoral neck BMD tests can be used to reassess fracture risk in treated individuals and NOGG intervention thresholds used to guide long-term management
- For men:
- femoral neck BMD values (g/cm2) should be entered and the manufacturer of the densitometer specified when using FRAX® online
- secondary causes of osteoporosis are common in men and require thorough investigation and possible referral to a specialist centre
- Bone protective treatment should be started at the onset of glucocorticoid therapy in people at high risk of fracture
- Assessment and advice on calcium intake and vitamin D is needed in postmenopausal women and older men on bone protective therapy; daily vitamin D3 is advised for postmenopausal women and men aged 50 years or older at increased risk of fracture
- Weight-bearing exercise is recommended, tailored to the individual
- A history of falls should be obtained from people with increased fracture risk and appropriate measures taken
- Fracture liaison services should be provided for all people sustaining a fragility fracture.
NOGG=National Osteoporosis Guideline Group
GP commissioning take home messages for England
written by Dr David Jenner, GP, Cullompton, Devon
- Fragility fractures are a major burden on NHS resources, so interventions to reduce them can be very cost effective
- Commissioners should ensure a local integrated fracture liaison service is in place—these services are well-evidenced in preventing further fractures after initial fragility fractures
- The NOGG guideline and FRAX® are not particularly simple to use for busy GPs, especially for primary prevention, so CCGs should consider supporting GPs through relevant education programmes and software solutions
- Local specialists working with primary care should produce clear guidance built from the NOGG guideline for reassessment of patients on bone protection treatment
- Local formularies should include therapeutic and licensed indications for bone protection treatment with cautions about their use (e.g. in renal failure, and the need for dental inspection before treatment)
- Many patients are non-compliant with bone protection medication so CCGs could look to ensure medication-use reviews through pharmacies and DRUMs through dispensing practices for these medicines
NOGG=National Osteoporosis Guideline Group; DRUM=dispensing review of use of medication
Read the Guidelines summary of NOGG 2017: clinical guideline for the prevention and treatment of osteoporosis for more recommendations on how to prevent and manage osteoporosis in primary care
- National Osteoporosis Guideline Group (NOGG). NOGG 2017: clinical guideline for the prevention and treatment of osteoporosis. Centre for Metabolic Bone Diseases, University of Sheffield, 2017. Available at: www.sheffield.ac.uk/NOGG/NOGG%20Guideline%202017.pdf
- Bliuc D, Nguyen N, Milch V et al. Mortality risk associated with low trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 2009; 301 (5): 512–521.
- Harvey N, Dennison E, Cooper C. Osteoporosis: impact on health and economics. Nat Rev Rheumatol 2010; 6 (2): 99–105.
- Johnell O, Kanis J. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006: 17 (12); 1726–1733.
- Svedbom A, Hernlund E, Ivergård M et al. Osteoporosis in the European Union: a compendium of country-specific reports. Arch Osteoporos 2013; 8: 137.
- Falls and Fragility Fracture Audit Programme. National Hip Fracture Database—annual report 2016. London: Royal College of Physicians, 2016. Available at: www.nhfd.co.uk/2016report
- Moon R, Harvey N, Curtis E et al. Ethnic and geographic variations in the epidemiology of childhood fractures in the UK. Bone 2016; 85: 9–14.
- Curtis E, van der Velde R, Moon R et al. Epidemiology of fractures in the United Kingdom 1988–2012: variation with age, sex, geography, ethnicity and socio-economic status. Bone 2016: 87; 19–26.
- van der Velde R, Wyers C, Curtis E et al. Secular trends in fracture incidence in the United Kingdom between 1990 and 2012. Osteoporos Int 2016; 27 (11); 3197–3206.
- Gulberg B, Johnell O, Kanis J. World-wide projections for hip fracture. Osteoporos Int 1997; 7 (5): 407–413.
- National Osteoporosis Guideline Group (NOGG). NOGG 2017: information for patients and the public on the NOGG clinical guideline for the prevention and treatment of osteoporosis. Centre for Metabolic Bone Diseases, University of Sheffield, 2017. Available at: www.sheffield.ac.uk/NOGG/NOGG%20PIL%202017.pdf
- Centre for Metabolic Bone Diseases. FRAX® Fracture risk assessment tool. University of Sheffield, 2008. www.sheffield.ac.uk/FRAX/tool.aspx?country=1 (accessed 7 August 2017).
- Kanis J, Oden A, Johnell O et al. The use of clinical risk factors enhances the performance of BMD in prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 2007; 18 (8): 1033–1046.
- Hippisley-Cox J, Coupland C. Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFracture scores. BMJ 2009; 339: b4229
- NICE. Osteoporosis: assessing the risk of fragility fracture. NICE Clinical Guideline 146. NICE, 2012 (updated February 2017). Available at: www.nice.org.uk/cg146
- Kanis J, Glüer C, for the Committee of Scientific Advisors, International Osteoporosis Foundation. An update on the diagnosis and assessment of osteoporosis with densitometry. Osteoporos Int 2000; 11 (3): 192–202.
- Kanis J, McCloskey E, Johansson H et al. A reference standard for the description of osteoporosis. Bone 2008; 42 (3): 467–475.
- McCloskey E, Kanis J, Johansson H et al. FRAX-based assessment and intervention thresholds—an exploration of thresholds in women aged 50 years and older in the UK. Osteoporos Int 2015; 26 (8): 2091–2099.
- Leslie W, Lix L, Johansson H et al for the Manitoba Bone Density Program. Does osteoporosis therapy invalidate FRAX for fracture prediction? J Bone Miner Res 2012; 27 (6): 1243–1251.
- Department of Health. Fracture prevention services: an economic evaluation. DOH, 2009. www.cawt.com/Site/11/Documents/Publications/Population%20Health/Economics%20of%20Health%20Improvement/fractures.pdf
- Granda K, Puech M, Chen J et al. Models of care for the secondary prevention of osteoporotic fractures: a systematic review and meta-analysis. Osteoporos Int 2013; 24 (2): 393–406.
- Javaid M, Kyer C, Mitchell P et al. Effective secondary fracture prevention: implementation of a global benchmarking of clinical quality using the IOF Capture the Fracture® Best Practice Framework Tool. Osteoporos Int 2015; 26 (11): 2573–2578