- Fragility fractures can be prevented by identifying those at risk, then preventing their falls and strengthening their bones
- Older people, especially women, are at risk of fragility fractures, and people:
- with a family history of osteoporotic fractures
- who smoke
- who consume excess alcohol
- who have previous fragility fractures.
- Screening high-risk individuals identifies those who need treatment, helped by measuring bone mineral density, necessary in men and women under 75 years of age
- Exercise of various types is recommended for improving flexibility, endurance, and balance; impact exercises strengthen bones, depending on existing bone strength
- Oral bisphosphonates are first-line agents, along with adequate calcium and vitamin D, continued for 5 years
- Where these cannot be used, other therapies include denosumab for 3 years, zolendronate for 3 years, and teriparetide for 2 years, provided certain criteria are met.
Fragility fractures can be defined as fractures that occur following a fall from a standing height or less.1,2 In 2007, the British Orthopaedic Association reported over 300,000 annual UK hospital attendances with fragility fractures.3 It is estimated that annually there are 180,000 osteoporosis-related symptomatic fractures in England and Wales, including 70,000 hip fractures, 25,000 clinical vertebral fractures, and 41,000 wrist fractures.4 After a vertebral fracture, a post-menopausal woman has an increased relative risk (RR) of 4.4 for a further vertebral fracture, 2.3 for a hip fracture, and 1.4 for a wrist fracture.5
Bone weakness and strength
Bone strength depends on the density of the bone (measured in g/cm2) and bone quality, which is dependent on bone architecture, bone turnover, and damage accumulation.6 Osteoporosis is a progressive, systemic skeletal disease characterised by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture (i.e. a bone mineral density [BMD] T-score of –2.5 standard deviations or below peak BMD [BMD for a young adult]).1 It is estimated that around 3 million people in the UK have osteoporosis.4
Who should be investigated and how?
According to NICE Clinical Guideline (CG) 146 for the diagnosis and management of osteoporosis in postmenopausal women and men from the age of 50 years in the UK (see www.nice.org.uk/guidance/cg146), screening can be offered to:7
- women from age 65 years
- men from age 75 years
- younger people with risk factors or other causes of secondary osteoporosis.
Screening tools such as FRAX® (for people between 40 and 90 years, with or without BMD measurement)8 and QFracture® (for people aged between 30 and 84 years)9 estimate absolute risk of fracture over 10 years, expressed as a percentage (for example, the predicted risk of major osteoporotic or hip fracture). Factors used in the tools include intrinsic risks, for example:7
- family history of hip fracture
- previous fragility fracture
- diseases predisposing to low bone density (e.g. rheumatoid arthritis)
- untreated premature menopause
- low body mass index
and extrinsic factors, such as:
- excessive alcohol consumption (more than 14 units per week for women, and more than 21 units per week for men)
- frequent recent use of oral or systemic glucocorticoids.
NICE does not recommend using BMD in isolation but does ask the clinician to consider measuring BMD before starting treatments that may have a rapid adverse effect on bone density (e.g. sex hormone deprivation for treatment for breast or prostate cancer).7
In patients older than 80 years, NICE acknowledges that predicted 10-year fracture risk may underestimate short-term fracture risk and that these patients have other influences that need to be taken into account, for example living in a care home, falls, or taking drugs that may impair bone metabolism (e.g. anti-convulsants, selective serotonin reuptake inhibitors, thiazolidinediones, proton pump inhibitors, and anti-retroviral drugs).7
The National Osteoporosis Guideline Group (NOGG) guideline10 takes a simpler stance, specifying the use of FRAX assessments in men aged above 50 years with or without fracture, and in postmenopausal women. The resultant graphs plot thresholds to determine risk. The National Osteoporosis Guideline Group recommends recomputing FRAX scores with a BMD in people between high- and low-risk categories. It also points out that secondary causes of osteoporosis are commonly found among men, so this population requires thorough investigation.10 It acknowledges that FRAX does not include falls as a risk factor.10
Management of weak bones
Once someone has been identified as having osteoporosis or a fragility fracture, lifestyle advice should be offered. Smoking cessation and reduction in alcohol consumption are important. Other considerations include an assessment of falls risk, particularly in the elderly.11 Exercise improves balance, co-ordination, strength, and flexibility, all of which decrease the risk of falls and so the risk of fracture.12–15 Regular weight-bearing exercise of differing impact can improve bone density and reduce fracture risk, depending on the individual person’s ability and the number of previous fractures.12–15 The National Osteoporosis Guideline Group recommendations include avoidance of immobilisation and correction of poor protein nutrition in patients with a recent hip fracture.10> Dietary advice is important; a daily intake of at least 1 g calcium and 800 international units (IU) vitamin D is required.11,15 This is inevitably short of what most people can ingest in food and drink or absorb from sunlight and will require supplementation.
Pharmacological bone-strengthening agents
For frail, elderly patients who are housebound (e.g. in care homes) and at risk of falls, clinicians are strongly advised to recommend vitamin D supplementation of at least 1000 IU/day, as well as calcium supplementation, to reduce the risk of fractures and falls.16 It is sensible to check serum calcium, alkaline phosphatase, and occasionally vitamin D levels before prescribing a suitable combination preparation (for which a range of formulations are available to aid compliance and patient tolerability).17 It is also important to remember that most agents used to treat osteoporosis (e.g. bisphosphonates, strontium, and denosumab) are contraindicated in patients with hypocalcaemia, and vitamin D deficiency (levels <25nmol/L), which must be corrected before initiating therapy with these agents. A loading dose of vitamin D totalling 300,000 IU, given in daily or weekly regimens, should be followed by maintenance therapy of vitamin D 800–2000 IU daily.18–19
Drug treatments for osteoporosis
The National Osteoporosis Guideline Group recommends pharmacological treatment strategies for all high-risk patients, both men and women.10 It does not recommend one drug over another when given with calcium and vitamin D. Agents with grade A evidence in reducing fractures at hips, vertebrae, and non-vertebrae include: alendronate, ibandronate, risedronate, zoledronic acid, denosumab, teriparatide and hormone replacement therapy in younger patients.10
NICE has separate technology appraisals for patients who have not yet sustained a fragility fracture and for those who have, somewhat confusingly calling these primary and secondary ‘prevention of osteoporosis’, respectively.4,20 It has subsequently clarified the links between fragility fracture risk assessment and osteoporosis in a NICE pathway.21
NICE’s guidance uses these independent clinical risk factors for fracture (ICRFF):4,20
- parental history of hip fracture
- alcohol intake of 4 or more units per day
- rheumatoid arthritis
- low body mass index (defined as less than 22 kg/m2)
- medical conditions such as ankylosing spondylitis, Crohn’s disease
- conditions that result in prolonged immobility
- untreated premature menopause.4
Primary prevention of fragility fractures
NICE TA160 on Alendronate, etidronate, risedronate, raloxifene and strontium ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women (amended) advocates treatment for women:4
- aged over 75 years with two or more ICRFF or ILBMD, without a DEXA scan if the responsible clinician considers a DEXA scan to be clinically inappropriate or not feasible
- aged between 70 and 75 years with osteoporosis (measured by T-score) and who have an ICRFF or an ILBMD
- aged 65–69 years and who have an ICRFF and osteoporosis confirmed by DEXA
- who are postmenopausal and younger than 65 years and who have osteoporosis confirmed by DEXA plus have an ICRFF and at least one additional ILBMD.
In women without a prior fragility fracture, NICE’s first-line recommendation is generic oral bisphosphonates (e.g. alendronate 70 mg once weekly). Risedronate (now available generically) and etidronate are alternatives for the primary prevention of osteoporotic fragility fractures in postmenopausal women who:
- are unable to comply with the special instructions for the administration of alendronate, or
- have a contraindication to, or are intolerant of, alendronate and fulfil the criteria in Table 1, below.
In practice, in the author’s opinion it is unlikely that someone who could not take alendronate is likely to be able to benefit from either etidronate or risedronate. Etidronate does not have grade A evidence for fracture reduction and so current evidence is not as strong as for alendronate or risedronate. The only extra indication for risedronate is for it to be cautiously tried in patients who have dysphagia. This is rarely temporary and resultant upper gastrointestinal symptoms often lead to loss of compliance.
Denosumab is a monoclonal antibody against RANK ligand (RANKL); prevention of activation of the RANK receptor reduces osteoclast activity, and so reduces bone breakdown.22 It is administered as a subcutaneous injection every 6 months and recommended as a treatment option for primary prevention of osteoporotic fragility in postmenopausal women at increased risk of fractures:
- who are unable to comply with the special instructions for administering alendronate and either risedronate or etidronate, or have an intolerance of, or a contraindication to, those treatments and
- who have a combination of T-score, age, and number of ICRFF for fracture as indicated in Table 2, below.22
Strontium ranelate, recommended with specific combinations of T-score, age, and number of ICRFF, has new contraindications that severely restrict its use.23,24 Medicines and Healthcare products Regulatory Agency advice to restrict its commencement to physicians with experience in the treatment of osteoporosis, and to assess the risk of developing cardiovascular disease before starting treatment and monitor this every 6–12 months, has been modified by the European Medicines Agency (EMA), which has concluded that strontium ranelate should only be used by people for whom there are no other possible treatments for osteoporosis.24
|Age (years)||Number of independent clinical risk factors for fracture|
|75 or older||–3.0||–3.0||–2.5|
|Age (years)||Number of independent clinical risk factors for fracture|
|75 or older||–4.0||–4.0||–3.0|
Secondary fragility fracture prevention
NICE has used a cut-off age of 75 years for women with prior fragility fractures; these women do not need a bone scan to diagnose their osteoporosis.20 Alendronate is one of the recommended drugs. Risedronate and etidronate are recommended alternatives in postmenopausal women who are unable to comply with the special instructions for (or have a contraindication to, or are intolerant of) alendronate and who also have a combination of T-score, age, and number of ICRFFF as shown in Table 3, below.
Denosumab is recommended as a treatment option for the secondary prevention of osteoporotic fragility fractures only in those postmenopausal women at increased risk of fractures who are unable to comply with the special instructions for, or who have a contraindication to, those treatments.22
Raloxifene, a weak oestrogen-receptor agonist, is a recommended option in the circumstances shown in Table 4, below, if the patient cannot take oral bisphosphonates.20
Strontium ranelate remains as an option, although an unlikely one, bearing in mind all the new restrictions and advice (e.g. it must not be prescribed in patients with a current or past history of ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, uncontrolled hypertension).23,24
Teriparatide is a recombinant fragment of human parathyroid hormone and, as an anabolic agent, stimulates new formation of bone and increases resistance to fracture. It is recommended as an alternative treatment option for the secondary prevention of osteoporotic fragility fractures in postmenopausal women:20
- who are unable to take or have a contraindication to or are intolerant of oral bisphosphonates or strontium ranelate, or who have had an unsatisfactory response to treatment with alendronate, risedronate, or etidronate, and
- who are aged 65 years or older and have a T-score of –4.0 SD or below, or a T-score of –3.5 SD or below plus more than two fractures, or who are aged 55–64 years and have a T-score of –4.0 SD or below plus more than two fractures.
Teriparatide is given as a daily subcutaneous injection for 24 months. It is contraindicated in pre-existing hypercalcaemia, severe renal impairment, metabolic bone diseases other than primary osteoporosis (including hyperparathyroidism and Paget’s disease of bone), unexplained elevations of alkaline phosphatase, and previous radiation treatment to the skeleton.20
Zoledronic acid, given annually as an intravenous infusion, can be initiated after 2 weeks or more following hip fracture surgery. The National Osteoporosis Guideline Group and the summary of product characteristics recommend that the patient receives a loading dose of 50,000–125,000 IU of vitamin D prior to the first infusion.10,25,26 This treatment can be given to both men and women.
|Age (years)||Number of independent clinical risk factors for fracture|
|70 or older||–2.5||–2.5||–2.5|
|Age (years)||Number of independent clinical risk factors for fracture|
|75 or older||–3.0||–2.5||–2.5|
The treatment of osteoporosis for men is not covered by NICE except for the use of denosumab when used for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures.27 The guidance advocates against the routine use of bisphosphonates to prevent osteoporosis in men with prostate cancer who have androgen deprivation therapy (ADT). It suggests considering the assessment of fracture risk in men with prostate cancer who are having ADT, in line with NICE CG146, and recommends offering bisphosphonates to those found to have osteoporosis; it also advises that denosumab can be used if bisphosphonates are contraindicated or not tolerated.7,27
Duration of treatment
The National Osteoporosis Guideline Group recommends that treatment with alendronate, risedronate, or ibandronate is reviewed after 5 years.10 If the treatment is discontinued, fracture risk should be reassessed 2 years following discontinuation of treatment, or after a new fracture, regardless of when this fracture occurs.10 Zoledronic acid should discontinued after three annual infusions. Its beneficial effects on BMD persist for at least another 3 years, after which a review is advocated.10 Teriparetide is given daily for 24 months and never repeated.10
The final relevant guidance deals with the use of percutaneous vertebroplasty and percutaneous balloon kyphoplasty in vertebral compression fractures. NICE recommends these techniques for osteoporotic vertebral compression fractures causing severe ongoing pain after a recent, unhealed fracture of the spine despite treatment for pain, and when the pain has been confirmed to be where the fracture is. This would be carried out after discussion with a specialist, multidisciplinary team, and in an appropriately resourced facility that has access to a spinal surgery service.28
Opportunistic screening of high-risk people, especially those who have suffered one fragility fracture, should lead to determination of their risk for further fractures. Intrinsic and extrinsic risk fractures and a person’s bone mineral density will determine their need for therapeutic agents. Exercises and vitamin D, along with calcium, should be offered to certain high-risk groups (people who are housebound or have fallen). Oral bisphosphonates for 5 years are the first-line therapy. However, in people in whom oral bisphosphonates are not tolerated, are contraindicated, or have failed, the injectables can be considered. These include subcutaneous denosumab (6-monthly for 3 years), teriparatide (daily for 2 years), and intravenous zolendronate (annually for 3 years); all of these agents have fairly stringent criteria for use.
- Guidance for the screening of osteoporosis and primary prevention of fragility fractures has proved a challenge for both CCGs and primary care to understand and implement
- Secondary prevention following fragility fracture has, however, been incentivised through the GP contract for several years and so is likely to be more consistently implemented
- Use of the FRAX® and QFracture® tools might be more widespread if these tools could be successfully integrated into GP computer systems to give a rapid assessment of likely fracture risk
- Clinical commissioning groups may wish to consider specific local incentives and education for primary care practitioners to help them screen for osteoporosis and to implement NICE primary prevention guidance:
- this could possibly be facilitated through community-employed specialist nurses to help support and assist general practices, and primary prevention schemes run by practice nurses.
- Clinical commissioning groups should also adapt local formularies and doctor and patient decision aids to inform the often complex decisions about which patient to treat with what drug, at what level of fracture risk.
- World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. WHO Technical Report Series No. 843. Geneva, WHO: 1994.
- Kanis J, Oden A, Jonell O et al. The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporosis Int 2001; 12 (5): 417–427.
- British Orthopaedic Association. The care of patients with fragility fracture. London: British Orthopaedic Association, 2007. Available at: bit.ly/BritishOrthopaedic-fragility-fracture-07
- NICE. Alendronate, etidronate, risedronate, raloxifene and strontium ranelate for the primary prevention of osteoporotic fragility fractures in postmenopausal women (amended). Technology Appraisal 160. NICE, 2008. Available at: www.nice.org.uk/guidance/TA160
- Black D, Arden N , Palermo L et al. Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. J Bone Miner Res 1999; 14 (5): 821–828.
- Bouxsein M. Bone quality and osteoporotic fracture. Osteoporosis clinical updates. National osteoporosis foundation, 2011.
NICE. Osteoporosis. Assessing the risk of fragility fracture. Clinical Guideline 146. NICE, 2012. Available at: www.nice.org.uk/guidance/cg146
FRAX® website. WHO fracture risk assessment tool. Available at: www.shef.ac.uk/FRAX/ (accessed 24 September 2014).
- Hippisley-Cox J, Coupland C. QFracture®-2013 risk calculator. ClinRisk Ltd, 2012–2013. Available at: www.qfracture.org (accessed 24 September 2014).
- National Osteoporosis Guideline Group on behalf of the Bone Research Society, British Geriatrics Society, British Orthopaedic Association, British Orthopaedics Research Society, British Society of Rheumatology, National Osteoporosis Society, Osteoporosis 2000, Osteoporosis Dorset, Primary Care Rheumatology Society, Royal College of Physicians and Society for Endocrinology. Osteoporosis clinical guideline for prevention and treatment. Executive summary. Updated March 2014. Available at: www.shef.ac.uk/NOGG/NOGG_Executive_Summary.pdf
- NICE. Falls: assessment and prevention of falls in older people. NICE Clinical Guideline 161. NICE, 2013. Available at: www.nice.org.uk/guidance/cg161
- Kelley G et al. Exercise and bone mineral density at the femoral neck in postmenopausal women: a meta-analysis of controlled clinical trials with individual patient data. Am J Obstet Gynecol 2006; 194 (3): 760–767.
- Kerr D, Morten A, Dick I. Exercise effects on bone mass in postmenopausal women are site-specific and load-dependent. J Bone Miner Res 1996; 11 (2): 218–225.
- Wolff I, van Croonenborg J, Kemper H et al. The effect of exercise training programs on bone mass: a meta-analysis of published controlled trials in pre- and postmenopausal women. Osteoporos Int 1999; 9 (1): 1–12.
- Bassey E. Exercise for prevention of osteoporotic fracture. Age and Ageing 2001; 30-S4: 29–31.
- American Geriatrics Society Workgroup on Vitamin D Supplementation for Older Adults. Recommendations abstracted from the American Geriatrics Society Consensus Statement on Vitamin D for Prevention of Falls and their Consequences. J Am Geriatr Soc 2014; 62 (1): 147–152.
- NHS Evidence website. UK Medicines Information. Medicines Q & A 82.2. What dose of vitamin D should be prescribed for the treatment of vitamin D deficiency? January 2013. www.evidence.nhs.uk (accessed 25 September 2014).
- East & South East England Specialist Pharmacy Services. East of England, London, South Central & South East Coast. Vitamin D deficiency and insufficiency in adults and paediatrics: a guideline collation document for London and East & South-East England. Available at: www.yumpu.com/en/document/view/16473190/vitamin-d-guideline-collation-document (accessed 6 October 2014).
- National Osteoporosis Society. National Osteoporosis Society practical guide. Vitamin D and bone health: a practical clinical guideline for patient management. Available at: www.nos.org.uk/page.aspx?pid=1074 (accessed 25 September 2014).
- NICE. Alendronate, etidronate, risedronate, raloxifene, strontium ranelate and teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women (amended). Technology Appraisal 161. NICE, 2008. Available at: www.nice.org.uk/guidance/TA161
- NICE Pathways website. Osteoporosis overview. NICE.org.uk/osteoporosis (accessed 25 September 2014).
- NICE. Denosumab for the prevention of osteoporotic fractures in postmenopausal women. Technology Appraisal 204. London: NICE, 2010. Available at: www.nice.org.uk/guidance/TA204.
- Medicines and Healthcare Products Regulatory Agency. Strontium ranelate: cardiovascular risk—restricted indication and new monitoring requirements. Drug Safety Update 2014 7; 8: S1. Available at: www.mhra.gov.uk/home/groups/dsu/documents/publication/con392897.pdf
- European Medicines Agency. Recommendation to restrict the use of Protelos/Osseor (strontium ranelate). 25 April 2013. Available at: www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/04/news_detail_001774.jsp&mid=WC0b01ac058001d126 (accessed 2 October 2014).
- Boonen S, Black D, Colon-Emeric C et al. Efficacy and safety of a once-yearly intravenous zoledronic acid 5 mg for fracture prevention in elderly postmenopausal women with osteoporosis aged 75 and older. J Am Geriatr Soc 2010; 58 (2): 292–299.
- Boonen S, Reginster J, Kaufman J et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Eng J Med 2012; 367 (18): 1714–1723.
- NICE. Prostate cancer: diagnosis and treatment. Clinical Guideline 175. NICE, 2014. Available at: www.nice.org.uk/guidance/CG175
- NICE. Percutaneous vertebroplasty and percutaneous balloon kyphoplasty for treating osteoporotic vertebral compression fractures. Technology Appraisal 279. NICE, 2013. Available at: www.nice.org.uk/TA27