Dr David Stephens introduces a consensus guideline to assist primary care in the assessment, management, and treatment of osteoporosis
Managing patients based on their future risk
Although bone-building medications and antiresorptive treatments have clearly been shown to reduce the risk of a further fracture, individual patient factors should be considered when deciding on treatment options.5 For example, people with serious illness such as advanced cancer or advanced dementia may not benefit from treatment, while a younger patient with a lower risk but who smokes, drinks too much alcohol, and is inactive may benefit from treatment lasting many years.
Lifestyle modification should be recommended for all patients irrespective of their level of risk (see Box 1).5
The consensus guideline recommends exercise for all, adequate dietary calcium and vitamin D, falls prevention, cessation of smoking, and a maximum of 14 units of alcohol per week. Postural care is recommended for people with vertebral fractures.
Box 1: Lifestyle modifications to improve bone health5
- Recommend lifestyle modifications for all patients irrespective of risk
- Modifications include:3
- diet, including adequate calcium/vitamin D intake
- reducing the risk of falls
- stopping smoking
- reducing alcohol intake to ≤2 units/day
- Tailor recommendations to each patient’s own circumstances and co-morbidities
- All patients with osteoporosis should exercise using ‘strong, steady, and straight’ guidance to:7,8
- promote bone strength
- improve balance and muscle strength to reduce falls and resulting fractures
- care for the spine by keeping the back straight to reduce the risk of vertebral fracture, and improve posture and relieve pain after vertebral fracture.
Patients at very high risk
In patients with osteoporosis who are at very high risk, the consensus guideline recommends prompt intravenous or injectable bone-building treatments to prevent a further fracture.5 The evidence indicates that after a fragility fracture, instead of patients having treatment with oral alendronate, they should be considered for urgent referral for treatment with one of the anabolic bone-building medications—teriparatide, biosimilar parathyroid hormone, or romosozumab. These treatments are usually delivered by a bone specialist. Antiresorptive therapy is subsequently given to maintain the effect. A more rapid and greater fracture risk reduction with anabolic treatments compared with antiresorptive treatments has been demonstrated, particularly in people at very high risk of fractures, and the effect of these agents on bone mineral density (BMD) can be maintained with bone-turnover inhibitors once anabolic treatment has stopped.7
Patients at high risk
Patients at high risk of future fracture should be treated with antiresorptive medication before referral for bone-forming drugs. Prescribe alendronate, risedronate, ibandronic acid, raloxifene, denosumab, or hormone replacement therapy, or refer to specialist services for intravenous zoledronic acid.5
Both alendronate and zoledronic acid reduce the refracture rate significantly and while alendronate is oral, zoledronic acid is given by an intravenous infusion. Zoledronic acid infusions are only required in a single dose once a year, for 3 years,10 potentially addressing the major issue of concordance, which has dogged oral resorptive treatments ever since they were introduced.
If antiresorptive medications have been tried and are not effective, due to either an adverse reaction or continuing deterioration in the bone density, then refer the patient to specialist services for bone-forming (anabolic) treatment with teriparatide, biosimilar teriparatide, or romosozumab.5
Patients at low risk
Patients who are at low risk should be reassured and given advice on lifestyle modifications (Box 1), calcium and vitamin D nutrition, hormone treatment in perimenopausal and postmenopausal in women, and testosterone replacement therapy in men with male hypogonadism.5
How to assess risk
The consensus guideline identifies the three presentations of osteoporosis: a recent (within the last 2 years) major fracture, opportunistic screening, and treatments that increase fracture risk (for example, steroids or other bone-damaging drugs).5
It includes the following definition of osteoporosis:3,5
‘People with a T-score that is 2.5 standard deviations or more below the young adult mean value for women are diagnosed with osteoporosis, and if in addition to this there are one or more documented fragility fractures they are diagnosed with severe or established osteoporosis.’
Some patients can be diagnosed with osteoporosis without the need for measurement of BMD, for example, after specific fragility fractures and by age.5
All patients with a prior fragility fracture are at least high risk and possibly very high risk depending on their FRAX® probability.5,9
Very high, high, and low risk categories
Professor Kanis and his team, who developed FRAX® (www.sheffield.ac.uk/FRAX/index.aspx), have published an article on the assessment and specific treatment of women that stratifies patients at risk of osteoporosis into very high, high, and low risk groups.9 FRAX® is a computerised risk tool that calculates the risk of a fragility fracture in an individual over the next 10 years. Using FRAX®, Kanis divided patients into these risk groups based on age and the 10-year probability of a further fracture and recommended prompt treatment for people in the very high risk group.9
Kanis defines people in the very high risk group (also sometimes termed the ‘imminent risk group’, see Figure 1) as patients with a high FRAX® score and a history of major fracture of the hip/pelvis/femur, vertebra, humerus, or ribs in the last 2 years. These patients have a fracture probability that lies above the upper assessment threshold after a FRAX® risk calculation. Risk can be calculated using FRAX® with or without the inclusion of BMD, so that where BMD testing is unavailable, the same probability threshold can be used.9 Measuring BMD using dual-energy X-ray absorptiometry (DXA) is the gold standard for the diagnosis of osteoporosis. The DXA result can be incorporated into FRAX® to increase the accuracy of the risk calculation. It is worth noting that patients should always have their risk recalculated after a fragility fracture.
The high risk category is divided by Kanis into those falling above his recommended intervention threshold and those below it.9 Patients whose initial risk assessment with FRAX®, using clinical factors alone, falls between the upper and lower assessment thresholds should have this initial FRAX® assessment followed by BMD assessment and recalculation of FRAX® probability including femoral neck BMD. The patient may then be reclassified; those reclassified as being at very high or at low risk are treated as described above, while those who remain above the ‘high risk’ intervention threshold but below the ‘very high risk’ assessment threshold are considered to be at high risk, and initial antiresorptive therapy should be considered.9 Those whose risk falls below the intervention threshold after BMD reassessment are shown to be ‘low risk’.
Patients older than the age limits for the tools (90 years for FRAX® and 99 years for QFracture®) should be considered at high risk (QFracture® is an alternative risk calculator).2
The consensus guideline notes the bone-forming anabolic medications teriparatide, biosimilar teriparatide, and the new monoclonal romosozumab. In the guideline, romosozumab has been added to the pharmaceutical interventions for patients at very high and high risk. See Box 2 for a summary of the drugs available to treat osteoporosis.5 Teriparatide, which in the 2017 NOGG guidance was second-line treatment and reserved for patients at very high risk, is now first-line treatment for patients at very high risk (Figure 1).3,5,9
Box 2: Drugs available to treat osteoporosis[A],5
- ibandronic acid (oral or injection)
- zoledronic acid (IV)
- raloxifene (in women only)
- denosumab (injection)
- hormone replacement therapy (menopausal women/testosterone replacement in male hypogonadism)
- Bone forming (anabolic)19–22
- teriparatide (self-injected)
- biosimilar teriparatide (self-injected)
- romosozumab (injection).
[A] Prescribers should refer to the individual summaries of product characteristics.11–16,19–22
The consensus guideline confirms the use of antiresorptive medications, that is, the bisphosphonates: alendronate, risedronate, ibandronic acid, and zoledronic acid. Raloxifene, a selective oestrogen receptor modulator, can be used in women, as well as hormone replacement for men and women. The monoclonal antibody denosumab can also be used.5
Duration of treatment
The duration and progression of treatments are reviewed, with a recommendation to continue with antiresorptive agents after 2 years of teriparatide, 1 year of romosozumab, and if stopping denosumab (only on specialist advice) to also continue with an antiresorptive. Switching from denosumab should be avoided and specialist advice should be sought.5
With regard to duration of treatment, the consensus guideline states that this should be as per local or national guidelines with review of the risks versus benefits of discontinuing therapy. It cites SIGN guidance that: alendronate and strontium can be continued for 10 years (if osteoporosis is severe and other treatments are unsuitable), risedronate for 7 years, and zoledronic acid for 3 years, although this can be used every 18 months for 6 years off licence. See Figure 1.4,5
There are organisational and resource challenges to arrange treatment in line with the consensus guidance. These include:
- how does secondary care identify patients who are at imminent and high risk?
- how do GPs, having identified patients at imminent and high risk, facilitate prompt treatment?
The first point relates to where patients have had a fragility fracture and secondary prevention has not been initiated in secondary care, and the second to where patients have only received care in primary care for their fracture. The author’s personal experience, working in Scotland and also having worked in rural New Zealand, is that fragility fractures may often be treated in primary care.
The consensus guideline acknowledges the need for seamless care from secondary to primary care; on discharge from hospital, patients need to be assessed in primary care by a pharmacist, GP, or maybe a bone health lead in the practice.5 At this assessment the need for intravenous therapy can be reassessed. Perhaps there is now an enhanced role for Fracture Liaison Services in supporting or providing these elements of care.23
How the consensus guideline fits in with other UK guidelines
Other current UK osteoporosis guidelines are SIGN 2015, updated in June 2020;4 NOGG 2017;3 and NICE 2012, updated 20172, whose guidance was on the assessment of the risk of fragility fracture with a separate technology appraisal (TA) on the medication.24
Both FRAX® and QFracture® intervention thresholds are based on expert recommendation rather than evidence. NICE declines to recommend intervention thresholds in its guidance on Osteoporosis: assessing the risk of fragility fracture.25 SIGN prefers the use of QFracture® for initially assessing the risk of fragility fracture, as FRAX® has not been available for independent verification.4 QFracture® does not define risk categories, so SIGN has an expert recommendation of a 10% risk threshold, and for treatment to be a professional decision. SIGN therefore did not categorise into very high, high, and low risk. However, SIGN recommends anabolic treatments in some patients at higher risk; teriparatide (parathyroid hormone 1-34) is recommended to prevent vertebral and non-vertebral fractures in postmenopausal women with severe osteoporosis. In addition, in postmenopausal women with at least two moderate or one severe low-trauma vertebral fractures, teriparatide is recommended over oral bisphosphonates, to prevent vertebral fracture.4 SIGN has also introduced treatment with zoledronic acid for osteopenia (that is a T-score of –1.0 to –2.5) in people aged 65 years and over.4
NICE recommends either FRAX® or QFracture® for the initial assessment before a DXA scan.2 NICE re-issued TA464 on Bisphosphonates for treating osteoporosis, in April 2019.24 This was because a TA should be an economic assessment and it was, in effect, a clinical assessment.26 NICE concluded the technology assessment by saying:24
‘The choice of treatment should be made on an individual basis after discussion between the responsible clinician and the patient, or their carers, about the advantages and disadvantages of the treatments available. If generic products are available, start treatment with the least expensive formulation, taking into account administration costs, the dose needed and the cost per dose.’
In effect, the lack of good evidence of intervention thresholds leaves clinicians to either make their own decisions (SIGN and NICE)2,4 or to go with the expert recommendations from Kanis’ paper,9 the NOGG guideline,3 and the recent consensus guideline where FRAX® is used to refine characterisation of risk.5
There is a broad spectrum of guidance on osteoporosis—SIGN takes a professional/patient-led approach, where the clinician, along with the patient, looks at the QFracture® and DXA scan risks and where there is a 10% fracture risk decides on treatment; NICE allows either QFracture® or FRAX® to aid decision-making but is unable currently to recommend intervention thresholds; and NOGG and the consensus guideline identify patients who are at imminent and high risk and treat on this basis.
As a GP in Scotland, I should adhere to SIGN guidance, but if I were to need further guidance on the identification of patients at very high risk I would need to go with FRAX®. It is hoped that the new consensus guideline will help practitioners manage patients at different levels of risk and guide appropriate treatment decisions.
Dr David Stephens
Member of the consensus guideline development group
Take-home messages for GPs
- Have systems that promptly identify all patients on your list who have had a fragility fracture
- Identify—either remotely or face to face—which patients are at imminent or very high risk, by using either FRAX® or QFracture®, with a follow up DXA scan
- do this within 1 week. If you make a decision that the patient is at imminent or very high risk, check they have been treated promptly in secondary care or refer urgently for bone-building medication. Consult with the patient (either on the telephone, by video conference, or in the surgery) as to whether they want to be seen for treatment in secondary care. Assess whether treatment in hospital is worth the risk in the COVID-19 environment
- Delays cost lives; a further fragility fracture, especially a hip fracture, can be fatal
- Commissioning is not only using the commissioned services, but you as a professional requesting and requiring that your patient gets the best care available
- Require your CCG or health board to provide care in a timely way for your patients
- Ensure appropriate follow up.
Guidance during the COVID-19 pandemic5
- In the absence of BMD measurements, do not delay initiating treatment for patients deemed high or very high risk; if appropriate, arrange a DXA scan when available
- Reiterate the importance of calcium/vitamin D intake and home exercise to patients who are staying at home/self-isolating
- Falls prevention advice and exercise advice can be given remotely; provide the following link to patients for exercise videos on the ROS website: theros.org.uk/information-and-support/osteoporosis/living-with-osteoporosis/exercise-and-physical-activity-for-osteoporosis/
- Follow up with care-home patients with fragility fractures using telephone clinics
- Some patients will require face-to-face assessments, especially if they have learning difficulties or cognitive decline
- Reiterate the importance of medication adherence to reduce fracture risk
- Denosumab treatment should be continued; if suitable, patients can be enrolled in the self-injection programme; refer to ROS guidance: theros.org.uk/healthcare-professionals/covid-19-hub/denosumab-prolia-treatment-and-the-covid-19-pandemic/
- COVID-19 guidance is also available from the IOF: www.capturethefracture.org/covid-19-all-ctf-fls-centers
BMD=bone mineral density; DXA=dual-energy X-ray absorptiometry; ROS=Royal Osteoporosis Society; IOF=International Osteoporosis Foundation
Implementation actions for STPs and ICSs
written by Dr David Jenner, GP, Cullompton, Devon
The following implementation actions are designed to support STPs and ICSs with the challenges involved with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources.
- Recognise that the management of osteoporosis represents a major challenge to healthcare systems due to multiple and sometimes conflicting guidelines
- Agree, define, and publish a local care pathway based on the available evidence and guidelines, and crafted by a multidisciplinary team including primary care
- Ensure rapid access to bone mineral density scanning as a vital component of any care pathway, supported by specialist advice and guidance
- Update local formularies with options for pharmacological treatments for osteoporosis, with clear guidance on which of these should be initiated by a specialist and which in primary care
- Make local recommendations for the periodic review of such products, because of the risk of atypical fractures with long-term use
- Consider commissioning and providing a fracture liaison service to rapidly assess and address fracture risk in people who have recently had a fracture.
STP=sustainability and transformation partnership; ICS=integrated care system
Implementation actions for clinical pharmacists in general practice
written by Nicola Cree, Pharmaceutical Services Manager, Soar Beyond Ltd
The following implementation actions are designed to support clinical pharmacists in general practice with implementing the guidance at a practice level.
Clinical practice pharmacists can enhance and improve patient outcomes. Any such work will also support the PCN DES, which lists patients who have had a recent fall as prime targets for structured medication reviews.[A]
- Identify patients at risk of fracture by opportunistically incorporating assessments into existing clinics such as those for the frail
- Assess the skills and competencies held by practice pharmacists and how they can be best used to support patients
- Search for patients suitable for a pharmacist-led review, which may include:
- postmenopausal women
- patients with recent fractures
- patients with known non-adherence
- Ensure osteoporosis reviews cover a wide range of priorities, including:
- lifestyle advice
- counselling on medicines use and adverse effects
- advice on, and strategies to improve, treatment adherence
- appropriate prescribing and deprescribing
- Support patients with adherence and optimisation of medicines use in osteoporosis.
Guidance and training for service development is available for a number of different clinical areas from Soar Beyond. If you have clinical pharmacists in your practice or organisation, contact Soar Beyond to see how we can support with their clinical delivery, training and development soarbeyond.co.uk
[A] NHS England and NHS Improvement. Network Contract Directed Enhanced Service Contract specification 2020/21—PCN requirements and entitlements. NHSEI, March 2020. Available at: www.england.nhs.uk/wp-content/uploads/2020/03/network-contract-des-specification-pcn-requirements-entitlements-2020-21.pdf
PCN=Primary Care Network; DES=Direct Enhanced Service
- Royal Osteoporosis Society. Quality standards for osteoporosis and prevention of fragility fractures. ROS, 2017. Available at: theros.org.uk/media/0dillsrh/ros-op-standards-november-2017.pdf
- NICE. Osteoporosis: assessing the risk of fragility fracture. Clinical Guideline 146. NICE, 2012 (updated 2017). Available at: www.nice.org.uk/cg146
- Compston J, Cooper A, Cooper C et al; National Osteoporosis Guideline Development Group. Clinical guideline for the prevention and treatment of osteoporosis. Arch Osteopororis 2017; 12 (1): 43. Available at: ww.sheffield.ac.uk/NOGG/NOGG%20Guideline%202017.pdf
- Scottish Intercollegiate Guidelines Network. Management of osteoporosis and the prevention of fragility fractures. SIGN, 2020. Available at: www.sign.ac.uk/media/1741/sign142.pdf
- Cooper C, Javaid K, Elliot M et al. UK consensus guideline on the management of patients at low, high, and very high risk of osteoporotic fracture. Guidelines, 2020. Available at: www.guidelines.co.uk/musculoskeletal-and-joints-/osteoporotic-fracture-guideline/455546.article
- General Medical Council. Good practice in prescribing and managing medicines and devices. GMC, 2013. Available at: www.gmc-uk.org/ethical-guidance/ethical-guidance-for-doctors/prescribing-and-managing-medicines-and-devices (accessed 6 December 2020).
- Royal Osteoporosis Society. Strong, steady and straight. ROS, 2018. Available at: theros.org.uk/clinical-publications-and-resources/
- Royal Osteoporosis Society. Strong, steady and straight—Quick guide. ROS, 2018. Available at: theros.org.uk/clinical-publications-and-resources/
- Kanis J, Harvey N, McCloskey E et al. Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures. Osteoporosis International 2020; 31: 1–12. link.springer.com/article/10.1007/s00198-019-05176-3
- Ranbaxy (UK) Ltd. Zoledronic acid 5 mg solution for infusion—summary of product characteristics. April 2020. www.medicines.org.uk/emc/medicine/28527
- Merck Sharp & Dohme Limited. Fosamax once weekly 70 mg tablets—summary of product characteristics. September 2020. www.medicines.org.uk/emc/product/1281
- Sandoz Limited. Risedronate sodium 35 mg film-coated tablets—summary of product characteristics. December 2015. www.medicines.org.uk/emc/product/4767/smpc
- Novartis Pharmaceuticals UK Ltd. Aclasta 5 mg solution for infusion—summary of product characteristics. March 2020. www.medicines.org.uk/emc/product/210
- Atnahs Pharma UK Ltd. Bonviva 150 mg film-coated tablets—summary of product characteristics. May 2019. Available at: www.medicines.org.uk/emc/product/9383/smpc
- Daiichi Sankyo UK Limited. Evista 60 mg film-coated tablets—summary of product characteristics. October 2017. Available at: www.medicines.org.uk/emc/product/3778
- Amgen Ltd. Prolia 60 mg solution for injection in pre-filled syringe—summary of product characteristics. September 2020. www.medicines.org.uk/emc/product/568
- Bowring C, Francis R. National Osteoporosis Society’s Position statement on hormone replacement therapy in the prevention and treatment of osteoporosis. Menopause Int 2011; 17 (2): 63–65.
- NICE. Menopause: diagnosis and management. NICE Guideline 23. NICE, 2015 (last updated 2019). Available at: www.nice.org.uk/guidance/ng23
- Eli Lilly and Company Limited. Forsteo 20 micrograms/80 microlitres solution for injection in pre-filled pen—summary of product characteristics. October 2020. www.medicines.org.uk/emc/product/2215
- Gedeon Richter (UK) Ltd. Terrosa 20 micrograms/80 microliters solution for injection—summary of product characteristics. March 2019. www.medicines.org.uk/emc/product/10717
- Thornton & Ross Limited. Movymia 20 micrograms/80 microliters solution for injection—summary of product characteristics. June 2019. www.medicines.org.uk/emc/product/10780
- UCB Pharma Limited. EVENITY 105 mg solution for injection in pre-filled pen. December 2019.www.medicines.org.uk/emc/product/10956
- Royal College of Physicians. Fracture Liaison Service database annual report. Beyond measurement: a focus on quality improvement. London: RCP, 2020. www.rcplondon.ac.uk/projects/outputs/fls-database-annual-report-2020
- NICE. Bisphosphonates for treating osteoporosis. Technology Appraisal 464. NICE, 2017 (updated 2019). Available at: www.nice.org.uk/guidance/ta464
- National Clinical Guideline Centre. Osteoporosis: assessing the risk of fragility fracture. Evidence and recommendations. Short Clinical Guideline 146. NCGC, 2012. Available at: www.nice.org.uk/guidance/cg146/evidence
- NICE. Bisphosphonates for treating osteoporosis. Evidence: review decision—July 2019. Technology appraisal 464. NICE, 2017 (updated 2019). www.nice.org.uk/guidance/ta464/evidence/review-decision-july-2019-6841170541?tab=evidence