See ‘Who to assess for risk of a fragility fracture’ below

Use the online fracture risk assessment tool FRAX to assess fracture risk in patients aged between 40 and 90 years (for more information, including guidance on patients below 40 years, see ‘How is fracture risk assessed’ below)

Re-assess fracture risk if a fracture occurs or if clinical risk factors change, otherwise refer to the following sections for when to re-assess fracture risk:

• If the patient is receiving treatment for osteoporotic fracture risk, see section ‘Duration of treatment and re-assessment’ below
• If the threshold for treatment was not met, see Green Zone under section ‘Decisions on DXA scan, Treatment and Referral’ below

Who to assess for risk of a fragility fracture

NICE guidance (CG146) recommends assessing fragility fracture risk in the following patients:

• All women aged 65 years and over
• All men aged 75 years and over
• Women aged 50 to 64 years and men aged 50 to 74 years with a previous fragility fracture
• Women aged 50 to 64 years and men aged 50 to 74 years who have any of the following risk factors:
  • current use of oral glucocorticoids (more than 7.5mg/day prednisolone or equivalent for 3 months or longer);
  • history of falls;
  • family history of hip fracture;
  • BMI less than 18.5 kg/m²;
  • smoking;
  • alcohol intake >14 units/week for men and women;
  • secondary causes of osteoporosis
    • hypogonadism in either sex and treatment with aromatase inhibitors or androgen deprivation therapy;
    • endocrine conditions – diabetes, Cushing’s disease, hyperthyroidism, hyperparathyroidism and hyperprolactinaemia;
    • conditions associated with malabsorption – IBD, coeliac disease, chronic pancreatitis; other causes of malabsorption;
    • rheumatoid arthritis & inflammatory arthritis;
    • haematological malignancy conditions such as multiple myeloma and haemoglobinopathies;
    • COPD;
    • chronic liver failure;
    • chronic kidney disease stage 3 or worse (eGFR<60mls/min/1.73m²);
    • immobility (due for example to neurological injury or disease)
• People younger than 50 years of age with any of the following risk factors:
  • Current use of oral glucocorticoids (more than 7.5mg/day prednisolone or equivalent for 3 months or longer);
  • Untreated premature menopause (under 40 years);
  • A previous fragility fracture

Which fractures should be classed as a fragility fracture?

• By definition, a fragility fracture occurs from an injury that would not ordinarily result in a fracture; pragmatically, use a fall from standing height or less as a benchmark.
• Fragility fractures occur most commonly in the spine (vertebrae), hip (femoral neck or proximal femur) or distal radius; they can also occur in the humerus, pelvis, & other long bones. Vertebral fractures may occur spontaneously and can be pain-free or incidental findings, or as a result of routine activities such as bending or lifting. An incidental vertebral fracture diagnosed on imaging is classed as a fragility fracture.
• Fractures in the skull or face, or long bones of the hand or foot fractures would not be considered a fragility fracture.

How is fracture risk assessed?

Patients aged between 40 and 90 years

Use the online fracture risk assessment tool FRAX to both assess the need for a DXA scan and to guide decisions about treatment before and after DXA scanning.

After calculating the 10-year probability of a fracture risk, click the “view NOGG guidance” button to show a chart that plots a person’s calculated fracture risk against their age.

Points to be aware of:

• Interpret the estimated absolute risk of fracture in people aged over 80 years with caution, because predicted 10-year fracture risk may underestimate their short-term fracture risk.
• Fracture risk may be underestimated in certain circumstances, for example if a person:
  • has a history of multiple fractures
  • has had previous vertebral fracture(s)
  • has a high alcohol intake
  • is taking oral glucocorticoids (more than 7.5mg/day prednisolone or equivalent for 3 months or longer).
  • has other causes of secondary osteoporosis
• Fracture risk can be affected by factors that may not be included in the risk tool, for example:
  • living in a care home, or
  • taking drugs that may impair bone metabolism (such as anti-convulsants, selective serotonin reuptake inhibitors, thiazolidinediones, proton pump inhibitors and antiretroviral drugs)

Patients below 40 years of age

Measure BMD to assess fracture risk in people aged under 40 years who have a major risk factor, such as history of multiple fragility fracture, major osteoporotic fracture, or current use of oral glucocorticoids (more than 7.5mg/day prednisolone or equivalent for 3 months or longer).

These recommendations are based on the 2022 guidelines from the National Osteoporotic Guideline Group. 

Use the NOGG fracture risk chart for major osteoporotic fractures to inform decisions on whether to refer for a DXA scan, start drug treatment and seek advice from a specialist. Recommendations apply to men and women.

Low risk of fragility fracture (green zone)

• Offer lifestyle advice (see below). Drug treatment not required.
• DXA scan not required.
• Re-assess FRAX in 5 years unless there has been a change in clinical risk factors.
• Start drug treatment promptly and re-emphasise lifestyle factors if the patient sustains a fragility fracture.

Intermediate risk of fragility fracture (amber zone)

• Offer lifestyle advice (see below).
• Refer for DXA scan. Repeat the FRAX assessment incorporating BMD and manage according to the patient’s risk of fracture (high, very high or low) on the NOGG fracture risk chart for a major osteoporotic fracture.
• Offer drug treatment if BMD measurement is unavailable, contraindicated, or impractical (e.g., in frail individuals) and there is a history of fragility fracture or if fracture risk exceeds the intervention threshold.

High risk/very high risk of fragility fracture (lower and upper red zone)

• Offer lifestyle advice (see below)
• Consider whether there are any reversible causes of low bone density which could be improved to reduce fracture risk including:
  • Use of oral glucocorticoid (more than 7.5mg/day prednisolone or equivalent for 3 months or longer);
  • BMI < 18.5 kg/m²;
  • Current smoking;
  • Alcohol intake > 14 units/week;
• If there are secondary causes of osteoporosis, are these managed optimally?
• Calcium / vitamin D supplementation if needed (see ‘Pharmacological treatments’ below)?
• Offer drug treatment. Consider seeking specialist advice on whether a DXA scan is required/appropriate in this group e.g., high risk patients who may be appropriate for teriparatide therapy. Do not wait for a DXA scan before starting treatment (see ‘Pharmacological treatments’) below.
• Patients in the upper red zone are at very high risk of fragility fracture: 
  • Consider seeking specialist advice for assessment and consideration of parenteral treatment. 
  • If specialist advice is not sought, treat as high risk.

Advise the person to:

• Exercise regularly;
• Eat a balanced diet, including adequate calcium and vitamin D;
• Stop smoking;
• Restrict alcohol to ≤ 2 units/day

There are excellent resources about osteopenia and lifestyle advice to maintain bone health on the Royal Osteoporosis Society website.

Approach to treatment:

• Calculate dietary calcium intake (see ‘Calcium and vitamin D’ below).
• Consider seeking specialist advice for patients at very high risk of a fragility fracture for assessment and consideration of parenteral treatment (some may need first-line anabolic drug treatment).
• In other patients for whom treatment is indicated, offer antiresorptive therapy with oral bisphosphonates.
• Consider alternative treatment options if these first-line bisphosphonates are unsuitable or not tolerated.

Calcium and vitamin D

If a person’s calcium intake is less than 700mg/day, prescribe a calcium and vitamin D supplement. Dietary intake can be calculated using this on-line calculator for calcium intake. For calcium and vitamin D supplements, see section 9.6.4 Vitamin D.

Vitamin D monotherapy can be considered if a person’s calcium intake is greater than 700mg/day. See section 9.6.4 Vitamin D.

Oral bisphosphonates

• Prescribe an oral bisphosphonate for patients with a fragility fracture or fracture threshold exceeding the intervention threshold on the NOGG graph, unless seeking advice from a specialist is appropriate (patients at very high risk of a fragility fracture) or contraindication to oral bisphosphonate (see below):
  • Alendronic acid
  • Risedronate
  • Ibandronic acid

• For information on individual drugs, see section 6.6.2 Bisphosphonates and other drugs affecting bone metabolism.
• Review 3 months after commencing treatment to discuss possible side effects and treatment adherence.
• Check adherence after 12 months of treatment.
• Review at 5 years of treatment and re-assess fracture risk (see ‘Duration of treatment and re-assessment’ below)

Which patients should be considered for parenteral treatment:

• People intolerant of both alendronic acid AND risedronate;
• People with reduced oral medication adherence;
• People where oral bisphosphonates are contraindicated:
  • Active GI bleeding, or GI ulcers in the last 12 months;
  • Dysphagia
  • Previous upper GI surgery
• People with an eGFR consistently less than 35mL/minute/1.73m²;
• People who have fractured despite adhering with oral bisphosphonate therapy;
• People with severe osteoporosis eligible for teriparatide or romosozumab therapy:
  • Advice will be offered on a DXA report if indicated or patients will be identified by a specialist team

Specialist options

Denosumab (Prolia)

• Subcutaneous injection administered by healthcare professional every 6 months. Initiated by specialist, may be continued in primary care under a shared care prescribing guideline. Initial treatment period 5 years.
• See section 6.6.2 Bisphosphonates and other drugs affecting bone metabolism.

Abaloparatide (anabolic agent)

• Once daily administration of subcutaneous injection for 18 months. Once only course, not to be repeated.
• See section 6.6.1 Calcitonin and parathyroid hormone

Romosozumab (anabolic agent)

• Subcutaneous injections administered once a month for 12 months. Once only course, not to be repeated.
• See section 6.6.2 Bisphosphonates and other drugs affecting bone metabolism.

Teriparatide (anabolic agent)

• Once daily administration of subcutaneous injection for 24 months. Once only course, not to be repeated.
• See section 6.6.1 Calcitonin and parathyroid hormone.

Zoledronic acid (bisphosphonate)

• Intravenous infusion. Initial treatment period 3 years.
• See section 6.6.2 Bisphosphonates and other drugs affecting bone metabolism.

See below for further information on ‘Duration of treatment and re-assessment’.

Oral bisphosphonates

Fracture risk should be re-assessed using FRAX at any time during treatment if re-fracture occurs or clinical risk factors change. Refer for a DXA scan as  appropriate. Seek advice from a specialist in cases of re-fracture, parenteral treatment may be appropriate.

Plan to prescribe for 5 years and re-assess fracture risk. Follow the NOGG flowchart for oral bisphosphonates: long-term treatment and monitoring (figure 4 or page 37 of pdf).

Treatment may be continued for a further 5 years in the following men and women:

• Age ≥70 years at the time that the bisphosphonate is started
• Who have a previous history of a hip or vertebral fracture(s)
• Current use of oral glucocorticoids more than 7.5 mg prednisolone/day or equivalent for 3 months or longer
• Who experience one or more fragility fractures during the first 5 years of treatment (if treatment is not changed following re-evaluation of treatment options)

Pause in treatment ‘drug holiday’

Consider a pause in treatment in appropriate patients for:

• 18 months for risedronate and oral ibandronic acid; re-assess fracture risk
• 3 years for alendronic acid; re-assess fracture risk

Calcium and vitamin D supplementation should continue throughout if needed.

Repeat a FRAX score at this point. Restart antiresorptive therapy if the patient is above the treatment threshold, a new fragility fracture has occurred, or if the patient has commenced long term oral glucocorticoid therapy of more than 7.5 mg/day of prednisolone or equivalent for 3 months or longer.

How should patients be managed after 10 years of therapy?

The NOGG guideline indicates that patient management should be considered on an individual basis.

There is little evidence to support treatment decisions after 10 years duration of bisphosphonate therapy. Local specialists advise most patients, at this point, may benefit from a 2 year treatment holiday to reduce the risk of atypical fracture; some high-risk patients, particularly those who have fractured on treatment, may require ongoing treatment.

Prescribing decisions in these circumstances should be taken on an individual shared-decision basis, with uncertainties about risk vs benefit discussed with the patient. Specialist advice and support may be appropriate.

Intravenous zoledronic acid

A treatment course usually consists of 3 infusions, with a review of fracture risk and the need for ongoing therapy at that point.

Denosumab

MHRA Drug Safety Update (August 2020): Denosumab 60mg (Prolia): increased risk of multiple vertebral fractures after stopping or delaying ongoing treatment

There is a shared care prescribing guideline for denosumab.

• Reassess fracture risk using FRAX, normally including a repeat DXA scan, after a maximum of 5 years of treatment.
• Denosumab cessation leads to rapid reductions in BMD and elevations in bone turnover to levels above those seen before treatment initiation. Denosumab should not be stopped without considering alternative treatment to prevent rapid bone mineral density loss and a potential rebound in vertebral fracture risk.
• GPs should seek advice from a specialist if they consider treatment with denosumab is no longer appropriate for a patient or the patient wishes to discontinue treatment.

Anabolic agents (romosozumab, abaloparatide, and teriparatide)

• Romosozumab, abaloparatide, and teriparatide are licensed for a once only treatment course of 12 months, 18 months, and 24 months respectively.
• Following completion of the course, treatment with a bisphosphonate or denosumab should be initiated without delay.
• A long-term management plan will be issued for patients receiving these treatments.

Bisphosphonates

MHRA Drug Safety Update (November 2009), MHRA Drug Safety Update (July 2015): Bisphosphonates: osteonecrosis of the jaw (ONJ)

• The risk of developing ONJ in association with oral bisphosphonates seems to be low. The risk of ONJ is substantially greater for patients receiving intravenous bisphosphonates for cancer indications than for patients receiving oral bisphosphonates for osteoporosis or Paget’s disease
• There is clear evidence to suggest bisphosphonate-specific and indication-specific risk factors such as potency (highest for zoledronate); route of administration (eg, intravenous ibandronate, pamidronate, and zoledronate); and cumulative dose. The evidence base is less robust for other proposed risk factors (eg, duration and type of malignant disease, concomitant treatment, smoking, and comorbid conditions). However, healthcare professionals should consider these risk factors when evaluating an individual’s risk of developing ONJ
• A history of dental disease—including invasive dental procedures, dental trauma, periodontal disease, and poorly fitting dentures—is associated with an increased risk of ONJ

Risk minimisation:

• All patients with cancer should have a dental check-up before bisphosphonate treatment. All other patients who start bisphosphonates should have a dental examination only if they have poor dental status
• During bisphosphonate treatment, patients should maintain good oral hygiene, receive routine dental check-ups, and report any oral symptoms such as dental mobility, pain, or swelling

MHRA Drug Safety Update (June 2011): Bisphosphonates: atypical femoral fractures

• atypical femoral fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture
• discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered while they are evaluated, and should be based on an assessment of the benefits and risks of treatment for the individual
• during bisphosphonate treatment, patients should be advised to report any thigh, hip, or groin pain. Any patient who presents with such symptoms should be evaluated for an incomplete femur fracture
• the optimum duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of bisphosphonate therapy for individual patients, particularly after 5 or more years of use

MHRA Drug Safety Update (December 2015): Bisphosphonates: very rare reports of osteonecrosis of the external auditory canal

• The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms, including chronic ear infections, or in patients with suspected cholesteatoma
• Possible risk factors include steroid use and chemotherapy, with or without local risk factors such as infection or trauma
• Patients should be advised to report any ear pain, discharge from the ear, or an ear infection during bisphosphonate treatment

Denosumab

MHRA Drug Safety Update (February 2013): Atypical femoral fractures

• during denosumab treatment, patients should be advised to report new or unusual thigh, hip, or groin pain; patients presenting with such symptoms should be evaluated for an incomplete femoral fracture
• atypical femoral fractures may occur with little or no trauma in the subtrochanteric and diaphyseal regions of the femur
• the contralateral femur should be examined in denosumab-treated patients who have sustained a femoral shaft fracture, as atypical femoral fractures are often bilateral (as noted from the bisphosphonates assessment)
• discontinuation of denosumab treatment should be considered if an atypical femur fracture is suspected, while the patient is evaluated; an individual assessment of the benefits and risks should be performed

MHRA Drug Safety Update (July 2015): Denosumab (Xgeva, Prolia); intravenous bisphosphonates: osteonecrosis of the jaw—further measures to minimise risk

Before prescribing denosumab or intravenous bisphosphonates:

• give patients the patient reminder card for their medicine
• explain the risk of osteonecrosis of the jaw and advise patients on precautions to take—advise patients to:
  • tell their doctor if they have any problems with their mouth or teeth before starting treatment; if they wear dentures they should make sure their dentures fit properly before starting treatment
  • maintain good oral hygiene and get routine dental check-ups during treatment
  • tell their doctor and dentist that they are receiving denosumab or an intravenous bisphosphonate if they need dental treatment or dental surgery
  • tell their doctor and dentist immediately if they have any problems with their mouth or teeth during treatment (eg loose teeth, pain, swelling, non-healing sores or discharge)
• do not prescribe denosumab 120 mg (cancer indication) to patients with unhealed lesions from dental or oral surgery

MHRA Drug Safety Update (June 2017): Osteonecrosis of the external auditory canal

• the possibility of osteonecrosis of the external auditory canal should be considered in patients receiving denosumab who present with ear symptoms including chronic ear infections or in those with suspected cholesteatoma
• possible risk factors include steroid use and chemotherapy, with or without local risk factors such as infection or trauma
• advise patients to report any ear pain, discharge from the ear, or an ear infection during denosumab treatment

MHRA Drug Safety Update (August 2020): Denosumab 60mg (Prolia): increased risk of multiple or vertebral fractures after stopping or delaying ongoing treatment

• an increased risk of multiple vertebral fractures has been reported in patients within 18 months of stopping or delaying ongoing denosumab 60mg treatment for osteoporosis; cases have been reported in patients in the UK
• patients with a previous vertebral fracture may be at highest risk
• evaluate a patient’s individual factors for benefits and risks before initiating treatment with denosumab, particularly in patients at increased risk of vertebral fractures for example those with previous vertebral fracture
• patients should not stop denosumab without specialist review
• the optimal duration of denosumab treatment for osteoporosis has not been established; re-evaluate the need for continued treatment periodically based on the expected benefits and potential risks of denosumab on an individual patient basis, particularly after 5 or more years of use
• risks of long-term treatment with denosumab include rare cases of osteonecrosis of the jaw and atypical femoral fractures; osteonecrosis of the external auditory canal has also been reported in association with denosumab.

Assess fracture risk using FRAX if current use of oral glucocorticoids (more than 7.5mg/day prednisolone or equivalent for 3 months or longer) in:

• Women aged 64 years and younger
  • Specialist advice should be sought before treatment is considered for premenopausal women (see below)
• Men aged 74 years and younger

Fracture risk assessment is recommended for all patients above these ages, regardless of risk factor status.

Start treatment to prevent osteoporosis at the same time as glucocorticoid therapy in the following people:

• anyone with a prior fragility fracture,
• women age ≥70 years,
• postmenopausal women, and men age ≥50 years:
  • prescribed high doses of oral glucocorticoids, more than 7.5 mg/day of prednisolone or equivalent for 3 months or longer, or
  • with a FRAX probability of major osteoporotic fracture exceeding the intervention threshold.

Treatment decisions in people taking corticosteroids

• Specialist advice and guidance should be sought before treatment is considered for pre-menopausal women. Bisphosphonates should be used with great caution in premenopausal women as they are released from the skeleton over many years, cross the placenta and teratogenic effects have been demonstrated in animals.
• Consider requesting specialist advice and guidance in other patients younger than 50 who are assessed to be at high risk of fracture.
• In those where treatment is recommended, continue treatment with bisphosphonates and calcium and vitamin D (if needed) until treatment with oral corticosteroids has stopped.
• Reassess fracture risk using FRAX after stopping steroid treatment to determine the need for further treatment.

HRT maintains BMD for as long as it is taken.

Should not be used for osteoporosis protection only unless all other therapies are contra-indicated or not tolerated: see section 6.4.1 Female sex hormones for further guidance.

• Avoid prolonged rest. The patient should be encouraged to mobilise within the first few days with adequate analgesia
• Strong opioids, e.g. morphine in adequate doses may be needed for a few weeks. Subsequently, consider simple analgesics and/or NSAIDs. If NSAIDs are prescribed, take into account the safety profile of NSAIDs and the age of the patient
• Calcitonin 100 IU im on alternate days for 3 weeks can reduce the duration of pain post vertebral fracture but this is probably equivalent in analgesic effect to strong opioids
• Commence therapy for osteoporosis to reduce risk of further fracture
• Advice from physiotherapy regarding lifting and upper body strengthening
• Patients for whom vertebroplasty may be an appropriate intervention should be discussed with the specialist for the service.
• NICE TA279: Percutaneous vertebroplasty and percutaneous balloon kyphoplasty are recommended as options for treating osteoporotic vertebral compression fractures only in people:
  • who have severe ongoing pain after a recent, unhealed vertebral fracture despite optimal pain management and
  • in whom the pain has been confirmed to be at the level of the fracture by physical examination and imaging