GP to review all patients taking a Bisphosphonate

[3yrs for zoledronate (hospital only); 5yrs for other bisphosphonates]

Has patient suffered a fragility fracture on treatment?

(Hip/vertebral/multiple fragility fracture)

No Yes

DOES PATIENT HAVE A “HIGH RISK” INDICATOR? GP TO CHECK COMPLIANCE GP TO CHECK COMPLIANCE

 Patient ≥ 75 years with frequent falls If good compliance then continue If good compliance then consider
 Previous hip or vertebral fracture bisphosphonate treatment4 treatment failure. Refer patient
 
Taking continuous oral glucocorticoid to the Osteoporosis Clinic (SGH)
 Taking an aromatase inhibitor 1 e.g. Letrozole (Femara®), Yes If poor compliance then discuss to consider switching to a drug
Anastrozole (Arimidex®) and Exemestane (Aromasin®) with patient. May require referral with different mode of action
 Taking a gonadotropin-releasing hormone (GnRH) agonists e.g. to the Osteoporosis Clinic (SGH). e.g. S/C Denosumab 60mg
Leuprorelin acetate (Prostap ® SR or 3) and Goserelin (Zoladex®
or LA) Plus If poor compliance then discuss
 Taking an anti-epileptic drug e.g. phenytoin (Epanutin),  Check calcium and vitamin D with patient. May require
carbamazepine (Tegretol), primidone (Mysoline) and sodium intake (including OTC) referral to the Osteoporosis
valproate (Epilim)  Exclude secondary causes, Clinic (SGH).
NOGG2 (next page)
 Advise patient to report any Plus
thigh, hip or groin pain which  Check calcium and vitamin D
may be indicative of an atypical intake (including OTC)
No femoral fracture  Exclude secondary causes,
 Patients to maintain good oral NOGG2 (next page)
hygiene, receive routine dental  Advise patient to report any
check-ups, and report any oral thigh, hip or groin pain which
PATIENTS <75yrs symptoms. may be indicative of an
1. Complete DXA to obtain T-scores atypical femoral fracture
2. Use T-score for femoral neck BMD (g/cm2) to calculate FRAX*  Patients to maintain good oral
score for patient hygiene, receive routine
3. Follow green or red2 outcome measure dental check-ups, and report
any oral symptoms.

Red HIGH RISK PATIENTS

PATIENTS >75yrs If patient total hip or femoral neck DXA T-score is <-2.5 or
1. Calculate FRAX* score8 (T-score not required as patient is If patient FRAX score is in the “red zone” then
>75yrs). “GP TO CHECK COMPLIANCE” above
2. Follow green, amber or red2 outcome measure

Yes
INTERMEDIATE RISK PATIENTS
Does patient have a new independent clinical risk factor or an
indicator of low BMD?
Amber
Clinical Risk factors
 Parental history of hip fracture
*http://www.shef.ac.uk/FRAX/tool.aspx  Alcohol intake (≥4units per day)
 Rheumatoid Arthritis

Indicators of Low Bone Mineral Density (BMD)

 Low body mass index (BMI) ≤ 19kg/m2
Green  Ankylosing spondylitis
 Immobilisation
 Long term smoking

Follow “yes” or “no” arrow

LOW RISK PATIENTS
If patient total hip or femoral neck DXA T-score is >-2.5
or
If patient FRAX score is in the “green zone” then patient to take a
“Drug Holiday”.3

No

PATIENT TO TAKE A “DRUG HOLIDAY”3

Alendronate 2yrs
Risedronate 1yr
Zolendronate 3yrs
[Patient to continue adequate intake of
calcium and vitamin D during drug holiday]

Repeat FRAX8 and DXA scan after “drug holiday” (No DXA scan required >75yrs)
Bisphosphonates Long term use and possible side effects

Bisphosphonates are widely prescribed for the treatment of osteoporosis. They
have a high affinity for bone and reduce bone resorption and increase bone
mineral density (BMD) by altering osteoclast activation and function.
Bisphosphonates have a long half-life in bones and their anti-fracture efficacy
continues for some years after stopping.
[Drugs: alendronate, risedronate, ibandronate and zolendronate]
Long term use of oral bisphosphonates is not without its
risks. This is related to accumulation of the bisphosphonate
in bone, reducing bone turnover and ultimately decreasing
healing. This has resulted in two identified clinical
syndromes Osteonecrosis of the Jaw (ONJ)6 and Atypical
Femur Fractures (AFF).7

Optimal duration

The optimal duration of bisphosphonate treatment for osteoporosis has not been established. Treatment should be re-evaluated periodically based
on the benefit and potential risks on an individual patient basis, particularly after 5 or more years of use.7

FRAX8 has been validated as an effective means of reassessment of fracture risk in treated individuals with osteoporosis. Patients should be re-
evaluated using FRAX8 possibly informed by a repeat DXA scan to calculate an individual’s risk. This may be used alongside National Osteoporosis
Guideline Group (NOGG)2 intervention thresholds to guide the decision as to whether treatment can be stopped for a period of time.

QFRACTURE* is an alternative tool which estimates the 10 year absolute risk of osteoporotic fractures and hip fractures in men and women. It doesn’t
require laboratory testing or clinical measurement (e.g. a DXA scan) and takes into account additional clinical risk factors in comparison to FRAX.

Treatment should be discontinued, for low risk patients. After review, treatment may be recommenced one to three years later if still indicated. In
those patients who remain at high risk of fracture, treatment should be continued. Treatment may continue for up to 10yrs (NOGG)2 for high risk
cases.2

*http://www.qfracture.org/

Drug holiday Secondary causes of osteoporosis (NOGG)2

The risks identified with longer-term bisphosphonate use have led to the concept of • Rheumatoid arthritis
a “drug holiday”3 in treatments. A drug holiday should be viewed as a temporary, • Untreated hypogonadism in men and women
suspension of active therapy. Due to the long half-life of bisphosphonates, the • Prolonged immobility
persistence of the anti-resorptive effects is expected for an undefined period of time. • Organ transplantation
• Type I diabetes
If treatment is stopped, fracture risk should be reassessed after a new fracture • Hyperthyroidism
regardless of when this occurs and/or after “drug holiday” (see below) • Gastrointestinal disease
• Chronic liver disease
 Alendronate 2yrs • Chronic obstructive pulmonary disease
 Risedronate 1yr
 Zolendronate 3yrs

Contact details Email address

Dr Katie Moss (Consultant Rheumatologist, St. George's Hospital) Katie.Moss@stgeorges.nhs.uk
Mohammed Swaleh (Integrated Falls and Bone Health Pharmacist, St. George's Hospital) Mohammed.Swaleh@stgeorges.nhs.uk
Wandsworth CCG Practice Prescribing Support Pharmacists

References
1. National Institute for Health and Clinical Excellence. Early and locally advanced breast cancer: diagnosis and treatment. (Clinical guideline 80) London: NICE,
2009. Available at: https://www.nice.org.uk/guidance/CG80
2. National Osteoporosis Guideline Group. Osteoporosis: Clinical guideline for prevention and treatment. Mar 2014.
Available at: http://www.shef.ac.uk/NOGG/NOGG_Executive_Summary.pdf
3.
9
QIPP detail aid. Bisphosphonates – is a holiday necessary? July 2013.
Available at: http://www.midlandsmedicines.nhs.uk/filestore/Bisphosphonate-DA.pdf
4. Black DM, Schwartz AV, Ensrud KE, et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-Term
Extension (FLEX): a randomized trial. JAMA 2006; 296:2927-2938. CrossRef | Web of Science | Medline
5. Bisphosphonates: osteonecrosis of the jaw. MHRA Drug Safety Vol 3: Issue4; Nov 2009.
Available at: https://www.gov.uk/drug-safety-update/bisphosphonates-osteonecrosis-of-the-jaw
6. Medicines and Healthcare Products Regulatory Agency. Drug Safety Update: Bisphosphonates: atypical femoral fractures Volume 4 Issue 11. Jun 2011.
Available at: https://www.gov.uk/drug-safety-update/bisphosphonates-atypical-femoral-fractures
7. WHO, The University of Sheffield. FRAX® WHO Fracture Risk Assessment Tool. Jun 2011.
Available at: http://www.shef.ac.uk/FRAX/tool.aspx