Previous changes

January 2025 — minor update. Information about the use of risedronate in people with severe renal impairment has been clarified.   

November 2024 — minor update. Recommendations from the updated National Osteoporosis Guideline Group (NOGG) Clinical guideline for the prevention and treatment of osteoporosis have been incorporated into this topic. 

April 2023 —  minor update. revised information about dental review prior to initiation of bisphosphonates aligned with BNF advice. 

October 2022 — minor update. Recommendations on prescribing bisphosphonates in people with renal impairment updated in line with manufacturers' summaries of product characteristics.  

May to July 2021 — reviewed. A literature search was conducted in May 2021 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. No major changes to the recommendations have been made.

May 2020 — minor update. The section on interpreting fragility fracture risk scores has been updated to clarify the SIGN recommendation that a 10-year fracture risk of 10% is considered to be the threshold for arranging a dual-energy X-ray absorptiometry (DXA) scan in men and women.

December 2016 — minor update. Information that dosage adjustments of calcium may be required in people with severe kidney disease has been added to the contraindications and cautions section for calcium and colecalciferol preparations.

July 2016 — minor update. The recommendation on alcohol intake in the section on Lifestyle information and advice has been linked to information in the CKS topic on Alcohol - problem drinking, which has been updated in line with the Alcohol Guidelines Review published by the Department of Health (2016).

December 2015 to January 2016 — reviewed. A literature search was conducted in December 2015 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. The topic has undergone minor restructuring and recommendations have been clarified in line with National Institute for Health and Care Excellence (NICE) guidance. Recommendations from the Scottish Intercollegiate Guidelines Network (SIGN) guideline Management of osteoporosis and the prevention of fragility fractures have also been incorporated into this topic.

June 2015 — minor update. Based on an update to the Summary of Product Characteristics for Calcichew D3® chewable tablets, the interaction of calcium salts with zinc and strontium ranelate has been added, and hypersensitivity reactions have been added as possible adverse effects of calcium and vitamin D preparations.

September 2014 — minor update. Text in the section on NOGG - who to assess has been amended to clarify the NOGG recommendations on when to assess for osteoporotic fracture risk. Text in the section on Drug treatment has been rewritten to clarify when a bisphosphonate should be offered.

February 2014 — minor update. Update to the text to reflect the European Medicines Agency's (EMA) recommendations regarding strontium ranelate use, which is restricted to people who cannot be treated with other medicines approved for osteoporosis.

June to September 2013 — reviewed. A literature search was conducted in April 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. The guideline has been extensively re-written to take into account the new method of assessment recommended by the National Institute of Health and Clinical Excellence (NICE) as well as new guidance issued by the National Osteoporotic Guideline Group (NOGG). The guideline also takes into account new recommendations for prescribing vitamin D issued by the Department of Health. Recommendations for Didronel PMO® (a two component drug containing 400 mg of etidronate disodium and 1250 mg of calcium carbonate) have been removed from the topic, following the discontinuation of the product.

January 2013 — minor update. Change to the text to reflect updated prescribing advice for strontium ranelate, issued by the Medicines and Healthcare products Regulatory Agency (MHRA) regarding venous thromboembolism and adverse skin reactions.

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.

March 2012 — minor update. The 2012/2013 QOF indicators have been added to this topic. Issued in April 2012.

January 2012 — minor update. Minor text change clarifying the definition of a T-score reference standard. Issued in January 2012.

September 2011 — minor update. A tool to assess if postmenopausal women meet NICE eligibility criteria for DXA scanning and drug treatment to prevent osteoporotic fragility fractures has been removed from the text. In addition a minor typographical error has been corrected. Issued in October 2011.

June 2011 — minor update. Prescribing information on atypical stress fractures and oral bisphosphonate treatment replaced. Issued in June 2011.

May 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic. Issued in June 2011.

November 2010 to December 2010 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 September 2021.    

HTAs (Health Technology Assessments)

• NICE (2022) Romosozumab for treating severe osteoporosis. National Institute for Health and Care Excellence. www.nice.org.uk [Free Full-text]

Economic appraisals

No new economic appraisals relevant to England since 1 July 2021.

Systematic reviews and meta-analyses

• Händel, M.N., Cardoso, I., von Bülow, C., et al. (2023) Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. BMJ. https://www.bmj.com/ [Free Full-text]
• Hoong, C. W. S., Saul, D., Khosla, S., & Sfeir, J. G. (2025). Advances in the management of osteoporosis. BMJ (Clinical research ed.), 390, e081250. [Free Full-text]

Primary evidence

• Sato, S., Sasabuchi, Y., Okada, A., & Yasunaga, H. (2024). Incidence of new fractures in older patients with osteoporosis receiving biosimilar teriparatide or reference products: A retrospective cohort study. British Journal of Clinical Pharmacology. [Absract]

New policies

No new national policies or guidelines since 1 July 2021.

New safety alerts

No new safety alerts since 1 July 2021.

Changes in product availability

• New product calcitriol 0.25 and 0.5 microgram is licensed for the correction of the abnormalities of calcium and phosphate metabolism in patients with renal osteodystrophy, and for the treatment of established post-menopausal osteoporosis. See more here. 
• New product Angeliq (drospirenone , estradiol hemihydrate) 1 mg/2 mg film-coated tablets. Licensed as treatment of oestrogen deficiency symptoms in postmenopausal women ≥ 1 year post menopause, and as prevention of osteoporosis in postmenopausal women at high risk of fractures who are intolerant of, or contraindicated for other osteoporosis prevention therapies. See more here.
• New product Obodence (denosumab) 60 mg solution for injection in pre-filled syringe. This biosimilar to Prolia is licensed for treatment of osteoporosis in postmenopausal women/men with increased fracture (Fx) risks, bone loss linked to hormone ablation in men with prostate cancer with Fx risks, & treatment of bone loss linked to long-term glucocorticoid therapy. See more here.
• New product Acvybra (denosumab) 60 mg solution for injection in pre-filled syringe. The biosimilar to Prolia is licensed for treatment of osteoporosis in postmenopausal women & men with increased fracture risks, bone loss due to hormone ablation in men with prostate cancer & fracture risk, & bone loss associated with long-term systemic glucocorticoid treatment. See more here.
• New product Ponlimsi (denosumab) 60 mg Solution for injection in Pre-Filled Syringe. Biosimilar to Prolia is licensed for treatment of osteoporosis in postmenopausal women and men, bone loss associated with hormone ablation in men with prostate cancer, and bone loss associated with long-term systemic glucocorticoid therapy. See more here.
• New product: Kefdensis (denosumab) 60 mg solution for injection in pre-filled syringe. Biosimilar licensed for the treatment of osteoporosis, bone loss associated with hormone ablation in men with prostate cancer with increased fracture risk, and treatment of bone loss associated with long-term systemic glucocorticoid therapy in adults with increased fracture risk. See more here.

Who should I assess for fragility fracture risk?

Identify high-risk groups of people to assess fragility fracture risk. Consider assessment of fracture risk in:

• All women aged 65 years and over, and all men aged 75 years and over.
• All women aged under 65 years and all men aged under 75 years who have any of the following risk factors: 
  • A previous osteoporotic fragility fracture.
  • Current use or frequent recent use of oral corticosteroids.
  • History of falls.
  • Family history of hip fracture. 
  • Low body mass index (less than 18.5 kg/m²).
  • Smoking.
  • Alcohol intake of more than 14 units per week.
  • A secondary cause of osteoporosis, including:
    • Hypogonadism in either sex, including untreated premature menopause (menopause before 40 years of age), treatment with aromatase inhibitors (such as exemastane) or gonadotrophin-releasing hormone agonists (such as goserelin).
    • Endocrine conditions, including diabetes mellitus, Cushing's disease, hyperthyroidism, hyperparathyroidism, and hyperprolactinaemia.
    • Conditions associated with malabsorption, including inflammatory bowel disease, coeliac disease, and chronic pancreatitis.
    • Rheumatoid arthritis and other inflammatory arthropathies.
    • Haematological conditions such as multiple myeloma and haemoglobinopathies.
    • Chronic obstructive pulmonary disease.
    • Chronic liver failure.
    • Chronic kidney disease.
    • Immobility.

Do not routinely assess fracture risk in people aged under 50 years unless they have major risk factors: 

• Current or frequent use of oral corticosteroids.
• Untreated premature menopause.
• A previous fragility fracture.

In people aged under 40 years, assess fracture risk if they have any major risk factors:

• Current or recent use of high-dose oral corticosteroids equivalent to, or more than, 7.5 mg prednisolone daily for 3 months or more.
• A previous major osteoporotic fracture. 
• History of multiple fragility fractures.

Consider assessing fracture risk for people taking the following medication, especially in the presence of other risk factors:

• Selective serotonin reuptake inhibitors. 
• Antiepileptic medication — particularly enzyme-inducing drugs, such as carbamazepine. 
• Aromatase inhibitors, such as exemastane.
• Gonadotropin-releasing hormone agonists, such as goserelin. 
• Proton pump inhibitors. 
• Thiazolidinediones, such as pioglitazone.

How should I assess a person for fragility fracture risk?

• Exclude non-osteoporotic causes for fragility fractures. These include:
  
  • Metastatic bone disease — suggested by bone pain, history of cancer (especially lung, thyroid, prostate, kidney, or breast cancer), or symptoms of undiagnosed cancer (for example unexplained general malaise or weight loss).
  • Multiple myeloma — suggested by bone pain, anaemia, recurrent infections, bleeding, symptoms of hypercalcaemia, or kidney disease. For further details, see the CKS topic on Multiple myeloma.
  • Osteomalacia — suggested by bone pain, muscle pain, or proximal muscle weakness.
  • Paget's disease — suggested by bone pain or deformity.
• Exclude secondary causes of osteoporosis (particularly in people with a fragility fracture despite apparently being at low risk), such as:
  • Endocrine conditions such as untreated premature menopause in women, hypogonadism in men, diabetes mellitus, and hyperthyroidism. For further details, see the CKS topics on Menopause, Diabetes - type 1, Diabetes - type 2, and Hyperthyroidism.
  • Rheumatological conditions such as rheumatoid arthritis, and other inflammatory arthropathies. For further details, see the CKS topics on Rheumatoid arthritis and Ankylosing spondylitis.
  • Gastrointestinal conditions that cause malabsorption such as Crohn's disease, ulcerative colitis, coeliac disease, and chronic pancreatitis. For further details, see the CKS topics on Crohn's disease, Ulcerative colitis, Coeliac disease, and Pancreatitis - chronic. 
  • Chronic liver disease. For further details, see the CKS topic on Hepatitis B, Hepatitis C, and Non-alcoholic fatty liver disease.
  • Chronic obstructive pulmonary disease. For further details, see the CKS topic on Chronic obstructive pulmonary disease.
• Offer a dual-energy X-ray absorptiometry (DXA) scan to measure bone mineral density (BMD) without calculating the fragility fracture risk in people:
  • Over 50 years of age with a history of fragility fracture.
  • Younger than 40 years of age who have a major risk factor for fragility fracture — depending on the BMD T-score, refer to a specialist experienced in the treatment of osteoporosis.
• Note: commencing drug treatment without a DXA scan can be considered for people with a vertebral fracture.
• For all other people with risk factors for osteoporosis, calculate the 10-year fragility fracture risk prior to arranging a DXA scan to measure BMD.
  • Consider using the online risk calculators QFracture® (preferred) or FRAX®, which predict the absolute risk of hip fracture and major osteoporotic fractures (spine, wrist, hip, or shoulder) over 10 years.
  • For information on interpreting the fragility fracture risk score, see the section on How should I interpret a fragility fracture risk score?.
    • Measure the BMD with DXA (at the spine and hip) in people found to be at high risk of fragility fracture.
    • Measure the BMD with DXA in people whose fracture risk is close to the recommended threshold, who have risk factors that may be underestimated by FRAX®. For more information, see the section How should I interpret a fragility fracture risk score?.
• Offer oral bisphosphonates to people taking glucocorticoid therapy without waiting for bone density assessment (which should follow later) if they have any of the following risk factors: 
  • A prior fragility fracture.
  • Women age 70 years or over.
  • Postmenopausal women, and men age 50 years or over taking high dose glucocorticoids (7.5 mg or more of prednisolone daily or equivalent over 3 months). 
  • Postmenopausal women, and men age 50 years or over with a FRAX probability of major osteoporotic fracture or of hip fracture exceeding the intervention threshold.
• Assess for vitamin D deficiency and inadequate calcium intake.
  • People are at risk of vitamin D deficiency if they are aged over 65 years, or are not exposed to much sunlight (because they are confined indoors for long periods or because they wear clothes that cover the whole body).
  • A calcium intake of at least 1000 mg/day is recommended for people at increased risk of a fragility fracture. To calculate dietary calcium intake, see the National Osteoporosis Foundation chart Steps to estimate your calcium intake.
• Identify any risk factors for falls. For further details, see the CKS topic on Falls - risk assessment.

How should I interpret a fragility fracture risk score?

The QFracture® and FRAX® risk assessment tools predict the absolute risk of hip fracture, and major osteoporotic fractures (spine, wrist, or shoulder) over 10 years.

• A 10-year fracture risk of 10% is considered to be the threshold for arranging a dual-energy X-ray absorptiometry (DXA) scan in men and women. However, a pragmatic approach is advised and clinical judgement and local pathways should be considered. 
  • When using the QFracture® calculator, be aware that for women the cut off for the top 10% at highest risk is a 10-year risk of 11.1%, and for men the cut off for the top 10% at highest risk is 2.6%.
• When using FRAX®, the fracture risk is calculated and clicking on the 'view NOGG guidance' button shows a chart that plots a person's calculated risk against their age. This graphically represents a person's risk as being at low (green zone), high (red zone), or intermediate (amber zone) risk for an osteoporotic fracture.
• Be aware that FRAX® underestimates some risk factors, including:
  • Regular use of corticosteroids equivalent to or less than 5 mg prednisolone daily.
  • Use of corticosteroids more than or equivalent to 7.5 mg prednisolone daily for more than 3 months. 
  • A history of multiple fragility fractures. 
  • High alcohol intake.
  • Heavy smoking.
• In people aged over 80 years of age, interpret the estimated 10-year fracture risk with caution, as the short-term fracture risk may be underestimated. 

Table 1. How to interpret a fragility fracture risk score.

How should I manage fragility fracture risk scores?

• For people at high risk of fragility fracture
  • For people whose fracture risk is above the recommended threshold, offer a dual-energy X-ray absorptiometry (DXA) scan, then bone-sparing drug treatment if the T-score is -2.5 or lower. 
  • If the T-score is greater than -2.5, modify risk factors where possible, treat any underlying conditions, and repeat the DXA at an interval appropriate for the person based on their risk profile, using clinical judgement (but usually within 2 years).
  • For more information, see the section on How should I follow up a person at risk of fragility fracture?.
• For people at intermediate risk of fragility fracture
  • For people whose fracture risk is close to the recommended threshold and who have risk factors that may be underestimated by FRAX® , arrange a DXA scan to measure their bone mineral density (BMD) and offer drug treatment if the T-score is -2.5 or lower.
• For people at low risk of fragility fracture
  • For people whose fracture risk is below the recommended threshold, do not offer drug treatment, offer lifestyle advice and follow up within 5 years.
• If measurement of bone mass density is not practicable (for example, due to frailty), use the intervention thresholds to guide treatment decisions. 
• Consider referring people at very high risk to an osteoporosis specialist for assessment and consideration of parenteral treatment. For example, people:
  • With important risk factors, including a recent vertebral fracture within the last 2 years.
  • Who have had two or more vertebral fractures (regardless of when they occurred).
  • With a BMD T-Score of -3.5 or lower.
  • Taking high-dose glucocorticoids (7.5 mg or more of prednisolone daily or equivalent over 3 months).
  • With multiple clinical risk factors, particularly with a recent fragility fracture indicating high imminent risk of re-fracture.
  • With other indicators of very high fracture risk.

What drug treatments are recommended for people at high risk of osteoporotic fracture?

• If bone-sparing treatment is indicated, offer an oral bisphosphonate if there are no contraindications and after appropriate counselling to:
  • Postmenopausal women and men over 50 years of age who have been confirmed by dual-energy X-ray absorptiometry (DXA) scan to have osteoporosis (bone mineral density [BMD] T-score of -2.5 or less). 
• Offer alendronate 70 mg once weekly, or risedronate 35 mg once weekly first-line.
  • If these are unsuitable or not tolerated, offer ibandronate 150 mg once monthly. 
  • If an oral bisphosphonate is not tolerated or is contraindicated, consider specialist referral. Specialist treatment options include zoledronic acid, strontium ranelate, raloxifene, denosumab, and teriparatide. 
  • Note: all oral bisphosphonates are licensed for use in postmenopausal women. However, only risedronate (once weekly) is licensed for use in men.
• Offer advice on the use of bisphosphonates and explain about possible adverse effects.
• If the person's calcium intake is adequate (700 mg/day), prescribe 10 micrograms (400 international units) of vitamin D (without calcium) for people not exposed to much sunlight. For more information, see the section on How should I assess a person for fragility fracture risk?.
• If calcium intake is inadequate:
  • Prescribe 10 micrograms (400 international units) of vitamin D with at least 1000 mg of calcium daily. 
  • Prescribe 20 micrograms (800 international units) of vitamin D with at least 1000 mg of calcium daily for elderly people who are housebound or living in a nursing home.  
• Consider prescribing hormone replacement therapy (HRT) to younger postmenopausal women to reduce the risk of fragility fractures and for the relief of menopausal symptoms. For further information on prescribing HRT, see the CKS topic on Menopause.

What lifestyle information and advice should I give?

• Advise the person to:
  • Take regular exercise (tailored to the person) to improve muscle strength. Encourage:
    • Walking, especially outdoors, as this will increase exposure to sunlight, increasing vitamin D production.
    • Strength training (such as weight training) of different muscle groups (for example hip, wrist, and spine).
    • A combination of exercise types, for example balance, flexibility, stretching, endurance, and progressive strengthening exercises. 
  • Eat a balanced diet as this may improve bone health.
  • Stop smoking if applicable, as it is a risk factor for fragility fracture. For more information, see the CKS topic on Smoking cessation.
  • Drink alcohol within recommended limits, as alcohol is a dose-dependent risk factor for fragility fracture. For more information, see the CKS topic on Alcohol - problem drinking.
• Provide the person with sources of information and support:
  • The Royal Osteoporosis Society provides support and information to people affected by osteoporosis, and works to improve public understanding of osteoporosis.
  • Healthtalkonline has a large collection of videos and transcripts of people's experiences of health and illness, including osteoporosis. There are also short articles for people with osteoporosis and the general public.
  • NHS has a health encyclopaedia that has a printable article on Osteoporosis. 

How should I follow up a person at risk of fragility fracture?

• After starting bone-sparing treatment:
  • Check treatment tolerance after 12-16 weeks — ask about adverse effects, in particular:
    • Upper gastrointestinal adverse effects, such as dyspepsia or reflux. These are common in the first month of treatment and often improve with continuing use. They are less likely if the recommended method of taking bisphosphonates is followed. For further information, see the section on What advice should I give someone taking bisphosphonates?.
    • Symptoms of atypical fracture, including new onset hip, groin, or thigh pain. If this occurs, stop treatment and arrange an X-ray of the femur.
  • Check adherence after 12 months of treatment.
    • See the section on drug treatment for recommended alternative treatments if adverse effects are unacceptable.
• For people taking oral corticosteroids:
  • Continue treatment with bisphosphonates and/or calcium and vitamin D until treatment with oral corticosteroids has stopped, then reassess the osteoporotic fragility fracture risk to determine the need for continuing treatment with a bisphosphonate and calcium and vitamin D.
  • If long-term corticosteroid treatment is necessary bone protection should be maintained. 
  • Reassess fracture risk in people 12-18 months after starting medium or low dose corticosteroid treatment who have a fracture risk near to but below the intervention threshold. 
• For all other people, reassess the need for continuing treatment with oral bisphosphonates after 5 years.
  • For people who remain at high risk of an osteoporotic fragility fracture, continue treatment for at least 10 years. This includes people with any of the following risk factors:
    • Aged 70 years or over at the start of bisphosphonate treatment. 
    • A previous hip or vertebral fracture.
    • People who experience one or more fragility fractures during the first 5 years of treatment (if treatment is not changed). 
  • In other people, arrange a dual-energy X-ray absorptiometry (DXA) scan and consider:
    • Continuing treatment for another 5 years if the T-score is -2.5 or lower, and then reassessing fracture risk. 
    • Pausing treatment for 1.5 to 3 years if the BMD T-score is greater than -2.5, and then reassessing fracture risk. 
• Reassess fracture risk at any time if: 
  • Re-fracture occurs.
  • Clinical risk factors change. 
• For people who sustain an osteoporotic fracture while on bone-sparing treatment, check adherence to treatment and exclude secondary causes for osteoporosis. If other underlying causes are excluded, consider referral to a specialist for advice on drug treatment.  
• For people whose fracture risk was intermediate the last time they were assessed, reassess after a minimum of 2 years.
• If a new fracture occurs after bisphosphonate treatment is discontinued, reassess fracture risk and restart treatment. 
• If bisphosphonate treatment is discontinued and no new fracture occurs, reassess fracture risk after 18 months for risedronate and ibandronate, 2 years for alendronate, and 3 years for zoledronate to inform whether treatment should be restarted. 

What calcium and vitamin D preparations are available?

• There are a number of calcium and vitamin D preparations that provide a daily intake of at least 1 g of calcium and 400 units of vitamin D.
• For people who are allergic to peanuts or soya, preparations which do not contain soya (or soya bean) oil are available, such as Accrete D3® chewable, and Calfovit D3®.
• For a complete list of available calcium and vitamin D products and the recommended doses, see the British National Formulary (BNF). 

[BNF, 2021]

What are the contraindications and cautions for calcium and vitamin D preparations?

• Do not prescribe calcium and vitamin D preparations to people with:
  • Any disease or condition that results in hypercalcaemia and/or hypercalciuria (for example some malignancies, such as myeloma).
  • Hyperparathyroidism.
  • Renal stone disease.
  • Hypervitaminosis D.
  • Severe chronic kidney disease (chronic kidney disease [CKD] stage 4 or 5).
  • An allergy to peanuts or soya — soya oil-free products are available.
• Prescribe calcium and vitamin D preparations with caution to people with:
  • Mild to moderate CKD (stages 2–3B) or mild hypercalciuria. Manufacturers recommend periodic checks of plasma calcium levels. 
    • In patients with severe renal failure (creatinine clearance of less than 30 mL/minute) dosage adjustments may be necessary.
  • A history of renal stone disease. 

[ABPI, 2021a; ABPI, 2021b; BNF, 2021; Micromedex, 2021]

What are the adverse effects of calcium and vitamin D preparations?

• Adverse effects are uncommon and are generally related to the calcium content of the preparation. They include: 
  • Gastrointestinal adverse effects (such as constipation, flatulence, nausea, abdominal pain, and diarrhoea).
  • Hypercalciuria (and rarely hypercalcaemia) — may occur with long term use of high doses of calcium and vitamin D preparations.
  • Hypersensitivity reactions (such as angio-oedema and laryngeal oedema).
• Vitamin D supplements can cause occasional skin rashes.

[BNF, 2021; Micromedex, 2021]

What are the key drug interactions with calcium and vitamin D preparations?

• The key drug interactions with calcium and vitamin D preparations include: 
  • Oral bisphosphonates — reduced absorption of bisphosphonates. Advise the person to avoid administration at the same time, and to leave a gap of at least 30 minutes. For more information, see the section on What advice should I give someone taking bisphosphonates?.
  • Strontium ranelate — reduced absorption of strontium ranelate. Strontium ranelate should be taken 2 hours before or after calcium supplements.
  • Quinolones and tetracyclines — reduced absorption of quinolones and tetracyclines. Quinolones should be taken at least 2 hours before taking a calcium supplement. Tetracyclines should be taken at least 2–3 hours before taking a calcium supplement.
  • Levothyroxine, iron, and zinc — reduced absorption. These drugs should be taken at least 2 hours before taking a calcium supplement.
  • Digoxin — increased effects of digoxin. Some manufacturers of calcium supplements recommend monitoring an ECG and renal function during long-term calcium supplementation, to check for cardiac arrhythmias.
  • Thiazide diuretics — reduced urinary calcium excretion. Due to the increased risk of hypercalcaemia:
    • Monitor serum calcium levels regularly during concomitant use of thiazide diuretics with calcium and vitamin D preparations.
    • Some manufacturers of calcium supplements recommend monitoring renal function during long-term calcium supplementation in people also taking a thiazide diuretic.
  • Oral corticosteroids — reduced calcium absorption. It may be necessary to increase the dose of the calcium and vitamin D preparations.
  • Phenytoin or barbiturates (long-term use) — there have been a few reports of decreased effects of vitamin D (due to an increase in its metabolism). Consider monitoring for vitamin D deficiency as a higher dose of vitamin D may be required.

[ABPI, 2021a; ABPI, 2021b; BNF, 2021; Micromedex, 2021; Preston, 2021]

What are the contraindications and cautions for bisphosphonates?

• Do not prescribe a bisphosphonate to:
  • People with hypocalcaemia or other disturbances of bone and mineral metabolism (such as parathyroid dysfunction and hypovitaminosis D) — these should be treated before starting alendronate or risedronate.
  • People with severe chronic kidney disease (CKD) — the threshold varies between the different drugs:
    • Alendronate is not recommended if creatinine clearance is less than 35 mL/minute.
    • Risedronate is not recommended if creatinine clearance is less than 30 mL/minute.
  • People who are unable to stand or sit upright for at least 30 minutes, or if there are any abnormalities of the oesophagus or other conditions which could delay oesophageal emptying (such as stricture or achalasia) — to reduce the risk of oesophageal reactions. 
  • Pregnant or breastfeeding women — data on pregnancy and breastfeeding are scarce. Oral bisphosphonates are only licensed for use in postmenopausal women.
• Prescribe bisphosphonates with caution to: 
  • People with upper gastrointestinal (GI) problems, due to the risk of oesophageal reactions. These include:
    • Dysphagia, oesophageal disease, gastritis, duodenitis, and peptic ulceration.
    • A recent history (within the past year) of major GI disease (such as peptic ulcer, active GI bleeding, or surgery of the upper GI tract [other than pyloroplasty]).
    • Barrett's oesophagus — consider the benefits and risks of treatment on an individual basis.

[ABPI, 2020a; ABPI, 2020b; BNF, 2022; Micromedex, 2021]

What are the adverse effects of bisphosphonates?

• Adverse effects of oral bisphosphonates include:
  • Gastrointestinal (most common) — nausea, dyspepsia, mild gastritis, and abdominal pain. They are more likely to occur in the first month of treatment.
  • Bone, joint, and/or muscle pain (common).
  • Oesophageal reactions (uncommon) — oesophagitis, oesophageal ulcers, oesophageal strictures, and oesophageal erosions.
  • Osteonecrosis of the jaw (rare) — an area of exposed or dead bone in the jaw that has lasted for more than 8 weeks.
  • Osteonecrosis of the external auditory canal (very rare).
  • Atypical stress fractures have been reported (mainly with alendronate). An increased risk cannot be excluded for other bisphosphonates.

[BNF, 2021; Micromedex, 2021]

What are the key drug interactions with bisphosphonates?

• There are few significant drug interactions, including:
  • Calcium supplements and antacids — concurrent use may result in decreased absorption of the bisphosphonate. A minimum of 30 minutes should be left between taking a bisphosphonate and calcium supplements or antacids.
  • Food and drink — reduced absorption of bisphosphonates may occur if they are taken with food and drinks (other than plain water). Coffee and orange juice reduce bioavailability of bisphosphonates by about 60%. A minimum of 30 minutes should be left between taking a bisphosphonate and food or drink.
  • Nonsteroidal anti-inflammatory drugs — some manufacturers of bisphosphonates advise caution if they are used in conjunction with bisphosphonates, due to the increased risk of gastrointestinal irritation.

[BNF, 2021; Preston, 2021]

What advice should I give a person taking a bisphosphonate?

• Oral bisphosphonates must only be taken on an empty stomach as their absorption is affected by food, drink, and other drugs — for more information, see the section on Drug interactions.
  • Risedronate should be taken before breakfast; however, if this is not practical, it can be taken between meals or in the evening at the same time each day, with strict adherence to the following instructions (to ensure that it is taken on an empty stomach):
    • Before breakfast — must be taken at least 30 minutes before the first food, other medicinal product, or drink (other than plain water) of the day.
    • Between meals — should be taken at least 2 hours before or at least 2 hours after any food, other medicinal product, or drink (other than plain water).
    • In the evening — should be taken at least 2 hours after any food, other medicinal product, or drink (other than plain water).
  • Alendronate must be taken at least 30 minutes before the first food, other medicinal product, or drink (other than plain water) of the day.
• Also advise that:
  • The tablet must be swallowed whole and taken with a glass of plain water (at least 200 mL); it must not be sucked or chewed because of a potential for oropharyngeal ulceration.
  • It should be taken while in an upright position.
  • The person must not lie down for at least 30 minutes after taking the medication.
  • The medication must not be taken at bedtime or before getting up in the morning.
  • Once weekly preparations should be taken on the same day each week.
• Give advice on missed doses:
  • For once-daily preparations of alendronate, advise the person:
    
    • To skip the missed dose for that day.
    • To continue on the next day as usual.
    • Not to take a double dose to make up for the missed dose.
  • For once-daily preparations of risedronate, advise the person:
    • Risedronate can be taken before breakfast, between meals, or in the evening as described above.
  • For once-weekly preparations of alendronate or risedronate, advise the person:
    • To take the missed tablet on the day that it is remembered.
    • To continue taking one tablet once a week, on the day the tablet is normally taken.
    • That two tablets should not be taken on the same day.
• Advise the person to be aware of possible adverse effects of bisphosphonates, including:
  • Upper gastrointestinal adverse effects, such as dyspepsia or reflux — these are common in the first month of treatment and often improve with continued use.
  • Symptoms of atypical fracture, including new onset hip, groin, or thigh pain.  
  • Symptoms of osteonecrosis of the jaw, including jaw pain, swelling, and redness.
• Advise the person to have a dental check up before starting bone-sparing treatment. All patients with cancer and patients with poor dental status should have a dental check-up (and any necessary remedial work should be performed) before bisphosphonate treatment, or as soon as possible after starting treatment. 
• Advise the person that after starting bone-sparing treatment, they should: 
  • Maintain good oral hygiene.
  • Attend routine dental check ups. 
  • Tell their dentist that they are taking bone-sparing medication.
  • Report any symptoms of osteonecrosis of the jaw to their dentist.

[ABPI, 2020a; ABPI, 2020b; BNF, 2023]