Veterans’MATES

Osteoporosis – Identifying and treating at risk patientsOsteoporosis is common but under-detected and under-treated.1 This therapeutic brief outlines ways to identify and treat osteoporosis in members of the veteran community.The Geelong Osteoporosis Study revealed that 87% of women aged over 79 years had a bone mineral density (BMD) result indicative of osteoporosis.2 The lifetime risk of osteoporotic fracture in people aged over 60 years is approximately 56% for women and 29% for men.1 Approximately 25% of patients with a hip fracture die within 12 months of sustaining the fracture.3

Mortality also increases in the first year after all major fractures, including vertebral fractures; however, vertebral fractures go largely undetected.3

While there is no known cure for osteoporosis, osteoporotic fractures can be prevented through identifying risk factors and appropriate management.4 However, despite high-level evidence for efficacy, safety and cost effectiveness, less than 30% of Australian women and only 10% of Australian men with osteoporosis (even with fragility fractures) take a specific anti-osteoporotic medicine.5,6

Identifying osteoporosis

Therapeutic Brief 28 – Osteoporosis – Identifying and treating at risk patients. Sep 2011.Veterans’ Medicines Advice and Therapeutics Education Services

Since osteoporosis lacks obvious clinical symptoms, it is important to review the patient’s medical history, including checking for previous low trauma fractures. Lifestyle factors that add to a patient’s risk include smoking, low level of physical activity and excessive alcohol consumption.1

Further investigate any individual with osteoporosis risk factors and consider measuring BMD (Box 1). The World Health Organization defines osteoporosis when BMD at any major skeletal site is equal to or more than 2.5 standard deviations below the mean for normal people aged 30 years (i.e. a T-score of –2.5 or lower).7

Box 1: Osteoporosis risk factors that indicate the need for BMD testing*1,8

pre-existing minimal trauma fracture(s)

women and men aged 70 years or older

female hypogonadism lasting more than 6 months before the age of 45

certain medicines – e.g. prolonged corticosteroid treatment

secondary causes – e.g. rheumatoid arthritis, hyperparathyroidism, chronic kidney or liver disease, male hypogonadism, proven malabsorption conditions, or conditions associated with excess corticosteroid secretion or thyroxine excess.

* Medicare reimburses DXA scanning for these risk factors.

Inside

Key pointsAssess risk of osteoporosis and consider BMD testing in high-risk patients.

Consider pharmacological treatment in patients:

• withaminimaltraumafracture• aged70yearsandolderwitha

T-scoreof–3.0orlower• onprolongedcorticosteroid

treatmentwithaT-scoreof –1.5orlower.

ConsideraHomeMedicinesReviewforpatientswithosteoporosistohelpidentifywhetheranymedicinesareincreasing their risk of falls.

Identifying osteoporosis

Treating osteoporosis

Ongoing management

Further information

1

2

4

4

www.veteransmates.net.au

28

Veterans’MATES

Therapeutic Brief 28 – Osteoporosis – Identifying and treating at risk patients. Sep 2011.Veterans’ Medicines Advice and Therapeutics Education Services

Treating osteoporosisThe efficacy and safety of most pharmacological treatments were demonstrated in studies where adequate calcium and vitamin D nutrition was a basic study condition.10,11 Adjunct vitamin D and calcium is recommended with all anti-osteoporotic treatment if intake is inadequate.

Bisphosphonates

Bisphosphonates slow bone loss, improve bone mineral density and reduce fracture rates.12-16 Alendronate, risedronate and zoledronic acid are recommended as first-line therapy in men and women for primary and secondary prevention of vertebral, nonvertebral and hip fractures, and corticosteroid-induced osteoporosis; they are PBS listed for these indications.1 Etidronate is only PBS listed for secondary prevention.

Evidence to indicate when bisphosphonate treatment should be ceased is lacking.1,9 Atypical femoral stress fractures with long-term bisphosphonate use have been reported rarely but the absolute risk is very low.1,9,17

Guidelines recommend reconsidering bisphosphonate therapy after 5–10 years in postmenopausal women and older men who respond well to treatment, as determined by BMD testing and fracture risk assessment (i.e. T-score above –2.5 and no recent fractures). If treatment has ceased, measure BMD a year later and assess the risk of falls. Restart treatment if BMD decreases significantly (lumbar spine decrease of 5% or more) or with any additional fracture.1,11

Denosumab

Denosumab is a monoclonal antibody that inhibits RANKL (receptor activator of nuclear factor kappa B ligand), which results in decreased bone resorption and bone loss. Clinical trials in postmenopausal women shows a reduced risk of vertebral, hip and nonvertebral fracture.18,19 Denosumab is listed on the PBS for postmenopausal women who meet the criteria for primary or secondary prevention.

Ensuring adequate calcium and vitamin D plus addressing lifestyle factors where possible are considered the foundations of osteoporosis prevention and management. Consider adjunct pharmacological treatment in patients:1

with a minimal trauma fracture (secondary prevention)

aged 70 years or older with a T-score of –3.0 or lower (primary prevention)

currently on prolonged (at least 3 months), high dose corticosteroid treatment (at least 7.5mg per day prednisolone or equivalent) and with a T-score of –1.5 or lower.

Pharmacological treatmentsMany factors influence the choice of pharmacological treatment such as gender, menopausal status, medical history, whether it is for primary or secondary fracture prevention, patient preference and eligibility for government subsidy. Note: Hormone Replacement Therapy (HRT) is not recommended for osteoporosis treatment.9

Table 1: Bisphosphonates to treat osteoporosis1,9,20

Medicine Examples of Brands Dose*^ Considerations for bisphosphonates^

Alendronate Fosamax® & various generic brands

70 mg tablet weekly (10 mg daily tablet also available but not PBS listed)

Contraindications:• hypocalcaemia• uveitis• fortablets(otherthanActonel® EC), an inability to sit or stand upright for 30 minutes, or any disorders which delay oesophageal emptying.

Not recommended in moderate to severe renal impairment (creatinine clearance < 35 mL/min).

Tablets taken in morning on empty stomach with a full glass of water; patient should remain upright for 30 minutes and not eat or drink anything else in that time. (Note: Actonel® EC can be taken with or without food.)

Calcium supplements should be taken 2 hours apart from oral bisphosphonates.

Vitamin D should be corrected to a level above 50 nmol/L before commencing therapy.

ONJ reported rarely. Good dental hygiene and care is essential. Consider dental assessment and complete any dental procedures before starting treatment to minimise risk of ONJ. Cease treatment if arises.

Zoledronic acid is an IV infusion over 15 minutes. Headache, myalgia and fever, may be experienced soon after IV infusion.

Alendronate plus vitamin D3

Fosamax Plus™, Dronalen™ Plus

70 mg/70 μg or 140 μg tablet weekly

Alendronate plus vitamin D3 with calcium carbonate

Fosamax Plus D-Cal™, Dronalen Plus D-Cal™

70 mg/140 μg tablet weekly; 1.25 g calcium tablets daily

Risedronate Actonel® & various generic brands (35 mg tablets only)

5 mg tablets daily, 35 mg tablets weekly, or 150 mg tablet monthly

Actonel® EC (enteric coated)**

35 mg tablets weekly

Risedronate with calcium carbonate

Actonel® Combi, Actonel® EC Combi (enteric coated)**

35 mg tablet weekly; 1.25 g calcium tablets daily on other 6 days of the week

Risedronate with calcium carbonate/ vitamin D

Actonel® Combi D, Actonel® EC Combi D (enteric coated)**

35 mg tablet weekly; 2.5 g calcium/ 22 μg vit D effervescent granules daily on other 6 days of the week

Zoledronic acid Aclasta® 5 mg in 100 mL I.V solution yearly

Etidronate with calcium carbonate

Didrocal® 2x200 mg tablets nightly for 14 days then 1.25 g calcium tablets daily for 76 days

Note: 1 μg vitamin D = 40 International Units (IU)21. ONJ: Osteonecrosis of the jaw. *Doses are for brands listed in the table. ^ Read individual product information leaflets for full details. **Replacing conventional Actonel® 35 mg tablets in Jan 2012.

Veterans’MATES

Veterans’ Medicines Advice and Therapeutics Education Services Therapeutic Brief 28 – Osteoporosis – Identifying and treating at risk patients. Sep 2011.

Medicine Examples of Brands

Dose*^ Practice Points^ Safety Considerations^

Denosumab Prolia® 60 mg in 1 mL subcutaneous injection, 6 monthly

Consider dental assessment and complete any dental procedures before starting treatment to minimise risk of ONJ.

No dose adjustment is necessary in renal impairment.

Contraindicated in hypocalcaemia. Correct hypocalcaemia before initiating.

Long-term safety and efficacy data are lacking; there are particular concerns regarding effects:

• ontheimmunesystem(e.g.increasedriskofinfection)• onbone,includingaftertreatmenthasstopped• oftakingdenosumabafterbisphosphonateuse.

Raloxifene Evista® 60 mg tablet daily Fasting is not required. Contraindicated in patients with a history of VTE.

VTE rarely reported. Cease in patients who require immobilisation for long periods (e.g. hospitalisation).

Strontium ranelate

Protos® 2 g sachet nightly Taken at bedtime, mixed with ≥ 30 mL of water at least 2 hours after food, calcium-containing products or antacids.

Contraindicated in severe renal impairment.

VTE reported rarely – use with caution in patients with or at risk of thromboembolic disorders.

Severe hypersensitivity reactions (e.g. Stevens-Johnson syndrome, DRESS) reported rarely. DRESS is a life-threatening allergic reaction; strontium should be ceased.

Teriparatide Forteo® 20 μg subcutaneous injection daily in the thigh or abdomen (multi-dose pre-filled pen).

Initiated by a specialist. Restricted to 18-month lifetime exposure (caused osteosarcoma in animal studies); informed consent required.

Raloxifene

Raloxifene is a selective oestrogen receptor modulator that has been shown to prevent postmenopausal bone loss. It has beneficial oestrogen-like effects on bone but also has anti-oestrogen effects on the breast and endometrium. Raloxifene produces a similar reduction in vertebral fractures to bisphosphonates; however, it has not been shown to prevent non-vertebral fractures.1,11,24,25 It is PBS listed for postmenopausal women with a minimal trauma fracture (secondary prevention).

Strontium ranelate

Strontium ranelate is an antiresorptive medicine and increases bone mineral density. Evidence supports the use of strontium ranelate 2 g/day for both primary and secondary prevention of vertebral fractures in postmenopausal women1,11,26,27; it is also PBS listed for this patient group.

Teriparatide

Teriparatide is a synthetic form of human parathyroid hormone, which acts by inhibiting bone resorption and increasing bone formation.1,11,23 Because of its expense, the PBS listing restricts it for patients with a very high risk of fracture and when other drugs have failed (i.e. fracture has occurred during antiresorptive treatment) or are not tolerated.

Ensure adequate calcium and vitamin DEvidence for calcium plus vitamin D supplementation mainly exists in frail older people, particularly for women in residential care where it has been shown to prevent fractures.1,8,10,28

The recommended daily calcium intake is 1200 mg for women aged over 50 years and men aged over 70 years.29 It can be difficult for many older people to meet these requirements through diet alone; therefore, supplements are often recommended.11,30 Since vitamin D is mainly obtained through sun exposure, older patients, particularly

those in residential care, are commonly deficient in vitamin D; most will need supplementation.8,11

To optimise efficacy, it is recommended that calcium supplements be taken together with at least 800 units of vitamin D3 (cholecalciferol) per day.1 Since calcium carbonate requires adequate stomach acid to be absorbed, consider calcium citrate in patients on proton pump inhibitors or with compromised gastric acidity.1,11 Note: calcium citrate (e.g. Citracal) is not available on the PBS.Vitamin D3 in combination with some bisphosphonates is available on the PBS (see Table 1). Calcium carbonate (e.g.CAL-600, Cal-Sup, or in combination with some bisphosphonates) is available on the RPBS.

The risk of cardiovascular events with calcium supplements

Recent publications suggesting an increased risk of cardiovascular events with the use of calcium supplements are the subject of international debate, and the findings are not universally accepted.31,32

Table 2: Other treatments for osteoporosis1,9,19,20,22,23

Note: 1 μg vitamin D = 40 International Units (IU)21. ONJ: Osteonecrosis of the jaw; VTE: Venous thromboembolism; DRESS: Drug rash with eosinophilia and systemic symptoms. *Doses are for brands listed in the table. ^ Read individual product information leaflets for full details.

Veterans’MATESProvided by: University of South Australia Quality Use of Medicines and Pharmacy Research CentreIn association with: Discipline of General Practice, The University of Adelaide Discipline of Public Health, The University of Adelaide Repatriation General Hospital, Daw Park NPS – Better choices, Better health Australian Medicines Handbook Drug and Therapeutics Information Service

Veterans’MATES

The RACGP Clinical guideline for the prevention and treatment of osteoporosis in post-menopausal women and older men. http://www.racgp.org.au/Content/NavigationMenu/ClinicalResources/RACGPGuidelines/osteoporosis1/RACGP_Osteo_guideline.pdf

Further information

Ongoing managementLifestyle measures include exercise, an adequate diet, reducing alcohol consumption, and smoking cessation.

Exercise maintains muscle strength, flexibility, mobility, and balance; all factors that help to reduce the risk of falls. Weight-bearing exercise is preferable, such as walking, Tai chi and gentle weights, as it can help to improve bone density.1,11 Exercise programs should be individualised to patients’ needs and abilities.1

BMD re-testing assesses treatment efficacy and disease progression. Consider BMD testing by DXA every two years after therapy begins, or every 12 months if there is significant change in therapy or patients are on prolonged corticosteroid treatment.1

In patients at high-risk of osteoporosis but not on pharmacological treatment, DXA may be repeated every 2 years to re-assess the fracture risk and the need for anti-osteoporotic treatment.1

Fullreferencelistavailableat: www.veteransmates.net.au

Box 2: Medicines which increase falls risk9,20

• Antidepressants

• Antihypertensives

• Antiparkinsonians

• Diuretics

• Hypnotics

• Sedatives

Consider a Home Medicines Review (HMR) byanaccreditedpharmacist to help:

educate patients about their osteoporosis medicines, particularly if initiated recently

optimise the medicine regime and identify issues affecting adherence

identify whether any medicines are increasing the patient’s risk of falls because of their side effects (Box 2). Accredited pharmacists have been provided with a modified Falls Risk Assessment Tool (FRAT) to assist them in reviewing a patient’s medicines in the context of overall falls risk. The accredited pharmacist may provide you with a copy of this assessment in their report.

Consider falls prevention strategies in patients with osteoporosis

Osteoporosis Australia: http://www.osteoporosis.org.au/

The DVA booklet HomeFront guide to preventing falls for older people: www.dva.gov.au/aboutDVA/publications/health/Documents/preventing_falls.pdf

Online Fracture Assessment tools:

WHO Fracture Risk Assessment tool (FRAX). Available at: http://www.shef.ac.uk/FRAX/

Garvan institute fracture risk calculator. Available at: http://garvan.org.au/promotions/bone-fracture-risk/calculator/

Consider referring to a falls clinic. Falls clinics are available at most major public hospitals and many community health centres throughout Australia.1

Falls prevention strategies are highly recommended, as falls are responsible for 90% of hip fractures and 50% of vertebral fractures in older patients. Multiple factors can contribute to falls, including some medicines (Box 2), poor balance and muscle strength, unsafe footwear, and poor eyesight.33

Consider a home visit by an occupational therapist who can advise patients on removing potential hazards to help reduce the risk of falls, and can also assess for falls prevention items available through either the HomeFront Program – a DVA falls and accident prevention program or for more specific aids or appliances, the Rehabilitation Appliances Program. See Further information.

Veterans’MATES

Home Medicines Review for patients with osteoporosis Over the next few months, accredited pharmacists may receive Home Medicines Review (HMR) referrals as a result of the latest release of Veterans’ MATES. This latest release aims to improve the detection and management of osteoporosis.

Few falls have a single cause and multifactorial assessment, including medicines review and assessment of home environment, can help to prevent fractures in patients with osteoporosis. Therefore, we have highlighted to GPs where patients with osteoporosis are receiving medicines that may increase their risk of falls and have asked them to consider a HMR for these patients.

When you do receive such a referral, consider the below points as part as your review process. The patient’s GP will value concise feedback that includes any education provided to the patient and your assessment of whether any medicines appear to be contributing to their risk of falls. If no problems are identified from the HMR, this positive result is just as important to feed back to the GP.

The patient will have received a veterans’ brochure, encouraging them to learn about osteoporosis and ask their doctor for a HMR, particularly if they have recently started treatment or as part of falls prevention measures.

Copies of the therapeutic brief, veteran brochure and this document (including the preliminary fall risk screening tool) are available on the Veterans’ MATES website. www.veteransmates.net.au

HMRs can improve health outcomes for members of the veteran community.1 Thank you for your work with veterans and we hope this information will help you respond to a GP’s HMR referral for patients with osteoporosis.

1 Roughead EE, Barratt JD, et al. The effectiveness of collaborative medicine reviews in delaying time to next hospitalisation for heart failure patients in the practice setting: results of a cohort study. Circulation: Heart Failure 2009; 2(5): 424-8.

Therapeutic Brief 28 – Osteoporosis – Identifying and treating at risk patients. Sep 2011.Veterans’ Medicines Advice and Therapeutics Education Services

Points to consider when conducting a HMR for a patient with osteoporosis: Identify whether any medicines are increasing the patient’s risk of falls because of their side effects.

For example are any of the patient’s medicines causing dizziness or impairing cognition.

To help you review a patient’s medicines in the context of their overall risk of falls, we have included a preliminary fall risk screening tool on the reverse of this page. This screening tool has been adapted from the Falls Risk Assessment Tool (FRAT) developed by Peninsula Health Falls Prevention Service. GPs have been advised that you have been provided with this tool which you may wish to complete and include in your HMR report.

Adherence to anti-osteoporotic therapy is often poor due to dosing inconvenience, adverse effects, and a lack of understanding of the benefits of therapy.

• Identify issues affecting adherence such as dosing requirements and possible adverse effects.• Reinforce the patient’s understanding of the on-going need for their osteoporosis medicine and highlight the

benefits of persistence to therapy.

Identify potential interactions with other prescribed or over-the-counter medicines.

Remind the patient of special considerations for use of each medicine.

Discuss requirements for adequate vitamin D and calcium intake.

Promote lifestyle changes to improve bone health such as; good nutrition, suitable exercises to improve balance, moderate alcohol intake, stopping smoking and steps to prevent falls and fractures.

Identify if the patient would benefit from a dose administration aid.

Veterans’MATES

Veterans’MATESProvided by: University of South Australia Quality Use of Medicines and Pharmacy Research CentreIn association with: Discipline of General Practice, The University of Adelaide Discipline of Public Health, The University of Adelaide Repatriation General Hospital, Daw Park NPS – Better choices, Better health Australian Medicines Handbook Drug and Therapeutics Information Service

Peninsula Falls Risk Assessment Tool https://www.health.vic.gov.au/agedcare/maintaining/falls/providers/rac/plans_frat.htm

Falls Prevention Guidelines from the Australian Commission on Safety and Quality in Health Care http://www.safetyandquality.gov.au/internet/safety/publishing.nsf/Content/publications-Falls%20Prevention%20Guidelines

Further information For further information about medicines which increase

falls risk, see therapeutic brief 20 Reviewing medications to reduce the risk of falls https://www.veteransmates.net.au/VeteransMATES/documents/module_materials/M20_TherBrief.pdf

For further information for veterans about falls and how to prevent them, see the DVA booklet HomeFront guide to preventing falls for older people http://www.dva.gov.au/aboutDVA/publications/health/Documents/preventing_falls.pdf

Preliminary fall risk screening*Risk Factor Level Risk Score

Recent falls (with or without hospitalisation)

none in last 12 months 2

one or more between 3 and 12 months ago 4

one or more in last 3 months 6

one or more in last 3 months whilst inpatient/resident 8

Medications (Sedatives, Antidepressants, Antiparkinsonians, Diuretics, Antihypertensives, Hypnotics)

not taking any medications known to increase risk of falls 1

taking one medication known to increase risk of falls 2

taking two medications known to increase risk of falls 3

taking three or more medications known to increase risk of falls 4

Psychological (Anxiety, Depression, Cooperation, Insight or Judgement esp. re mobility)

does not appear to have any of these 1

appears mildly affected by one or more 2

appears moderately affected by one or more 3

appears severely affected by one or more 4

Cognitive status intact 1

mildly impaired 2

moderately impaired 3

severely impaired 4

(Low Risk: 5-11 Medium Risk: 12-15 High Risk: 16-20) RISK SCORE: /20

Automatic High Risk Status: (if ticked then circle HIGH risk below)

Recent change in functional status and/or recent change in medications affecting safe mobility (or anticipated)

Dizziness/postural hypotension

FALL RISK STATUS: LOW / MEDIUM / HIGH

*The screening tool has been adapted from the Falls Risk Assessment Tool (FRAT) developed by Peninsula Health Falls Prevention Service. Tool validated in sub-acute and residential care setting (average age 79 years, 80% prediction accuracy of faller status).

Veterans’MATES

Topic 28Osteoporosis – Identifying and treating at risk patients

Full reference list for Therapeutic Brief

Veterans’MATESProvided by: University of South Australia Quality Use of Medicines and Pharmacy Research CentreIn association with: Discipline of General Practice, The University of Adelaide Discipline of Public Health, The University of Adelaide Repatriation General Hospital, Daw Park NPS – Better choices, Better health Australian Medicines Handbook Drug and Therapeutics Information Service

1. The Royal Australian College of General Practitioners (RACGP). Clinical guideline for the prevention and treatment of osteoporosis in post-menopausal women and older men. South Melbourne: RACGP, 2010. http://www.racgp.org.au/Content/NavigationMenu/ClinicalResources/RACGPGuidelines/osteoporosis1/RACGP_Osteo_guideline.pdf [Accessed 5 May 2011].

2. Henry M et al. Prevalence of osteoporosis in Australian women: Geelong osteoporosis study. Journal of Clinical Densitometry 2000; 3 (3): 261–268.

3. Department of Medicine, University of Melbourne, Western Hospital, Footscray, Victoria. The burden of brittle bones – epidemiology, costs and burden of osteoporosis in Australia – 2007. http://www.osteoporosis.org.au/images/stories/documents/research/burdenbrittle_oa_2007.pdf [Accessed 31 May 2011].

4. AIHW 2011. A snapshot of osteoporosis in Australia 2011. Arthritis series no. 15. Cat. no. PHE 137. Canberra: AIHW. http://www.aihw.gov.au/publication-detail/?id=10737418750&libID=10737418749 [Accessed 5 May 2011].

5. Eisman J et al. Osteoporosis prevalence and levels of treatment in primary care: the Australian bone care study. J Bone Miner Res 2004; 19: 1969–1975.

6. Bleicher K et al. Prevalence and treatment of osteoporosis in older Australian men: findings from the CHAMP study. MJA 2010; 193: 387–391.

7. Prevention and management of osteoporosis: report of a WHO scientific group (WHO technical report series; 921). http://whqlibdoc.who.int/trs/who_trs_921.pdf [Accessed: 31 May 2011].

8. National Prescribing Service. NPS News 73: Reducing fracture risk in osteoporosis, 2011. http://www.nps.org.au/health_professionals/publications/nps_news/current/reducing_fracture_risk_in_osteoporosis

9. Rossi S, ed. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook Pty Ltd, 2011.

10. Sanders KM et al. Calcium and bone health: position statement for the Australian and New Zealand Bone and Mineral Society, Osteoporosis Australia and the Endocrine Society of Australia. Med J Aust 2009; 190: 316–320.

11. Endocrinology Writing Group. Therapeutic Guidelines: Endocrinology, Version 4 Updated March 2010 [eTG complete online]. Melbourne: Therapeutic Guidelines Ltd, 2009.

12. Black DM et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996; 348: 1535–1541.

13. Liberman U et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 1995; 333: 1437–1443.

14. Harris S et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. JAMA 1999; 283: 1344–1352.

15. Orwoll E et al. Alendronate for the treatment of osteoporosis in men. N Eng J Med 2000; 343: 604–610.

16. Häuselmann HJ and Rizzoli R. A comprehensive review of treatments for postmenopausal osteoporosis. Osteoporos Int 2003; 14: 2–12.

17. Schilcher et al. Bisphosphonate use and atypical fractures of the femoral shaft. N Engl J Med 2011; 364: 1728–1737.

18. Cummings SR et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009; 361: 756–765.

19. National Prescribing Service. Denosumab (Prolia) for postmenopausal osteoporosis. NPS RADAR December 2010. Sydney: NPS, 2010. http://www.nps.org.au/health_professionals/publications/nps_radar/2010/december_2010/denosumab [Accessed 29 May 2011].

20. Australian Medicines Handbook Drug Choice Companion: Aged Care 3rd edition. Australian Medicines Handbook Pty Ltd, Adelaide, 2010.

21. Nutrient reference values for Australia and New Zealand: Vitamin D. Australian Government, National Health & Medical Research Council and the New Zealand Ministry of Health. http://www.nrv.gov.au/nutrients/vitamin%20d.htm [Accessed 29 May 2011].

22. National Prescribing Service. Strontium (Protos) for postmenopausal osteoporosis. NPS RADAR November 2007. Sydney: NPS, 2007. http://www.nps.org.au/__data/assets/pdf_file/0017/24119/Strontium.pdf [Accessed 29 May 2011].

23. National Prescribing Service. Teriparatide (Forteo) for postmenopausal osteoporosis. NPS RADAR May 2009. Sydney: NPS, 2009. http://www.nps.org.au/__data/assets/pdf_file/0003/70869/OKA7115_NPS_RADAR_Teriparatide_Article_V2.pdf [Accessed 29 May 2011].

24. Cauley JA et al. Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Breast Cancer Res Treat 2001; 65: 125–134.

25. Ettinger B et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. JAMA 1999; 282: 637–645.

26. Meunier PJ et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004; 350: 459–468.

27. Reginster JY et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study. J Clin Endocrinol Metab 2005; 90: 2816–2822.

28. Tang B et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 2007; 370: 632–34.

29. Ross CA et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. JCEM 2011; 96: 53–58.

30. Osteoporosis Australia. Calcium, Vitamin D and Osteoporosis guide for GPs. Sydney: Osteoporosis Australia, 2008. http://www.osteoporosis.org.au/images/stories/documents/internal/oa_calcvitd_gp.pdf [Accessed 29 May 2011].

31. Bolland MJ et al. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ 2011; 342: d2040.

32. Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010; 341: c3691.

33. Osteoporosis Australia. Stop the next fracture. Consumer guide – managing osteoporosis. Sydney: Osteoporosis Australia, 2010. http://osteoporosis.org.au/images/stories/documents/internal/Stopfracture_consumer.pdf [Accessed 29 May 2011].