Osteoporosis practical management 2011

Osteoporosis – Practical Management of primary and

secondary prevention of fragility fractures

Recommendations of NICE ,NOGG, CKS, NHSSummary compiled from CKS site.

http://www.cks.nhs.uk/home

Vinod NaneriaChoithram Hospital & Research Centre, Indore

India

National Institute for Health and Clinical Excellence (NICE)

National Osteoporosis Guideline Group (NOGG)

Clinical Knowledge Summaries (CKS)

National Health Services (NHS)

Self-care and lifestyle advice• Eat a balanced diet containing foods which are

rich in calcium and vitamin D. • Take regular exercise (tailored to the individual)

to improve muscle strength, and reduce pain and stiffness.

• A systematic review provides evidence that exercise reduces the rate of falls, risk of falling, and risk of fracture.

• Encourage walking, especially outdoors, as this will increase exposure to sunlight, increasing vitamin D production.

Self-care cont…

• Encourage strength training of different muscle groups.

• If smoking, quit. Indirect evidence from cohort studies suggests that stopping smoking may reduce the risk of osteoporotic fragility fracture in women.

• Consume alcohol prudently.• Take practical steps to identify and modify any

factors that increase the risk of falling.

Basis for recommendation

• Healthy lifestyle measures are recommended for their other known benefits when the evidence on their protective effect on osteoporosis and risk of fragility fracture is too uncertain for this to be a sufficient reason.

Multi-factorial lifestyle interventions

• A systematic review provides evidence that multi-factorial lifestyle interventions (including environmental modifications; exercise programmes; and review of medicines, diet, and aids) may be associated with a lower risk of hip fractures. However, the effects were not statistically significant and the studies had methodological problems.

Advice regarding calcium and vitamin D

• Advise the person to eat a balanced diet containing foods that are rich in calcium and vitamin D.

• Consider supplementation for people who are unable to achieve an adequate intake by dietary means — in particular, for vitamin D.

calcium and vitamin D cont…

• Consider supplementation for people who are receiving drug treatment for osteoporosis (such as biphosphonates).

• Supplementation with calcium (1.0 g to 1.2 g) and vitamin D (20 micrograms) is recommended for elderly people who are housebound or living in nursing homes (to reduce the risk of hip fracture).

Calcium

• Dietary sources of calcium include bread, milk, and hard cheeses. All dairy products are sources of calcium. Poor sources of calcium include butter, cream, and soft cheeses

• The person should aim for an intake of 1000–1200 mg of calcium per day.

Calcium

• Advise against excessive calcium intake (greater than 2500 mg daily) if the person has impaired renal function.

• In the absence of renal dysfunction, calcium intake of up to 2500 mg daily does not promote hypercalciuria or stone formation.

Vitamin D• The main source of vitamin D is exposure of the skin

to the sun.• Vitamin D supplementation is not indicated for

active people younger than 65 years of age who are not at-risk.

• Small amounts of vitamin D are found in relatively few foods — such as oily fish, eggs, meat, some margarines, and some breakfast cereals, and soya and dairy products.

• Vitamin D requirement from diet alone is on average, provides 2-4 micrograms daily.

Vitamin D• People older than 65 years of age should aim for a

daily vitamin D intake of 10 micrograms (400 units). In most cases, this will only be achieved by supplementation.

• Vitamin D supplementation (10 micrograms) is also recommended for people at risk of vitamin D deficiency — for example those who have little or no exposure to sunlight because they:– Are housebound or being confined indoors for long

periods.– Wear clothes that cover the whole body.

Role of calcium and vitamin D

• There is a close physiological relationship between calcium and vitamin D in maintaining bone homeostasis. Vitamin D modulates the intestinal absorption of dietary calcium, with low levels impairing calcium absorption, resulting in a compensatory increase in parathyroid hormone secretion, causing net bone resorption.

Role of calcium and vitamin D

• Moreover, with age, the intestinal absorption of calcium in response to vitamin D declines. Elderly people are at risk of vitamin D insufficiency due to their reduced mobility and consequently reduced exposure to sunlight. The skin’s capacity to synthesize vitamin D also declines with age. Calcium and vitamin D insufficiency therefore commonly coexist in older adults.

Dietary calcium intake

• For the prevention of osteoporotic fractures, the evidence on dietary calcium is uncertain.

• Postmenopausal women should aim for a dietary intake of 1000 mg calcium per day . This is based on evidence from a meta-analysis of case-control and cohort studies which reported that such an intake reduces the risk of hip fractures in postmenopausal women.

• However a subsequent meta-analysis of cohort studies did not support this finding.

Daily vitamin D intake

• Due to a lack of supporting evidence, vitamin D supplementation for active people younger than 65 years of age is not recommend .

• People older than 65 years of age and those at risk of vitamin D deficiency should aim for a daily vitamin D intake of 10 micrograms (400 units).

Daily vitamin D intake• Although evidence suggests that vitamin D alone

is not effective in reducing fractures in older people (when compared with placebo), it can reduce the risk of falls in people 60 years of age and older living in institutionalized care or in the community.

• For elderly people who are housebound or living in a nursing home, a higher dose of 20 micrograms (800 units), along with a daily dose of 1.0 g to 1.2 g calcium, is recommended to reduce the risk of fractures.

Calcium and vitamin D supplementation

• Evidence suggests that calcium plus vitamin D is more effective than either placebo, no treatment, or vitamin D alone in reducing the risk of hip fractures in older people. For elderly people living in nursing homes or residential care, supplementation can reduce the risk of both hip and non-vertebral fractures.

Use of natural health products, dietary supplements, and homeopathy

• Phytoestrogens are not recommended as a sole treatment to reduce the risk of osteoporotic fragility fracture.

• The following treatments are not recommended for the management of osteoporosis or prevention of fracture:• Natural health products or dietary supplements

(other than calcium, vitamin D and strontium ranelate) — for example, dehydroepiandrosterone (DHEA) and vitamin K.

• Homeopathic remedies.

Phytoestogens

• Phytoestrogens (isoflavones, lignans, and coumestans) are plant-derived compounds with chemical structures similar to mammalian oestrogens. Consequently, they have been proposed as treatments for osteoporosis. However, evidence is lacking on any ability to reduce the risk of fracture. Evidence is inconsistent regarding their effect on bone mineral density (BMD).

• Consequently, phytoestrogens are not recommended as a sole treatment to reduce the risk of osteoporotic fragility fracture.

Other treatments

• Although they have been proposed as treatments for osteoporosis, no evidence found on the use of magnesium, boron, and homeopathic remedies for the management of osteoporosis and prevention of fractures.

• Due to the lack of good evidence to support their use, natural health products, dietary supplements or homeopathy for the management of osteoporosis and prevention of fractures are not recommend.

Assess and manage the risk of falls in osteoporosis

• Assess the person for their risk of falls, including the presence of:

• One or more falls in the previous year — this is the strongest risk factor for further falls.

• Hazards in the home — such as poor lighting, slippery floors, loose carpets and other obstacles over which people can trip, and weak or absent hand rails. A falls clinic can make a full assessment.

• Frailty (for example physical disability, general weakness).

Assess and manage cont…

• Mobility or balance difficulties — these are common with arthritis, stroke, Parkinson's disease, arrhythmias, and heart failure.

• Visual impairment.• Cognitive impairment.• Excessive alcohol consumption.• Urinary incontinence.


• Drug treatment:• Polypharmacy (taking four or more drugs).• Drugs that can cause postural hypotension.• Psychoactive drugs (such as benzodiazepines,

antidepressants).• Address any modifiable risk factors, where this is

possible.


• For people who are at a high risk of falls, consider referral to a specialist falls service. In particular, refer people who meet any of the following criteria:

• Two or more falls in the previous 12 months.• One fall plus a disorder of gait and balance or

with syncopal features.


• A fall causing an injury.• For people who would benefit from

improved muscular strength and coordination, consider referral to a physiotherapist or other healthcare professional providing evidence-based interventions.

Risk factors

• Risk factors for falls include poor eye sight, cardiovascular disease, neurological disorders, medication that impairs alertness and balance, and home environmental hazards (slippery floors, obstacles, insufficient lighting, and loose or absent handrails).

Risk factors for falls

• The strongest risk factor for falls is a previous fall. NICE recommends that all older people in regular contact with healthcare professionals should be asked about this at least annually. The other risk factors were reported as being statistically significantly associated with falls.

• The reviews done by NICE and NOGG found evidence that interventions can prevent falls.

Risk factors cont…

• The review by NOGG found no evidence that falls prevention measures in the community also reduce the risk of fragility fractures. The NOGG recommendation to assess and manage the risk of falls is therefore based on expert opinion.

• However, there is evidence from a small study that falls prevention strategies in residential care facilities may prevent fractures.

NICE guidance on drug treatment to prevent osteoporotic fractures

in postmenopausal women

NICE Guideline cont…

• The CKS online tool can be used to assess the eligibility of postmenopausal women according to the NICE guidance.

• If it is not practical to use the eligibility tool, consider:• Eligibility for alendronate (first-line).• Eligibility for risedronate, etidronate (second-line).• Eligibility for strontium ranelate, raloxifene,

denosumab (third-line).• Eligibility for teriparatide (fourth-line).

NICE guidance cont…

• If drug treatment is recommended, additionally offer calcium and vitamin D (unless dietary intakes of calcium and the risk of vitamin D deficiency have been assessed and are adequate).


• If the woman is unable to use the treatment she is eligible for, and she does not meet the NICE criteria for alternative drugs, advise her that no other drug treatment is recommended by NICE at her current level of fracture risk, but that her fracture risk will be reassessed within 2–5 years.

• If no drug treatment is indicated:• Reassure the woman that she needs only self-care

and a healthy lifestyle.• Arrange follow up within 5 years, depending on her

fracture risk.


• NICE states that 'This guidance assumes that women who receive treatment have an adequate calcium intake and are vitamin D replete. Unless clinicians are confident that women who receive treatment meet these criteria, calcium and/or vitamin D supplementation should be considered.'

• Effectiveness of drugs to reduce the risk of osteoporotic fragility fractures in postmenopausal women.

• The evidence on the effectiveness of the drugs used in primary care is summarized in the sections on the individual drugs.


• Table 1 - shows the effect of the various drugs on fractures of the vertebrae, hips, and other sites.

• Although the NICE guidance recommends risedronate and etidronate as options for second-line treatment, the evidence to support risedronate is more robust than that for etidronate and risedronate and is therefore preferred by CKS .


• For younger postmenopausal women who are at high risk of osteoporotic fragility fracture and also have menopausal symptoms, discuss the option of hormone replacement therapy to target both conditions.


• When a woman is eligible for more than one drug, choose the most suitable drug according to its spectrum of anti-fracture effects across skeletal sites, adverse effects, and practical issues such as administration requirements, availability, and cost.


• Obtain specialist advice or referral when there are uncertainties about diagnosis or management.

• For example, consider obtaining specialist advice for women who do not meet the NICE eligibility criteria, but for whom drug treatment seems clinically indicated.


• Options for treatment in secondary care include denosumab, ibandronate, zoledronate, teriparatide, and parathyroid hormone. However, service arrangements and patterns of usage may change (for example with the development of community fracture liaison clinics).


• Denosumab is usually started in secondary care and continued in primary care, but there are no significant barriers to starting it in primary care. Renal failure is not a contraindication to using denosumab as it is with most of the alternatives.


• Intravenous ibandronate and zoledronate are usually given in secondary care.

• Ibandronate can be given by intravenous injection, and is practical for administration in primary care.

• Zoledronate is given by slow intravenous infusion and requires particular training. It is therefore less practical for primary care.

Clinical assessment of fracture risk and low BMD with NICE guidance on drugs to

prevent osteoporotic fractures

• For the purpose of their guidance on drug treatments to prevent osteoporotic fragility fractures, the National Institute for Health and Clinical Excellence (NICE) recommends that the risk of fracture and the risk of low bone mineral density (BMD) be assessed.

Clinical assessment cont…

• Clinical indicators of fracture risk (independent of age and bone mineral density [BMD])

• Parental history of hip fracture.• Alcohol intake of 4 units or more per day (the

UK National Osteoporosis Guideline Group [NOGG] recommends a threshold of 3 units per day).

• Rheumatoid arthritis.

Clinical assessment cont…

• Clinical indicators of low BMD• Body mass index less than 22 kg/m2 (NOGG

recommends a threshold of 19 kg/m2).• Conditions such as ankylosing spondylitis,

Crohn’s disease.• Conditions that result in prolonged immobility.• Untreated premature menopause, and other

causes of secondary osteoporosis.

Alendronate recommended by NICE for postmenopausal women

• National Institute for Health and Clinical Excellence (NICE) guidance on alendronate to prevent osteoporotic fragility fractures applies to postmenopausal women with osteoporosis.

• It does not apply to premenopausal women, to men, to women with osteopenia, or to those with normal bone mineral density (BMD) or who are taking long-term systemic glucocorticosteroids.

Alendronate cont…

• To assess if the postmenopausal woman is eligible for treatment with alendronate, use the CKS online tool. Alternatively:

• If she has had an osteoporotic fragility fracture, use Table1 to assess eligibility for treatment.

Alendronate cont…

• If she has not had an osteoporotic fragility fracture:

• Assess the number of clinical indicators of fracture risk and low BMD.

• Use Table2 to assess eligibility for treatment.

Age Eligibility criteria

Less than 75 years T-score –2.5 or less

75 years or older T-score –2.5 or less*

Table 1. Alendronate eligibility criteria recommended by the National Institute for Health and Clinical Excellence (NICE) for postmenopausal women who have had an osteoporotic fragility fracture (secondary prevention).

In women aged 75 years or older, a dual energy X-ray absorptiometry (DXA) scan may not be required if the responsible clinician considers it to be clinically inappropriate or unfeasible.Source [NICE, 2011a]

Alendronate: NICE eligibility criteria for postmenopausal women without an osteoporotic fragility fracture

Age Eligibility criteria in NICE guidance

T-score Independent clinical risk factors*

Clinical indicators of low bone mineral density*

Less than 65 years –2.5 or less at least 1 AND at least one

65–69 years –2.5 or less at least 1 — —

70 years or older –2.5 or less† at least 1 OR at least one

Table 2. Alendronate eligibility criteria recommended by the National Institute for Health and Clinical Excellence (NICE) for postmenopausal women who have not had an osteoporotic fragility fracture.

•See Clinical indicators of fracture risk and low BMD.•† In women aged 75 years or older who have two or more independent clinical risk factors for fracture or indicators of low bone mineral density, a dual energy X-ray absorptiometry (DXA) scan may not be required if the responsible clinician considers it to be clinically inappropriate or unfeasible.


• These recommendations are based on the National Institute for Health and Clinical Excellence (NICE) guidance on the prevention of osteoporotic fractures in postmenopausal women.

• Alendronate as first-line drug treatment for osteoporosis.


• A systematic review of 15 randomized controlled trials provides evidence that alendronate reduces the risk of osteoporotic fragility fractures (vertebral, non-vertebral, and hip) in postmenopausal women.

• Alendronate is regarded as the most cost-effective of the drugs used to prevent osteoporotic fragility fractures (by both NICE and National Institute for Health and Clinical Excellence [NOGG]).

Risedronate or etidronate (second-line drug treatment) recommended by NICE for

postmenopausal women

• National Institute for Health and Clinical Excellence (NICE) guidance on risedronate and etidronate to prevent osteoporotic fragility fractures applies to postmenopausal women in whom alendronate is contraindicated or poorly tolerated, or in whom in cannot be administered correctly.

Risedronate or etidronate cont…

• It does not apply to premenopausal women, to men, to women with osteopenia, or to those with normal bone mineral density (BMD) or who are taking long-term systemic glucocorticosteroids.

• To assess if the postmenopausal woman is eligible for treatment with risedronate or etidronate, use the CKS online tool. Alternatively:


• Assess the number of independent clinical indicators for risk of osteoporotic fragility fracture.

• If she has had an osteoporotic fragility fracture, use the decision rules in Table 1 to assess if she is eligible for treatment.

• If she has not had an osteoporotic fragility fracture, use the decision rules in Table 1 to assess if she is eligible for treatment.


• If the woman does not meet the NICE eligibility criteria for risedronate, advise her that:• No other drug treatment is recommended by NICE

at her current level of fracture risk.• She will be followed up in 2–5 years, to reassess

her fracture risk and any new need for drug treatment.


• If measurement of BMD is not required prior to treatment initiation, CKS recommends considering a baseline BMD measurement to facilitate assessment of response to treatment.

• For eligible women in whom alendronate and either risedronate or etidronate are contraindicated or poorly tolerated, or in whom they cannot be administered correctly, assess for eligibility for strontium ranelate, raloxifene, and denosumab.

Table 3 – women with fracture

• T-scores at or below which risedronate and etidronate are recommended by the National Institute for Health and Clinical Excellence (NICE) when alendronate cannot be taken by postmenopausal women who have had an osteoporotic fragility fracture (secondary prevention).

Age (years) Number of independent clinical risk factors for osteoporotic fragility fracture*

0 1 >=250–54 (Not

recommended)–3.0 –2.5

55–59 –3.0 –3.0 –2.560–64 –3.0 –3.0 –2.565–69 –3.0 –2.5 –2.570 or older –2.5† –2.5† –2.5†

* See Clinical indicators of fracture risk and low BMD.† In a woman 75 years of age or more without a bone mineral density score, a dual energy X-ray absorptiometry (DXA) scan may not be required if the healthcare professional considers it to be clinically inappropriate or unfeasible.Source [NICE, 2011a]

Table 3

Table 4 – women with no fracture

• T-scores at or below which risedronate and etidronate are recommended by the National Institute for Health and Clinical Excellence (NICE) when alendronate cannot be taken by postmenopausal women who have not had an osteoporotic fragility fracture (primary prevention).


0 1 265–69 (Not


70–74 –3.5 –3.0 –2.575 or older –3.0† –3.0† –2.5†

* See Clinical indicators of fracture risk and low BMD.† In women aged 75 years or older who have two or more independent clinical risk factors for fracture or indicators of low bone mineral density, a dual energy X-ray absorptiometry (DXA) scan may not be required if the responsible clinician considers it to be clinically inappropriate or unfeasible.Source [NICE, 2011b]



• These recommendations are based on the National Institute for Health and Clinical Excellence (NICE) guidance on the prevention of osteoporotic fractures in postmenopausal women.

• Risedronate as second-line drug treatment for osteoporosis


• A systematic review of seven randomized controlled trials (RCTs) provides evidence that risedronate reduces the risk of osteoporotic fragility fractures (vertebral, non-vertebral, and hip) in postmenopausal women.

• A systematic review of 12 RCTs provides evidence that etidronate reduces the risk of vertebral fractures during the first 2 years of treatment, and that it does not reduce the risk of non-vertebral fractures.

Strontium ranelate, raloxifene, and denosumab recommended by NICE for


• National Institute for Health and Clinical Excellence (NICE) guidance on strontium ranelate, raloxifene, and denosumab to prevent osteoporotic fragility fractures applies to postmenopausal women in whom alendronate and either risedronate or etidronate are contraindicated or poorly tolerated, or in whom they can not be administered correctly.

Strontium ranelate cont…

• It does not apply to premenopausal women, to men, to women with osteopenia, or to those with normal bone mineral density or who are taking long-term systemic glucocorticosteroids.

• To assess if the postmenopausal woman is eligible for treatment with strontium ranelate, raloxifene, or denosumab, use the CKS online tool.


• Alternatively:• Assess the number of independent clinical

indicators for risk of osteoporotic fragility fracture.

• If she has had an osteoporotic fragility fracture:• Use the decision rules in Table 5 to assess if she is

eligible for strontium ranelate or raloxifene.• She will always be eligible for denosumab in this

situation.


• If she has not had an osteoporotic fragility fracture:

• Use the decision rules in Table 5 to assess if she is eligible for strontium ranelate or denosumab.

• She will never be eligible for raloxifene in this situation.

• If the woman does not meet the NICE eligibility criteria for strontium ranelate, raloxifene, or denosumab, advise her that:


• No other drug treatment is recommended by NICE at her current level of fracture risk.

• She will be followed up in 2–5 years, to reassess her fracture risk and any new need for drug treatment.

• Obtained prescription information for contraindications, adverse effects, and advice on drug administration.

Table 5 - women with fracture

• T-scores at (or below) which strontium ranelate or raloxifene are recommended by the National Institute for Health and Clinical Excellence (NICE) when alendronate and either risedronate or etidronate cannot be used in postmenopausal women with a fragility fracture (secondary prevention).


0 1 250–54 (Not


55–59 –4.0 –3.5 –3.560–64 –4.0 –3.5 –3.565–69 –4.0 –3.5 –3.070–74 –3.0 –3.0 –2.575 or older –3.0† –2.5† –2.5†

* See Clinical indicators of fracture risk and low BMD.† In women aged 75 years or older who have one or more independent clinical risk factors for fracture or indicators of low bone mineral density, a dual energy X-ray absorptiometry (DXA) scan may not be required if the responsible clinician considers it to be clinically inappropriate or unfeasible. Source [NICE, 2011a].

Table 5 - women with fracture


• T-scores at (or below) which strontium ranelate and denosumab are recommended by the National Institute for Health and Clinical Excellence (NICE) when alendronate and either risedronate or etidronate cannot be used in postmenopausal women without a fragility fracture (primary prevention). Raloxifene is not recommended by NICE for postmenopausal women who have not had a fragility fracture.



0 1 265–69 (Not


70–74 –4.5 –4.0 –3.575 or older –4.0 –4.0 –3.0

* See Clinical indicators of fracture risk and low BMD. Sources [NICE, 2011a; NICE, 2010b].

Basis for recommendation Strontium ranelate

• A systematic review of randomized controlled trials (RCTs) provides evidence that, compared with placebo, treatment with strontium ranelate reduces the risk of vertebral and non-vertebral fractures in postmenopausal women with low bone mineral density (BMD).

• No head-to-head trials have compared strontium ranelate with other drugs for reduction of fracture risk.

Raloxifene in prior fragility fracture

• A systematic review of RCTs provides evidence that, compared with placebo, treatment with raloxifene reduces the risk of vertebral fractures in postmenopausal women with low BMD. No head-to-head trials have compared raloxifene with other drugs for reduction of fracture risk.

• NICE did not recommend raloxifene for women who had not had an osteoporotic fragility fracture, because this was found to be not cost-effective.

Denosumab for fracture prevention in postmenopausal women with and

without a prior fragility fracture

• One large RCT provides evidence that, compared with placebo, denosumab reduces the risk of vertebral, hip, and non-vertebral fractures.

Denosumab cont…

• NICE describes and justifies its approach to assessing eligibility for treatment in the guidance [NICE, 2010b; NICE, 2011a; NICE, 2011b] and on the website (www.nice.org.uk).

• The differences in approach between NICE and the National Osteoporosis Guideline Group (NOGG) have been discussed by [Kanis et al, 2010].

Teriparatide recommended by NICE for postmenopausal women

• National Institute for Health and Clinical Excellence (NICE) guidance on teriparatide to prevent osteoporotic fragility fractures applies to postmenopausal women with osteoporosis.

• It does not apply to premenopausal women, to men, to women with osteopenia, or to those with normal bone mineral density or who are taking long-term systemic glucocorticosteroids.

Teriparatide cont…

• To assess if the postmenopausal woman is eligible for treatment with teriparatide, use the CKS online tool. Alternatively, apply the following criteria:• Teriparatide is recommended as an option for

women who have problems with other drug treatments for the prevention of osteoporotic fragility fractures, including those who:

• Are unable to take alendronate and either risedronate or etidronate.

Teriparatide cont…

• Have a contraindication to, or are intolerant of, alendronate and either risedronate or etidronate.

• Have a contraindication to, or are intolerant of, strontium ranelate.

• Have had an unsatisfactory response to treatment with alendronate, risedronate, or etidronate.

• Women are eligible for treatment with teriparatide if they have had more than two osteoporotic fragility fractures, and they are:

• Aged 55–64 years, with a T-score of –4 or less, or• Aged 65 years or more, with a T-score of –3.5 or less.


• These recommendations are based on National Institute for Health and Clinical Excellence (NICE) guidance on the prevention of osteoporotic fractures in postmenopausal women.

• Teriparatide for fracture prevention in postmenopausal women with a prior fragility fracture

• A systematic review provides evidence (based on one randomized controlled trial), that teriparatide reduces the risks of vertebral and non-vertebral fractures in postmenopausal women with low bone mineral density.


• NICE describes and justifies its approach to assessing eligibility for treatment in the guidance [NICE, 2010b; NICE, 2011a; NICE, 2011b] and on the website (www.nice.org.uk).

• The differences in approach between NICE and the National Osteoporosis Guideline Group (NOGG) have been discussed in [Kanis et al, 2010].

• National Osteoporosis Guideline Group (NOGG) recommendations on drug treatment to prevent osteoporotic fragility fractures in men and postmenopausal women.

NOGG guidance on drug treatment to prevent osteoporotic

fractures in postmenopausal women

NOGG guidelines cont…

• National Osteoporosis Guideline Group (NOGG) guidelines on drugs to prevent osteoporotic fragility fractures apply to men from 50 years of age, and to postmenopausal women. The guidelines cover people taking systemic glucocorticoids.

• Offer self-care and lifestyle advice to all people at risk of osteoporosis.


• For postmenopausal women with an osteoporotic fragility fracture:

• Treatment is recommended without measuring bone mineral density (BMD) or calculating the risk of further fractures.

• Nevertheless, BMD measurement may sometimes be appropriate, particularly in younger postmenopausal women.


• For men and postmenopausal women who do not have an osteoporotic fragility fracture:

• Use the online FRAX® calculator to assess the 10-year probability of fracture.


• Go to the 'intervention threshold' charts from the FRAX® calculator to assess eligibility for treatment.

• If drug treatment is recommended, choose treatment according to its spectrum of anti-fracture effects across skeletal sites, adverse effects, and practical issues such as administration requirements, availability, and cost.


• Alendronate 70 mg weekly is the first-line choice.• Risedronate, ibandronate, strontium ranelate,

denosumab, and zoledronate are second-line options.

• Teriparatide and parathyroid hormone are third-line options.

• For younger postmenopausal women who are at high risk of fracture and who also have menopausal symptoms, discuss the option of hormone replacement therapy.


• For men:• Alendronate, risedronate, zoledronate, and

teriparatide are licensed for the treatment of osteoporosis.

• Consider referral, particularly for younger men and for men with severe osteoporosis — secondary causes are common in these groups and require specialist investigation.

• If drug treatment is recommended, additionally offer calcium and vitamin D supplementation (unless the dietary intake of calcium and the risk of vitamin D deficiency have been assessed and found to be adequate).


• These recommendations are based on guidelines published by the National Osteoporosis Guideline Group (NOGG) [National Osteoporosis Guideline Group, 2008; National Osteoporosis Guideline Group, 2010].


• Effectiveness of drugs to reduce the risk of osteoporotic fragility fractures in postmenopausal women

• Table 6 has an overview of the effects of the various drugs on fractures of the vertebrae, hips, and non-vertebral sites.

• Obtaining a dual energy X-ray absorptiometry scan (DXA) as a baseline when NOGG guidelines suggest treatment is indicated without measuring bone mineral density.


• CKS recommends, when it is practical, considering obtaining a DXA scan when the FRAX® calculator suggests that the clinical risk factors are sufficient for treatment initiation without a DXA scan. This is because the NOGG guidance was developed at a time when the availability of DXA scanning was restricted [Cooper, 2009].


• NOGG describes and justifies its approach in the guidance and supporting publications []. Kanis et al, 2008a; Kanis et al, 2008b; Compston et al, 2009

• Limitations to the approach taken by NOGG have been described [Bayly, 2009; Kanis et al, 2009; National Osteoporosis Guideline Group, 2010].


• The FRAX® calculator does not take account of the dose–response effects of risk factors (such as alcohol consumption, smoking, and use of glucocorticoids), or the number and type of osteoporotic fragility fractures [Kanis et al, 2008c; Kanis et al, 2009].

• There are a number of risk factors that the FRAX® calculator does not take into account (such as risk factors for falls, and previous treatments) [kanis et al, 2009].

http://www.cks.nhs.uk/osteoporosis_prevention_of_fragility_fractures/evidence/references#A66455



• The 'threshold charts' to which the online UK FRAX® calculator links may overestimate the need for treatment in younger people and underestimate the need for treatment in older people, particularly if treatment is based on a 10-year risk of major osteoporotic fragility fracture (forearm, humeral, hip, or clinical vertebral fracture) [Bayly 2009].

NOGG's guidance on drug treatment to prevent osteoporotic fractures in


• Follow local protocols and service arrangements when these are available.

• Use clinical judgement when applying the guidance.

• Obtained prescription information on administration, drug doses, cautions, contraindications, and interactions.

NOGG's guidance cont…

• Obtain specialist advice or referral when there are uncertainties about diagnosis or management.

• Options for treatment in secondary care include denosumab, ibandronate, zoledronate, teriparatide, and parathyroid hormone. However, service arrangements and patterns of usage may change (for example with the development of community fracture liaison clinics).

NOGG's guidance cont...

• Denosumab is usually started in secondary care and continued in primary care, but there are no significant barriers to starting it in primary care. Renal failure is not a contraindication to using denosumab as it is with many other alternatives.

• Intravenous ibandronate and zoledronate are usually given in secondary care.

NOGG's guidance cont..

• Ibandronate can be given by intravenous injection, and is practical for administration in primary care.

• Zoledronate is given by intravenous infusion and requires particular training. It is therefore less practical for primary care.

FRAX® calculator to assess risk of osteoporotic fracture and eligibility for

treatment according to NOGG guidelines

• National Osteoporosis Guideline Group (NOGG) guidelines on drugs to prevent osteoporotic fragility fractures apply to men from the age of 50 years, and to postmenopausal women. The NOGG guidelines cover people taking systemic glucocorticoids.

FRAX® calculator cont…

• Women with a fragility fracture can be offered treatment on this risk alone, without using the FRAX® calculator.

• Use the online FRAX® calculator to assess if a dual energy X-ray absorptiometry (DXA) scan is indicated to measure bone mineral density. See Scenario: Diagnosis.


• Use the online FRAX® calculator to assess the 10-year probabilities of a hip fracture and of a major osteoporotic fracture (clinical spine, hip, wrist, or proximal humerus).

• Link from the FRAX® calculator to the 'intervention threshold' charts for hip fracture and major fracture, and NOGG guidance.


• Men and women whose 10-year probability for a hip fracture or for a major fracture is above the intervention threshold (in the red zone) should be considered for treatment. Intervention thresholds are for guidance only, and the final decision to initiate treatment lies with the individual clinician.


• Men and women with both probabilities below the intervention thresholds (in the green zone) should be re-assessed within 5 years, depending on the clinical context.

Risk factors recommended by NOGG for assessing the risk of osteoporotic fractures

• The National Osteoporosis Guideline Group (NOGG) recommends the following factors (all but one of which are used in the online FRAX® calculator) to clinically assess the risk of an osteoporotic fragility fracture:

• Age.• Sex.• Low body mass index (less than or equal to

19 kg/m2).• Previous fragility fracture, particularly of the hip,

wrist, and spine.


• Parental history of hip fracture.• Current glucocorticoid treatment (any oral

dose, for 3 months or more).• Current smoker.• Alcohol intake of 3 units or more daily.• Secondary causes of osteoporosis, including:


• Rheumatoid arthritis.• Untreated hypogonadism (men and women).• Prolonged immobility.• Organ transplantation.• Type 1 diabetes.


• Hyperthyroidism.• Gastrointestinal disease.• Chronic liver disease.• Chronic obstructive pulmonary disease.• Increased risk of falls (this is not used by the

FRAX® calculator).


• These recommendations reflect guidelines published by the National Osteoporosis Guideline Group (NOGG) [National Osteoporosis Guideline Group, 2008; National Osteoporosis Guideline Group, 2010].

• Using the FRAX® calculator and decision threshold charts for assessing eligibility for treatment

• NOGG describes and justifies its approach of using the FRAX® calculator and decision threshold charts for assessing eligibility for treatment in the guidance and in [Kanis et al, 2008a; Kanis et al, 2008b; Compston et al, 2009].

Drugs to prevent osteoporotic fractures in men and women according to NOGG guidance

Drugs to prevent cont…

• National Osteoporosis Guideline Group (NOGG) guidelines on drugs to prevent osteoporotic fragility fractures apply to men from the age of 50 years, and to postmenopausal women. The NOGG guidelines cover people using systemic glucocorticoids.


• For women and men eligible for treatment, choose the drug according to its spectrum of anti-fracture effects across skeletal sites, its adverse effects, practical issues (such as administration and availability), and cost.


• Alendronate 70 mg weekly is the first-line treatment for most women and men, given its low cost and its effectiveness in reducing the risk of vertebral, non-vertebral, and hip fractures.

• For women who cannot tolerate alendronate or in whom it is contraindicated, other bisphosphonates, denosumab, strontium ranelate, or raloxifene may be appropriate and cost-effective treatment options.


• For people with renal failure and high risk of an osteoporotic fragility fracture, denosumab may be more appropriate than a bisphosphonate.

• For younger postmenopausal women who are at high risk of fracture and also have menopausal symptoms, consider hormone replacement therapy.


• Alendronate, risedronate, zoledronate, and teriparatide are licensed for use in men.

• Parathyroid hormone and teriparatide should be restricted to those at very high risk (particularly for vertebral fractures).

• Obtained prescription information on doses, administration, contraindications, adverse effects, and interactions.

Basis for recommendation• These recommendations are based on guidelines

published by the National Osteoporosis Guideline Group [National Osteoporosis Guideline Group, 2008; National Osteoporosis Guideline Group, 2010].

• Effectiveness of drugs to reduce the risk of osteoporotic fragility fractures in postmenopausal women

• Table 6 summarizes the evidence on the effects of the various drugs on fractures of the vertebrae, hips, and non-vertebral sites.

Management of fragility fracture during treatment

• Consider referral for orthopaedic assessment and management of the fracture.

• Vertebral fractures often do not require referral.• Fractures of the hips and other limb bones

usually require admission to a trauma unit.• Confirm that the fracture is a true fragility

fracture, and exclude non-osteoporotic causes of fragility fracture such as bone metastases. See Causes of non-osteoporotic fragility fractures.

• Manage the person's pain.

Management of fragility fracture during treatment

• Manage any functional impairments.• Assess for adherence problems, and offer any

appropriate advice or consider an alternative drug.

Management cont…

• Advise the person that having a fracture does not necessarily mean that the treatment has not been beneficial. Treatment reduces, but does not eliminate, the risk of fracture. If the person has been taking their treatment for at least a year, it may already have prevented one or more fractures. This can be assessed by the change in bone mineral density since treatment started.

Management cont…

• Consider bone mineral density measurement for people who have a fracture after fully adhering to drug treatment for at least 1 year and the result of the scan will influence management (for example, if the T-score is below the pre-treatment level, an alternative treatment would be considered, but would not not be considered if the T-score was greater than the pre-treatment level).

Management cont…

• After acute management of the fracture, reassess and manage the person's risk for falls, including referral to the falls liaison service if required. See the separate CKS topic on Falls - risk assessment.

Basis for recommendation• These recommendations are considered to be

good practice.• CKS found no relevant UK national guidance with

specific recommendations, and found no relevant direct evidence.

• The National Osteoporosis Guideline Group recommends that 'all individuals with fracture should be fully assessed for fall risk factors and appropriate interventions to reduce falls should be undertaken' [National Osteoporosis Guideline Group, 2010].

Referral of a person with osteoporosis

• For people who may benefit from an exercise programme, or balance and gait training, especially if they are at risk of falling:

• Consider referral to a physiotherapist or other therapist for evidence-based interventions. See the CKS topic on Falls - risk assessment.

• For people who present with a new osteoporotic fragility fracture:

Referral cont…

• Admit to a trauma unit if indicated — see Fracture during treatment.

• For people who are not able to use any of the drugs used in primary care to prevent osteoporotic fragility fractures:

• Obtain specialist advice or referral. Options for treatment in secondary care include denosumab, ibandronate, zoledronate, and teriparatide.

People with secondary osteoporosis

• Obtain specialist advice or referral. See secondary osteoporosis.

• For people who do not meet the eligibility criteria in guidelines, but for whom drug treatment seems clinically indicated:

• Obtain specialist advice or referral for assessment.

• For men with osteoporosis, especially younger men and those with severe disease:

• Consider referral.

Basis for recommendation• These recommendations take account of the

National Institute for Health and Clinical Excellence (NICE) guidance on the prevention of osteoporotic fractures in postmenopausal women [NICE, 2010b; NICE, 2011a; NICE, 2011b], and guidelines developed by the UK National Osteoporosis Guideline Group (NOGG) for the National Osteoporosis Society and other professional organizations [Kanis et al, 2008a; Compstom et al, 2009; Kanis et al, 2009; National Osteoporosis Guideline Group, 2010].




• The NOGG guidance recommends (on the basis of expert opinion) that 'Consideration should be given to referring men with osteoporosis to specialist centres, particularly younger men or those with severe disease' [National Osteoporosis Guideline Group, 2010].

Follow up and monitor people on drug treatment to reduce the risk of osteoporotic fragility fracture

Follow up cont…

• For people with risk factors for osteoporotic fragility fractures who are not eligible for drug treatment:

• Follow up within 5 years to reassess fracture risk (or sooner if new risk factors for fracture develop).

• For people who have been started on drug treatment:

• Follow up 2–3 months after starting treatment. If the person is finding it difficult to adhere to treatment, before changing or stopping their drug consider.

Follow up cont…

• Reinforcing the benefits of treatment (such as fracture prevention).

• Reminding them of sources of support and printed information such as the National Osteoporosis Society (www.nos.org.uk).

follow up cont…

• Home support services (where available) for help with drug administration (for example family or social services).

• The use of intermittent dosing regimens. For more information.

• Consider repeating bone mineral density (BMD) measurement with dual energy X-ray absorptiometry (DXA) scan at 2 years and 5 years after treatment initiation.

BMD measurement is not recommended

• For people using strontium ranelate, because strontium in bone affects BMD measurements.

• More frequently than every 2 years, because T-scores are unlikely to change significantly over shorter intervals.

• If the result will not affect management decisions.

BMD measurement cont…

• If the new BMD is below the pre-treatment level, assess adherence and consider alternative treatment.

• Measuring bone turnover markers to assess response to treatment is not recommended for routine primary care. However, bone turnover markers are often measured in secondary care and during research studies.

• For more information, see Stopping treatment.


• These recommendations are in line with guidelines developed by the National Institute for Health and Clinical Excellence (NICE) [NICE, 2010b; NICE, 2011a; NICE, 2011b], the National Osteoporosis Guidelines Group (NOGG) [Compston et al, 2009; National Osteoporosis Guideline Group, 2010], and the Scottish Intercollegiate Guidelines Network (SIGN) [SIGN, 2003].


• CKS found no national policy for following up women with osteoporosis. These recommendations are based partly on the SIGN guideline Management of osteoporosis [SIGN, 2003]. Follow up helps to identify adverse effects of drugs, which typically occur during the first 2–3 months of use [NICE, 2011a; NICE, 2011b].

Basis for recommendationDuration of follow up

• Asking about adherence• Taking bisphosphonates can be difficult for some

people, especially if they have problems with memory or sitting. A systematic review of 24 observational studies investigated adherence to drug treatment in osteoporosis and concluded that one third to half of people do not take their mediation as directed, and nonadherence occurs shortly after treatment initiation [Kothawala et al, 2007].

Monitoring with dual energy X-ray absorptiometry (DXA)

• Bone mineral density (BMD) does not provide a perfect indicator of treatment efficacy, as it does not reflect other factors that affect bone strength (for example bone size, shape, turnover, and architecture) [Small, 2005].

• BMD changes at the lumbar spine (the preferred site) are difficult to interpret after 65 years of age (because of confounding effects, such as degenerative changes) [Compston 2009].



• Most women who lose BMD during the first year of treatment with alendronate or raloxifene will gain BMD if the same treatment is continued for a second year. For example, a double-blind placebo controlled trial in 2634 women taking alendronate reported a decrease in hip BMD of more than 4% during the first year; but 83% of the women had an increase in BMD in the second year, and there was an overall mean increase of 4.7% [Cummings et al, 2000].

Monitoring with bone turnover markers

• Markers of bone formation (serum procollagen type I N propeptide, s-PINP) and resorption (serum C-terminal telopeptide of type I collagen, s-CTX) are recommended for use in clinical studies, and may prove to be useful in clinical practice for assessing fracture risk and monitoring response to treatment. However, their value in routine primary care has not been assessed [SIGN, 2003; National Osteoporosis Guideline Group, 2010; Vasikaran et al, 2011].

Stopping drug treatment to reduce the risk of osteoporotic fragility fracture

• CKS recommends a pragmatic approach, because there is no consensus about when to stop treatment that reduces the risk of osteoporotic fragility fractures (except when treatment is no longer indicated, for example because of adverse effects). For people who are not at higher risk of osteoporotic fragility fracture, many experts stop alendronate after about 5 years and reassess after a 2–3-year-long drug holiday. Most experts continue treatment with other anti-osteoporosis drugs started in primary care (as their protective effects do not last long after treatment cessation).

Stopping drug treatment cont…

• Follow local protocols when available.• After 5–7 years of treatment, and every few

years thereafter, reassess the risk of osteoporotic fragility fracture and the need to continue treatment.

• Ensure the person understands the advantages and disadvantages of continuing and of stopping treatment.

• If treatment is continued, a fragility fracture may still occur, and adverse effects are possible.


• There have been concerns that long-term treatment with bisphosphonates might increase the risks of fracture of the shaft of the femur, osteonecrosis of the jaw, or oesophageal cancer. These associations are rare, and causality has not been established.


• Osteonecrosis of the jaw may be a particular risk for people with cancer who are receiving intravenous bisphosphonates. Poor oral hygiene should be managed (with advice or dental referral), and specialist advice obtained if major dento-alveolar surgery is planned.

• Any increase in the risk of atypical subtrochanteric fractures is more than offset by the decreased risk of fracture of the hip and other sites.


• The risk of oesophageal cancer is low, and does not outweigh the benefits of treatment.

• If alendronate is stopped, its benefits reduce over a period of 3–5 years. For other drugs, the benefits are lost more rapidly after cessation.


• A decision to stop treatment is supported if:• There has been no osteoporotic fragility

fracture and no vertebral fracture in the past 12–24 months.

• Bone mineral density (BMD) is currently above the threshold for treatment, or has substantially improved during treatment.


• A cause of secondary osteoporosis has been removed (for example treatment with systemic glucocorticoids has been stopped).

• The person is younger than 70 years of age, and treatment could potentially be given for many more years (the risk of rare but serious adverse effects with long-term treatment is uncertain).


• A decision to continue treatment is supported if:

• A major risk factor (such as rheumatoid arthritis) remains.

• There is a high risk of falls.


• If treatment is to be continued, reassess every 2–5 years (with BMD measurement if possible), depending on risk.

• If treatment with alendronate is to be stopped, reassess with BMD measurement after a drug holiday of 2–3 years, depending on risk.

• If treatment with another drug is to be stopped, consider obtaining specialist advice about further management.


• These recommendations are in line with guidelines developed by the National Institute for Health and Clinical Excellence (NICE) [NICE, 2010b; NICE, 2011a; NICE, 2011b], the National Osteoporosis Guidelines Group (NOGG) [Compston et al, 2009; National Osteoporosis Guideline Group, 2010], and the Scottish Intercollegiate Guidelines Network (SIGN) [SIGN, 2003].

Benefits of continuing treatment with alendronate after 5 years

Benefit cont…

• The FLEX randomized controlled trial provides evidence that a drug holiday after 5 years of treatment with alendronate is associated with an increase in clinical vertebral fractures, but not morphometric vertebral fractures or non-vertebral fractures. Post hoc subgroup analysis suggests that in women with a T-score less than –2.5, discontinuing treatment is associated with an increased risk of non-vertebral fractures. Large observational studies have consistently found that continued treatment is protective against hip fractures in people who are known to be compliant with treatment and who have been treated for longer.

Risks of long-term treatment with bisphosphonates

• Evidence on the risks of long-term treatment with bisphosphonates is available from clinical trials designed to assess the effect of treatment on fracture risk, bone mineral density, and bone turnover markers. Because these trial were not statistically powered to detect rare events, uncertainty remains about the possible hazards of long-term treatment.


• A number of trials have found that long-term treatment with alendronate is associated with a two- to three-fold increased relative risk of atypical subtrochanteric or femoral shaft fractures, but that the absolute risk is small (around 0.13% per year).


• Osteonecrosis of the jaw has been associated bisphosphonates. The risk is greater in people with cancer who are receiving intravenous bisphosphonates than in people being treated for osteoporosis. The risk is low for people taking oral bisphosphonates.

• There have been concerns over a risk of oesophageal cancer. The risk (if real) is small, and is outweighed by the benefits of treatment.

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Health & Medicine

Osteoporosis practical management 2011