Osteoporosis Resources for Primary Care: Initiation

Specific information is given in other sections on use of calcium and vitamin D in patients with osteoporosis or patients living in residential or care homes.

The recommended daily intake of calcium is 700 mg for adults. A pint of milk a day or equivalent, together with a balanced diet of other foods should be sufficient.

Sources of dietary calcium are milk, cheese and yogurt (these can be reduced fat), certain types of oily fish that are eaten with the bones, such as sardines (which also provide vitamins D and K) and vegetables such as broccoli and cabbage.

Sunlight is the best natural source of vitamin D. Sufficient vitamin D can be made through 10 minutes of sun exposure to the face and arms without sunscreen once or twice a day, every day, between May and September. Care should be taken not to burn. From October to April, vitamin D supplementation can be considered.

Patients should also:

• Be encouraged to eat their 'five a day' of fruit and vegetables
• Aim for a healthy weight (a body mass index of 20-25 kg/m2)
• Take alcohol in moderation (less than 2-3 units/day for women and 3-4 units/day for men)
• Be advised to stop smoking

For further dietary information, refer to the Eatwell Guide.

A detailed examination of the importance of diet and safe sunlight exposure is reported in the Inquiry into the Role of Nutrition in Preventing Osteoporosis and Promoting Good Bone Health carried out by the All-Party Parliamentary Osteoporosis Group (APPOG).

Management of osteoporosis to reduce fracture risk has been addressed by a variety of bodies in the past decade, giving different approaches. Links to summaries of national guidance are given below and some areas may have locally agreed protocols in place that describe which patients can access which treatments.

In England and Wales, NICE Technology Appraisals provide guidance on postmenopausal women with osteoporosis. Whether or not a postmenopausal woman with osteoporosis is offered one of the drugs to prevent bone fractures will depend on her age, her bone density and how many risk factors for fracture and indicators of fragile bones she has. In the Quality and Outcomes Framework indicators, it is assumed that the NICE treatment thresholds should also be applied to men over 50, and this is the practice in many locations.

Please note Strontium ranelate will not be available after August 2017.

NICE has produced technology appraisals for the treatment of osteoporosis alongside its Osteoporosis Clinical Standard. View a summary of NICE osteoporosis publications here.

Please note that TA160 and TA161 have been partially updated by GID-TAG462

NICE TA160: Alendronate, Etidronate, Risedronate, Raloxifene and Strontium Ranelate for the Primary Prevention of Osteoporotic Fragility Fractures in Postmenopausal Women.

NICE TA161: Alendronate, Etidronate, Risedronate, Raloxifene, Strontium Ranelate and Teriparatide for the Secondary Prevention of Osteoporotic Fragility Fractures in Postmenopausal Women.

NICE TA204: Denosumab for the Prevention of Osteoporotic Fractures in Postmenopausal Women. NICE recommends denosumab as a possible treatment for preventing bone fractures in postmenopausal women with osteoporosis who can't take alendronate and either risedronate or etidronate. It is appropriate to use for both primary and secondary fracture prevention.

Osteoporosis (prevention) - bisphosphonates (inc part rev TA160, TA161) [ID782]: In development [GID-TAG462] Expected publication date: TBC

In Scotland, the Scottish Intercollegiate Guidelines Group published SIGN 142: Management of Osteoporosis and the Prevention of Fragility Fractures 2015. A quick reference guide is also available. The guidance makes recommendations on the management of osteoporosis in men and women over the age of 60. This guideline is currently being updated. In Northern Ireland, England and Wales, guidance produced by NICE is generally applied.

The Royal College of Physicians published Glucocorticoid-Induced Osteoporosis: Guidelines for Prevention and Treatment in 2002, which makes recommendations specific to this high risk group. The administration of oral glucocorticoids is associated with a significant increase in fracture risk at the hip and spine. Although the greatest increase in risk is observed with higher dose therapy, increased risk is seen even at daily doses of prednisolone less than 7.5 mg. Fracture risk increases rapidly after the onset of treatment and declines rapidly after stopping therapy.

The National Osteoporosis Guideline Group (NOGG) has published Guideline for the Diagnosis and Management of Osteoporosis in Postmenopausal Women and Men from the Age of 50 Years in the UK. It makes recommendations on the UK interpretation of the fracture risk assessment tool, FRAX(r), providing intervention thresholds and recommendations. The guidance was updated in 2013 to include sections on treatment of glucocorticoid-induced osteoporosis, rare side effects, and duration and monitoring of treatment.

All the available drugs are effective in reducing fracture risk in those with osteoporosis, although some, due to their higher cost, are usually reserved for severe disease or people who are intolerant of first-line therapies. An overview of osteoporosis drug treatments can be found on the National Osteoporosis Society website as well as an information leaflet for patients. Further information on the individual treatment options is available from the links below:

Bisphosphonates

• Alendronic acid
• Disodium etidronate
• Ibandronic acid
• Risedronate sodium
• Zoledronic acid
• Bentexo (Alendronic Acid + Vit D)

NICE and NOGG both agree that generic alendronate should be first-line therapy unless contraindicated, since this is the most cost-effective. Giving the choice of a liquid preparation for alendronate may improve adherence.

Risedronate is now also generic, may be better tolerated and is also recommended for first-line use in some areas, although this was not its positioning in the NICE appraisals. This was simply due to the fact that at the time of the economic modeling for the NICE guidelines risedronate was more expensive: the TAG 161 has not yet been updated to take this change of lower cost risedronate into account. Although cyclical etidronate is recommended in NICE guidance, it is a weaker bisphosphonate and has no randomised controlled trial evidence of hip fracture reduction and is therefore very rarely prescribed now. This treatment was previously available as Didronel PMO. However, as it is used infrequently in clinical practice, it has been withdrawn.

Intravenous zoledronate is given by an infusion, and is generally well-tolerated but may cause flu-like symptoms due to an acute phase reaction, especially after the first dose. NICE has not provided guidance on thresholds for use and as a result it is used at the discretion of the clinician. Intravenous zoledronate is approved for the use of glucocorticoid-induced osteoporosis (whereas, for example, denosumab does not have that license). It is also used in Paget's disease. It can be used in those who qualify for but are intolerant of oral bisphosphonates, and who do not meet the criteria for other therapies. But it is up to the whim of individual CCGs policy across England (check local guidelines).

Bisphosphonates are poorly absorbed and it is important that they are taken correctly to optimise absorption and minimise side effects. Guidance on how to take these drugs should be provided when treatment is initiated and at every review (and be reiterated by pharmacists). Upper gastrointestinal side effects should prompt change of therapy rather than attempts to treat these with proton pump inhibitors.

There may be an increased risk of osteonecrosis of the jaw (ONJ) and atypical subtrochanteric fractures with prolonged therapy (i.e. more than 5-10 years of use.) Although these side effects are uncommon, some patients may be very concerned about them. Discussion about the benefit of treatment versus the occurrence of these side effects may help alleviate their anxiety. The incidence of ONJ in oral bisphosphonate therapy for osteoporosis is low - between 1 in 10,000 and 1 in 100,000. For each case of atypical fracture occurring during long-term bisphosphonate therapy, it is estimated that 50 hip fractures are prevented.

Calcium and vitamin D

• Accrete D3
• Adcal
• Cacit
• Calceos
• Calcichew
• Calfovit D3
• Fultium (vitamin D only)
• Kalcipos-D
• Natecal D3
• Sandocal
• InVita D3 (vitamin D only)
• Calci-D
• Cadelius
• Altavita

NICE guidance assumes that women receiving osteoporosis treatment have an adequate calcium intake and are vitamin D replete, and NOGG advocates correction of nutritional deficiencies, particularly of calcium and vitamin D. Those with osteoporosis and who are taking drug treatments may benefit from increasing their intake of calcium to around 1000 mg and vitamin D to around 800 IU daily as patients did in the clinical trials that proved osteoporosis treatments were effective.

Calcium and vitamin D3 supplementation is routine practice in those on treatment with bone-sparing agents who are unlikely to be replete. It is worth highlighting that large-scale meta-analyses have suggested that calcium supplements with or without vitamin D, in those with an adequate dietary intake, may be associated with a small increase in cardiovascular events. However, there has been much controversy around this data and experts suggest that there is insufficient data to change practice. Food remains the best source of calcium but supplements should be considered if dietary calcium intake is insufficient.

Denosumab

Denosumab is a monoclonal human antibody to RANK ligand, which has antiresorptive effects. It is given twice-yearly by subcutaneous injection. Currently some CCGs recommended that treatment be initiated in secondary care but transferred to primary care after one or two doses. But in other CCGs (e.g. Oxfordshire) denosunab can be initiated by a GP in primary care for secondary prevention, provided the guidelines are adhered to. NICE has recommended treatment thresholds for primary and secondary prevention.

Hormone Replacement Therapy

HRT is an effective treatment for menopausal symptoms that also offers protection against fractures at both hip and spine. For the large proportion of women affected by osteoporosis who are over the age of 60, HRT is not considered a suitable treatment for osteoporosis. However, in the under-60 age group HRT still has a role to play in the management of osteoporosis.

Read more about HRT for women and osteoporosis here

Parathyroid hormone

Parathyroid hormone (teriparatide and recombinant human PTH 1-84) use is restricted to patients with a low T-score (NICE) or high risk of fracture (NOGG).

Raloxifene

Raloxifene is only suitable for post-menopausal women. Raloxifene reduces vertebral fractures but not hip fractures and is therefore less cost-effective and is restricted in NICE secondary prevention guidance (found at the top of this page) to use in those with previous fractures and a specified combination of risk factors and DXA T-scores. It reduces the risk of developing an oestrogen receptor positive breast cancer.

Alternatives to oral therapies

People with osteoporosis who cannot tolerate oral therapies should be referred to secondary care (or if allowed in your local CCG guidelines, initiated in primary care) for consideration of subcutaneous denosumab, or intravenous zoledronate.

Falls are an important independent contributor to fracture risk and most non-vertebral fractures are associated with a fall. While some falls interventions have been shown to reduce falls, there is no good evidence for any impact on fracture rates or health care resource utilisation. The benefits of falls interventions are also the indirect costs associated with fear of falling and consequent reduced health-related quality of life. Ask older people about their falls history opportunistically and at least annually. Those at highest risk are:

• Individuals with two or more falls in the previous 12 months
• A fall resulting in injury
• A fall associated with a disorder of gait and/or balance

The principal role of the GP is to case-find the high-risk faller and offer referral to a falls service. Individuals unwilling to attend falls services may best be managed pragmatically within the primary care team, focusing on obvious risk factors.

The best-evidenced interventions to reduce falls risk and/or rate of falling are:

• Multi-factorial, multi-professional falls assessments and interventions
• Tailored strength and balance training of adequate duration, frequency and amplitude and home-based exercise programmes
• Other unifactorial interventions with limited evidence of efficacy include vitamin D3 supplementation in those who are inadequately replete, home safety interventions in those with poor eyesight, first cataract surgery and prescribing modification programmes.

The relevant guidance is to be found in NICE Clinical Guideline 161 and the Department of Health's Falls and fractures: consensus statement and resources pack.

• Obtain a relevant medical history and make a cognitive and functional assessment
• Check whether the patient is taking any medications that increase falls risk which can be safely withdrawn
• Check for remedial abnormalities of gait and balance; a 'sit to stand test', 'get up and go' test or abnormal body sway may be indicators
• Check for remedial disorders of visual acuity
• Check for evidence of an underlying physical, cardiac or neurological cause requiring further investigations or interventions
• Check for evidence of postural hypotension
  Investigate whether there are modifiable environmental hazards, including footwear
• Check whether there are risk factors for osteoporosis or a prior fragility fracture indicating that a DXA scan or osteoporosis treatment may be necessary
• Check whether vitamin D insufficiency is likely
• Offer education and written information whenever possible
• Offer referral for a multi-factorial assessment and intervention through the local falls service
  
  • If unwilling, the patient may be suitable for exercise and balance training or a home exercise programme if available through trained physiotherapists or an 'active balance' class;
  • If this is inappropriate or the patient is unwilling, offer specific advice, guidance and interventions to the patient and carer to modify or minimise the impact of identified risk factors for falls
• Recruit other members of the primary health care team, such as district nurses, to follow up

Frailty is reduced resilience and increased vulnerability to decompensation after a stressor event.

Identifying frailty in an older person can help us predict who is likely to have a fall, become dependent on other people to help with basic care tasks, experience an unplanned admission to hospital or a care home, or die within the next year. Frailty is also associated with anxiety, depression and a poorer quality of life.

NHS England’s ‘updated guidance on supporting routine frailty identification and frailty care through the GP Contract 2017/18 requires that GP Practice use an appropriate evidence based tool to identify patients aged 65 and over who may be living with moderate or severe frailty and deliver a series of interventions for those patients confirmed through clinical judgement as to be living with severe frailty.

NHS England has developed some useful resources for GP Practice to help in managing frailty all of which are available at the NHS England website.

At present there is no evidence that complementary and alternative therapies (CATs) increase bone density or reduce the risk of fractures. However, for those people who have sustained fractures as a result of osteoporosis, a range of CATs may offer additional relief from pain and other symptoms.

In all situations, it is important that the therapist is made fully aware of an individual's medical history before commencing treatment. Patients with an interest in CATs should be advised to explain to their therapist that they have osteoporosis and may be at higher risk of fracture. Some of the most commonly used therapies are acupuncture, osteopathy, herbal medicine, the Alexander Technique, aromatherapy, chiropractic and reflexology. Pilates, tai chi and yoga are exercise methods that can help to improve posture and develop muscle strength. For some people they may also help to alleviate pain resulting from vertebral fractures.

The Royal Osteoporosis Society's fact sheets ‘Complementary therapies, bone health and osteoporosis’ and ‘Complementary therapies for pain and symptoms after fractures’ provide more detail.

Also refer to 'What advice should GPs give patients about nutrition and exercise' section of this resource.

'How long should I prescribe osteoporosis treatments for?' is a difficult and controversial question to answer. Bisphosphonates have a long half-life in bone and probably continue to be effective for some time after they are withdrawn. Because of potential concerns about the safety of long-term treatment with bisphosphonates, a drug holiday may be considered in some patients following a period of treatment. Calcium and vitamin D supplements should be continued during this time.

In patients receiving oral bisphosphonates (alendronate, ibandronate, risedronate), treatment is usually given for 5 years in the first instance. If BMD remains the same or has improved from baseline, the post-treatment T-score is > −2.5 and no fractures have occurred during treatment, it may be reasonable to withdraw bisphosphonate treatment for 2 to 3 years with reassessment of fracture risk at the end of that time and re-continuation of treatment if indicated. Because the effects of intravenous zoledronic acid last for longer than oral bisphosphonates, a drug holiday should be considered after 3 rather than 5 years of treatment.

The rationale for giving bisphosphonate holidays is that there is an association between two rare conditions, namely atypical femoral fractures and osteonecrosis of the jaw (ONJ), and prolonged bisphosphonate therapy. However, a direct causal relationship has not been established and these conditions can occur in people who have never received bisphosphonates. Patients with severe osteoporosis (e.g. multiple vertebral fractures) need to continue bisphosphonates as the benefits of osteoporotic fracture prevention outweigh the potential risks of continuing treatment. Similarly, if fractures have occurred during treatment and/or BMD remains low, bisphosphonate therapy should be continued.

Atypical fractures usually occur in the subtrochanteric region of the femur or the femoral shaft. They are associated with minimal trauma, are usually transverse or oblique, heal poorly and are bilateral in nearly 50% of cases. They are often preceded by prodromal pain in the groin or thigh and X-ray or magnetic resonance imaging (MRI) imaging should be considered in patients with these symptoms. Osteonecrosis of the jaw is characterised by exposed bone in the maxillofacial region for at least 8 weeks in the absence of previous radiation. Both conditions are very rare.

The effects of other osteoporosis treatments (denosumab, raloxifene, strontium ranelate - which has now been discontinued - and teriparatide) wear off more rapidly when treatment is stopped and there is no clear case for drug holidays in patients receiving these drugs. In the case of strontium ranelate there is evidence for continued efficacy for up to at least 10 years of treatment. Withdrawal of denosumab is followed by rapid bone loss, and if it is stopped treatment with another antiresorptive drug should be considered. Teriparatide is approved for a maximum of 24 months and its beneficial effects may be maintained by subsequent treatment with an antiresorptive drug.

About half of patients on bisphosphonates may not have been prescribed calcium and D3. Start with your list of patients on bone-sparing therapies. Assess dietary calcium intake and whether the patient is taking over-the-counter preparations. In light of your findings, check whether each patient has been appropriately co-prescribed a calcium (1000 – 1200 mg/day) and vitamin D (800 IU/day) preparation. See the list of treatments within the Initiation section. Ensure that all are prescribed generically but that generic 'calcium and vitamin D tablets BPC' are not used as these contain very little calcium. Review compliance/adherence with therapy.

You may want to check that individuals not receiving adjuvant therapy do not have hypercalcaemia or other contraindications. These supplements are not contraindicated in stone-formers.

Review interactions, contraindications and precautions according to the Summary of Product Characteristics and British National Formulary (BNF).

Corticosteroids, aromatase inhibitors and androgen deprivation therapy (in men) represent the principal causes of drug-induced osteoporosis. Assessment of fracture risk and the need for prophylaxis with bone-sparing agents amongst patients treated with these agents should be a priority for GPs.

There are European Oncology Guidelines for bone health in breast cancer and prostate cancer, as well as NICE Prostate Cancer Guidelines that should have been assimilated into algorithms by your local oncology services specifically to manage these patients.

Hip fractures are 3.3 times more common in residential-home populations than in community-dwelling older people; therefore, this is an important target group. Those who have had prior fragility fractures require bone-sparing therapy and high-dose calcium and vitamin D, as recommended by NICE and NOGG. Often, previous fractures will not have been coded so a review of case records may be needed if a reliable history is not available from the patient or family.

For institutionalised elderly people without prior fragility fractures, high-dose calcium and vitamin D supplements (1200 mg/800 IU per day) used alone can reduce hip fracture risk by 43% within 18 months, and improve falls risk. Giving a choice between preparations that can be swallowed, chewed or dissolved may improve adherence.

Bisphosphonates need to be taken correctly to optimise absorption, so dosing instructions need to be discussed in detail with those responsible for drug administration in care homes and filtered down to all staff. Giving once-weekly or monthly bisphosphonates all on the same day may improve dosing accuracy. High staff turnover means frequent reminders are important.

Every practice will have patients who need bone-sparing therapy and who have lapsed. Many more will fail to continue calcium and vitamin D supplements. Reasons for lapse include:

• Not being aware of the need to continue or that long-term therapy is required
• Being intolerant of the therapy
• Difficulties remembering to take the therapy
• Difficulties complying with dosing instructions
• Accidentally discontinuing on admission/discharge

Comparing those taking each drug one year previously with a list of current users will identify recent lapsers, who can be reviewed first. Searching backwards will identify preceding cohorts of lapsers. Identifying lapsed patients can be combined with reviewing the appropriateness of the therapy and co-prescribing calcium and vitamin D.

Alerts can be added to notes/prescribing screens for opportunistic discussion in surgery or when ordering prescriptions. Alternatively, patients can be written to and invited to discuss with a doctor or nurse restarting therapy with an appropriate drug.

Every practice will have patients on bone-sparing therapies who do not need them. As many as 50% of patients in receipt of bone-remodelling agents have no record of a diagnosis of osteoporosis. These may be people who were started inappropriately, those using adjuvant therapies during steroid therapy that have been stopped or those who have been on therapy long term and no longer have osteoporosis.

To find these patients:

• Search for those taking bisphosphonates and raloxifene on acute and repeat prescriptions.
• Agree which guidance or guidelines you will follow (e.g. NICE or SIGN guidelines for post-menopausal women, NOGG for men, Royal College of Physician corticosteroid-induced osteoporosis guidelines for those on corticosteroids). If using NICE guidance, decide how rigidly you will interpret it.
• Work your way through the list of patients, identifying when and why therapy was initiated and judge whether it is still appropriate. Make notes initially on your search sheets.
• While reviewing each record, check that the drugs are prescribed generically, that the patient is persisting with therapy, that adjuvant calcium and vitamin D are prescribed and whether coding is accurate

You are likely to identify:

• Patients being treated appropriately: continue treatment
• Lapsed patients: phone to discuss therapy; many will be intolerant of their prescribed treatment and need a therapy change
• Patients where it is not clear why therapy was started or continues: discuss these in a clinical meeting as colleagues may be able to clarify; many may be able to discontinue treatment

Keep notes of patients in each category. Repeat the process after 6 months.