Managing osteoporosis

Osteoporosis can result in disability and lost quality of life, but there are ways to manage it, writes Eamonn Brady MPSI

Osteoporosis is a condition where bones lose density, making fractures more likely. The origin of the word ‘osteoporosis’ comes from ancient Greece and means ‘porous bones’, and was first used as a medical term in France the 1820s, and it was not until the 20th Century it was used as a medical term in the English language. Approximately 50 per cent of women and 20 per cent of men over 50 will experience a fracture due to osteoporosis. According to the Osteoporosis Society of Ireland, approximately 300,000 people in Ireland have osteoporosis. It can affect all age groups, but it is most common in postmenopausal women. Osteoporosis does not automatically mean bones will fracture; it just means fractures are more likely. Osteoporosis is a bigger cause of disability than common non-communicable diseases such as Parkinson’s disease, rheumatoid arthritis, and breast cancer.

Symptoms

Osteoporosis may have no symptoms initially, and patients may be unaware of any problems until they fracture a bone or start to lose height. Symptoms can include:

• Upper, middle, or lower back pain than can be severe.
• Loss of height (greater than 2cm).
• Development of a hump on the back or a change in body shape, for example, the rib cage may rest on pelvic rim, or a pot belly develops.

Complications

The most common fractures associated with osteoporosis are broken wrists, hips, and spinal bones, but fractures can occur in any bone. This leads to pain, disability, loss of independence and influences self-esteem.

Diagnosis

Diagnosis often only occurs after a fall or a bone fracture. Bone density is measured using a dual-energy x-ray absorptiometry (DEXA) scanner. A DEXA scan uses low-energy x-rays to determine the density profile of x-rays that pass through the bone and from this information, the average density of bone is determined. Osteoporosis is diagnosed when bone density is found to be significantly lower than average. DEXA scans are painless, take 10-to-20 minutes, and are the gold standard for the diagnosis of osteoporosis. The results of the scan are available immediately or very soon after, depending on where it is done. Scan results are in the form of a T-score. A T-score value greater than -1 shows that bone density level is normal and there is no osteoporosis. A T-score value of between -1 and -2.5 indicates osteopenia. Osteopenia indicates early stages of osteoporosis and is an opportunity for early interventions like modification of risk factors including diet, smoking and excessive alcohol intake to prevent osteoporosis developing. A T-score of below -2.5, meanwhile, indicates osteoporosis.

Increased GP access to diagnostic services

There is no comprehensive osteoporosis screening programme in Ireland. People generally only get a DEXA scan when referred by their GP. The average waiting time to get a DEXA scan in 2008 for public patients was 20 weeks, and waiting times increased early in the pandemic. Private patients can get a scan upon request in private facilities. The website of the Osteoporosis Society of Ireland has a comprehensive list of all locations in Ireland where DEXA scans are performed. It lists DEXA scan locations on a bycounty basis and includes both private and public hospitals and clinics. Minister for Health at the time, Stephen Donnelly, announced in January 2021 that the HSE is making direct access available to GPs to diagnostic services for public patients. The initiative gives GPs across Ireland the ability to access an additional 94,000 diagnostic procedures, such as x-rays, CT scans, MRIs, and DEXA scans by giving access to designated private hospitals for scans paid for by the HSE. This new initiative aims to reduce waiting times, with GP referrals classed as urgent getting a scan within one month of the referral date and routine patients getting a scan within three months of the referral date. The HSE allocated €13 million to this speedier referral scheme for scans (including DEXA scans) in 2021. There are no recent updates from the HSE on DEXA scan waiting times, so with time we will learn if the new faster GP referral scheme is reducing waiting times as intended. The HSE plans to add further diagnostics to this “faster referral and scanning programme”, including GP access to BNP testing (brain natriuretic peptide or BNP tests for the presence of heart failure), spirometry, and echocardiography services.

Causes

Strong healthy bones comprise of a mix of protein and minerals, including calcium and phosphorous. Bone is living tissue that is maintained and renewed by two types of cells. Osteoblast cells build up new bone, and osteoclast cells break down old bone. Up to the mid-20s age, the skeleton strengthens, but from the 40s onwards, bones gradually lose their density as a natural part of ageing. There is a genetic influence with osteoporosis, so women who have family members with the condition are more at risk. However, other factors increase the risk of osteoporosis. Oestrogen protects women from osteoporosis from puberty until the menopause. After menopause, the breakdown of bone is quicker in women as the protective effect of oestrogen on the bones is gone. Factors that increase risk of osteoporosis:

• Early menopause, especially before the age of 45.
• Hysterectomy before turning 45, especially if both ovaries are removed.
• Excessive exercising — this can reduce hormone levels for women and as a result, periods may stop for a prolonged time. Other factors include:
• Age — the risk increases with age.
• Race — Caucasian or Asian patients are at increased risk compared to African-Caribbean patients.
• Gender — having smaller bones and less muscle mass than men puts women at more risk of fractures.
• Family history of osteoporosis, particularly a history of hip fracture in a parent. ? Previous fragility fracture (fracturing a bone after only a minor accident).
• Long-term immobility (ie, confined to bed).
• Very low body mass index (less than 18.5kg/m2).
• Excessive alcohol consumption or smoking.
• Low dietary intake of vitamin D and calcium.
• Diet-related factors include:
• Being vegan: As it limits the amount of calcium and vitamin D consumed.
• Excess fibre: While fibre is healthy in the diet, more than 30 grams of fibre per day can reduce calcium absorption. However, the association between fibre and osteoporosis is not strong and high-fibre foods like fruit and veg are good for overall health, while green leafy vegetables are a good source of calcium.
• Caffeine: Excess caffeine can increase calcium excretion, thus increasing osteoporosis risk.

Medication and disorders can increase risk, including:

• Long-term use of corticosteroids.
• Long-term use of heparin.
• Aromatase inhibitors (for breast cancer treatment).
• Overactive thyroid disorders. ? Rheumatoid arthritis.
• Digestive disorders that affect nutrient absorption, such as Crohn’s disease, chronic liver disease, or coeliac disease.

Causes in pre-menopausal women

Oestrogen prevents osteoporosis in premenopausal women. However, there are certain medical conditions and medication which reduce the oestrogen level and hence cause early-onset osteoporosis. Examples include:

• Hypogonadotropic hypogonadism caused by low body weight, eating disorders, excessive exercise, hyperprolactinemia, and hypopituitarism.
• Hypergonadotropic hypogonadism (premature ovarian failure) is associated with bone loss if oestrogen is not replaced. Women with Turner syndrome (condition which occurs in less than one-in-2,500 due to abnormal X chromosome) may have an additional selective reduction in bone mineral density that is independent of oestrogen exposure.
• In premenopausal women with breast cancer, chemotherapy often results in premature ovarian failure, and as a result, oestrogen deficiency and bone loss. Drugs that may be associated with bone loss in premenopausal women include glucocorticoids, anticonvulsants, ie, phenytoin, antidepressants, ie, lithium, and anticoagulants, ie, warfarin and heparin.

Criteria for assessing for osteoporosis fracture risk

National Institute for Health and Care Excellence (NICE) guideline in the UK on osteoporosis recommends an assessment of fracture risk should be considered for:

• Women aged 65 years and older and men aged 75 years and older.

Women aged under 65 years and men aged under 75 years where the following risk factors are present:

• Previous fracture(s).
• History of falls.
• Family hip fracture history.
• BMI less than 18.5kg/m2.
• Frequent recent use of oral or systemic glucocorticoids.
• High levels of alcohol consumption: Classified as more than 21 units per week for men and more than 14 units per week for women.
• Smoking.
• Other causes of secondary osteoporosis.
• Fracture risk does not need to be routinely assessed in people under 50 unless they have major risk factors, ie, premature menopause in women, previous fracture(s), or current or frequent recent glucocorticoids use.

Non-pharmacological management

Non-pharmacological management includes prevention of falls and modification of risk factors including diet, smoking, and excessive alcohol intake. Important measures aimed at preventing falls include attention to modifiable factors including checking eyesight, exercise, reduced consumption of medication that alters alertness and balance, and improvement of the home environment. There is debate regarding the use of hip protectors to prevent hip fractures, with evidence casting doubt on this preventive measure. Attention to diet is important, because there is a high prevalence of calcium and vitamin D insufficiency in the elderly, particularly those with chronic conditions. Calcium helps maintain strong bones and vitamin D aids the absorption of calcium. A diet with adequate calcium (>1,200mg daily) and vitamin D (800 IU daily) is recommended for those with risk factors. Adults over 50 years often only consume 700mg calcium daily, so the use of supplements, including fortified food products, may be required. The benefits of calcium and vitamin D supplements to maintain optimum bone density in healthy adults with normal dietary intake are limited. The reason may be the fact that most healthy adults get sufficient calcium and vitamin D from their diet. A systematic review found that the ingestion of calcium or calcium with vitamin D reduced osteoporotic fractures in men and women over 50 years by 12 per cent. They should be considered for patients in nursing/residential homes and the housebound elderly. Immobility is a major cause of bone loss.

Self-help

Osteoporosis patients need to be careful of vigorous, high-impact exercise; however, being active improves balance, co-ordination, and increases muscle strength, so reducing the risk of falls and bone fractures. Beneficial exercise includes swimming, gardening, walking and golf. Eating a diet rich in calcium is important for maintaining healthy bones. Dairy products and green leafed vegetables are good sources of calcium. There is a misconception that low- or non-fat versions of dairy products have less calcium than full-fat versions, but this is not the case. People with an intolerance of dairy can as an alternative drink orange, grapefruit, and apple juice, which are calcium-fortified and have just as much calcium as milk. The body also needs vitamin D to absorb calcium properly. Examples of food high in vitamin D include cod liver oil, oily fish such as mackerel, sardines and herrings, margarine, and egg yolks. Vitamin D is also produced by the skin when exposed to sunlight. The Osteoporosis Society of Ireland recommends about 20 minutes of sun exposure to the face and arms every day during the summer to provide enough vitamin D for the year. Avoid fizzy drinks and reduce caffeine, salt, or animal protein, as these can affect the balance of calcium in the body.

Vitamin D requirement to prevent fractures

Research has found that a daily supplement of 700 to 1,000 IU of vitamin D reduces the risk of fractures from falls among older people by 19 per cent. A study published in the British Medical Journal indicated that a dose of less than 700 IU per day has no effect in reducing fractures.

Risk of osteoporosis from corticosteroids

Patients on corticosteroids require preventive treatment for osteoporosis if the patient is starting oral corticosteroids and is likely to be on these for at least three months. More than three or four courses of corticosteroids taken in the previous 12 months are equivalent to more than three months of continuous treatment. Evidence supports the use of bisphosphonates as a first-line treatment.

Physiotherapy falls prevention programme

Many physiotherapy departments in Ireland have a falls prevention programme that GPs or hospital consultants can refer patient to. Criteria for referral to a physiotherapy falls prevention programme includes reduced mobility, history of falls, and fear of falling. The programme is often based on the OTAGO exercise programme and aims to strengthen muscles, thus preventing falls and reducing the risk of fracture if the patient does fall.

HSE fall prevention policy

The following is the HSE fall prevention policy outlined in the HSE’s 2008 fall prevention report. There have been little updates in HSE fall prevention policy since this 2008 report. HSE Fall Prevention Policy is as follows: Older patients should be asked these questions a minimum of once a year:

• Have you fallen during the past year? If yes, did you fall more than once?
• Have you any problems with your balance?
• Are you afraid of falling?

Older persons who have had a single explained fall should be evaluated for gait and balance annually. This test is more important if they experience:

• Recurrent falls (two or more in the past year).
• An unexplained fall.
• Problems with gait and balance.
• A fear of falling.

The HSE states in the 2008 report the following risk factors and interventions that give reduced falls risk and should be included in multifactorial assessment and intervention:

• Individualised exercise programme that includes a combination of resistance training, gait, balance, and co-ordination training.
• Medication review and withdrawal of psychotropic and other medications. ? Home environment assessment and modification by health professional.
• Managing postural hypotension.
• Vision assessment and referral for intervention.
• Assessment of vitamin D deficiency and insufficiency and treated if identified.
• Identification of foot problems and appropriate treatment.
• Behavioural modification and educational programmes should be considered.

The following are recommendations for residential care settings in the 2008 HSE Fall prevention report.

• All residential care settings should have a fall prevention policy and be resourced to implement it.
• All residents should receive a Fall Risk Assessment annually. A Fall Risk Assessment should also take place on admission and when health status changes occur.
• Falls in residential care and nursing care homes should be recorded on a register. Each fall should be critically analysed for corrective action. The fall prevention procedures of residential care homes are assessed in Health Information and Quality Authority (HIQA) inspections.

Medication

Bisphosphonates

Examples include alendronic acid, risedronate sodium, and ibandronic acid. They work by slowing down bone loss. Bisphosphonates work by targeting osteoclast cells; osteoclasts break down old bone. By absorbing bisphosphonates, osteoclast activity slows down, which reduces breakdown of bone. Oral bisphosphonates are taken once weekly, apart from ibandronic acid, which is once a month. They can reduce the frequency of fractures by 50 per cent. Bisphosphonates have been studied in trials for up to 10 years, which suggests that bone quality remains normal and that reduction in fracture risk is sustained for as long as treatment continues. Bisphosphonates should be reviewed every two years. There is consensus that longer-term treatment with bisphosphonates will not cause the patient any adverse effects once the patient does not experience any of the recognised possible side-effects listed below. There is no difference in the efficacy or safety profiles of bisphosphonates in the patients aged under 65 and over 65.

Assessing the need to prescribe bisphosphonates

Oral bisphosphonates are advised for patients with osteoporosis only if:

• The 10-year risk of a fracture is at least 1%. An intravenous bisphosphonate available in Ireland is zoledronic acid (Aclasta) and is advised for patients with osteoporosis only if:
• The 10-year risk of fracture is at least 10%; or
• The 10-year risk of fracture is at least 1% and the patient is contraindicated or cannot tolerate oral bisphosphonates such as alendronic acid, risedronate sodium or ibandronic acid. Zoledronic acid (Aclasta 5mg/100ml) is administered once a year by an intravenous (IV) infusion. Infusions take about 15 minutes and are undertaken under specialist supervision. Zoledronic acid is 100-to-1,000 times more potent compared to other bisphosphonates, such as alendronate and risedronate. IV infusion of ibandronic acid is licensed in the UK and other countries but is not available in Ireland.

Bioavailability, tolerability, and side-effects of oral bisphosphonates

The oral bioavailability of bisphosphonates is low and impaired by food. Oral formulations must be taken fasting, sitting upright with a full glass of water, followed by no food for up to one hour. Patients are asked to sit upright to reduce gastrointestinal effects such as oesophageal irritation. Compliance with treatment is a problem, particularly in view of these requirements. Common side-effects (over onein-100) of bisphosphonates are:

• Gastrointestinal side-effects, including non-ulcer dyspepsia.
• Muscle, joint or back pain and stiffness.
• Headache.
• Tiredness.

Less common side-effects ofbisphosphonates include:

• Oesophagitis, which is inflammation oesophagus lining.
• Oesophageal strictures (narrowing of oesophagus).
• Gastric and duodenal ulcers.
• An unusual fracture of the thigh bone (very rare).
• Fracture of the jaw or ear bones. Bisphosphonates are contraindicated in the presence of abnormalities of the oesophagus, and hypocalcaemia.

Alendronates in tablet form should not be crushed and this increases risk of esophageal irritation. For patients with slow or poor swallow, alendronic acid is available in a 70mg/100ml strength liquid form and does not cause esophageal irritation; however, the same precautions, such as sitting upright after taking and not eating for an hour after taken, still holds true for the liquid version.

Risk of ONJ

There have been reports of osteonecrosis of the jaw (ONJ), particularly with IV formulations given in high doses for metastatic bone disease. ONJ is a condition where the jaw breaks. The prevalence of ONJ with bisphosphonates is about one-in-100,000 patient-years, which is similar to the prevalence in the overall population. Patients who present with sudden pain in the jaw while on bisphosphonates, especially IV versions, should report to their doctor, as this can be a sign of ONJ. Patients prescribed the IV infusion forms of bisphosphonates can experience flu-like symptoms for a few days after the infusion, especially after their first infusion.

Other indications of zoledronic acid I/V infusion

In addition to osteoporosis, Zoledronic Acid I/V infusion is indicated for Paget’s disease and metastatic bone disease (cancer that has spread to the bones). Paget’s disease is a bone disease of unknown cause that causes interference of the bone’s normal recycling process, meaning interference of the process where new bone tissue gradually replaces old bone tissue. Paget’s disease causes fragile and misshapen bones over time, with the legs, pelvis, skull, and spine being most affected. Bone metastasis is when cancer cells spread (metastasize) from the original site of cancer (ie, breast, prostate) to the bone. The dose of zoledronic acid is higher (ie, given more regularly) for metastatic bone disease compared to its dose for osteoporosis. For osteoporosis, the dose is 5mg/100mg infusion once a year. Aclasta 5mg/100ml infusion is licensed for osteoporosis and Paget’s disease but not for metastatic bone disease. For metastatic bone disease, the dose is 4mg/100mg infusion once every three-to-four weeks. Brands of zoledronic acid 4mg/100ml infusion licensed in Ireland include Zometa 4mg/100ml infusion and Zoledronic Acid 4mg infusions from the likes of Mylan, Accord, Activas, Teva and others. The risk of side-effects such as ONJ is higher due to the more frequent dosage regimen of zoledronic acid for metastatic bone disease. For metastatic bone disease, zoledronic acid is used to:

• Increase bone density and reduce pain caused by myeloma (cancer of bone marrow) or metastatic bone disease.
• Reduce raised calcium levels caused by some forms of metastatic bone disease.
• Protect the bones from the effects (like reducing bone density) of cancer treatments like aromatase inhibitors used for some breast cancers.
• Adjuvant treatment to reduce risk of recurring cancer. There is early evidence that zoledronic acid has anti-tumour effects in post-menopausal women with breast cancer. Anti-tumour effects mean reducing the risk of tumours developing, growing, and spreading. However, more research is needed to prove this and to determine if it is also true for other cancers.

Denosumab

Denosumab (ie, Prolia) is an alternative option if the patient is intolerant of oral bisphosphonates, or they are otherwise unsuitable. It is given by six-monthly subcutaneous injections. Denosumab is a monoclonal antibody that works by slowing the natural rate bones break down. Denosumab works by inhibiting the cytokine RANKL (receptor activator of NF?B ligand). RANKL is an essential factor promoting bone turnover. Denosumab inhibition of RANKL blocks osteoclast maturation, function, and survival, thus reducing bone resorption so increasing bone density. Patients should take adequate calcium and vitamin D while on denosumab as it can lower calcium levels and hypocalcaemia should be avoided. Side-effects include:

• Skin infections.
• Hypocalcaemia, which can lead to:* Numbness or tingling in extremities including fingers, toes and around the mouth. Muscle cramps, spasms, and twitches. *Hence calcium supplementation with Denosumab is important. Denosumab is a treatment option for the primary prevention of fractures in postmenopausal women (diagnosed with osteoporosis) at increased risk of fractures who:
• Find difficulty complying with the specific instructions for administering oral bisphosphonates (hour before food, sit or stand for period after taking) or oral bisphosphonates are contraindicated or not tolerated; and
• Have a combination of T-score, age, and number of independent clinical risk factors for fracture as indicated in Table 1. Independent clinical risk factors for fracture include:
• Parental history of hip fracture.
• Alcohol intake more than four units per day.
• Rheumatoid arthritis.

Xgeva is a higher-strength Denosumab preparation (ie, Denosumab 120mg) that is licensed for the prevention of skeletal-related events (pathological fracture, radiation to bone, spinal cord compression or surgery to bone) in adults with advanced cancers involving the bone. The dose is 120mg by subcutaneous injection every four weeks but there may be additional doses over the first four weeks for some bone cancers, ie, giant cell tumour of bone. Unlike Prolia, Xgeva is available via the Hi-Tech scheme.

Parathyroid hormone peptides (ie, teriparatides)

Mechanism of Action: Stimulating Bone Formation

Teriparatides are recombinant fragments of parathyroid hormone (PTH 1-34). They work by directly stimulating osteoblast activity via the PTH1 receptor, promoting intracellular signaling cascades that result in increased bone turnover, favouring formation over resorption. Unlike antiresorptive medications, which reduce bone loss, teriparatides build new bone, improving skeletal architecture and increasing bone mineral density (BMD). This unique mechanism underpins its use in patients with severe osteoporosis.

Designation of Movymia® as a Best Value Medicine (BVM)

In 2023, the HSE’s Medicines Management Programme (MMP) undertook a comprehensive cost-effectiveness analysis of teriparatide products on the High-Tech Arrangement. The report concluded that Movymia® and Sondelbay® offer the best value to the Irish healthcare system due to their equivalent clinical efficacy and lower acquisition cost compared to the originator Forsteo.® At the time, the MMP report stated Movymia and priced at €214.49 per cartridge (ex VAT), less than Forsteo, which cost over €270 per cartridge (ex VAT, after rebates) at the time. This price difference translates into significant savings for the HSE, particularly given that teriparatide prescriptions exceeded €4.2 million in spend under the High-Tech Scheme in 2021. The MMP formally recommends that:

• All new patients requiring teriparatide be initiated on Movymia or Sondelbay.
• All existing patients on Forsteo be considered for switching to one of the BVMs at their next repeat prescription. Please note, just because Movymia is one of the preferred teriparatides by HSE due to cost, ie, cost savings for HSE, it is nothing to do with relative effectiveness compared to other teriparatides; all teriparatide brands/ biosimilars have the exact same bioequivalence. I refer to Movymia in this section on teriparatides as pharmacists in Ireland are seeing it prescribed, hence are dispensing it more regularly, thus referring to it here aims to help Irish pharmacists get more familiar with a brand of teriparatide encountered more frequently.

Table 1: T-scores at (or below) which denosumab is recommended when oral bisphosphonates are unsuitable.

Administration: Device, Storage and Patient Support

Movymia is administered via daily subcutaneous injection (20mcg/day), delivered using a reusable Movymia Pen and disposable cartridges. Each cartridge contains a 28-day supply. The reusable pen is supplied with the first prescription only; patients should liaise with Clonmel Healthcare if a replacement is needed due to loss or damage. The cartridge must be kept refrigerated (2°C to 8°C), and once in use, can remain at room temperature (up to 25°C) for up to 28 days. After this, any remaining solution must be discarded.

Table 2: T-scores at (or below) which raloxifene is recommended when oral bisphosphonates are unsuitable

Importantly, the pen must not be stored with the needle attached, and patients should be reminded how to safely dispose of needles. Pharmacists can help patients with education about device usage. A trained nurse, arranged via the manufacturer, can visit the patient’s home to provide instruction.

Pharmacovigilance and safety

Movymia shares the same safety profile as the reference product Forsteo. Common side-effects include nausea, headache, dizziness, and limb pain. Transient orthostatic hypotension may occur after injection, particularly during the early stages of treatment. Local injection site reactions (ie, erythema, bruising, pruritus) are generally mild and self-limiting. Contraindications include:

• Severe renal impairment.
• Pre-existing hypercalcaemia.
• Skeletal malignancies or bone metastases.
• Paget’s disease of bone.
• Unexplained elevated alkaline phosphatase.
• Prior radiation therapy involving the skeleton.

Renal function should be reviewed before initiation. Patients are usually co-prescribed calcium and vitamin D supplements unless their intake is already adequate. Pharmacists should screen for contraindications at the point of dispensing and reinforce the importance of supplement adherence where applicable.

Duration of use and sequential therapy planning

Teriparatide therapy, including Movymia, is restricted to a maximum of two years over a patient’s lifetime. Evidence indicates that the greatest fracture risk reduction is achieved when the full course is completed. Following cessation of therapy, BMD bone gains and improvements are best preserved through transition to an antiresorptive agent such as a bisphosphonate or denosumab. This ‘follow-on treatment’ approach should be communicated clearly to prescribers and patients from the outset. Pharmacists are ideally placed to prompt prescribers at the two-year mark, helping coordinate the switch and ensure continuity of care.

Pharmacists’ role in implementation and monitoring

Pharmacists are critical to the effective implementation of Movymia-based therapy. Their responsibilities include:

• Screening prescriptions for clinical appropriateness and patient eligibility.
• Educating patients on injection technique, storage, and pen/cartridge use.
• Monitoring side-effects and managing common adverse events.
• Promoting adherence through routine follow-up and counselling.
• Co-ordinating therapy transitions at the end of the two-year course.

Interchangeability and confidence in biosimilars

The European Medicines Agency (EMA) and Health Products Regulatory Authority (HPRA) have both confirmed that biosimilar medicines such as Movymia are interchangeable with their reference products, with no expected difference in treatment effect. Head-to-head studies have shown no meaningful differences in efficacy or safety and the formulation and pharmacokinetics of biosimilars are all aligned with established standards. As more Irish prescribers and pharmacists gain familiarity with biosimilars, confidence in their use continues to grow. This enables a broader range of patients to access biologic therapy without budgetary restrictions, a crucial step in addressing the unmet needs of high-risk osteoporosis patients.

Selective oestrogen receptor modulator

Ie, raloxifene. This is a synthetic hormone that mimics the effect of oestrogen on the bones. The dose is raloxifene 60mg daily. It reduces risk of fractures by approximately 47 per cent. There have been no studies to show the effect of raloxifene for more than five years. However, according to the manufacturer, there is no minimum time that raloxifene can be used once an improvement is seen. According to NICE guidelines,raloxifene is an alternative treatment option for the primary prevention of fractures only in postmenopausal women (diagnosed with osteoporosis) at increased risk of fractures who fulfill the criteria below and in Table 2.

Independent clinical risk factors for fracture include:

• Find difficulty complying with the specific instructions for administering oral bisphosphonates (hour before food, sit or stand for period after taking) or oral bisphosphonates are contraindicated or not tolerated (ie, persistent upper gastrointestinal disturbance); and
• Have a combination of T-score, age, and number of independent clinical risk factors for fracture as indicated in Table 2. Raloxifene has been associated with an increased risk of venous thrombosis similar to that for hormone therapy (HRT), and with exacerbation of hot flushes. An increased risk of death due to stroke has been reported with raloxifene, and it should be used with caution in women with a history of, or risk factors for, stroke. It is contraindicated in women with child-bearing potential, history of venous thromboembolism (VTE) or unexplained uterine bleeding, hepatic impairment, and severe renal impairment.

Hormone replacement therapy (HRT)

HRT is considered for use more often nowadays as the increased risk of, ie, cancer, has been disproven. HRT relieves symptoms of menopause by restoring hormones to a premenopausal level. HRT reduces osteoporosis risk because of oestrogen.

Strontium ranelate (now discontinued)

Protelos was a drug in sachet form that could be prescribed if a patient could not take bisphosphonates. It stimulated new bone to grow and reduced bone loss. However, it was discontinued by the manufacturer in 2018 due to lack of demand.

First new osteoporosis drug in over 10 years: Romosozumab

Romosozumab (Evenity 105mg subcutaneous Injection) is a new monoclonal antibody treatment option for severe osteoporosis and is the first new osteoporosis drug to come to market in over 10 years. Romosozumab (brand name Evenity) received FDA approval in the US and EU authorisation by the European Medicines Agency in 2019. Romosozumab is now available in Ireland (since October 2024) after a review by the National Centre for Pharmacoeconomics (NCPE Ireland) on behalf of the HSE under the Hi-Tech scheme after prescribing by a consultant. Romosozumab works by inhibiting sclerostin, so increasing bone formation and decreasing bone resorption. It is reserved for use in postmenopausal women with severe osteoporosis, meaning they are at high risk of fracture, ie, previously experienced a fracture and are at imminent risk of another within 24 months and in patients intolerant to other treatments or when other treatments have failed. While not directly compared to denosumab yet, it appears to be as effective as denosumab in preventing fractures and there are early indications it may be more effective than denosumab in preventing non-spinal fractures, including hip fractures. In postmenopausal women, criteria for selecting romosozumab over bisphosphonates is one severe or two moderate low-trauma fractures, ie, same criteria as teriparatide. The recommended dose of romosozumab is 210mg (administered as two subcutaneous injections of 105mg) once monthly for 12 months. After 12 months, it should be followed by an alternative osteoporosis treatment such as denosumab or a bisphosphonate to allow continued protection, as its benefits wear off quickly after stopping. Contraindications of romosozumab:

• History of stroke or heart attack.
• Hypocalcaemia: An adequate intake of calcium and vitamin D before commencing romosozumab is advised, as romosozumab can rarely cause a significant drop in calcium levels.
• Pregnancy or breast feeding: While it is only licensed for women postmenopause, it may be prescribed by specialists for women pre-menopause.

Osteoporosis in men

Oral bisphosphonates alendronic acid and risedronate sodium are recommended first-line treatments for osteoporosis in men. Zoledronic acid or denosumab are alternatives in men intolerant of oral bisphosphonates, or they are otherwise unsuitable. Teriparatide is an additional alternative option for men. Men undergoing androgen blocking therapy for prostate cancer have increased risk of fracture and a bisphosphonate can be offered to these male patients with confirmed osteoporosis and where fracture risk is present. Denosumab may be considered as an alternative for these patients where bisphosphonates are unsuitable or not tolerated.

References on request

Disclaimer: Brands mentioned in this article are meant as examples only and not meant as preference to other brands.