Osteoporosis

This How to Treat may assist with the development of the following domains of competence in the general practice curriculum:

• Domain 1: Communication
• Domain 2: Clinical expertise
• Domain 3: Professionalism
• Domain 4: Scholarship
• Domain 5: Context of general practice
• Domain 6: Management

Osteoporosis is a chronic condition characterised by brittle bones with reduced bone mineral density leading to increased risk of fragility fractures, defined as fractures sustained from low-impact trauma (eg, a fall from standing height or less).

Bone mass reaches its peak in young adulthood and gradually declines beyond middle age. It is, therefore, not surprising that incidences of osteoporosis and fragility fractures are rising with our ageing population.

It is estimated that well over 20,000 New Zealanders experience one or more fragility fractures each year. With these fractures, there is tremendous individual suffering, such as pain, temporary or permanent loss of independence, and even increased mortality.

Fragility fractures also incur a huge and ever-increasing burden on our already strained healthcare system. ACC data from 2020 estimated that falls and fracture-related injuries among New Zealanders aged 65 and over cost $195 million per year, representing a 47 per cent increase since 2013. ACC estimates that “doing nothing” will more than double the cost burden by 2035 (tinyurl.com/ACC-prevent-FF).

With appropriate screening for, and management of, osteoporosis, a significant proportion of fragility fractures can be prevented.

The vast majority of those who experience fragility fractures are, at least in part, assessed and managed in primary care. Even if the initial care around the incident fracture is delivered by local secondary services, further follow-up and management of related issues (eg, pain, return to normal activities and future fracture prevention interventions) are often dealt with in primary care.

With widespread implementation of Fracture Liaison Services (FLS) in all regions of New Zealand, a large proportion of fragility fracture cases are now being identified and assessed in a timely fashion, with appropriate management strategies implemented or recommended. This secondary fracture prevention programme, mostly based in secondary settings, cannot function without cooperation and coordination with primary care for its care delivery, including patient investigation, initiation and continuation of pharmacotherapy and implementation of falls prevention.

In those not known to have osteoporosis or never having had a fragility fracture, screening for osteoporosis and treating the appropriate population can lead to early diagnosis and fracture prevention.

Osteoporosis and fragility fractures occur in a reasonably predictable manner in terms of demographics and clinical background. Those deemed to be at risk can be identified in primary care and assessed with dual-energy x-ray absorptiometry (DEXA or DXA) or by using readily available tools, such as the FRAX Fracture Risk Assessment Tool.

In addition, Know Your Bones is a relatively new online tool that can be used by patients, and its results discussed with their GPs.

As well as lifestyle modifications and falls prevention strategies, which have been shown to reduce fragility fracture incidence, well-proven anti-osteoporosis treatment options are available in New Zealand. There have been significant changes to funding and access to some of these medications in recent years, as discussed later.

The key functions of an FLS – identification, investigation, information, intervention, integration and quality

Perhaps the biggest change in the osteoporosis landscape in New Zealand over the last several years has been nationwide implementation of Fracture Liaison Services. While the majority of FLS are based in secondary care, primary care plays a crucial role in effective delivery of FLS function.

Epidemiological studies over the years have repeatedly shown that without a systematic approach, 80–90 per cent of those experiencing a fragility fracture do not get appropriate workup and treatment for future fracture prevention, highlighting the need for a systematic secondary fracture prevention strategy. FLS is a secondary fracture prevention programme that is broadly adopted throughout the world. Its efficacy in fracture prevention and resulting cost effectiveness have been well validated in the literature.

FLS was introduced in some regions of New Zealand over 10 years ago. In 2015, the Ministry of Health recommended for all District Health Boards to implement FLS. There has been progressive establishments and expansion of FLS over the past decade. This was made possible particularly by the implementation drive of Osteoporosis New Zealand and its strategic partnership with, and support from, ACC.

Osteoporosis New Zealand published its first Clinical Standards for Fracture Liaison Services in New Zealand in 2016, which created the initial framework and direction for local FLS. After achieving “full coverage” of New Zealand in 2019, the clinical standards were updated in 2021.

The “5IQ” approach underpins the clinical standards and relates to the key functions of an FLS – identification, investigation, information, intervention, integration and quality. Under each of these 5IQ headings, 15 key performance indicators are set out and modified for the New Zealand setting, having been adopted from the International Osteoporosis Foundation, the organisation that launched and mentors FLS internationally.

Central to FLS delivery is the FLS coordinator, a healthcare professional with relevant fracture care/osteoporosis management experience with a nursing or allied health background, who systematically identifies fragility fracture cases in patients over age 50, communicates with the patient and their primary care provider, arranges appropriate investigations (eg, laboratory tests, DXA scans), and implements and/or recommends anti-osteoporosis medication and fracture prevention interventions if appropriate. All FLS coordinators in New Zealand are supported by FLS lead clinicians who provide clinical oversight for patient care and leadership for the service.

The New Zealand arm of the Australian and New Zealand Fragility Fracture Registry (ANZFFR) was established in 2022. The registry requires all New Zealand FLS to participate, and data fields are in line with the KPIs set out in the clinical standards. The first ANZFFR Annual Report was published in March (fragilityfracture.co.nz/2024-annual-report), and it presents New Zealand FLS data from 1 July 2022 to 30 June 2023. We are proud to be leading our trans-Tasman colleagues in this achievement.

The report details the national effort in identifying and managing fragility fracture patients. In summary, it shows that 11,600 patients with fragility fractures were identified and managed by FLS, representing a 55 per cent capture rate of the fragility fractures expected, with participation from 19 of the 20 districts in New Zealand. This represents over 90 per cent of those with access to a participating FLS at the time of their injury.

Of the patients registered in the ANZFFR, 95 per cent had a bone health assessment within 12 weeks, approximately 25 per cent had a DXA scan performed, and nearly 100 per cent had their falls risk assessed. Over 50 per cent of patients were either started on anti-osteoporosis treatment or advised to start or continue treatment. Nearly 90 per cent of patients had a 16-week follow-up – this is important in terms of confirmation of treatment initiation and DXA result review in relevant individuals.

There is still a lot of work to be done in this space, and further progress will undoubtedly be made, leading to improved fracture prevention.

Most fragility fractures occur in those over the age of 50, and about three-quarters occur in women

While those having had a fragility fracture hopefully would have already been identified by FLS and/or primary care and managed accordingly, it is important not to overlook those at risk of having bone fragility who have not yet fractured. Risk factors can broadly be divided into hereditary/demographic (non-modifiable) and acquired (modifiable) factors.

Hereditary factors are generally the most important determinant of peak bone mass and bone strength; therefore, family history is quite relevant. Additionally, nutritional and environmental factors, particularly during earlier life, are important determinants of bone health. On the other hand, age and gender are potent determinants of one’s absolute fracture risk – most fragility fractures occur in those over the age of 50, and about three-quarters occur in women. Osteoporosis and fragility fractures occur in all ethnicities, but a significantly higher incidence is observed in the European population than in other ethnicities in Aotearoa New Zealand.

During adult life, there is an equilibrium in bone turnover, where bone resorption by osteoclasts is balanced by new bone formation by osteoblasts. This equilibrium tends to get distorted as we age, particularly beyond menopause for women, where osteoclast activity outpaces that of the osteoblasts. Over time, this disequilibrium leads to gradual loss of both trabecular and cortical bone, leading to increased porosity and fragility (Figure 1). Similar increases in bone loss are also observed in certain “physiological states”, diseases and with certain medications. Panel 1 lists significant acquired/modifiable risk factors for osteoporosis.

Patients with one or more of these risk factors should be considered for clinical risk assessment for osteoporosis and fragility fracture. The main tools for risk assessment are the DXA scan and fracture risk calculators (covered next).

There is also an online bone-health self-assessment tool for lay persons – Know Your Bones (knowyourbones.org.nz). It is free and user friendly, and it takes just a few minutes to complete. After filling in bone-health-relevant fields, a personalised report is produced instantly (Figure 2). The report provides recommendations for the areas of risk identified, which can be further discussed with a GP or other healthcare professional.

Dual-energy x-ray absorptiometry

Bone mineral density, assessed by DXA, is the well-validated, most widely used and recommended diagnostic test for osteoporosis. It is also routinely used in assessing treatment response and fracture risk in those with established osteoporosis. DXA uses a very low level of radiation to determine bone density, and the lumbar spine (L1–L4) and hips are the two primary sites scanned. It is precise, reproducible and relatively inexpensive.

Most regions of New Zealand have access to funded DXA, but there is significant heterogeneity in terms of threshold for a funded scan. In synchrony with nationwide implementation of FLS and ANZFFR, there are ongoing efforts to improve access to funded DXA and to reduce inter-regional variability in its access.

While it is recommended that a DXA scan be performed in those presenting with fragility fracture, DXA is not always necessary in those at very high risk of fractures (eg, over age 75 with a fragility fracture); their future fracture risk is sufficiently high that anti-osteoporosis medication is almost always indicated regardless of the bone density.

Trabecular bone score (TBS) is an analytical tool that measures grey-level texture on lumbar spine DXA images and provides information on bone microarchitecture. While this technique has been around for many years and has been shown to have additional utility in fracture risk prediction (now incorporated in FRAXplus, discussed below), TBS is currently unavailable in New Zealand. Some centres in New Zealand, including Te Whatu Ora Waitematā, will be introducing TBS in the foreseeable future.

DXA scan results

An individual’s bone mineral density, measured in g/cm², is then expressed as a T-score that represents the number of standard deviations above or below that of a healthy, young-adult population of the same gender. T-scores above -1.0 are interpreted as normal, between -1.0 and -2.49 as osteopaenia, and -2.5 or less as osteoporosis.

Z-scores are also often reported on DXA scans and represent standard deviations above or below that of the age-matched population of the same gender. Regardless of age, people with a Z-score below -2.0 should be assessed further with relevant laboratory investigations to exclude secondary causes of bone loss (summarised in Panel 2).

Specialists will produce a report for the DXA scan, which generally incorporates interpretation of bone density parameters and a suggested management plan.

Fracture risk calculators

Fracture risk calculators are well-validated and easy-to-use online tools to help estimate future fracture risk. The most widely used is FRAX, which has country-specific tools, including New Zealand (fraxplus.org/calculation-tool). After entering several clinical parameters, 10-year risks for major osteoporotic fracture and hip fracture are generated.

FRAXplus was launched in 2023 and has additional fields (eg, recency of fracture, falls, TBS) that improve fracture prediction (fraxplus.org/frax-plus). However, unlike FRAX, there is a cost associated with using FRAXplus, which is perhaps the reason why it is not yet broadly adopted.

Another well-validated online calculator is the Garvan Institute of Medical Research Bone Fracture Risk Calculator (tinyurl.com/Garvan-calc). It tends to produce significantly higher fracture risk.

Both FRAX and Garvan calculators can be used with or without a DXA result, which is helpful when a DXA scan is not readily available.

It is imperative that any underlying condition that contributes to accelerated bone loss be actively managed and treated

Lifestyle and non-pharmacological interventions should be encouraged and implemented in all individuals with fragility fracture history or an established diagnosis of osteoporosis or osteopaenia on DXA, and in those with significant risk factors for osteoporosis.

Healthy body weight and nutrition

Maintaining a healthy body weight is difficult to achieve but is critically important for bone density and strength. Significant weight loss is detrimental to bone density and should be avoided in those with a normal or low BMI (ie, <25kg/m²) who are at increased risk of fractures.

Good nutrition through a balanced diet, ideally rich in calcium and vitamin D, is recommended. The standard diet consumed by most New Zealanders contains adequate amounts of calcium over 500mg per day (this is a controversial topic, with some experts still recommending 1000mg per day, and more for older adults). A few servings each day of foods rich in calcium will achieve this – dairy products, calcium-fortified products (eg, soy and rice milks, cereals, orange juice), tofu, tinned sardines or salmon, and certain vegetables (eg, leafy greens).

Consumption of vitamin D-rich foods, such as oily fish, eggs and vitamin D-fortified foods, helps boost circulating vitamin D levels.

However, the best source of vitamin D is via production in our skin after exposure to sunlight. Vitamin D deficiency, in most cases, can be prevented by five to 10 minutes of sunlight exposure to the face, arms and hands several times a week.

Individuals at risk of vitamin D deficiency include frail or institutionalised older people, veiled women and those with dark skin who are living at higher latitudes. Supplementation, most commonly in the form of monthly 1.25mg cholecalciferol capsules, should be considered in these individuals.

Regular exercise

Exercising for 30 minutes or more several times a week has been shown to modestly increase bone density and significantly reduce fractures. Traditionally, weight-bearing exercises such as walking or jogging were recommended, but resistance exercises and balance training have also been shown to be effective. It is believed that fracture risk is reduced not only due to positive effects on bone density but also through improved muscle tone and strength leading to fewer falls.

Smoking cessation and curbing alcohol

Smoking cigarettes and consuming excess alcohol can both adversely affect bone density. Improving bone health is, therefore, an additional motivating factor for smoking cessation and moderating alcohol intake, the latter ideally to no more than two standard drinks per day with at least two alcohol-free days a week. Cigarette smoking is becoming less prevalent while vaping is increasing. Skeletal effects of vaping are yet unclear, though there are some early signals suggesting a negative effect.

Falls prevention

Avoiding falls is certainly not straightforward but is paramount for fracture prevention. Falls risk should be assessed routinely by asking about falls in the past year and screening for other risks for falls, such as frailty, poor vision and polypharmacy that includes blood pressure lowering medications and psychoactive medications.

Patients deemed at high risk of falls should either be encouraged to self-enrol or be referred to a local falls prevention programme, such as strength and balance classes, and/or do in-home strength and balance exercises (livestronger.org.nz).

ACC, through its Live Stronger for Longer initiative, has also introduced a new app called Nymbl, which is free and easy to download from the app stores. It is simple to use and provides step-by-step instructions on doing balance exercises. There are also very helpful resources for home-based exercises available from the Live Stronger for Longer website (tinyurl.com/safe-exercise).

Patients and carers can implement other practical measures at home to reduce falls, such as removing loose obstacles on the floor, having rails and a bath mat in the bathroom, and having easily accessible night-lights (see the checklist at tinyurl.com/home-safety-checklist).

Correct underlying medical conditions

It is imperative that any underlying condition that contributes to accelerated bone loss be actively managed and treated. There is good evidence that adequately treating these secondary causes, such as inflammatory, malabsorptive and endocrine conditions, leads to partial or full recovery of bone density and fracture risk reduction.

Zoledronate infusion has the advantage that it only needs to be administered every 18 to 24 months, resulting in better patient acceptance and adherence

Regardless of whether there has been a fragility fracture or not, those at sufficiently high risk of future fractures should be considered for pharmacotherapy (a 10-year hip fracture risk above 3 per cent, using the FRAX or Garvan calculators, is often used as the threshold). This would include the majority of those having had any fragility fracture, especially those over age 75. This is the reason why a DXA scan is generally not necessary prior to initiating anti-osteoporosis treatment in this cohort. In particular, those with vertebral or hip fractures (associated with the highest risk of further fractures) should have lower threshold for treatment initiation after the sentinel fracture.

In the absence of fracture, treatment is also generally indicated in those whose DXA T-score is less than or equal to -2.5, or less than or equal to -1.5 with significant risk factors such that their fracture risk is high.

Oral and intravenous bisphosphonates

Bisphosphonates remain the first line and mainstay of anti-osteoporosis treatment, both locally and internationally. The ANZFFR Annual Report 2024 shows 95 per cent of anti-osteoporosis treatment used is either oral or intravenous bisphosphonate. Oral agents available in New Zealand are alendronate (Fosamax and Fosamax Plus) and risedronate, and the intravenous agent for use in osteoporosis is zoledronate. In the past, alendronate and zoledronate were funded under Special Authority restrictions, but both are now fully funded without restriction.

Studies suggest poor adherence to oral bisphosphonates. Therefore, it is recommended that adherence is checked periodically and that a blood test for procollagen-1 N-terminal peptide (P1NP) is performed about six months after starting treatment. P1NP is a bone formation (and hence turnover) marker that is suppressed (below 35µg/L) when oral bisphosphonate is taken regularly and absorbed adequately. Switching to intravenous zoledronate should be considered if P1NP is above 35µg/L despite seemingly good adherence or where consistent adherence is problematic.

Zoledronate infusion has the advantage that it only needs to be administered every 18 to 24 months, resulting in better patient acceptance and adherence. It can be used in patients who experienced side effects from, or have contraindications to, oral bisphosphonates.

A very common adverse effect of zoledronate infusion is post-dose flu-like symptoms that occur in up to one-third of patients after the first dose. This acute-phase response typically occurs in the first few days of drug infusion and resolves within three days or so. Paracetamol with or without an NSAID can be used to alleviate symptoms (the latter only if safe to use for the individual patient and deemed necessary). Incidence of this post-infusion adverse effect markedly decreases with subsequent infusions.

A recent New Zealand study showed that a three-day course of oral dexamethasone (4mg daily, started on the day of infusion) significantly reduced the acute-phase response (J Bone Miner Res 2023;38[5]:631–38). This approach could be considered either routinely or in those with significant prior post-infusion acute-phase response.

With the recent funding change for zoledronate, the fully funded product is no longer the well-known Aclasta but the generic version Zoledronic Acid Viatris. Therefore, we should avoid prescribing it as Aclasta, but instead prescribe zoledronate or zoledronic acid.

There remains an access inequality issue due to the zoledronate infusion fee that is charged by private and primary care providers. Due to the sheer volume of patients treated with zoledronate, secondary care in most regions of New Zealand is unable to offer infusions for all. There is an ongoing push by Osteoporosis New Zealand and Fracture Liaison Network New Zealand towards equitable and improved access for zoledronate infusions nationally.

Contraindications and adverse effects

Contraindications to bisphosphonates include renal failure – denoted in Medsafe data sheets as creatinine clearance (CrCl) <35ml/min for zoledronate and oral bisphosphonates. It is common practice to reduce the administration dose of zoledronate (eg, from 5mg to 2.5mg) and/or slow the infusion rate (over 30 to 60 minutes) when treating patients with a lower CrCl of 35–50ml/min.

Use of zoledronate in those with lower renal functions (eg, CrCl 25–35ml/min) and use of estimated glomerular filtration rate instead of CrCl remain controversial. Lower renal function threshold – possibly CrCl down to 15ml/min – for oral bisphosphonates is believed to be safe. Evidence for safety of this off-label use for oral bisphosphonates in stage 4 chronic kidney disease is scant, and hopefully will not be necessary once the access of denosumab (discussed in the next section) improves.

Oral bisphosphonates should also be avoided in those with significant impairment or delay in oesophageal emptying, such as oesophageal stricture or achalasia.

A well-publicised side effect of bisphosphonates is osteonecrosis of the jaw (ONJ). It manifests as an area of exposed bone in the mouth that does not heal within eight weeks. In reality, it is extremely rare in the setting of osteoporosis management. It is, nevertheless, recommended that significant dental issues requiring major dental work (eg, dental implants, multiple teeth extractions or jaw surgery) are resolved before initiation of bisphosphonate therapy.

Another bisphosphonate-related long-term adverse effect is that of atypical femoral fracture (AFF). These initially begin as stress fractures in the lateral cortex of the femoral shaft and can spontaneously progress to full-thickness transverse fractures of the femur. Before fracture, the lateral cortex of the femur may appear thickened on x-ray, with a “beaked” appearance (Figure 3).

The incidence of AFF, albeit very low in absolute risk terms (several cases per 100,000 person-years), appears to increase steeply with increasing duration of bisphosphonate use, largely with oral forms, beyond five to seven years of treatment, and risk drops off dramatically within one to two years of treatment intermission or cessation. Thus, it is important to periodically review the need for continued bisphosphonate therapy and provide “drug holidays” (discussed below) for patients requiring therapy for more than five years.

It is important to…provide “drug holidays” for patients requiring therapy for more than five years

Long-term follow-up

As alluded to above, it is recommended that the serum P1NP level be checked about six months after initiation of oral bisphosphonate therapy. P1NP can be checked at any stage of treatment if adherence and/or efficacy is being questioned, although there are certain situations where P1NP will not be reliable (eg, within a few months of a fracture). Total duration of bisphosphonate therapy and drug holidays are frequently debated and remain contentious issues.

Most patients established on bisphosphonate therapy should have a repeat DXA scan after four to five years of treatment. If the T-score has improved to -2.5 or higher without a recurrent fracture, treatment should be ceased for three to five years before reassessing fracture risk.

On the other hand, treatment should be continued for a further four to five years if the T-score remains less than -2.5. During this period, a one to two-year drug holiday should be considered if staying on oral bisphosphonates, to minimise the risk of AFF. For those on zoledronate infusion, the dosing interval could be increased to 24–30 months for the same reason, although AFF risk seems much lower in patients treated with zoledronate.

There is still limited evidence to guide bisphosphonate therapy (or any other anti-osteoporosis medication) beyond 10 years. Individuals with persistently high fracture risk should be considered for continued medical therapy with drug holidays every several years, and guidance from secondary care could be sought. Similarly, patients with recurrent fractures despite adequate therapy, or those with intolerances and/or contraindications to both oral and intravenous bisphosphonates, should be referred to secondary care.

Some of these agents are simply superior in terms of anti-fracture efficacy

There has been a recent secular trend of increasing use of non-bisphosphonate medications for osteoporosis, although they still only make up 5 per cent of treatments used, according to the ANZFFR Annual Report 2024. However, their use is expected to continue to increase with likely easing of Pharmac funding restrictions in coming years and with increasing familiarity and experience of prescribers using non-bisphosphonate agents.

These agents can overcome issues that bisphosphonates may have, and some agents are simply superior in terms of anti-fracture efficacy.

Oestrogen-based therapies

Hormone replacement therapy, these days referred to as menopausal hormone therapy, incorporates oral or transdermal oestrogen. Once deemed unsafe in all postmenopausal women, MHT has made a noticeable comeback in recent years. There have been reappraisals of the evidence to suggest the risk–benefit profile has moved significantly in favour of its use, including for preventing and treating osteoporosis or high fracture risk states in younger menopausal women.

In the original Women’s Health Initiative study, women on HRT were found to have lower fracture risk, and other studies also consistently show favourable bone effects of MHT. Safety in women within the first 10 years of menopause has been well demonstrated in a number of studies, and MHT could be used as a second-line agent in women under age 60 (sometimes even a little above this age threshold) who do not have additional risk factors for cardiovascular disease, breast cancer or venous thromboembolism.

Oral forms of oestrogen, such as conjugated oestrogen and oestradiol valerate, can be used. The transdermal preparation fully funded in New Zealand is the oestradiol patch (Estradot or Estradiol Transdermal System). Oral oestrogens are perhaps more convenient, though the transdermal route theoretically carries a lower side-effect risk, bypassing first-pass metabolism.

Regardless of whether oral or transdermal oestrogen is used, in those with an intact uterus, a progestogen should be used for endometrial protection – cyclical or continuous medroxyprogesterone (Provera) or micronised progesterone (Utrogestan).

Risk versus benefit of MHT should be considered before treatment initiation.

Contraindications to oestrogen therapy include history of ischaemic heart disease, breast cancer or sex hormone-responsive tumours, liver tumours, venous thromboembolism and severe liver disease. MHT use in those with significant cardiovascular risk factors should also be avoided.

Dosing information for oestrogen and corresponding progestogen is well summarised in the Australasian Menopause Society’s AMS Guide to MHT/HRT Doses New Zealand Only (tinyurl.com/MHT-doses).

Teriparatide

Teriparatide (Forteo) is a synthetic parathyroid hormone (PTH 1–34) analogue that has been available in New Zealand for many years. Given as a daily subcutaneous injection (20μg), it stimulates osteoblast activity and acts as an anabolic agent for bone.

Current funding criteria (Panel 3) is quite restrictive, in that patients only qualify if they have had two or more fragility fractures, at least one of which after having had adequate bone protection therapy (bisphosphonate or raloxifene for more than one year), and with very low bone mineral density (T-score less than -3.0). Any relevant practitioner can apply for the Special Authority. There is a compelling argument for its use as a first-line agent in very severe osteoporosis. Pharmac is currently reconsidering teriparatide funding.

Teriparatide comes in a pre-filled injection device that patients need to learn to self-inject. Often, drug initiation is done in secondary care, although many primary care practices are now initiating therapy independently

The approved duration of use for teriparatide is 18 months in New Zealand (up to 24 months in some other countries), and it is not to be used in conjunction with bisphosphonates. Bisphosphonate therapy, usually in the form of intravenous zoledronate, is recommended at the end of the 18-month treatment course.

Denosumab

Denosumab (Prolia) is available as a six-monthly subcutaneous injection. It is a potent antiresorptive agent that works in a similar fashion to the bisphosphonates but via a different cellular pathway and with superior anti-fracture efficacy. Denosumab is not cleared renally; therefore, it can be used safely in those with moderate to severe (stages 3 and 4) chronic kidney disease.

Denosumab has been available in New Zealand for several years and remains under highly restrictive funding criteria that include the presence of severe osteoporosis with recurrent fracture despite being on adequate antiresorptive therapy for over one year and CrCl <35ml/min (Panel 4). Efforts to broaden funding indications for denosumab over the years have been unsuccessful, although it is hoped that criteria will relax in coming years. Drug cost (generally under $1000 per year) is not overly prohibitive for many patients, and an increasing number of patients with severe osteoporosis are choosing to self-fund denosumab.

In patients receiving denosumab, ONJ and AFF have been described but are very rare, and there are long-term (10-year) safety and efficacy data. It has been shown to be superior to bisphosphonates in terms of bone density gains and anti-fracture efficacy, and its long-term efficacy is particularly impressive.

Denosumab could serve as a second-line agent for patients who are intolerant of, or refracture while on, bisphosphonate therapy. Easy and infrequent administration makes it an attractive treatment option, especially in patients in whom administration of bisphosphonates poses difficulty.

Arguably the most important drawback of denosumab is the well-described phenomenon of rapid offset of drug effect if discontinued or if dosing is significantly delayed. Especially in those who have been on denosumab therapy for more than three years, a dramatic rise in bone turnover markers and rapid fall in bone density are observed after treatment cessation, with significant increase in vertebral compression fractures.

The importance of continuation of therapy with regular six-monthly dosing cannot be overemphasised. For this reason, denosumab treatment is often considered in relatively older patients with severe osteoporosis who are committed to taking it for the rest of their life. If denosumab is to be ceased, the case must be discussed with a secondary care colleague with relevant experience and expertise.

Raloxifene

Raloxifene (Evista) is a daily oral therapy for osteoporosis that is available under relatively loose funding criteria, which includes DXA, clinical fracture or fracture risk criteria. Raloxifene is rarely used for osteoporosis, largely due to a lack of anti-fracture efficacy for non-vertebral fractures as well as a side-effect profile that includes flushing.

Romosozumab

This potent, highly effective anti-osteoporosis agent has both bone anabolic and antiresorptive properties. It is delivered as a monthly subcutaneous injection for one year only. Romosozumab has recently become available in Australia under strict funding restrictions but is not yet available here.

Details have been changed to protect patient confidentiality

David Kim is an endocrinologist and general physician at Te Whatu Ora Waitematā and Apollo Health & Wellness, Auckland