A new bone builder on the block!

Sarah is a fit and healthy 52-year-old lady who attends for review of her HRT. She has seen on the news that there is a new ‘bone-building drug coming for post-menopausal women’, and would like to know more about it. 

Sarah is particularly concerned about her bone health as she saw how her mother’s life was devastated as a result of osteoporosis. ‘She was an independent social person, until she tripped and broke her wrist whilst out shopping. After that she became worried about leaving the house. Her world shrank. She became weaker and had another fall that broke her hip. She needed to live in a care home after that’. 

This is sadly an all too common scenario. So, what is the new ‘bone-building’ drug? Could it be helpful for Sarah? 

In August 2024 abaloparatide was approved by NICE TA991 as an option for treating osteoporosis after menopause, with guidance that it should be available on the NHS within the next 3 months. 

So how does abaloparatide work? 

We can think of osteoporosis medication in two broad categories; namely antiresorptive treatments that slow down the rate of bone breakdown (e.g. bisphosphonates), and osteoanabolic medications that trigger new bone formation. Abaloparatide (marketed as Eladynos) is an example of an anabolic medication. It activates the PTH1 receptor, stimulating osteoblast activity. Notably, it is a peptide medication and must be administered by daily subcutaneous injection, which could be a barrier to some. Use is limited to 18 months, and typically an antiresorptive medication would be started afterward to maintain gains in BMD.

NICE considered data on efficacy from the ACTIVE trial ( a randomised multicentre double bind placebo and open label active comparator controlled trial), which had a primary end point of incidence of one of more new vertebral fractures. It included 2463 post-menopausal women from 49-86 with a mean age of 69, and varying severities of osteoporosis. Of note, the trial population differed slightly from the patient group eligible for treatment with abaloparatide, as it included some women not at ‘very high risk’ of fracture (inclusion criteria). Participants were divided into three groups, to receive an 18-month course of either placebo, abaloparatide or teriparatide (an established anabolic treatment), alongside calcium and vitamin D. 

There was an 88% relative risk reduction (absolute risk difference -3.64% (95%CI -5.42 to-2.10) in new vertebral fractures at 18 months in the abaloparatide group versus placebo (the study was underpowered to compare abaloparatide to teriparatide). The ACTIVExtend trial then assessed 18 months of treatment with abaloparatide followed by 24 months of alendronate, versus placebo followed by alendronate. People in the abaloparatide-alendronate arm had an 84% lower relative risk of vertebral fracture.

What about side effects? Significant side effects reported in the ACTIVE study included hypercalciuria, nausea, dizziness, headache and palpitations. The spc advises CVS assessment prior to treatment given risks of transient orthostatic hypotension and tachycardia. Additionally, its contraindicated in patients with unexplained rises in ALP, skeletal malignancies, or risk factors for osteosarcoma, noting that studies in rats showed an increased risk of osteosarcoma with long term use. As with any new medication, long-term risks versus benefits remain to be seen.

Where does it sit in osteoporosis management?

At a list price just shy of £300/ month (pre-undisclosed NHS discount) NICE recommend abaloparatide as an option for treating osteoporosis after menopause in women, trans men and non-binary people ONLY if they have a very high risk of fracture (they refer to NOGG guidelines which defines ‘very high risk’ based on FRAX as a risk of fracture exceeding the threshold for intervention by 60%). It is an alternative to the anabolic medications teriparatide and romosozumab (notably romosuzumab is contraindicated for those with previous MI or CVA). 

How does this apply to Sarah? Given her risk factors she certainly warrants an osteoporosis assessment. However, assessment with the FRAX tool and a subsequent normal DEXA shows that she does not have osteoporosis. You discuss lifestyle factors and the benefits of HRT for bone health, but abaloparatide is not indicated.

In summary, abaloparatide offers a new anabolic treatment option for a subset of post-menopausal patients at very high risk of fracture. NOGG guidance suggests we should consider referral of very high-risk patients to secondary care for assessment of parenteral or anabolic treatment options, being particularly aware of patients with a recent vertebral fracture, multiple vertebral fractures, multiple clinical risk factors (especially if there is a recent fragility fracture indicating high risk of imminent fracture), those with a BMD T-score ≤ -3.5 and those on high dose glucocorticoids. However, in most people with osteoporosis, anti-resorptive medication remains first line.