Abaloparatide is used to treat osteoporosis in postmenopausal women who have a high risk of bone fracture. It is also used to increase bone density in men with osteoporosis who are at high risk for bone fracture and is used to treat people who cannot use another treatment for osteoporosis or other treatments did not work well. Abaloparatide may also be used for purposes not listed in this medication guide. Abaloparatide may sometimes be given at home to patients who do not need to be in a hospital or clinic. If you are using this medicine at home, your doctor or nurse will teach you how to prepare and inject the medicine. Be sure that you understand how to use the medicine. You should receive the first several injections of this medicine while sitting or lying down if needed, until you know how this medicine affects you.

Abaloparatide for treating osteoporosis after menopause

Clinical trial evidence shows that abaloparatide followed by alendronic acid is more effective at reducing the risk of some types of fracture than placebo followed by alendronic acid. Indirect comparisons suggest that it is likely to work at least as well as romosozumab and teriparatide. People with a very high fracture risk may be offered romosozumab or teriparatide (anabolic treatments). Teriparatide, romosozumab and abaloparatide can only be taken for a limited time (24 months, 12 months and 18 months, respectively). After taking them, people have an antiresorptive treatment (such as an oral bisphosphonate) to maintain the bone mineral density gained during anabolic treatment. The clinical expert said that romosozumab and teriparatide are not suitable for everyone. For example, romosozumab is not used for people with a history of myocardial infarction or stroke. The patient experts said that the existing treatments can have side effects (such as hypercalcaemia and osteonecrosis) that can stop people from taking them. The ACTIVE trial showed that abaloparatide reduced the risk of new vertebral fractures by 88% compared with placebo at 18 months.[1]

For non-vertebral fractures, the results were not statistically significant for abaloparatide compared with placebo or teriparatide. The EAG said the results for ACTIVExtend were consistent with the findings of the ACTIVE trial. People who had abaloparatide then alendronic acid had an 84% lower risk of 1 or more new vertebral fractures compared with people who had placebo then alendronic acid (relative risk reduction ?0.84, CI ?0.94 to ?0.53, statistically significant). The clinical expert said that the side-effect profile for it was similar to romosozumab and teriparatide. The incremental benefit of abaloparatide over romosozumab and teriparatide was considered by comparing the size of the net health benefit for each comparison. The committee noted that there was uncertainty around the treatment effect of abaloparatide compared with romosozumab and teriparatide. It explored this uncertainty through a range of scenarios. These included a scenario using the hazard ratios from the NMA, a scenario that assumed equal efficacy for some comparisons, and a scenario assuming equal efficacy for all comparisons.

Effects of systemically administered abaloparatide

Spinal fusion is a common procedure for patients with degenerative disc disease, spinal stenosis, spondylolisthesis, spondylosis, spinal fractures, scoliosis, and kyphosis. Successful fusion surgery creates an environment that allows endochondral and intramembranous ossification processes to form a solid stabilizing bony bridge across decompressed segments, but several biological and biomechanical challenges can hinder formation of this bridge. However, BMP‐2 does not improve vertebral bone mass and is sometimes associated with vertebral osteolysis, endplate erosion, ectopic bone formation, graft and cage subsidence, and other complications. Abaloparatide is selective PTHR agonist approved in the US for the treatment of PMO. It increases bone formation in women with PMO, leading to greater increases in spine BMD vs teriparatide during the first year of therapy and an overall 86% reduction in vertebral fracture risk vs placebo. Abaloparatide is a parathyroid hormone receptor agonist that increases bone formation and reduces vertebral and nonvertebral fracture risk in women with postmenopausal osteoporosis. Animal studies indicate abaloparatide stimulates vertebral bone formation and enhances bony bridging and biomechanical stability of fracture calluses.[2]

Strengths of this study include excellent inter‐observer and inter‐modality concordance in fusion assessments. Abaloparatide increased serum levels of the bone formation marker osteocalcin compared with vehicle controls. Regression analyses indicated that serum osteocalcin was associated with fusion mass microarchitectural parameters, suggesting the osteoblast‐stimulating effects of abaloparatide may influence fusion processes. This hypothesis is tempered by the lack of fusion mass histomorphometry data, and it is possible that abaloparatide effects on fusion mass microarchitecture were related at least in part to increased chondrogenesis (endochondral ossification). In summary, systemic abaloparatide administration was associated with early positive effects on fusion mass architecture in rats undergoing non‐instrumented PLF, in association with elevated bone formation markers without increased bone resorption markers. These findings, which were accompanied by a 2‐fold higher fusion rate at day 28, warrant follow‐up in larger species to provide additional insights into abaloparatide's potential efficacy in spinal fusion settings.

Abaloparatide as an Effective Treatment Option for Postmenopausal Osteoporosis

Abaloparatide (ABL) is a 34-amino acid peptide designed to be a selective activator of the parathyroid hormone receptor type 1 (PTHR1) signaling pathway. ABL binds selectively to the RG versus R0 conformation of PTHR1, consistent with a net anabolic effect in contrast with PTH. Preclinical and clinical studies of ABL resulted in increases in bone mass and bone mineral density (BMD), restoration of bone microarchitecture, and increased bone strength with no adverse effects on bone quality and no apparent concerns regarding bone safety. To further elucidate the effectiveness of abaloparatide, we evaluated the number needed to treat (NNT) to prevent one fracture (vertebral, nonvertebral, clinical, and major osteoporotic) using data from ACTIVE. To understand the potential effectiveness of abaloparatide in patient populations at greater risk of fracture and with varying treatment durations, we also estimated the NNT for ABL using reference populations from historical placebo-controlled trials of treatments for postmenopausal women with osteoporosis. ACTIVE included an open-label teriparatide (TPTD) arm, and ABL significantly increased BMD at nonvertebral sites and significantly decreased the risk of major osteoporotic fractures compared with TPTD.[3]

In summary, The NNT is the reciprocal of the ARR and is expressed as a single value, representing the number of patients who must be treated to prevent one event of interest. The analyses described here show that following 18 months of treatment in ACTIVE, the NNT for ABL versus placebo was lower than that of TPTD versus placebo for multiple fracture endpoints. The NNT for ABL and TPTD in ACTIVE were similar for new vertebral fractures: 28 for abaloparatide; 30 for TPTD. Additional fracture types beyond new vertebral fractures of course contribute significantly to disease burden and are of clinical interest when evaluating treatments for osteoporosis. The observed treatment differences between ABL and TPTD may be explained at least in part by the underlying physiological differences, and subsequent different binding profiles, of TPTD, a PTH analog, and abaloparatide, a PTHrP analog. After 18 months of treatment in ACTIVE, the NNT for ABL was similar to that for TPTD for new vertebral fractures and lower than that for TPTD for nonvertebral, clinical, and major osteoporotic fractures. These data are useful for further evaluating ABL for the treatment of osteoporosis in postmenopausal women.

References

[1]Abaloparatide for treating osteoporosis after menopause. London: National Institute for Health and Care Excellence (NICE); 2024 Aug 7. (National Institute for Health and Care Excellence: Technology Appraisals, No. TA0991.)

[2]Arlt H, Besschetnova T, Ominsky MS, Fredericks DC, Lanske B. Effects of systemically administered abaloparatide, an osteoanabolic PTHrP analog, as an adjuvant therapy for spinal fusion in rats. JOR Spine. 2020 Nov 25;4(1):e1132. doi: 10.1002/jsp2.1132. PMID: 33778406; PMCID: PMC7984001.

[3]Reginster JY, Hattersley G, Williams GC, Hu MY, Fitzpatrick LA, Lewiecki EM. Abaloparatide is an Effective Treatment Option for Postmenopausal Osteoporosis: Review of the Number Needed to Treat Compared with Teriparatide. Calcif Tissue Int. 2018 Nov;103(5):540-545. doi: 10.1007/s00223-018-0450-0. Epub 2018 Jun 27. PMID: 29951742; PMCID: PMC6182596.