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. 2025 Jul 11.
doi: 10.1007/s00198-025-07588-w. Online ahead of print.

Effect of FRAXplus adjustments on fracture risk reclassification in older Swedish women-results from the SUPERB-study

M Zoulakis  1   2 , H Johansson  1 , N C Harvey  3   4 , K F Axelsson  1 , H Litsne  1 , L Johansson  1   5 , M Schini  6 , L Vandenput  1 , E V McCloskey  7   8 , J A Kanis  8 , Mattias Lorentzon  9   10
Affiliations
Free article

Effect of FRAXplus adjustments on fracture risk reclassification in older Swedish women-results from the SUPERB-study

M Zoulakis et al. Osteoporos Int. .
Free article

Abstract

FRAXplus® facilitates adjustment of FRAX® fracture probabilities for additional clinical risk factors. This study examined how FRAXplus adjustments affect the proportion of older Swedish women eligible for treatment at a major osteoporotic fracture (MOF) probability intervention threshold (IT) ≥ 26%.

Background: FRAXplus enables adjustments based on additional clinical information, such as recency of osteoporotic fractures, high-dose oral glucocorticoids, T2DM duration, lumbar spine (LS) bone mineral density (BMD), trabecular bone score (TBS), falls in the previous year, and hip axis length. We aimed to determine how these adjustments alter treatment eligibility in older Swedish women.

Methods: Ten-year fracture probabilities with femoral neck BMD were calculated using FRAX and adjusted by FRAXplus in the SUPERB cohort of 3028 Swedish women aged 75 to 80 years. Clinical risk factors (CRFs) and outcomes were collected via questionnaires and national registers over 8 years, with incident X-ray-verified MOFs. FRAXplus adjustments were applied one factor at a time; if multiple were available, the most influential factor was used. Net reclassification improvement (NRI) was calculated.

Results: Overall, 90% (n = 2723) had their 10-year MOF probability adjusted upwards, with a mean (± SD) change of 4.25% (5.12%). Common adjustments included HAL (31%), TBS (23%), falls (20%), LS BMD (8%), and recent fracture (5%). Similar patterns were observed for hip fracture probabilities. Among those below the IT using FRAX alone, 1785 remained below, with 365 (20.4%) experiencing incident MOFs. Of 339 women uplifted above the IT using FRAXplus, 119 (35.1%) sustained incident MOFs. Among 904 above the IT with both FRAX and FRAXplus, 324 (35.8%) experienced incident MOFs. The NRI was 4.82% (95% CI: 1.87-7.77%; p < 0.01).

Conclusions: FRAXplus improved risk stratification, with a significant proportion of older Swedish women having their fracture probabilities uplifted above the IT, more accurately reflecting their elevated fracture risk, thereby enhancing the utility of risk assessment tools and improving patient management.

Keywords: FRAXplus; Fracture risk prediction; Hip fracture; Major osteoporotic fracture (MOF); Osteoporosis; Swedish woman.

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Conflict of interest statement

Declarations. Conflict of interest: JA Kanis led the team that developed FRAX as director of the WHO Collaborating Centre for Metabolic Bone Diseases; he is a director of Osteoporosis Research Ltd that maintains FRAX. EV McCloskey, WD Leslie, M Lorentzon, NC Harvey, M Schini, E Liu, L Vandenput, and H Johansson are members of the FRAX team. JA Kanis, NC Harvey, and EV McCloskey are members of the advisory body to the National Osteoporosis Guideline Group. M Schini received funding for her fellowship from the Medical Research Council Centre of Excellence for Musculoskeletal Ageing, from the Osteoporosis 2000 support group, and from Roche Diagnostics and honoraria from MA Health care and Kyowa Kirin—all unrelated to this work. Dr. Johansson received lecture fees from UCB Pharma outside the scope of this work. Dr. Axelsson received personal fees from Amgen, Meda/Mylan, and Lilly, also outside the scope of this work.EV McCloskey has received consultancy/lecture fees/grant funding/honoraria from AgNovos, Amgen, AstraZeneca, Consilient Healthcare, Fresenius Kabi, Gilead, GSK, Hologic, Internis, Lilly, Merck, Novartis, ObsEva, Pfizer, Radius Health, Redx Oncology, Roche, Sanofi Aventis, UCB, ViiV, Warner Chilcott and I3 Innovus. M. Lorentzon has received lecture fees from Amgen, Astellas, Meda, Jansen-Cilag, Medison Pharma, Gedeon Richter, UCB Pharma, and consulting fees from Amgen, UCB Pharma, Medac, Gedeon Richter, Pharmacosmos, and Parexel International, all outside the presented research. NC Harvey has received consultancy/lecture fees/honoraria/grant funding from Alliance for Better Bone Health, Amgen, MSD, Eli Lilly, Ra- dius Health, Servier, Shire, UCB, Kyowa Kirin, Consilient Healthcare, Theramex, and Internis Pharma. No other conflicts of interest were reported. Role of the funder/sponsor: The funders were not involved in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Drs Zoulakis and Lorentzon had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

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