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New Analysis Challenges FRAX Use to
Predict Osteoporosis in 40-to-49 HIV Group
  European Workshop on Healthy Living With HIV 2019, Barcelona, September 13-14, 2019
Mark Mascolini
FRAX, the much-studied Fracture Risk Assessment Tool [1], failed to predict osteoporosis in 40-to-49-year-olds with HIV in a longitudinal European analysis [2]. The finding challenges current international guidelines recommending FRAX to screen HIV-positive men 40 to 49 years old and premenopausal HIV-positive women over 40 [3].
FRAX is an online algorithm that lets clinicians enter easily collected data to get a 10-year prediction of (1) hip fracture risk and (2) major osteoporotic fracture risk (involving spine, hip, wrist, or upper arm) [1]. In 2015 international HIV bone experts recommended FRAX screening for HIV-positive men and premenopausal women 40 to 49 years old to guide management and use of DXA scanning [3]. Notably, though, FRAX did not predict DXA-determined osteoporosis or prevalent fracture in older US men with HIV [4]. And two HIV bone mavens noted that "10-year FRAX risk for both major osteoporosis and hip fractures without bone mineral density generally [has] limited precision in predicting the presence of osteoporosis severe enough to initiate treatment" [5]. Guidelines recommend DXA scans for HIV-positive men 50 or older and for postmenopausal women with HIV [3].
University Medical Center Utrecht researchers began their FRAX analysis by focusing on HIV-positive 50- to 59-year-olds who had HIV for at least 10 years and recently had a DXA scan. Then they figured FRAX scores for participants when they were in their 40s by collecting the necessary data from 10 years earlier. Next the Utrecht team determined for which patients in their 40s FRAX would have called for DXA scanning by calculating a 10-year major osteoporotic fracture risk of 10% or greater. The analysis excluded sub-Saharan Africans because they did not have data from when they were 40 to 49, and it excluded people using corticosteroids, according to FRAX guidelines.
Among 126 people analyzed, osteoporosis developed in 23 (18.3%) during follow-up. Compared with participants without osteoporosis, the 23 with eventual osteoporosis had a significantly lower body mass index (22.1 versus 23.9 kg/m2, P = 0.016) and a lower nadir CD4 count (111 versus 194 CD4s, P = 0.02). But the groups did not differ in gender, age, years with HIV, excessive alcohol use, current smoking, or parental hip fracture.
Ten years before these 23 people with eventual osteoporosis had their DXA scan, none had a FRAX-predicted 10-year risk of major osteoporotic fracture. In other words, FRAX had a sensitivity of 0% in predicting future osteoporosis. FRAX-predicted major osteoporotic fracture risk and osteoporotic hip fracture risk were virtually identical in the group with versus without eventual osteoporosis regardless of whether participants' parents had a hip fracture. Moreover, median FRAX score at 40 to 49 years of age proved virtually identical in people who eventually had osteoporosis and in those who did not (3.3% and 3.4%, P = 0.55).
The Utrecht investigators believe their findings "show that FRAX is insufficient for the identification of (future) osteoporosis in younger HIV-infected patients." Therefore they argued that "FRAX should not be used in its current form in the international HIV guidelines." They called for more research to devise a useful screening strategy for osteoporosis in younger people with HIV.
1. FRAX. Fracture Risk Assessment Tool. https://www.sheffield.ac.uk/FRAX/
2. Van Welzen B , Anders J, Hoepelman A, Mudrikova T, Yesilay S. Very low sensitivity of Fracture Risk Assessment Tool in young HIV-infected patients: The need for new screening strategies. European Workshop on Healthy Living With HIV 2019. Barcelona. September 13-14, 2019. Abstract 6.
3. Brown TT, Hoy J, Borderi M, et al. Recommendations for evaluation and management of bone disease in HIV. Clin Infect Dis. 2015;60:1242-1251. https://academic.oup.com/cid/article-pdf/60/8/1242/16787300/civ010.pdf
4. Yin MT, Shiau S, Rimland D. Fracture prediction with modified-FRAX in older HIV-infected and uninfected men. J Acquir Immune Defic Syndr. 2016;72:513-520.
5. Yin MT, Falutz J. How to predict the risk of fracture in HIV? Curr Opin HIV AIDS. 2016;11:261-267.
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