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Fracture risk may be decreased by enzyme replacement therapy\u00a0(ERT) but not eliminated. When considering initiation of treatment, it is useful to know to what extent fixed patient-specific factors determine risk for future fractures beyond standard risk factors that change with time and treatment, such as decreased bone mineral density. We developed a tool called the GRAF score (Gaucher Risk Assessment for Fracture) that applies 5 widely available characteristics (sex, age at treatment initiation [ATI], time interval between diagnosis and treatment initiation, splenectomy status, history of pre-treatment bone crisis) and provides a practical method to assess future fracture risk when imiglucerase ERT is initiated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Inclusion criteria: GD1 patients in the International Collaborative Gaucher Group Gaucher Registry as of September 2019 initially treated with alglucerase\/imiglucerase; known splenectomy status; at least one skeletal assessment on treatment (3216 of 6422 patients). Data were analyzed by ATI group (&lt;\u200918,\u2009\u2265\u200918 to\u2009&lt;\u200950, or\u2009\u2265\u200950\u00a0years of age) using Cox proportional hazards regression with all 5 risk factors included in the multivariable model. A composite risk score was calculated by summing the contribution of each parameter weighted by the strength of its association (regression coefficient) with fracture risk.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Patients were followed from the date of treatment initiation (or age 18\u00a0years for patients if treatment started earlier) to the date of first adult fracture (n\u2009=\u2009288 first fracture endpoints), death, or end of follow-up. The GRAF score for each ATI group was associated with a 2.7-fold increased risk of adult fracture for each one-point increase (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.02 for\u2009&lt;\u200918 ATI, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001 for\u2009\u2265\u200918 to\u2009&lt;\u200950 ATI and\u2009\u2265\u200950 ATI).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The GRAF score is a tool to be used with bone density and other modifiable, non-GD-specific risk factors (e.g. smoking, alcohol intake, frailty) to inform physicians and previously untreated GD1 patients about risk for a future fracture after starting imiglucerase regardless of whether there is an eventual switch to an alternative ERT or to substrate reduction therapy. GRAF can also help predict the extent that fracture risk increases if initiation of treatment is further delayed.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-020-01656-6","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T14:44:04Z","timestamp":1613832244000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The International Collaborative Gaucher Group GRAF (Gaucher Risk Assessment for Fracture) score: a composite risk score for assessing adult fracture risk in imiglucerase-treated Gaucher disease type 1 patients"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9427-9900","authenticated-orcid":false,"given":"Patrick","family":"Deegan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aneal","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Jos\u00e9 Simon","family":"Camelo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie L.","family":"Batista","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neal","family":"Weinreb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,18]]},"reference":[{"issue":"18","key":"1656_CR1","doi-asserted-by":"publisher","first-page":"2835","DOI":"10.1001\/archinte.160.18.2835","volume":"160","author":"J Charrow","year":"2000","unstructured":"Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, et al. 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Informed consent was obtained from all subjects at the time of enrollment in the Registry.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"PD has received honoraria, travel reimbursement, and consulting fees from Sanofi Genzyme and is a member of the European Board of ICGG, which is sponsored by Sanofi Genzyme. AK has received research support, speaker fees, travel costs, and consulting fees from Sanofi Genzyme, Actelion, and Cytonet LLC; research support, speaker fees and travel costs from Shire HGT; consulting fees, travel costs and research support from Alexion, Biomarin, and Horizon; research support from Amicus, Idorsia, and Ultragenyx. JSC is a member of the International Advisory Board for ICGG sponsored by Sanofi Genzyme and has received educational grants for travel and conferences from Sanofi Genzyme. JLB is an employee of Sanofi Genzyme. NW has received research support, consultation fees, honoraria and travel reimbursement for attending advisory boards or for speaking from Sanofi Genzyme, Shire HGT, and Pfizer Corporation. He is a member of the North American and International Advisory Boards for the ICCG Gaucher Registry.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"92"}}