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Novel therapies and accurate predictors of response are needed. The primary objective of this study was to identify surrogate biomarkers of future change in orthopedic disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>As part of a 9\u2010year observational study of MPS I, range\u2010of\u2010motion (ROM), height, pelvic radiographs were measured annually. Biomarkers in year 1 were compared to healthy controls. Linear regression tested for associations of change in biomarkers over the first year with change in long\u2010term outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MPS I participants (N = 19) were age 5 to 16\u2009years and on average 6.9 \u00b1\u20092.9\u2009years post treatment initiation. Healthy controls (N = 51) were age 9 to 17\u2009years. Plasma IL\u20101\u03b2, TNF\u2010\u03b1, osteocalcin, pyridinolines, and deoxypyridinolines were higher in MPS than controls. Within MPS, progression of hip dysplasia was present in 46% to 77%. A 1 pg\/mL increase in IL\u20106 was associated with \u221222\u00b0\/year change in ROM (\u221228 to \u221215; <jats:italic>P<\/jats:italic> &lt;\u2009.001), a 20\u2009nmol\/mmol creatinine\/year increase in urine PYD was associated with a \u22120.024 Z\u2010score\/year change in height Z\u2010score (\u22120.043 to \u22120.005; <jats:italic>P<\/jats:italic> =\u2009.016), and a 20\u2009nmol\/mmol creatinine\/year increase in urine PYD was associated with a \u22122.0%\/year change in hip dysplasia measured by Reimers migration index (\u22123.8 to \u22120.1; <jats:italic>P<\/jats:italic> =\u2009.037).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Inflammatory cytokines are high in MPS I. IL\u20106 and PYD were associated with progression in joint contracture, short stature, and hip dysplasia over time. Once validated, these biomarkers may prove useful for predicting response to treatment of skeletal disease in MPS I.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmd2.12190","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T10:07:06Z","timestamp":1607422026000},"page":"89-99","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Biomarkers for prediction of skeletal disease progression in mucopolysaccharidosis type I"],"prefix":"10.1002","volume":"58","author":[{"given":"Troy C.","family":"Lund","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terence M.","family":"Doherty","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The Lundquist Institute at Harbor\u2010UCLA Medical Center  Torrance California 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