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On a genetic level, BS is caused by biallelic mutations in either <jats:italic>FKBP10<\/jats:italic> or <jats:italic>PLOD2<\/jats:italic>. <jats:italic>PLOD2<\/jats:italic> encodes the lysyl hydroxylase 2 (LH2) enzyme, which is responsible for the hydroxylation of cross\u2010linking lysine residues in fibrillar collagen telopeptide domains. This modification enables collagen to form chemically stable (permanent) intermolecular cross\u2010links in the extracellular matrix. Normal bone collagen develops a unique mix of such stable and labile lysyl\u2010oxidase\u2013mediated cross\u2010links, which contribute to bone strength, resistance to microdamage, and crack propagation, as well as the ordered deposition of mineral nanocrystals within the fibrillar collagen matrix. Bone from patients with BS caused by biallelic <jats:italic>FKBP10<\/jats:italic> mutations has been shown to have abnormal collagen cross\u2010linking; however, to date, no direct studies of human bone from BS caused by <jats:italic>PLOD2<\/jats:italic> mutations have been reported. Here the results from a study of a 4\u2010year\u2010old boy with BS caused by compound heterozygous mutations in <jats:italic>PLOD2<\/jats:italic> are discussed. Diminished hydroxylation of type I collagen telopeptide lysines but normal hydroxylation at triple\u2010helical sites was found. Consequently, stable trivalent cross\u2010links were essentially absent. Instead, allysine aldol dimeric cross\u2010links dominated as in normal skin collagen. Furthermore, in contrast to the patient's bone collagen, telopeptide lysines in cartilage type II collagen cross\u2010linked peptides from the patient's urine were normally hydroxylated. These findings shed light on the complex mechanisms that control the unique posttranslational chemistry and cross\u2010linking of bone collagen, and how, when defective, they can cause brittle bones and related connective tissue problems. \u00a9 2020 The Authors. <jats:italic>JBMR Plus<\/jats:italic> published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbm4.10454","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T21:52:03Z","timestamp":1608328323000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Abnormal Bone Collagen Cross\u2010Linking in Osteogenesis Imperfecta\/Bruck Syndrome Caused by Compound Heterozygous <scp><i>PLOD2<\/i><\/scp> Mutations"],"prefix":"10.1093","volume":"5","author":[{"given":"Charlotte","family":"Gistelinck","sequence":"first","affiliation":[{"name":"Department of Orthopaedics and 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