ppharmПедиатрическая фармакологияPediatric pharmacology1727-57762500-3089Издательство «ПедиатрЪ»10.15690/pf.v15i3.1902ppharm-1629Research ArticleОБЗОР ЛИТЕРАТУРЫREVIEWНесовершенный остеогенез: особенности диагностикиOsteogenesis Imperfecta: Diagnostic Featurehttps://orcid.org/0000-0002-6265-7281ИгнатовичО. Н.IgnatovichOlga N.

Игнатович Ольга Николаевна, врач-аспирант, отделение нефроурологических, метаболических болезней и заместительной почечной терапии

Адрес: 119991, Москва, Ломоносовский проспект, д. 2, стр. 3, тел.: +7 (499) 134-07-43

pochka_nczd@mail.ruhttps://orcid.org/0000-0002-2209-7531Намазова-БарановаЛ. С.Namazova-BaranovaLeyla S.https://orcid.org/0000-0002-2395-1322МаргиеваТ. В.МargievaТea V.ЯхяеваГ. Т.YakhyaevaGuzal Т.ЖурковаН. В.ZhurkovaNatalia V.СавостьяновК. В.SavostyanovКirill V.ПушковА. А.PushkovAlexander A.КротовИ. А.KrotovIvan A.Национальный медицинский исследовательский центр здоровья детейРоссияNational Medical Research Center of Children’s HealthRussian FederationНациональный медицинский исследовательский центр здоровья детей; Российский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияNational Medical Research Center of Children’s Health; Pirogov Russian National Research Medical UniversityRussian FederationНациональный медицинский исследовательский центр здоровья детейРоссияNational Medical Research Center of Children’s Health; Sechenov first Moscow State Medical University (Sechenov University)Russian Federation201806072018153224232Copyright © Игнатович О.Н., Намазова-Баранова Л.С., Маргиева Т.В., Яхяева Г.Т., Журкова Н.В., Савостьянов К.В., Пушков А.А., Кротов И.А., 20182018Игнатович О.Н., Намазова-Баранова Л.С., Маргиева Т.В., Яхяева Г.Т., Журкова Н.В., Савостьянов К.В., Пушков А.А., Кротов И.А.Ignatovich O.N., Namazova-Baranova L.S., Мargieva Т.V., Yakhyaeva G.Т., Zhurkova N.V., Savostyanov К.V., Pushkov A.A., Krotov I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pedpharma.ru/jour/article/view/1629

Несовершенный остеогенез — редкое генетически опосредованное заболевание соединительной ткани, характеризуемое частыми переломами, возникающими как у детей, так и у взрослых вследствие повышенной хрупкости костей. В настоящее время известно, что генетической основой заболевания являются мутации в 20 генах, из них COL1A1 и COL1A2 ответственны за 90% случаев развития патологии. Однако, диагностика несовершенного остеогенеза основана главным образом на клинических и рентгенологических данных. Вспомогательное значение могут иметь некоторые лабораторные показатели крови и мочи, низкая специфичность которых ограничивает их широкое использование. Нерешенной проблемой остается и своевременная дифференциальная диагностика несовершенного остеогенеза. В настоящее время стандарт ведения больных с несовершенным остеогенезом подразумевает мультидисциплинарный подход с привлечением таких специалистов, как педиатр, эндокринолог, хирург-ортопед, специалисты по реабилитации, стоматолог, генетик, социальный работник/психолог, что позволяет выполнить необходимое обследование пациента, выставить точный диагноз и вовремя начать адекватную терапию.

КОНФЛИКТ ИНТЕРЕСОВ

Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи.

Osteogenesis imperfect (OI) is a rare genetic disease of connective tissue, the main manifestation are fractures that are developing due to increased bone fragility in both children and adults. Currently, it is known that the genetic basis of the disease in 90% of cases are violations in the genes COL1A1 and COL1A2. Diagnosis of this disease is mostly based on clinical and radiological data; some laboratory parameters of blood and urine can provide additional information but, due to the low specificity, these tests are not widely used in clinical practice when diagnosing the bone pathology. Separate extensive problem is the realization of timely differential diagnosis followed by the establishment of correct diagnosis and development of the right tactics. Currently, the standard of management of patients with OI is a multidisciplinary approach that allows to perform the necessary examination of a child, to make an accurate diagnosis, and start the therapy in time. A practitioneer should have sufficient knowledge about the disease and be able to apply it practically to realize the treatment tactics.

детинесовершенный остеогенезпереломыостеопорозостеопетрозголубые склерынесовершенный дентиногенезмаркерыкостное ремоделированиеbone fracturesosteoporosisosteopetrosisblue scleraed entinogenesis imperfectamarkers of bone turnoverReferencesRauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. 2004;363(9418):1377–1385. doi: 10.1016/S0140- 6736(04)16051-0.Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. 2004;363(9418):1377–1385. doi: 10.1016/S0140- 6736(04)16051-0.Zambrano Marina B, Félix Têmis M, de Mello Elza D. Difference between between methods for estimation of basal metabolic rate and body composition in pediatric patients with osteogenesis imperfecta. Ann Nutr Metab. 2018;72(1):21–29. doi: 10.1159/000481918.Zambrano Marina B, Félix Têmis M, de Mello Elza D. Difference between between methods for estimation of basal metabolic rate and body composition in pediatric patients with osteogenesis imperfecta. Ann Nutr Metab. 2018;72(1):21–29. doi: 10.1159/000481918.Rizkallah J, Schwartz S, Rauch F, et al. Evaluation of the severity of malocclusions in children affected by osteogenesis imperfecta with the peer assessment rating and discrepancy indexes. Am J Orthod Dentofacial Orthop. 2013;143(3):336–341 doi: 10.1016/j. ajodo.2012.10.016.Rizkallah J, Schwartz S, Rauch F, et al. Evaluation of the severity of malocclusions in children affected by osteogenesis imperfecta with the peer assessment rating and discrepancy indexes. Am J Orthod Dentofacial Orthop. 2013;143(3):336–341 doi: 10.1016/j. ajodo.2012.10.016.Bardai G, Moffatt P, Glorieux FH, Rauch F. DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum. Osteoporos Int. 2016;27(12):3607–3613 doi: 10.1007/s00198-016-3709-1.Bardai G, Moffatt P, Glorieux FH, Rauch F. DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum. Osteoporos Int. 2016;27(12):3607–3613 doi: 10.1007/s00198-016-3709-1.Forlino A, Marini JC. Osteogenesis imperfecta. Lancet. 2016;387(10028):1657–1671. doi: 10.1016/S0140- 6736(15)00728-X.Forlino A, Marini JC. Osteogenesis imperfecta. Lancet. 2016;387(10028):1657–1671. doi: 10.1016/S0140- 6736(15)00728-X.Marini JC. Osteogenesis imperfecta. In: Nelson WE, Behrman RE, Kliegman RM, Arvin AM, editors. Nelson textbook of pediatrics. 18th ed. Philadelphia, USA: W.B. Saunders Company; 2007. pp. 2887–2890.Marini JC. Osteogenesis imperfecta. In: Nelson WE, Behrman RE, Kliegman RM, Arvin AM, editors. Nelson textbook of pediatrics. 18th ed. Philadelphia, USA: W.B. Saunders Company; 2007. pp. 2887–2890.iofbonehealth.org [Internet]. Radiological assessment and bone turnover markers. Radiological assessment of vertebral fracture [cited 2018 Apr 12]. Available from: https://www.iofbonehealth.org/ radiological-assessment-and-bone-turnover-markers.iofbonehealth.org [Internet]. Radiological assessment and bone turnover markers. Radiological assessment of vertebral fracture [cited 2018 Apr 12]. Available from: https://www.iofbonehealth.org/ radiological-assessment-and-bone-turnover-markers.ifcc.org [Internet]. International Osteoporosis Foundation. IOF-IFCC study summarizes fracture prediction strength of reference bone turnover markers [cited 2018 Apr 12]. Available from: http://www.ifcc.org/media/252902/BTM-release-Feb2014-final.pdf.ifcc.org [Internet]. International Osteoporosis Foundation. IOF-IFCC study summarizes fracture prediction strength of reference bone turnover markers [cited 2018 Apr 12]. Available from: http://www.ifcc.org/media/252902/BTM-release-Feb2014-final.pdf.Szulc P, Delmas PD. Biochemical markers of bone turnover: potential use in the investigation and management of postmenopausal osteoporosis. Osteoporos Int. 2008;19(12):1683– 1704. doi: 10.1007/s00198-008-0660-9.Szulc P, Delmas PD. Biochemical markers of bone turnover: potential use in the investigation and management of postmenopausal osteoporosis. Osteoporos Int. 2008;19(12):1683– 1704. doi: 10.1007/s00198-008-0660-9.Bauer DC. Biochemical markers of bone turnover: the Study of Osteoporotic Fracture. In: Eastell R, Baumann M, Hoyle N, Wieczorek L, editors. Bone markers — biochemical and clinical perspectives. London, UK: Martin Dunitz; 2001. pp. 219–223.Bauer DC. Biochemical markers of bone turnover: the Study of Osteoporotic Fracture. In: Eastell R, Baumann M, Hoyle N, Wieczorek L, editors. Bone markers — biochemical and clinical perspectives. London, UK: Martin Dunitz; 2001. pp. 219–223.Dobnig H, Piswanger-Solkner JC, Obermayer-Pietsch B, et al. Hip and nonvertebral fracture prediction in nursing home patients: role of bone ultrasound and bone marker measurements. J Clin Endocrinol Metab. 2007;92(5):1678–1686. doi: 10.1210/jc.2006- 2079.Dobnig H, Piswanger-Solkner JC, Obermayer-Pietsch B, et al. Hip and nonvertebral fracture prediction in nursing home patients: role of bone ultrasound and bone marker measurements. J Clin Endocrinol Metab. 2007;92(5):1678–1686. doi: 10.1210/jc.2006- 2079.Tromp AM, Ooms ME, Popp-Snijders C, et al. Predictors of fractures in elderly women. Osteoporos Int. 2000;11(2):134–140. doi: 10.1007/PL00004174.Tromp AM, Ooms ME, Popp-Snijders C, et al. Predictors of fractures in elderly women. Osteoporos Int. 2000;11(2):134–140. doi: 10.1007/PL00004174.Martin E, Shapiro JR. Osteogenesis imperfecta:epidemiology and pathophysiology. Curr Osteoporos Rep. 2007;5(3):91–97.Martin E, Shapiro JR. Osteogenesis imperfecta:epidemiology and pathophysiology. Curr Osteoporos Rep. 2007;5(3):91–97.Monti E, Mottes M, Fraschini P, et al. Current and emerging treatments for the management of osteogenesis imperfecta. Ther Clin Risk Manag. 2010;6:367–381. doi: 10.2147/TCRM.S5932.Monti E, Mottes M, Fraschini P, et al. Current and emerging treatments for the management of osteogenesis imperfecta. Ther Clin Risk Manag. 2010;6:367–381. doi: 10.2147/TCRM.S5932.Basel D, Steiner RD. Osteogenesis imperfecta: recent findings shed new light on this once well-understood condition. Genet Med. 2009;11(6):375–385. doi: 10.1097/GIM.0b013e3181a1ff7b.Basel D, Steiner RD. Osteogenesis imperfecta: recent findings shed new light on this once well-understood condition. Genet Med. 2009;11(6):375–385. doi: 10.1097/GIM.0b013e3181a1ff7b.Byers PH, Tsipouras P, Bonadio JF, et al. Perinatal lethal Osteogenesis Imperfecta (OI Type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen. Am J Hum Genet. 1988;42(2):237–248.Byers PH, Tsipouras P, Bonadio JF, et al. Perinatal lethal Osteogenesis Imperfecta (OI Type II): a biochemically heterogeneous disorder usually due to new mutations in the genes for type I collagen. Am J Hum Genet. 1988;42(2):237–248.Van Dijk FS, Sillence DO. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A. 2014;164A(6):1470–1481. doi: 10.1002/ajmg.a.36545.Van Dijk FS, Sillence DO. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A. 2014;164A(6):1470–1481. doi: 10.1002/ajmg.a.36545.Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979;16(2):101–116.Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979;16(2):101–116.Homan EP, Rauch F, Grafe I, et al. Mutations in SERPINF1 cause osteogenesis imperfecta type VI. J Bone Miner Res. 2011;26(12):2798–2803. doi: 10.1002/jbmr.487.Homan EP, Rauch F, Grafe I, et al. Mutations in SERPINF1 cause osteogenesis imperfecta type VI. J Bone Miner Res. 2011;26(12):2798–2803. doi: 10.1002/jbmr.487.Rauch F, Moffatt P, Cheung M, et al. Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of theIFITM5c.–14C>T mutation in all patients. J Med Genet. 2012;50(1):21–24. doi: 10.1136/jmedgenet-2012-101307.Rauch F, Moffatt P, Cheung M, et al. Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of theIFITM5c.–14C>T mutation in all patients. J Med Genet. 2012;50(1):21–24. doi: 10.1136/jmedgenet-2012-101307.Chang PC, Lin SY, Hsu KH. The craniofacial characteristics of osteogenesis imperfecta patients. Eur J Ort. 2006;29(3):232–237. doi: 10.1093/ejo/cjl035.Chang PC, Lin SY, Hsu KH. The craniofacial characteristics of osteogenesis imperfecta patients. Eur J Ort. 2006;29(3):232–237. doi: 10.1093/ejo/cjl035.Rizkallah J, Schwartz S, Rauch F, et al. Evaluation of the severity of malocclusions in children affected by osteogenesis imperfecta with the peer assessment rating and discrepancy indexes. Am J Orthod Dentofacial Orthop. 2013;143(3):336–341. doi: 10.1016/j. ajodo.2012.10.016.Rizkallah J, Schwartz S, Rauch F, et al. Evaluation of the severity of malocclusions in children affected by osteogenesis imperfecta with the peer assessment rating and discrepancy indexes. Am J Orthod Dentofacial Orthop. 2013;143(3):336–341. doi: 10.1016/j. ajodo.2012.10.016.Thomas IH, DiMeglio LA. Advances in the classification and treatment of osteogenesis imperfecta. Curr Osteoporos Rep. 2016;14(1):1–9. doi: 10.1007/s11914-016-0299-y.Thomas IH, DiMeglio LA. Advances in the classification and treatment of osteogenesis imperfecta. Curr Osteoporos Rep. 2016;14(1):1–9. doi: 10.1007/s11914-016-0299-y.Trejo P, Rauch F. Osteogenesis imperfecta in children and adolescents — new developments in diagnosis and treatment. Osteoporos Int. 2016;27(12):3427–3437. doi: 10.1007/s00198- 016-3723-3.Trejo P, Rauch F. Osteogenesis imperfecta in children and adolescents — new developments in diagnosis and treatment. Osteoporos Int. 2016;27(12):3427–3437. doi: 10.1007/s00198- 016-3723-3.Lindahl K, Langdahl B, Ljunggren O, Kindmark A. Therapy of endocrine disease: treatment of osteogenesis imperfecta in adults. Eur J Endocrinol. 2014;171(2):R79–R90. doi: 10.1530/eje-14- 0017.Lindahl K, Langdahl B, Ljunggren O, Kindmark A. Therapy of endocrine disease: treatment of osteogenesis imperfecta in adults. Eur J Endocrinol. 2014;171(2):R79–R90. doi: 10.1530/eje-14- 0017.Marini JC, Forlino A, Cabral WA, et al. Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat. 2007;28(3):209–221. doi: 10.1002/humu.20429.Marini JC, Forlino A, Cabral WA, et al. Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat. 2007;28(3):209–221. doi: 10.1002/humu.20429.Cho TJ, Lee KE, Lee SK. A single recurrent mutation in the 5’-UTR of IFITM5 causes osteogenesis imperfecta type V. Am J Hum Genet. 2012;91(2):343–348. doi: 10.1016/j.ajhg.2012.06.005.Cho TJ, Lee KE, Lee SK. A single recurrent mutation in the 5’-UTR of IFITM5 causes osteogenesis imperfecta type V. Am J Hum Genet. 2012;91(2):343–348. doi: 10.1016/j.ajhg.2012.06.005.Semler O, Garbes L, Keupp K, et al. A mutation in the 5’-UTR of IFITM5 creates an in-frame start codon and causes autosomaldominant osteogenesis imperfecta type V with hyperplastic callus. Am J Hum Genet. 2012;91(2):349–357. doi: 10.1016/j. ajhg.2012.06.011.Semler O, Garbes L, Keupp K, et al. A mutation in the 5’-UTR of IFITM5 creates an in-frame start codon and causes autosomaldominant osteogenesis imperfecta type V with hyperplastic callus. Am J Hum Genet. 2012;91(2):349–357. doi: 10.1016/j. ajhg.2012.06.011.Becker J, Semler O, Gilissen C, et al. Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. 2011;88(3):362–371. doi: 10.1016/j.ajhg.2011.01.015.Becker J, Semler O, Gilissen C, et al. Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. 2011;88(3):362–371. doi: 10.1016/j.ajhg.2011.01.015.Pyott SM, Schwarze U, Christiansen HE, et al. Mutations in PPIB (cyclophilin B) delay type I procollagen chain association and result in perinatal lethal to moderate osteogenesis imperfecta phenotypes. Hum Mol Genet. 2011;20(8):1595–1609. doi: 10.1093/hmg/ ddr037.Pyott SM, Schwarze U, Christiansen HE, et al. Mutations in PPIB (cyclophilin B) delay type I procollagen chain association and result in perinatal lethal to moderate osteogenesis imperfecta phenotypes. Hum Mol Genet. 2011;20(8):1595–1609. doi: 10.1093/hmg/ ddr037.Alanay Y, Avaygan H, Camacho N, et al. Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. 2010;86(4):551–559. doi: 10.1016/j.ajhg.2010.02.022.Alanay Y, Avaygan H, Camacho N, et al. Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. 2010;86(4):551–559. doi: 10.1016/j.ajhg.2010.02.022.Marini JC, Reich A, Smith SM. Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation. Curr Opin Pediatr. 2014;26(4):500–507. doi: 10.1097/ MOP.0000000000000117.Marini JC, Reich A, Smith SM. Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation. Curr Opin Pediatr. 2014;26(4):500–507. doi: 10.1097/ MOP.0000000000000117.Kadler KE, Holmes DF, Trotter JA, Chapman JA. Collagen fibril formation. Biochem J. 1996;316(Pt 1):1–11. doi: 10.1042/ bj3160001.Kadler KE, Holmes DF, Trotter JA, Chapman JA. Collagen fibril formation. Biochem J. 1996;316(Pt 1):1–11. doi: 10.1042/ bj3160001.Byers PH. Osteogenesis imperfecta: perspectives and opportunities. Curr Opin Pediatr. 2000;12(6):603–609. doi: 10.1097/00008480-200012000-00016.Byers PH. Osteogenesis imperfecta: perspectives and opportunities. Curr Opin Pediatr. 2000;12(6):603–609. doi: 10.1097/00008480-200012000-00016.Rowe DW, Shapiro JR. Osteogenesis imperfecta. In: Avioli LV, Krane SM, editors. Metabolic bone disease and clinically related disorders. 3rd ed. San Diego: Academic Press; 1998. pp. 651–695.Rowe DW, Shapiro JR. Osteogenesis imperfecta. In: Avioli LV, Krane SM, editors. Metabolic bone disease and clinically related disorders. 3rd ed. San Diego: Academic Press; 1998. pp. 651–695.Gioia R, Panaroni C, Besio R, et al. Impaired osteoblastogenesis in a murine model of dominant osteogenesis imperfecta: a new target for osteogenesis imperfecta pharmacological therapy. Stem Cells. 2012;30(7):1465–1476. doi: 10.1002/stem.1107.Gioia R, Panaroni C, Besio R, et al. Impaired osteoblastogenesis in a murine model of dominant osteogenesis imperfecta: a new target for osteogenesis imperfecta pharmacological therapy. Stem Cells. 2012;30(7):1465–1476. doi: 10.1002/stem.1107.Canty EG. Procollagen trafficking, processing and fibrillogenesis. J Cell Sci. 2005;118(7):1341–1353. doi: 10.1242/jcs.01731.Canty EG. Procollagen trafficking, processing and fibrillogenesis. J Cell Sci. 2005;118(7):1341–1353. doi: 10.1242/jcs.01731.Andriotis OG, Chang SW, Vanleene M, et al. Structure–mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model. J R Soc Interface. 2015;12(111):20150701. doi: 10.1098/rsif.2015.0701.Andriotis OG, Chang SW, Vanleene M, et al. Structure–mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model. J R Soc Interface. 2015;12(111):20150701. doi: 10.1098/rsif.2015.0701.Lindahl K, Åström E, Rubin C-J, et al. Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta. Eur J Hum Genet. 2015;23(8):1042–1050. doi: 10.1038/ejhg.2015.81.Lindahl K, Åström E, Rubin C-J, et al. Genetic epidemiology, prevalence, and genotype–phenotype correlations in the Swedish population with osteogenesis imperfecta. Eur J Hum Genet. 2015;23(8):1042–1050. doi: 10.1038/ejhg.2015.81.Bailey A. Molecular mechanisms of ageing in connective tissues. Mech Ageing Dev. 2001;122(7):735–755. doi: 10.1016/s0047- 6374(01)00225-1.Bailey A. Molecular mechanisms of ageing in connective tissues. Mech Ageing Dev. 2001;122(7):735–755. doi: 10.1016/s0047- 6374(01)00225-1.Huang RP, Ambrose CG, Sullivan E, Haynes RJ. Functional significance of bone density measurements in children with osteogenesis imperfecta. J Bone Joint Surg Am. 2006;88:1324– 1330. doi: 10.2106/JBJS.E.00333.Huang RP, Ambrose CG, Sullivan E, Haynes RJ. Functional significance of bone density measurements in children with osteogenesis imperfecta. J Bone Joint Surg Am. 2006;88:1324– 1330. doi: 10.2106/JBJS.E.00333.Bachrach LK. Consensus and controversy regarding osteoporosis in the pediatric population. Endocr Pract. 2007;13(5):513–520. doi: 10.4158/EP.13.5.513.Bachrach LK. Consensus and controversy regarding osteoporosis in the pediatric population. Endocr Pract. 2007;13(5):513–520. doi: 10.4158/EP.13.5.513.Viora E, Sciarrone A, Bastonero S, et al. Increased nuchal translucency in the first trimester as a sign of osteogenesis imperfecta. Am J Med Genet. 2002;109(4):336–337. doi: 10.1002/ajmg.1033.Viora E, Sciarrone A, Bastonero S, et al. Increased nuchal translucency in the first trimester as a sign of osteogenesis imperfecta. Am J Med Genet. 2002;109(4):336–337. doi: 10.1002/ajmg.1033.Marini JC, Cabral WA, Barnes AM. Null mutations in LEPRE1 and CRTAP cause severe recessive osteogenesis imperfecta. Cell Tissue Res. 2010;339(1):59–70. doi: 10.1007/s00441-009-0872-0.Marini JC, Cabral WA, Barnes AM. Null mutations in LEPRE1 and CRTAP cause severe recessive osteogenesis imperfecta. Cell Tissue Res. 2010;339(1):59–70. doi: 10.1007/s00441-009-0872-0.van Dijk FS, Byers PH, Dalgleish R, et al. EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta. Eur J Hum Genet. 2012;20(1):11–19. doi: 10.1038/ejhg.2011.141.van Dijk FS, Byers PH, Dalgleish R, et al. EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta. Eur J Hum Genet. 2012;20(1):11–19. doi: 10.1038/ejhg.2011.141.Vasikaran S, Eastell R, Bruyère O, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporosis Int. 2011;22:391–420. doi: 10.1007/s00198-010-1501-1.Vasikaran S, Eastell R, Bruyère O, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporosis Int. 2011;22:391–420. doi: 10.1007/s00198-010-1501-1.Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev. 2005;26(4):97–122.Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev. 2005;26(4):97–122.Eastell R, Walsh JS. Bone: microarchitecture of bone predicts fractures in older women. Nat Rev Endocrinol. 2018;14(5):255– 256. doi: 10.1038/nrendo.2018.27.Eastell R, Walsh JS. Bone: microarchitecture of bone predicts fractures in older women. Nat Rev Endocrinol. 2018;14(5):255– 256. doi: 10.1038/nrendo.2018.27.Robins SP. Fibrillogenesis and maturation of collagens. In: Seibel MJ, Robins SP, Bilezikian JP, editors. Dynamics of bone and cartilage metabolism. San Diego: Academic Press; 1999. pp. 31–42. doi: 10.1016/B978-012088562-6/50002-9.Robins SP. Fibrillogenesis and maturation of collagens. In: Seibel MJ, Robins SP, Bilezikian JP, editors. Dynamics of bone and cartilage metabolism. San Diego: Academic Press; 1999. pp. 31–42. doi: 10.1016/B978-012088562-6/50002-9.Szulc P, Delmas P. Biochemical markers of bone turnover: potential use in the investigation and management of ostmenopausal osteoporosis. Osteoporos Int. 2008;19:1683–1704. doi: 10.1007/ s00198-008-0660-9.Szulc P, Delmas P. Biochemical markers of bone turnover: potential use in the investigation and management of ostmenopausal osteoporosis. Osteoporos Int. 2008;19:1683–1704. doi: 10.1007/ s00198-008-0660-9.Garnero P, Vergnaud P, Hoyle N. Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. Clin Chem. 2008;54(1):188–196. doi: 10.1373/clinchem.2007.094953.Garnero P, Vergnaud P, Hoyle N. Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. Clin Chem. 2008;54(1):188–196. doi: 10.1373/clinchem.2007.094953.Garnero P, Ferreras M, Karsdal MA, et al. The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation. J Bone Miner Res. 2003;18(5):859–867. doi: 10.1359/jbmr.2003.18.5.859.Garnero P, Ferreras M, Karsdal MA, et al. The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation. J Bone Miner Res. 2003;18(5):859–867. doi: 10.1359/jbmr.2003.18.5.859.Gajewska J, Ambroszkiewicz J, Laskowska-Klita T. Osteoprotegerin and C-telopeptide of type I collagen in polish healthy children and adolescents. Adv Med Sci. 2006;51:269–272.Gajewska J, Ambroszkiewicz J, Laskowska-Klita T. Osteoprotegerin and C-telopeptide of type I collagen in polish healthy children and adolescents. Adv Med Sci. 2006;51:269–272.Halleen JM, Alatalo SL, Suominen H, et al. Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption. J Bone Miner Res. 2000;15:1337–1345. doi: 10.1359/ jbmr.2000.15.7.1337.Halleen JM, Alatalo SL, Suominen H, et al. Tartrate-resistant acid phosphatase 5b: a novel serum marker of bone resorption. J Bone Miner Res. 2000;15:1337–1345. doi: 10.1359/ jbmr.2000.15.7.1337.Kaija H. Tartrate-resistant acid phosphatase: three-dimensional structure and structure-based functional studies. Studies on the enzyme using recombinant protein produced by baculovirus expression vector system in insect cells. Oulu, Finland: University of Oulu; 2002. pp. 27–30. doi: 10.1359/jbmr.1999.14.3.424.Kaija H. Tartrate-resistant acid phosphatase: three-dimensional structure and structure-based functional studies. Studies on the enzyme using recombinant protein produced by baculovirus expression vector system in insect cells. Oulu, Finland: University of Oulu; 2002. pp. 27–30. doi: 10.1359/jbmr.1999.14.3.424.Capeller B, Caffier H, Sutterlin MW, Dietl J. Evaluation of tartrate-resistant acid phosphatase (TRAP) 5b serum marker of bone metastases in human breast cancer. Anticancer Res. 2003;23(2A):1011–1015.Capeller B, Caffier H, Sutterlin MW, Dietl J. Evaluation of tartrate-resistant acid phosphatase (TRAP) 5b serum marker of bone metastases in human breast cancer. Anticancer Res. 2003;23(2A):1011–1015.Delmas PD, Eastell R, Garnero P, et al. The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int. 2000;11 Suppl 6:S2–17.Delmas PD, Eastell R, Garnero P, et al. The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int. 2000;11 Suppl 6:S2–17.Baumgrass R, Williamson MK, Price PA. Identification of peptide fragments generated by digestion of bovine and human osteocalcin with the lysosomal proteinases cathepsin B, D, L, H, and S. J Bone Miner Res. 1997;12:447–455. doi: 10.1359/jbmr.1997.12.3.447.Baumgrass R, Williamson MK, Price PA. Identification of peptide fragments generated by digestion of bovine and human osteocalcin with the lysosomal proteinases cathepsin B, D, L, H, and S. J Bone Miner Res. 1997;12:447–455. doi: 10.1359/jbmr.1997.12.3.447.Pedersen BJ, Schlemmer A, Hassager C, Christiansen C. Changes in the carboxyl-terminal propeptide of type I procollagen and other markers of bone formation upon five days of bed rest. Bone. 1995;17(1):91–95. doi: 10.1016/8756-3282(95)00149-8.Pedersen BJ, Schlemmer A, Hassager C, Christiansen C. Changes in the carboxyl-terminal propeptide of type I procollagen and other markers of bone formation upon five days of bed rest. Bone. 1995;17(1):91–95. doi: 10.1016/8756-3282(95)00149-8.Garnero P, Fledelius C, Gineyts E, et al. Decreased betaisomerization of the C-terminal telopeptide of type I collagen alpha 1 chain in Paget’s disease of bone. J Bone Miner Res. 1997;12(9):1407–1415. doi: 10.1359/jbmr.1997.12.9.1407.Garnero P, Fledelius C, Gineyts E, et al. Decreased betaisomerization of the C-terminal telopeptide of type I collagen alpha 1 chain in Paget’s disease of bone. J Bone Miner Res. 1997;12(9):1407–1415. doi: 10.1359/jbmr.1997.12.9.1407.Garnero P, Bauer DC, Mareau E, et al. Effects of PTH and alendronate on type I collagen isomerization in postmenopausal women with osteoporosis: the PaTH study. J Bone Miner Res. 2008;23(9):1442–1448.doi: 10.1359/jbmr.080413.Garnero P, Bauer DC, Mareau E, et al. Effects of PTH and alendronate on type I collagen isomerization in postmenopausal women with osteoporosis: the PaTH study. J Bone Miner Res. 2008;23(9):1442–1448.doi: 10.1359/jbmr.080413.Freisinger P, Stanescu V, Jacob B, et al. Achondrogenesis type IB (Fraccaro): study of collagen in the tissue and in chondrocytes cultured in agarose. Am J Med Genet. 1994;49(4):439–446. doi: 10.1002/ajmg.1320490418.Freisinger P, Stanescu V, Jacob B, et al. Achondrogenesis type IB (Fraccaro): study of collagen in the tissue and in chondrocytes cultured in agarose. Am J Med Genet. 1994;49(4):439–446. doi: 10.1002/ajmg.1320490418.Waller S, Kurzawinski T, Spitz L, et al. Neonatal severe hyperparathyroidism: genotype/phenotype correlation and the use of pamidronate as rescue therapy. Eur J Pediatr. 2004;163(10):589– 594. doi: 10.1007/s00431-004-1491-0.Waller S, Kurzawinski T, Spitz L, et al. Neonatal severe hyperparathyroidism: genotype/phenotype correlation and the use of pamidronate as rescue therapy. Eur J Pediatr. 2004;163(10):589– 594. doi: 10.1007/s00431-004-1491-0.Whyte MP. Hypophosphatasia: an overview for 2017. Bone. 2017;102:15–25. doi: 10.1016/j.bone.2017.02.011.Whyte MP. Hypophosphatasia: an overview for 2017. Bone. 2017;102:15–25. doi: 10.1016/j.bone.2017.02.011.Schmidt T, Amling M, Barvencik F. Hypophosphatasia: what is currently available for treatment? Internist (Berl). 2016;57(12):1145–1154. doi: 10.1007/s00108-016-0147-2.Schmidt T, Amling M, Barvencik F. Hypophosphatasia: what is currently available for treatment? Internist (Berl). 2016;57(12):1145–1154. doi: 10.1007/s00108-016-0147-2.Millán JL, Narisawa S, Lemire I, et al. Enzyme replacement therapy for murine hypophosphatasia. J Bone Miner Res. 2008;23(6):777– 787. doi: 10.1359/jbmr.071213.Millán JL, Narisawa S, Lemire I, et al. Enzyme replacement therapy for murine hypophosphatasia. J Bone Miner Res. 2008;23(6):777– 787. doi: 10.1359/jbmr.071213.Paterson CR, McAllion SJ. Classical osteogenesis imperfecta and allegations of nonaccidental injury. Clin Orthop Relat Res. 2006;452:260–264. doi: 10.1097/01.blo.0000229344.79963.31.Paterson CR, McAllion SJ. Classical osteogenesis imperfecta and allegations of nonaccidental injury. Clin Orthop Relat Res. 2006;452:260–264. doi: 10.1097/01.blo.0000229344.79963.31.Jerry R. Dwek, the radiographic approach to child abuse. Clin Orthop Relat Res. 2011;469(3):776–789. doi: 10.1007/s11999- 010-1414-5.Jerry R. Dwek, the radiographic approach to child abuse. Clin Orthop Relat Res. 2011;469(3):776–789. doi: 10.1007/s11999- 010-1414-5.van Dijk FS, Pals G, van Rijn RR, et al. Classification of osteogenesis imperfecta revisited. Eur J Med Genet. 2010;53(1):1– 5. doi: 10.1016/j.ejmg.2009.10.007.van Dijk FS, Pals G, van Rijn RR, et al. Classification of osteogenesis imperfecta revisited. Eur J Med Genet. 2010;53(1):1– 5. doi: 10.1016/j.ejmg.2009.10.007.Steiner RD, Pepin M, Byers PH. Studies of collagen synthesis and structure in the differentiation of child abuse from osteogenesis imperfecta. J Pediatr. 1996;128(4):542–547. doi: 10.1016/S0022- 3476(96)70367-0.Steiner RD, Pepin M, Byers PH. Studies of collagen synthesis and structure in the differentiation of child abuse from osteogenesis imperfecta. J Pediatr. 1996;128(4):542–547. doi: 10.1016/S0022- 3476(96)70367-0.Mokete L, Robertson A, Viljoen D, Beighton P. Bruck syndrome: congenital joint contractures with bone fragility. J Orthop Sci. 2005;10(6):641–646. doi: 10.1007/s00776-005-0958-9.Mokete L, Robertson A, Viljoen D, Beighton P. Bruck syndrome: congenital joint contractures with bone fragility. J Orthop Sci. 2005;10(6):641–646. doi: 10.1007/s00776-005-0958-9.Colombi M, Dordoni C, Cinquina V, et al. A classical EhlersDanlos syndrome family with incomplete presentation diagnosed by molecular testing. Eur J Med Genet. 2018;61(1):17–20. doi: 10.1016/j.ejmg.2017.10.005.Colombi M, Dordoni C, Cinquina V, et al. A classical EhlersDanlos syndrome family with incomplete presentation diagnosed by molecular testing. Eur J Med Genet. 2018;61(1):17–20. doi: 10.1016/j.ejmg.2017.10.005.Cole DE, Carpenter TO. Bone fragility, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features: a newly recognized type of osteogenesis imperfecta. J Pediatr. 1987;110(1):76–80. doi: 10.1016/s0022-3476(87)80292-5.Cole DE, Carpenter TO. Bone fragility, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features: a newly recognized type of osteogenesis imperfecta. J Pediatr. 1987;110(1):76–80. doi: 10.1016/s0022-3476(87)80292-5.Frontali M, Stomeo C, Dallapiccola B. Osteoporosis-pseudoglioma syndrome: report of three affected sibs and an overview. Am J Med Genet. 1985;22(1):35–47. doi: 10.1002/ajmg.1320220104.Frontali M, Stomeo C, Dallapiccola B. Osteoporosis-pseudoglioma syndrome: report of three affected sibs and an overview. Am J Med Genet. 1985;22(1):35–47. doi: 10.1002/ajmg.1320220104.Lee DH, Wenkert D, Whyte MP, et al. Congenital blindness and osteoporosis-pseudoglioma syndrome. J AAPOS. 2003;7(1):75–77. doi: 10.1067/mpa.2003.S109185310300051X.Lee DH, Wenkert D, Whyte MP, et al. Congenital blindness and osteoporosis-pseudoglioma syndrome. J AAPOS. 2003;7(1):75–77. doi: 10.1067/mpa.2003.S109185310300051X.Teebi AS, Al-Awadi SA, Marafie MJ, et al. Osteoporosis-pseudoglioma syndrome with congenital heart disease: a new association. J Med Genet. 1988;25(1):32–36. doi: 10.1136/jmg.25.1.32.Teebi AS, Al-Awadi SA, Marafie MJ, et al. Osteoporosis-pseudoglioma syndrome with congenital heart disease: a new association. J Med Genet. 1988;25(1):32–36. doi: 10.1136/jmg.25.1.32.Hussain MM, Strickland DK, Bakillah A. The mammalian lowdensity lipoprotein receptor family. Annu Rev Nutr. 1999;19:141– 172. doi: 10.1146/annurev.nutr.19.1.141.Hussain MM, Strickland DK, Bakillah A. The mammalian lowdensity lipoprotein receptor family. Annu Rev Nutr. 1999;19:141– 172. doi: 10.1146/annurev.nutr.19.1.141.Allen CM, Claman L, Feldman R. The acro-osteolysis (Hadju-Cheney) syndrome. Review of the literature and report of a case. J Periodontol. 1984;55(4):224–229. doi: 10.1902/ jop.1984.55.4.224.Allen CM, Claman L, Feldman R. The acro-osteolysis (Hadju-Cheney) syndrome. Review of the literature and report of a case. J Periodontol. 1984;55(4):224–229. doi: 10.1902/ jop.1984.55.4.224.Armstrong L, Jimenez C, Hunter AG. A boy with developmental delay, malformations, and evidence of a connective tissue disorder: possibly a new type of cutis laxa. Am J Med Genet. 2003;119A:57– 62. doi: 10.1002/ajmg.a.10175.Armstrong L, Jimenez C, Hunter AG. A boy with developmental delay, malformations, and evidence of a connective tissue disorder: possibly a new type of cutis laxa. Am J Med Genet. 2003;119A:57– 62. doi: 10.1002/ajmg.a.10175.Paul R, Kapoor S, Puri R, Bijarnia S. Gerodermia osteodysplastica. Indian J Pediatr. 2004;71(12):e77–79.Paul R, Kapoor S, Puri R, Bijarnia S. Gerodermia osteodysplastica. Indian J Pediatr. 2004;71(12):e77–79.Villa А, Pangrazio A, Caldana E, et al. Prognostic potential of precise molecular diagnosis of Autosomal Recessive Osteopetrosis with respect to the outcome of bone marrow transplantation. Cytotechnology. 2008;58(1):57–62. doi: 10.1007/s10616-008- 9165-9.Villa А, Pangrazio A, Caldana E, et al. Prognostic potential of precise molecular diagnosis of Autosomal Recessive Osteopetrosis with respect to the outcome of bone marrow transplantation. Cytotechnology. 2008;58(1):57–62. doi: 10.1007/s10616-008- 9165-9.Wilson C, Vellodi A. Autosomal recessive osteopetrosis: diagnosis, management, and outcome. Arch Dis Child. 2000;83(5):449–452. doi: 10.1136/adc.83.5.449.Wilson C, Vellodi A. Autosomal recessive osteopetrosis: diagnosis, management, and outcome. Arch Dis Child. 2000;83(5):449–452. doi: 10.1136/adc.83.5.449.Pettifor JM. Vitamin D deficiency and nutritional rickets in children. In: Feldman D, Pike JW, Glorieux FH, editors. Vitamin D. 2nd ed. Boston, MA, USA: Elsevier Academic Press; 2005. pp. 1065– 1084. doi: 10.1016/b978-012252687-9/50068-1.Pettifor JM. Vitamin D deficiency and nutritional rickets in children. In: Feldman D, Pike JW, Glorieux FH, editors. Vitamin D. 2nd ed. Boston, MA, USA: Elsevier Academic Press; 2005. pp. 1065– 1084. doi: 10.1016/b978-012252687-9/50068-1.Krassas GE. Idiopathic juvenile osteoporosis. Ann N Y Acad Sci. 2000;900:409–412. doi: 10.1111/j.1749-6632.2000.tb06253.x.Krassas GE. Idiopathic juvenile osteoporosis. Ann N Y Acad Sci. 2000;900:409–412. doi: 10.1111/j.1749-6632.2000.tb06253.x.Kim JW, Simmer JP. Hereditary dentin defects. J Dent Res. 2007;86(5):392–399. doi: 10.1177/154405910708600502.Kim JW, Simmer JP. Hereditary dentin defects. J Dent Res. 2007;86(5):392–399. doi: 10.1177/154405910708600502.Walter JD. The use of overdentures in patients with dentinogenesis imperfecta. J Paediatr Dent. 1988;4(1):17–25.Walter JD. The use of overdentures in patients with dentinogenesis imperfecta. J Paediatr Dent. 1988;4(1):17–25.Butler WT. Dentin matrix problems. Eur J Oral Sci. 1998;106:204– 210. doi: 10.1111/j.1600-0722.1998.tb02177.x.Butler WT. Dentin matrix problems. Eur J Oral Sci. 1998;106:204– 210. doi: 10.1111/j.1600-0722.1998.tb02177.x.Robinson C, Collins MT, Boyce AM. Fibrous dysplasia/McCuneAlbright Syndrome: clinical and translational perspectives. Curr Osteoporos Rep. 2016;14(5):178–186. doi: 10.1007/s11914- 016-0317-0.Robinson C, Collins MT, Boyce AM. Fibrous dysplasia/McCuneAlbright Syndrome: clinical and translational perspectives. Curr Osteoporos Rep. 2016;14(5):178–186. doi: 10.1007/s11914- 016-0317-0.Prie D, Huart V, Bakouh N, et al. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med. 2002;347(13):983–991 doi: 10.1056/NEJMoa020028.Prie D, Huart V, Bakouh N, et al. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med. 2002;347(13):983–991 doi: 10.1056/NEJMoa020028.Baum M. Renal fanconi syndrome secondary to deferasirox: where there is smoke there is fire. J Pediatr Hematol Oncol. 2010;32(7):525–526. doi: 10.1097/MPH.0b013e3181ec0c4d.Baum M. Renal fanconi syndrome secondary to deferasirox: where there is smoke there is fire. J Pediatr Hematol Oncol. 2010;32(7):525–526. doi: 10.1097/MPH.0b013e3181ec0c4d.Klusmann M, Van’t Hoff W, Monsell F, Offiah AC. Progressive destructive bone changes in patients with cystinosis. Skeletal Radiol. 2014;43(3):387–391. doi: 10.1007/s00256-013-1735-z.Klusmann M, Van’t Hoff W, Monsell F, Offiah AC. Progressive destructive bone changes in patients with cystinosis. Skeletal Radiol. 2014;43(3):387–391. doi: 10.1007/s00256-013-1735-z.Chong WH, Molinolo AA, Chen CC, Collins MT. Tumor-induced osteomalacia. Endocr Relat Cancer. 2011;18(3):R53–R77. doi: 10.1530/ERC-11-0006.Chong WH, Molinolo AA, Chen CC, Collins MT. Tumor-induced osteomalacia. Endocr Relat Cancer. 2011;18(3):R53–R77. doi: 10.1530/ERC-11-0006.Reyes-Múgica M, Arnsmeier SL, Backeljauw PF, et al. Phosphaturic mesenchymal tumor-induced rickets. Pediatr Dev Pathol. 2000;3(1):61–69. doi: 10.1007/s100240050008.Reyes-Múgica M, Arnsmeier SL, Backeljauw PF, et al. Phosphaturic mesenchymal tumor-induced rickets. Pediatr Dev Pathol. 2000;3(1):61–69. doi: 10.1007/s100240050008.Florenzano P, Gafni RI, Collins MT. Tumor-induced osteomalacia. Bone Rep. 2017;7:90–97. doi: 10.1016/j.bonr.2017.09.002.Florenzano P, Gafni RI, Collins MT. Tumor-induced osteomalacia. Bone Rep. 2017;7:90–97. doi: 10.1016/j.bonr.2017.09.002.

The authors declare that there are no conflicts of interest present.