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Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation.
J Bone Miner Res. 2017 Sep; 32(9):1884-1892.JB

Abstract

In contrast to "classical" forms of osteogenesis imperfecta (OI) types I to IV, caused by a mutation in COL1A1/A2, OI type V is due to a gain-of-function mutation in the IFITM5 gene, encoding the interferon-induced transmembrane protein 5, or bone-restricted interferon-inducible transmembrane (IFITM)-like protein (BRIL). Its phenotype distinctly differs from OI types I to IV by absence of blue sclerae and dentinogenesis imperfecta, by the occurrence of ossification disorders such as hyperplastic callus and forearm interosseous membrane ossification. Little is known about the impact of the mutation on bone tissue/material level in untreated and bisphosphonate-treated patients. Therefore, investigations of transiliac bone biopsy samples from a cohort of OI type V children (n = 15, 8.7 ± 4 years old) untreated at baseline and a subset (n = 8) after pamidronate treatment (2.6 years in average) were performed. Quantitative backscattered electron imaging (qBEI) was used to determine bone mineralization density distribution (BMDD) as well as osteocyte lacunar density. The BMDD of type V OI bone was distinctly shifted toward a higher degree of mineralization. The most frequently occurring calcium concentration (CaPeak) in cortical (Ct) and cancellous (Cn) bone was markedly increased (+11.5%, +10.4%, respectively, p < 0.0001) compared to healthy reference values. Treatment with pamidronate resulted in only a slight enhancement of mineralization. The osteocyte lacunar density derived from sectioned bone area was elevated in OI type V Ct and Cn bone (+171%, p < 0.0001; +183.3%, p < 0.01; respectively) versus controls. The high osteocyte density was associated with an overall immature primary bone structure ("mesh-like") as visualized by polarized light microscopy. In summary, the bone material from OI type V patients is hypermineralized, similar to other forms of OI. The elevated osteocyte lacunar density in connection with lack of regular bone lamellation points to an exuberant primary bone formation and an alteration of the bone remodeling process in OI type V. © 2017 American Society for Bone and Mineral Research.

Authors+Show Affiliations

Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre, Meidling, 1st Medical Department Hanusch Hospital, Vienna, Austria.Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre, Meidling, 1st Medical Department Hanusch Hospital, Vienna, Austria.Shriners Hospital for Children, Montreal, Quebec, Canada.Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre, Meidling, 1st Medical Department Hanusch Hospital, Vienna, Austria.Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre, Meidling, 1st Medical Department Hanusch Hospital, Vienna, Austria.Bone and Extracellular Matrix Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.Shriners Hospital for Children, Montreal, Quebec, Canada.

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

28548288

Citation

Blouin, Stéphane, et al. "Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 32, no. 9, 2017, pp. 1884-1892.
Blouin S, Fratzl-Zelman N, Glorieux FH, et al. Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation. J Bone Miner Res. 2017;32(9):1884-1892.
Blouin, S., Fratzl-Zelman, N., Glorieux, F. H., Roschger, P., Klaushofer, K., Marini, J. C., & Rauch, F. (2017). Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 32(9), 1884-1892. https://doi.org/10.1002/jbmr.3180
Blouin S, et al. Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation. J Bone Miner Res. 2017;32(9):1884-1892. PubMed PMID: 28548288.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypermineralization and High Osteocyte Lacunar Density in Osteogenesis Imperfecta Type V Bone Indicate Exuberant Primary Bone Formation. AU - Blouin,Stéphane, AU - Fratzl-Zelman,Nadja, AU - Glorieux,Francis H, AU - Roschger,Paul, AU - Klaushofer,Klaus, AU - Marini,Joan C, AU - Rauch,Frank, Y1 - 2017/06/26/ PY - 2017/03/17/received PY - 2017/05/10/revised PY - 2017/05/25/accepted PY - 2017/5/27/pubmed PY - 2018/4/26/medline PY - 2017/5/27/entrez KW - BISPHOSPHONATE TREATMENT KW - MATRIX MINERALIZATION KW - OSTEOCYTE LACUNAE KW - OSTEOGENESIS IMPERFECTA TYPE V KW - QUANTITATIVE BACKSCATTERED ELECTRON IMAGING SP - 1884 EP - 1892 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 32 IS - 9 N2 - In contrast to "classical" forms of osteogenesis imperfecta (OI) types I to IV, caused by a mutation in COL1A1/A2, OI type V is due to a gain-of-function mutation in the IFITM5 gene, encoding the interferon-induced transmembrane protein 5, or bone-restricted interferon-inducible transmembrane (IFITM)-like protein (BRIL). Its phenotype distinctly differs from OI types I to IV by absence of blue sclerae and dentinogenesis imperfecta, by the occurrence of ossification disorders such as hyperplastic callus and forearm interosseous membrane ossification. Little is known about the impact of the mutation on bone tissue/material level in untreated and bisphosphonate-treated patients. Therefore, investigations of transiliac bone biopsy samples from a cohort of OI type V children (n = 15, 8.7 ± 4 years old) untreated at baseline and a subset (n = 8) after pamidronate treatment (2.6 years in average) were performed. Quantitative backscattered electron imaging (qBEI) was used to determine bone mineralization density distribution (BMDD) as well as osteocyte lacunar density. The BMDD of type V OI bone was distinctly shifted toward a higher degree of mineralization. The most frequently occurring calcium concentration (CaPeak) in cortical (Ct) and cancellous (Cn) bone was markedly increased (+11.5%, +10.4%, respectively, p < 0.0001) compared to healthy reference values. Treatment with pamidronate resulted in only a slight enhancement of mineralization. The osteocyte lacunar density derived from sectioned bone area was elevated in OI type V Ct and Cn bone (+171%, p < 0.0001; +183.3%, p < 0.01; respectively) versus controls. The high osteocyte density was associated with an overall immature primary bone structure ("mesh-like") as visualized by polarized light microscopy. In summary, the bone material from OI type V patients is hypermineralized, similar to other forms of OI. The elevated osteocyte lacunar density in connection with lack of regular bone lamellation points to an exuberant primary bone formation and an alteration of the bone remodeling process in OI type V. © 2017 American Society for Bone and Mineral Research. SN - 1523-4681 UR - https://www.unboundmedicine.com/medline/citation/28548288/Hypermineralization_and_High_Osteocyte_Lacunar_Density_in_Osteogenesis_Imperfecta_Type_V_Bone_Indicate_Exuberant_Primary_Bone_Formation_ L2 - https://doi.org/10.1002/jbmr.3180 DB - PRIME DP - Unbound Medicine ER -