Craniofacial Bone Mineral Density in Mice with Osteogenesis Imperfecta (OI)

Osteogenesis imperfecta (OI) is a heterogenous group of heritable bone dysplasias characterized by bone fragility, typically low bone mass, joint laxity, easy bruising, and variable short stature. Classical OI is caused by autosomal dominant pathogenic variants in COL1A1 or COL1A2 that result in either reduced production of normal type 1 collagen or structurally abnormal collagen molecules. Pathogenic variants in these genes generally result in low bone mass. Here, we report a family that had 2 affected individuals who presented with minimal trauma fractures and were found to have elevated bone mineral density (BMD) and a previously unreported variant in COL1A2 c.3356C>T p.(Ala1119Val). We report the change in BMD using dual-energy X-ray and peripheral quantitative computed tomography over a 2.3-year period in the proband. This case report highlights the importance of BMD studies and genetic testing in the diagnostic process for brittle bone disorders.

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Association Between Physical Activity With Bone Mineral Density And Handgrip In Children With Osteogenesis Imperfecta

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000677156.58271.8a ◽

2020 ◽

Vol 52 (7S) ◽

pp. 324-325

Author(s):

Andréa Cassimiro de Oliveira ◽

Rafael Mancini ◽

Ellen de Oliveira Goiano ◽

Miguel Akkari ◽

Victor Keihan Rodrigues Matsudo ◽

...

Keyword(s):

Physical Activity ◽

Bone Mineral Density ◽

Osteogenesis Imperfecta ◽

Bone Mineral ◽

Mineral Density

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Growth hormone effect on bone mineral density in a girl with osteogenesis imperfecta - a case presentation

Bone Abstracts ◽

10.1530/boneabs.7.p128 ◽

2019 ◽

Author(s):

Sofia Leka ◽

Fani Athanasouli ◽

Elpis Vlachopapadopoulou ◽

Artemis Doulgeraki ◽

Vassilios Petrou ◽

...

Keyword(s):

Bone Mineral Density ◽

Growth Hormone ◽

Osteogenesis Imperfecta ◽

Bone Mineral ◽

Mineral Density ◽

Case Presentation ◽

Hormone Effect

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Bone mineral density in healthy children and in osteogenesis imperfecta

Bone and Mineral ◽

10.1016/0169-6009(92)91958-l ◽

1992 ◽

Vol 17 ◽

pp. 155 ◽

Cited By ~ 1

Author(s):

M.W.J. Davie ◽

M.J. Haddaway

Keyword(s):

Bone Mineral Density ◽

Osteogenesis Imperfecta ◽

Bone Mineral ◽

Healthy Children ◽

Mineral Density

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Individualized treatment with denosumab in children with osteogenesis imperfecta – follow up of a trial cohort

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-019-1197-z ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 2

Author(s):

Heike Hoyer-Kuhn ◽

Mirko Rehberg ◽

Christian Netzer ◽

Eckhard Schoenau ◽

Oliver Semler

Keyword(s):

Bone Mineral Density ◽

Lumbar Spine ◽

Side Effects ◽

Osteogenesis Imperfecta ◽

Bone Mineral ◽

Bone Pain ◽

Mineral Density ◽

Osteoclastic Activity ◽

Activity Marker

Abstract Background Osteogenesis imperfecta (OI) is a rare disease leading to hereditary bone fragility. Nearly 90% of cases are caused by mutations in the collagen genes COL1A1/A2 (classical OI) leading to multiple fractures, scoliosis, short stature and nonskeletal findings as blue sclera, hypermobility of joints, bone pain and delayed motor function development. Bisphosphonates are used in most moderate and severely affected patients assuming that an increase of bone mineral density might reduce fractures and bone pain in patients with OI. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. First data from small clinical trials promised a high efficacy of Denosumab in children with OI. Aim of this analysis was a retrospective evaluation of an individualized biomarker-associated treatment regime with Denosumab in 10 children with classical OI which were followed for 1 year after their participation in a pilot trial with Denosumab. Therefore urinary deoxypyridinoline levels were evaluated frequently as an osteoclastic activity marker and depending on that levels Denosumab injections were scheduled individually. Methods Ten patients (age range: 6.16–12.13 years; all participated in the former OI-AK phase 2 trial (NCT01799798)) were included in the follow-up period. Denosumab was administered subcutaneously depending on the individual urinary excretion course of deoxypyridinoline (DPD/Crea) as osteoclastic activity marker with 1 mg/kg body weight. DPD/Crea levels were evaluated before denosumab administration and afterwards. If patients present after an initial decrease after injection with a re-increase up to the DPD/crea level before Denosumab injection next dosage was planned. Changes of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 12 month was evaluated. Safety was assessed by bone metabolism markers and side effect reporting. Results During follow-up mean relative change of lumbar aBMD was − 6.4%. Lumbar spine aBMD z-Scores decreased from − 1.01 ± 2.61 (mean ± SD) to − 1.91 ± 2.12 (p = 0.015). Mobility changed not significantly (GMFM-88 -6.49 ± 8.85% (p = 0.08). No severe side effects occurred. Dose intervals could be extended in the mean from 12 weeks previously to 20.3 weeks. Conclusions On average, it was possible to prolong the intervals between drug administrations and to reduce the total dose about by 25% without a decrease of mobility or change of vertebral shape despite a reduction of lumbar aBMD during 1 year of biomarker-directed Denosumab treatment. Further trials are necessary to balance side effects and highest efficacy in children.

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