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Review
. 2019 Feb 1;13(1):1-11.
doi: 10.1302/1863-2548.13.180190.

Current concepts in osteogenesis imperfecta: bone structure, biomechanics and medical management

Affiliations
Review

Current concepts in osteogenesis imperfecta: bone structure, biomechanics and medical management

W H Nijhuis et al. J Child Orthop. .

Abstract

The majority of patients with osteogenesis imperfecta (OI) have mutations in the COL1A1 or COL1A2 gene, which has consequences for the composition of the bone matrix and bone architecture. The mutations result in overmodified collagen molecules, thinner collagen fibres and hypermineralization of bone tissue at a bone matrix level. Trabecular bone in OI is characterized by a lower trabecular number and connectivity as well as a lower trabecular thickness and volumetric bone mass. Cortical bone shows a decreased cortical thickness with less mechanical anisotropy and an increased pore percentage as a result of increased osteocyte lacunae and vascular porosity. Most OI patients have mutations at different locations in the COL1 gene. Disease severity in OI is probably partly determined by the nature of the primary collagen defect and its location with respect to the C-terminus of the collagen protein. The overall bone biomechanics result in a relatively weak and brittle structure. Since this is a result of all of the above-mentioned factors as well as their interactions, there is considerable variation between patients, and accurate prediction on bone strength in the individual patient with OI is difficult. Current treatment of OI focuses on adequate vitamin-D levels and interventions in the bone turnover cycle with bisphosphonates. Bisphosphonates increase bone mineral density, but the evidence on improvement of clinical status remains limited. Effects of newer drugs such as antibodies against RANKL and sclerostin are currently under investigation. This paper was written under the guidance of the Study Group Genetics and Metabolic Diseases of the European Paediatric Orthopaedic Society.

Keywords: bisphosphonates; collagen I; fracture; hypermineralization; osteogenesis imperfecta.

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Figures

Fig. 1
Fig. 1
Schematic view of the basic multicellular unit with interaction between bone resorbing osteoclasts and bone matrix producing osteoblasts, which become osteocytes over time.
Fig. 2
Fig. 2
On the left side, a schematic view on the formation of collagen, both intracellular and extracellular. On the right side the same formation but with a mutation in one of the alpha chains as is seen in osteogenesis imperfecta (OI). Step 1: formation of three alpha chains by ribosomes (note the bigger amino acid in one of the chains in OI). Step 2: hydroxylation and glycosylation and the triple helix formation (note the slower folding in OI with increased hydroxylation and glycosylation: Glucose (Glc), Galactose (Gal), Lysine (Lys), Hydroxylysine (Hyl), Proline (Pro)). Step 3: extracellular cleavage of the C- and N-terminus. Step 4: quarter-staggered arrays (note the increased space between the molecules in OI). Step 5: the formation of cross-links which is unaffected in OI. Step 6: mineralization between the collagen molecules with an increased amount of mineral crystals of the same size in OI.
Fig. 3
Fig. 3
Multiple collagen fibrils form into collagen fibres. Amino acids on the alpha chain proline (PRO), glycine (GLY) and hydroxyproline (HYP).
Fig. 4
Fig. 4
Haematoxylin and eosin stain of both normal bone (left) and osteogenesis imperfecta (OI) bone (right). Note the difference in architecture between normal cancellous bone and cancellous bone in OI with a typical increased number of osteocytes and thinner trabeculae.
Fig. 5
Fig. 5
Brittle bone. Hypothetical stress-strain curve of bone with some of the most essential mechanical properties. For cortical bone, the deformations at yield are up to 1%, whereas for cancellous bone this can reach 5% to 10% or even higher. Bone can absorb a substantial amount of energy and can be considered a relatively tough material (see area under the curve). Osteogenesis imperfecta bone is considered brittle which means that it cannot absorb much energy (small area under the curve, right side). In fact, brittleness represents a combination of low strength and little plastic deformation.

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References

    1. Kivirikko KI. Collagens and their abnormalities in a wide spectrum of diseases. Ann Med 1993;25:113-126. - PubMed
    1. Byers PH, Steiner RD. Osteogenesis imperfecta. Annu Rev Med 1992;43:269-282. - PubMed
    1. Prockop DJ. Mutations that alter the primary structure of type I collagen. The perils of a system for generating large structures by the principle of nucleated growth. J Biol Chem 1990;265:15349-15352. - PubMed
    1. Van Dijk FS, Sillence DO. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A 2014;164A:1470-1481. - PMC - PubMed
    1. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 1979;16:101-116. - PMC - PubMed

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