Osteogenesis Imperfecta Type VI: A Form of Brittle Bone Disease with a Mineralization Defect

Abstract

Osteogenesis imperfecta (OI) is a heritable disease of bone in which the hallmark is bone fragility. Usually, the disorder is divided into four groups on clinical grounds. We previously described a group of patients initially classified with OI type IV who had a discrete phenotype including hyperplastic callus formation without evidence of mutations in type I collagen. We called that disease entity OI type V. In this study, we describe another group of 8 patients initially diagnosed with OI type IV who share unique, common characteristics. We propose to name this disorder "OI type VI." Fractures were first documented between 4 and 18 months of age. Patients with OI type VI sustained more frequent fractures than patients with OI type IV. Sclerae were white or faintly blue and dentinogenesis imperfecta was uniformly absent. All patients had vertebral compression fractures. No patients showed radiological signs of rickets. Lumbar spine areal bone mineral density (aBMD) was low and similar to age-matched patients with OI type IV. Serum alkaline phosphatase levels were elevated compared with age-matched patients with type IV OI (409 ؎ 145 U/liter vs. 295 ؎ 95 U/liter; p < 0.03 by t-test). Other biochemical parameters of bone and mineral metabolism were within the reference range. Mutation screening of the coding regions and exon/intron boundaries of both collagen type I genes did not reveal any mutations, and type I collagen protein analyses were normal. Qualitative histology of iliac crest bone biopsy specimens showed an absence of the birefringent pattern of normal lamellar bone under polarized light, often with a "fish-scale" pattern. Quantitative histomorphometry revealed thin cortices, hyperosteoidosis, and a prolonged mineralization lag time in the presence of a decreased mineral apposition rate. We conclude that type VI OI is a moderate to severe form of brittle bone disease with accumulation of osteoid due to a mineralization defect, in the absence of a disturbance of mineral metabolism. The underlying genetic defect remains to be elucidated. (J Bone Miner Res 2002;17:30 -38)

Osteogenesis imperfecta

“…Bone tissue histomorphometry is also distinct, with a mesh like lamellation pattern under polarized light. By contrast, patients with osteogenesis imperfecta 91 .…”

Bone Material Properties in Osteogenesis Imperfecta

“…Two exceptions, however, may be the types V and VI OI initially identified as having distinct bone histological appearances (type V mesh-like under polarized light; type VI osteomalacic) at the level of light microscopy. (38,39) Type V infants initially display altered metaphyseal modeling suggestive of a delay in endochondral ossification, (40) with a subsequent increase in metaphyseal density but no alteration in mineralization rate or extent of remodeling sites in the trabecular bone of transiliac bone biopsies. (38) By contrast, although there is a clear mineralization defect at remodeling sites in type VI patients, (39) there is no apparent defect in endochondral ossification.…”

Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial

“…The worldwide prevalence of OI is estimated to be approximately 1 per 10,000 births [2][3][4]. To this day, twelve distinct types of OI have been distinguished based on genetic mutations and phenotype [5][6][7][8]. Clinical manifestations of the disease vary in severity depending on the type of OI diagnosed.…”