BoneKEy Reports | BoneKEy Watch
Case history of juvenile osteoporosis associated with LRP5 abnormality
DOI:10.1038/bonekey.2013.202
This case history describes a 6-year old boy presenting with a history of multiple low-energy long-bone fractures starting in infancy.
The boy showed normal development and was tall for his age (95th percentile) but the areal bone mineral density (BMD) of his lumbar spine was below normal (z-score −3.2). His cortical thickness was within the normal range but he was found to have low trabecular volumetric BMD at the distal radius (z-score −5.1). The cross-sectional area of the muscle was normal but he had a low bone mineral content (z-score −3.1)
The researchers performed whole-exome sequencing, but a heterozygous mutation was identified in exon 12 of LRP5, corresponding to a loss-of-function mutation. This gene encodes a plasma membrane protein involved in the Wnt signaling pathway, which regulates bone formation. Treatment with intravenous zoledronic acid was started, with the drug given by injection every 6 months. After 30 months of treatment he showed significant increase in the areal BMD of the lumbar spine and his trabecular volumetric BMD had improved at the radius. He had no further fractures of his long bones. However, his long-bone diameter and total bone cross-sectional area have remained low.
Editor’s comment: This is a rare mutation associated with severe bone fragility in young children—it is only the second case documented. The case illustrates the role of LRP5 in development of bone and demonstrates that such genetic disorders can be treated with some success.
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