BoneKEy Reports | BoneKEy Watch
Pregnancy-associated osteoporosis: clues to a possible genetic origin
DOI:10.1038/bonekey.2013.234
Cook et al. report the case history of a woman aged 37 years who developed vertebral compression fractures indicative of the rare idiopathic disorder pregnancy-associated osteoporosis (PAO), when pregnant for the first time 11 years previously.
She was healthy until her first pregnancy but had undergone enucleation of her left eye as a baby, due to hyperplastic primary vitreous. Following delivery, she experienced severe upper back pain; X-rays showed compression deformities and osteopenia in three mid-thoracic vertebrae. She had close family relatives with back pain, height loss, low bone mineral density (BMD), blindness and premature osteoporosis.
After two subsequent miscarriages she was diagnosed with homozygosity for the MTHFR C677T polymorphism; treatment to prevent thrombosis resulted in a successful pregnancy. Family studies reported here revealed a 12-base pair deletion in exon 21 of the gene encoding LDL receptor-related protein 5 (LRP5), present in the woman, her mother and her sons, but absent from her brother and father (who had a history of early osteoporosis and blindness).
The combination of being homozygous for the MTHFR polymorphism and having a heterozygous LRP5 mutation is suggested to have led to the woman having a very low peak BMD.
Editor’s comment: It seems likely, however, that additional genetic, or even non-genetic factors are at work in this family, since osteoporosis did not co-segregate with either the homozygous MTHFR polymorphism, the heterozygous LRP5 mutation or even a combination of both. The cause of PAO, even in this patient, remains elusive.
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