Skeletal integrity in patients with nail patella syndrome

Nail patella syndrome (NPS) is a rare autosomal dominant disorder resulting from a heterogeneous loss of function in the LMX1B gene. It is associated with multiple skeletal deformities, yet it is unknown whether this is associated with osteoporosis. To examine bone mass and the prevalence of fragility fractures, we assessed bone mineral density (BMD) of the spine and hip in 31 adults and 12 children with mutation-confirmed NPS and 60 healthy age- and gender-matched adult controls. For the adults with NPS, BMD was 11-20% lower at the hip sites (P < or = 0.001) and 8% lower at the spine (P < 0.05) than that of controls. Even when adjusted for body mass index, the BMD remained significantly lower in patients with NPS in all hip regions but not in the spine. Adults with NPS also had a significantly lower Z-score (sd values from normal) at all hip sites (all P < 0.05), compared with age- and gender-matched controls in the manufacturer's database. However, children had significantly lower Z-scores only at the femoral neck and trochanter. Participants with NPS also had a higher prevalence of fractures (odds ratio 30.9, 95% confidence interval 6.4-149.6, P < 0.001) and scoliosis (odds ratio 16.0, 95% confidence interval 3.3-78.2, P < 0.001). The majority of these fractures occurred in women before puberty and in long bones, especially the clavicle. We conclude that adults with NPS have a BMD that is 8-20% lower than controls, which is associated with an increase in the prevalence of fractures and scoliosis. Future studies are needed to determine whether bone quality, geometry, or turnover could account for these findings.