Bone Abstracts

Objectives: Marfan syndrome (MFS) is a connective disorder caused by mutations in FBN1 gene which encodes the extracellular matrix protein fibrillin 1. Pathogenesis relies on a dysregulation of activated TGF-β. Cardiovascular, ocular and skeletal systems are involved with a variable expressivity. Findings evolve with age, making the diagnosis in children more difficult. Skeletal involvement includes disproportionate long bone overgrowth, scoliosis, and chest deformity. Although several surveys investigated bone mineral density (BMD) in adult MFS patients, data on children are scarce. Aim of our study was to assess BMD in a large cohort of children with an ascertained diagnosis of MFS.

Methods: Sixty Caucasian patients with MFS diagnosis based on 2010 Ghent nosology (29 females and 31 males, mean age 10 (3.7) years), were investigated. Neither calcium or vitamin D supplementation, nor exercise restriction was performed. Height, as expected, was above mean values (1.5 (0.2) m, Z-score 1.9 (1.4)). We measured BMD by DXA (Discovery W- Hologic) at the lumbar spine and proximal femur. PTH and 25(OH)D₃ concentrations were measured in serum.

Results: BMD Z-score were lower than normal: −0.9 (1.1) at lumbar spine, −0.69 (1.3) total femur, −1.1 (1.4) at the femoral neck (FN). As DXA overestimates density of large bones, an accurate estimate of bone mass requires a correction of the potential confounding effects of body size. The adjustments for tall stature were made using height-for-age Z-score (HAZ). Corrected data showed worse values than those standardised only to age and gender: −1.8 (1.0) at lumbar spine, −1.5 (1.3) at total femur and −0.97 (1.7) at FN. All these data were significantly different from 0 (P<0.0001). Four fractures were reported (6.6%), above the mean incidence per year from literature. PTH levels were within normal range (44.3 (25.8) pg/ml), while 25(OH)D₃ levels were below international reference values (22.6 (7.8) ng/ml).

Conclusions: MFS children have low BMD values and a high prevalence of fractures. Bone density should be considered among the skeletal features in MFS. Management guidelines should take into account bone density impairment.