rhIGF-1 Treatment Increases Bone Mineral Density and Trabecular Bone Structure in Children with PAPP-A2 Deficiency.

Aim: Our objective was to determine changes in bone mineral density (BMD), trabecular bone score (TBS), and body composition after 2 years of therapy with recombinant human insulin-like growth factor-1 (rhIGF-1) in 2 prepubertal children with a complete lack of circulating PAPP-A2 due to a homozygous mutation in PAPP-A2 (p.D643fs25*) resulting in a premature stop codon.

Methods: Body composition, BMD, and bone structure were determined by dual-energy X-ray absorptiometry at baseline and after 1 and 2 years of rhIGF-1 treatment.

Results: Height increased from 132 to 145.5 cm (patient 1) and from 111.5 to 124.5 cm (patient 2). Bone mineral content increased from 933.40 to 1,057.97 and 1,152.77 g in patient 1, and from 696.12 to 773.26 and 911.51 g in patient 2, after 1 and 2 years, respectively. Whole-body BMD also increased after 2 years of rhIGF-1 from baseline 0.788 to 0.869 g/cm2 in patient 1 and from 0.763 to 0.829 g/cm2 in patient 2. After 2 years of treatment, both children had an improvement in TBS. During therapy, a slight increase in body fat mass was seen, with a concomitant increase in lean mass. No adverse effects were reported.

Conclusion: Two years of rhIGF-1 improved growth, with a tendency to improve bone mass and bone microstructure and to modulate body composition.