Long-term follow-up in osteogenesis imperfecta type VI.

Abstract

Osteogenesis imperfecta (OI) type VI is an ultra-rare bone fragility disorder caused by recessive mutations in SERPINF1. Here, we describe long-term outcomes in OI type VI and compare the clinical phenotypes caused by different types of SERPINF1 mutations. This study includes a retrospective chart review of 13 individuals with OI type VI. In the absence of therapy, lumbar spine areal bone mineral density (BMD) did not increase during childhood and longitudinal growth seemed to stall after the age of 6 to 8years. The phenotype was similar between individuals with different types of SERPINF1 mutations. Intravenous bisphosphonate treatment was associated with an increase in lumbar spine areal BMD and some reshaping of compressed vertebral bodies. Patients who had started bisphosphonate treatment early (before the age of 6years) were taller than patients who had received bisphosphonate treatment later during their growing years. Lower extremity fractures were frequent despite bisphosphonate treatment and scoliosis was present in all patients who had reached the final height. Most patients had restricted mobility. In four patients, intravenous bisphosphonate treatment was eventually substituted by subcutaneous injections of denosumab, without clear changes in the clinical picture. Patients with OI type VI who received intravenous bisphosphonate treatment during growth had an increase in lumbar spine areal BMD, a higher final height z-score, and presented some reshaping of vertebral bodies. More effective treatment modalities are clearly required in OI type VI.