The Role of Total Vitamin D in the Diagnosis and Monitoring of Skeletal Involvement in Gaucher Disease

Gaucher disease (GD) is the most prevalent LSD, and skeletal disease is one of the most disabling and difficult to treat forms of the disease. This narrative review aims to assess the potential of total serum vitamin D [TSVD] (25 hydroxyvitamin D [25(OH)D]) as a biomarker for the diagnosis and monitoring of skeletal disease in GD. English-language data from PubMed, Scopus and Google Scholar databases were analyzed and searched for evidence using vitamin D, GD, bone disease, enzyme replacement therapy (ERT) and the terms relevant to biomarkers. Additionally, data from an unpublished case-control study were included in the review, consisting of 67 Iraqi children with GD, and 20 healthy children. The evidence suggests a high prevalence of vitamin D deficiency in GD patients, both geographically and potentially with lower BMD in adults with GD1. Total vitamin D, in the unpublished pediatric cohort, showed good discrimination of children with GD at initial presentation with the area under the receiver operating characteristic curve (AUC) of 0.90–1.00. After more than one year of ERT, however, vitamin D levels were still decreased compared to healthy controls. In addition, it was not very effective at distinguishing the different treatment-duration groups (AUC 0.52–0.68), meaning that it could not be used effectively for monitoring treatment response in short- to medium-term treatment. Overall, there is no existing evidence to support vitamin D as a standalone biomarker of skeletal response to ERT or substrate reduction therapy (SRT). The clinical relevance must be related to other direct skeletal evaluations and known markers like chitotriosidase. Nevertheless, vitamin D status should be measured at diagnosis and at regular intervals during follow up and corrected if deficiency is found; this is supportive care. Other prospective studies involving larger populations, the use of a standardized measurement of vitamin D, and validated skeletal endpoints are required to establish its utility for monitoring GD.