Long-term clinical and bone mineral density changes of adult patients with sclerostin deficiency due to van Buchem disease: a follow-up study

Abstract

Van Buchem disease (VBD) is an inherited rare sclerosing bone disorder, due to defective synthesis of sclerostin, a negative regulator of bone formation. Our earlier cross-sectional studies of patients with VBD and the closely related sclerosteosis suggested that the accrual of bone mass does not continue after puberty but longitudinal studies of patients with sclerostin deficiency are not available. The aim, therefore, of the present study was the long-term assessment of adult patients with VBD. Fifteen previously evaluated patients with genetically confirmed VBD were invited to participate in the study and 11 (4 women) consented. Mean follow-up time was 8.9 +/- 1.1 yr and median age at follow-up was 47 yr (range 20-60). Seven patients developed permanent facial paresis, 9 had progressing hearing loss, and 2 developed had increased intracranial pressure requiring cranial surgery. Dental problems were common, and 3 patients developed osteoarthritis during follow-up. None experienced a cardiovascular event. BMD did not change at the LS or the left FN; Z-scores were 10.2 +/- 1.3 SD vs 9.4 +/- 2.3 SD, p=.62, and 8.9 +/- 2.2 SD vs 7.7 +/- 2.2 SD, p=.15, respectively. The variability of the clinical expression and progression of the disease, despite the stabilization of BMD but with progressive cranial nerve compression, requires continuous monitoring of these patients for whom no disease-specific therapy is currently available.Van Buchem disease (VBD) is a rare genetic disorder. It causes dense bones and high bone mass. The disease is caused by a decreased sclerostin, a protein that inhibits bone formation. In VBD bones continue to grow thicker till adulthood and we think that it stops becoming thicker afterwards. A total of 11 patients with VBD were followed over 9 yr. We found that their bones do not become thicker but the thick skull bone can give complaints like hearing loss or facial nerve problems. Since patients can still develop complaints despite reaching adulthood we advocate that patients are monitored on regular intervals.