Leiden University Scholarly Publications

Lierop, A.H. van; Hamdy, N.A.T.; Egmond, M.E. van; Bakker, E.; Dikkers, F.G.; Papapoulos, S.E. 2012

Van Buchem disease: Clinical, biochemical and densitometric features of patients and disease carriers

Article / Letter to editor

metadata only

Van Buchem disease (VBD) is a rare bone sclerosing dysplasia caused by the lack of a regulatory element of the SOST gene, which encodes for sclerostin, an osteocyte-derived negative regulator of... Show moreVan Buchem disease (VBD) is a rare bone sclerosing dysplasia caused by the lack of a regulatory element of the SOST gene, which encodes for sclerostin, an osteocyte-derived negative regulator of bone formation. We studied the demographic, clinical, biochemical and densitometric features of 15 patients with VBD (12 adults and 3 children) and 28 related carriers of the gene mutation. The most common clinical findings in patients were facial palsy (100%) and various degrees of hearing impairment (93%) while raised intracranial pressure had been documented in 20%. The clinical course of the disease appeared to stabilize in adulthood with the majority of patients reporting no progression of symptoms or development of complications with time. Carriers of the disease had none of the clinical features or complications of the disease. Sclerostin could be detected in the serum in all but one VBD patients [mean 8.0 pg/ml; 95% Confidence Intervals (CI) 4.9-11.0 pg/ml], and were lower than those of carriers (mean 28.7 pg/ml; 95%CI 24.5-32.9 pg/ml, p < 0.001) and healthy controls (mean 40.0 pg/ml; 95%CI 34.5-41.0 pg/ml, p < 0.). Serum procollagen type 1 amino-terminal propeptide (P1NP) levels were also significantly higher in adult patients (mean 96.0; 95%CI 54.6-137.4 ng/ml vs 47.8; 95%CI 39.4-56.2 ng/ml, p = 0.003 in carriers and 37.8; 95%CI 34.5-41.0, p = 0.028 in healthy controls) and declined with age. Bone Mineral Density (BMD) was markedly increased in all patients (mean z-score 8.7 ± 2.1, and 9.5 ± 1.9 at the femoral neck and spine respectively); BMD of carriers was significantly lower than that of patients but varied widely (mean z-scores 0.9 ± 1.0 and 1.3 ± 1.5 at the femoral neck and spine, respectively). Serum sclerostin levels were inversely correlated with serum P1NP levels (r = -0.39, p = 0.018) and BMD values (femoral neck r = -0.69, p < 0.001; lumbar spine r = -0.78, p < 0.001). Our results show that there is a gene-dose effect of the VBD deletion on circulating sclerostin and provide further in vivo evidence of the role of sclerostin in bone formation in humans. The small amounts of sclerostin produced by patients with VBD may explain their milder phenotype compared to that of patients with sclerosteosis, in whom serum sclerostin is undetectable. © 2012 American Society for Bone and Mineral Research. Show less