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Patients with Van Buchem Disease, an Osteosclerotic Genetic Disease, Have Elevated Bone Formation Markers, Higher Bone Density, and Greater Derived Polar Moment of Inertia than Normal

Musculoskeletal Disease Center, J. L. Pettis Memorial Veterans Affairs Medical Center and Loma Linda University (J.E.W., K.V., M.H., C.N., C.L., D.J.B.), Loma Linda, California 92357; Department of Medical Genetics, University of Antwerp (W.B., W.V.H.), and Department of Radiology, University Hospital (F.M.V.), B-2610 Antwerp, Belgium; and Dr. J. H. Jansenziekenhuis (J.T.), 8303 BX Emmeloord, The Netherlands

Address all correspondence and requests for reprints to: Jon E. Wergedal, Ph.D., J. L. Pettis Veterans Affairs Medical Center, Loma Linda, California 92357. E-mail: jon.wergedal{at}med.va.gov.

Van Buchem disease is an autosomal recessive disease characterized by overgrowth of the skeleton. In a group of Dutch patients the disease is thought to be due to a 52-kb deletion that results in decreased expression of the SOST gene. To further characterize the disease, the morphology of the metacarpals of six adult subjects and two juveniles with Van Buchem disease were measured on hand x-rays along with nine normal adults and nine adult carriers of the disease. Serum bone formation markers, alkaline phosphatase, type I procollagen peptide, and osteocalcin, and the urinary bone resorption marker, cross-linked N-telopeptide, were determined. Van Buchem patients had increased metacarpal outer diameter, inner diameter, cortical thickness, and bone mineral density. Calculated bone volume and derived polar moment of inertia were markedly elevated (elevations of 158 ± 33% and 497 ± 95%, respectively) consistent with increased bone strength. Serum procollagen peptide and osteocalcin were significantly higher in Van Buchem patients. Urinary cross-linked N-telopeptide was significantly elevated in Van Buchem patients. None of these changes was found in Van Buchem carriers. These observations indicate that decreased expression of the SOST gene can lead to increased bone formation and to stronger bones.

This material is based upon work supported by the Office of Research and Development, Medical Research Service, Department of Veterans Affairs. The information contained in this publication does not necessarily reflect the position or the policy of the U.S. government, and no official endorsement should be inferred.

Abbreviations: ALP, Alkaline phosphatase; BMP, bone morphogenic protein; CED, Camurati-Englemann disease; NTx, type I collagen cross-linked N-telopeptide; PINP, type I procollagen.

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