Bone mineral density in sclerosteosis; affected individuals and gene carriers.

Content Provider	Semantic Scholar
Author	Gardner, Jessica C. Bezooijen, R. L. Van Mervis, Benjamin Hamdy, N. A. Löwik, Clemens W. G. M. Hamersma, Herman A. Beighton, Peter Papapoulos, Socrates E.
Copyright Year	2005
Abstract	BACKGROUND Sclerosteosis is an autosomal recessive sclerosing bone disorder due to deficiency of sclerostin, a protein secreted by the osteocytes that inhibits bone formation. In the present study we assessed the effect of variable expression of the genetic defect on bone mineral density (BMD) in patients and carriers of the determinant gene. METHODS We studied 25 individuals (seven patients and 18 phenotypically normal heterozygotes). BMD was measured by dual x-ray absorptiometry at the lumbar spine, total hip, and distal forearm, and lateral radiographs of the skull were obtained. RESULTS Individuals with sclerosteosis had markedly increased BMD at all skeletal sites (Z-score ranges: lumbar spine, +7.73 to +14.43; total hip, +7.84 to +11.51; forearm, +4.44 to +9.53). In heterozygotes, BMD was above the mean value of healthy age-matched individuals at all skeletal sites and had a wide range of normal and clearly increased values. Skull radiographs showed the typical hyperostotic changes in affected individuals and mild or no changes in heterozygotes. CONCLUSIONS Heterozygous carriers of sclerosteosis have BMD values consistently higher than the mean of healthy subjects without any of the bone complications encountered in homozygotes. This finding suggests that the production and/or activity of sclerostin can be titrated in vivo, leading to variable increases in bone mass without any unwanted skeletal effects, a hypothesis of obvious significance for the development of new therapeutics for osteoporosis.
Starting Page	1
Ending Page	4
Page Count	4
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://jcem.endojournals.org/content/90/12/6392.full.pdf
PubMed reference number	16189254v1
Volume Number	90
Issue Number	12
Journal	The Journal of clinical endocrinology and metabolism
Language	English
Access Restriction	Open
Subject Keyword	Autosomal recessive inheritance Bone Density Bone Diseases Bone Marrow Diseases Bone Mineral Density Test Bone Tissue Cell secretion Dual Dual-Energy X-Ray Absorptiometry Forearm Heterozygote Homozygote Lumbar spine structure Osteocytes Osteogenesis Osteoporosis Patients Plain x-ray SOST gene Sclerosteosis Staphylococcal Protein A Therapeutic procedure
Content Type	Text
Resource Type	Article