Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 16 P97

Bone and calcium

A new form of hereditary low-turnover osteoporosis in a 3-generation Finnish family

Christine Laine1, Anne Saarinen1, Tero Laine2 & Outi Mäkitie2


1Folkhälsan Institute of Genetics, University of Helsinki, Helsinki, Finland; 2Hospital for Children and Adolescents, University Hospital of Helsinki, Helsinki, Finland.

Juvenile primary osteoporosis, unless diagnosed as osteogenesis imperfecta, has previously been considered a sporadic and self-limiting disease. New genetic findings, including osteoporosis-causing mutations in the LDL-receptor related protein (LRP) 5 and LRP6 genes, challenge this view. The pathogenesis of juvenile osteoporosis still remains largely unknown. We describe findings in a three-generation pedigree with a new form of autosomal dominant osteoporosis.

The proband, at age 35, presented with multiple painful thoracic vertebral compression fractures causing a loss of 7 cm of her adult height. Secondary causes of osteoporosis were excluded. She has no features of OI and no peripheral fractures. The lumbar bone mineral density (BMD) Z-score is −2.9. Assessment of the pedigree revealed osteoporosis in eight additional family members, many with asymptomatic compression fractures. The youngest is a boy of 12 years with asymptomatic compression fractures in his thoracic spine and a lumbar BMD Z-score of −1.7. Transilial bone biopsies from two treatment-naïve adult family members revealed severe low-turnover osteoporosis with low trabecular bone volume, decreased osteoid and low numbers of osteoblasts. Mineralization and resorption rates were normal.

A genome-wide micro-satellite analysis yielded a maximum lod score of 2.8 and further analyses are under way to identify the disease-causing genetic defect. No linkage was found in areas encoding type 1 collagen. Genetic testing for mutations in LRP5 and LRP6 was negative.

The described three-generation family represents a new form of autosomal dominant early onset primary osteoporosis. The discovery of the underlying genetic defect may provide important new information about the biological and pathogenetic mechanisms of osteoporosis.

Article tools

My recent searches

No recent searches.

My recently viewed abstracts

No recent abstracts.