Background: High bone mass (HBM) disorders are a group of clinically and genetically
heterogeneous bone diseases characterized by increased bone density on radiographs, due to progressive
bone overgrowth or impaired bone resorption, or both. Some HBM cases are secondary to other
diseases, such as chronic hepatitis C virus infection. Despite the great advance in gene diagnostic
technology, the majority of HBM individuals remain undiagnosed.
Objective: In this review, we will summarize the clinical, radiological and biochemical characteristics
of HBM cases due to varying etiologies, since these features are helpful in the differential diagnosis of
Results: Each subgroup of HBM cases shows distinctive clinical, radiological and biochemical characteristics.
HBM, due to bone overgrowth, was designated as sclerosteosis, as a result of mutations
located in genes critically involved in the Wnt/beta-catenin signal pathway. Mutations in genes encoding
factors relevant to the differentiation and maturation of osteoclasts, or critical for the acidification
and resorption of osteoclasts may lead to osteopetrosis. Hepatitis C associated osteosclerosis is characterized
by a generalized increase in bone mass and markedly elevated serum levels of bone specific
Conclusion: The clarification of the etiologies of HBM may have a breakthrough role in understanding
the molecular mechanisms involved in bone metabolism and may provide new pathways for the
intervention of osteoporosis.