History of the Management of Metabolic Bone Disorders in Children

Understanding of Disease

  • References date back to 1000 B.C.: References to conditions characterized by short stature (e.g., dwarfism) and abnormal facies (e.g., gargoylism) that would now be recognized as metabolic bone disorders can be found in numerous historical texts, artworks (see Velazquez below), and architecture. The Egyptian god Bes is depicted as having achondroplasia, and it has been suggested that Aesop himself suffered from the condition (12) (see below). An Egyptian mummy dating back to 1000 B.C. has been described with osteogenesis imperfecta.

Depiction of dwarfism by Velaquez:
Egyptian god Bes: The image is thought to have been modeled on an individual with achondroplasia.
Achondroplasia in Egyptian culture: This engraving on an Egyptian sarcophagus illustrates the typical profile of a child with achondroplasia.


  • 20th century – grouping according to metabolic derangement: It was not until the 20th century that these conditions were more formally described and grouped, and their underlying metabolic aberrations elucidated.

Technological Development

Increasing knowledge and techniques in both biochemistry and genetics have advanced the understanding of metabolic bone disease.

  • Biochemistry: During the 20th century the key steps in a number of metabolic pathways were discovered. Specific enzyme defects have been linked to particular metabolic diseases. For example, lysosomal enzymes are required for the breakdown of a group of chemicals known as glycosaminoglycans, which are polysaccharides that are essential for the maintenance of connective tissues. Deficiency of lysosomal enzymes results in accumulation of specific metabolites. Distinct clinical syndromes will result according to the exact point along the metabolic pathway that is affected. Metabolic assays of serum and urine are now available to diagnose many of the metabolic disorders. Treatment by administration of the affected enzyme, enzyme replacement therapy, is now available for many of these conditions.
  • Genetics: The mode of inheritance of most metabolic bone disorders has been established. Moreover, in many cases the underlying gene defect responsible for many of these conditions is now also known.
  • Imaging: MRI and high resolution CT have improved the evaluation and surveillance of these conditions. CT can define the vertebral anomalies in 2D or 3D and evaluate suitability for instrumented fixation. Additionally CT angiography (CTA) can demonstrate the relationship of the vertebral anomalies to major vascular structures (4). MRI is used to assess the impact of the skeletal anomalies on the neuraxis.

Surgical Technique

Spinal surgery in metabolic bone disease is required to treat deformity, neuraxial compression, and instability. In children, the combination of small stature, intrinsic bone abnormality, and neurological disability has often resulted in high complication rates (1). The surgery for these conditions has been improved as a result of advances in biomechanical engineering and intraoperative monitoring.

  • Instrumented fixation: Stabilizing the spine in children has traditionally involved onlay grafting techniques, supplemented by sublaminar wiring and external orthoses. Advances in spinal instrumentation technology in adult practice are being increasingly applied to pediatric practice with improved outcomes (15). Instrumented fixation is the preferred treatment where possible, as it results in a more immediate and stronger construct.
  • IOM: Over the past 20 years the use of continuous real-time monitoring of spinal cord function with SSEPs and MEPs during complex spine surgery has become widespread. IOM provides a sensitive early indicator of spinal cord dysfunction and is applicable and effective in pediatric practice (9).