Bisphosphonate Therapy in Children

Pediatric patients with cerebral palsy and osteogenesis imperfecta can be treated with bisphosphonates for low mineral density. In addition, third-generation bisphosphonates, such as zoledronic acid and minodronic acid have been shown to have antitumor effects in various cancers such as osteosarcoma and Ewing sarcoma. The use in children is classified as "off-label."

Radiographs reveal dense stripes parallel to the growth plate, an appearance that has been termed zebra lines. Dense metaphyseal bands tend to occur in patients treated continuously, while thin bands tend to occur in patients treated intermittently. In addition, patients treated intermittently tend to have increased bone density, increased growth, and decreased number of fractures.

The sclerotic bands correspond to decreased osteoclastic activity during drug administration, and the spaces between the bands corresponds to resumption of osteoclastic activity and linear growth of bone between treatments. With time (3-4 years), these dense bands become less distinct and eventually disappear into the diaphysis.

While similar to Harris growth arrest lines, zebra lines tend to be more widespread in epiphyseal, apophyseal, and metaphyseal regions of all growing bones. Growth arrest lines, on the other hand, are seen in the metaphyses of rapidly growing bones (e.g., distal femur, proximal and distal tibia, and proximal humerus) and may be limited to a single bone (e.g., following a major fracture).

References

• Al Muderis M, Azzopardi T, Cundy P. Zebra lines of pamidronate therapy in children. J Bone Joint Surg Am. 2007 Jul;89(7):1511-6.
• Grissom LE, Harcke HT. Radiographic features of bisphosphonate therapy in pediatric patients. Pediatr Radiol. 2003 Apr;33(4):226-9.