ESPE2014 Working Groups Bone & Growth Plate (4 abstracts)
Osteoclasts are bone-resorbing cells important in normal growth plate development and bone remodeling. The development of osteoclasts is potently driven by mononuclear RANK and osteogenic cell RANKL interaction. Denosumab is a monoclonal antibody drug that targets RANKL and inhibits osteoclastogenesis. It is a potent and effective treatment for pathologic processes that involve bone resorption, such as osteoporosis and bone metastases, conditions for which it is approved. Denosumab is also approved for the treatment of giant cell tumors, benign neoplasms composed primarily of fibroblast-like cells of osteogenic origin with abundant osteoclast-like multinucleated giant cells the highly express RANK.
Denosumab has been successfully used off-label, including in children, in other bone diseases that involve osteoclast-driven bone resorption and giant cell-rich diseases such as hypercalcemia of malignancy and fibrous dysplasia of bone. However, its use and discontinuation, especially in diseases with high bone turnover, can be associated with significant adverse side effects. In addition, the use of this potent drug in children raises concerns of untoward effects at the growth plate. This concern is similar to that raised when bisphosphonates were first used in children. While the stigmata of bisphosphonate use in growing children are evident for years after discontinuation in the sclerotic bands seen on radiographs, over 10 years of experience has assured us that at appropriate doses normal linear growth can be maintained. This point, and our case report demonstrating resumption of normal growth plate histopathology 17 months after discontinuation of denosumab in a child with fibrous dysplasia, offers reassurance that denosumab use in children may be safe once appropriate regimens have been determined. Before this promising drug can be used in children, work remains to identify and manage patients at high risk for side effects, and determination of a regimen that allows normal growth to proceed.
18 Sep 2014 - 20 Sep 2014