Response to Zoledronic Acid Infusion in Children With Fibrous Dysplasia

Abstract

Objective: This retrospective study evaluated the outcome and safety of long-term treatment with zoledronic acid, in both polyostotic and mono-ostotic fibrous dysplasia (FD) of children. Methods: The case records of children and adolescents with symptomatic FD who received zoledronic acid (0.1 mg/kg IV infusion over 1 h) and have completed at least 2 years follow-up were analyzed. The relevant details were recorded in a predesigned chart. Clinical assessment [pain assessment by visual analog scale (VAS) and incidence of new fracture], radiological changes (cortical thickening, ossification, and decrease in the diameter of the osteolytic lesions) and biochemical parameters [alkaline phosphatase (ALP)] were used to evaluate the improvement. Results: The mean age of presentation was 9.1 years, with four males and six females. All patients had symptomatic FD in the lower limb with complaints of pain, tenderness, swelling, or deformity. Four children had associated pathological fracture. The radiological evaluation with bone scan revealed polyostotic involvement in eight patients and mono-ostotic involvement in two patients. Three patients had associated systemic features like café-au-lait spots or precocious puberty. The fracture united within 3 months and the radiological improvement was evident in the form of filling of the osteolytic defect. The pain score in six patients showed significant improvement (VAS < 3). The ALP level decreased to 544.12 ± 47.35 IU/L from an initial value of 895.75 ± 79.64 IU/L (p = 0.04) at 12 months. One patient had symptomatic hypocalcaemia after zoledronic acid infusion. Conclusion: The clinical and radiological response of zoledronic acid treatment in FD of children is promising. Further randomized control trials with a larger sample size are required to establish this drug as a first-line medical treatment in FD.

Keywords: adolescent; benign bone disease; bisphosphonates; cafe-au-lait spots; lytic lesion; pediatric; zoledronic acid.

Figure 1

A 5-year-old female child with polyostotic fibrous dysplasia (PFD) of tibia, fibula (A); follow up radiograph at 6 months revealed complete healing of the lesion (B).

Figure 2

A 5-year-old male child with mono-ostotic fibrous dysplasia (MFD) of proximal tibia (A). The lesion completely healed at3 months after zoledronic acid infusion (B).

Figure 3

A 17-year-old adolescent girl presented with PFD involving the right tibial shaft and fibula (A,B). After 2 months of zoledronic acid infusion, corrective osteotomy and intramedullary nailing was performed (C), follow-up radiograph at 6 months shows complete healing of the lesion (D).

Figure 4

A 17-year-old male presented with PFD involving the right tibial shaft and fibula with an inability to walk (A). Zoledronic acid was infused, and then complete excision of the lesion (of 12 cm length) with bone transport was performed over an intramedullary nail (B); desired bone transport was completed after 6 months. After subsequent consolidation of the transported bone, the patient was allowed to walk. He presented after 1.5 years with nonunion at the distal tibia (C), and it was bone grafted (D). The lesion healed completely.

Figure 5

A 4-year-old female child presented with PFD involving tibia and fibula with pathological fracture (A); the fracture got united, and the lesion healed up within 3 months of IV zoledronic acid infusion and plaster casting (B).

Figure 6

A 7-year-old male child presented with (PFD) involving left proximal femur, femoral shaft, left tibia and pelvis (A). MRI showed T2W hyperintense signal, and T1W hypointense signal (B). Three-phase bone scan revealed increased uptake at the involved sites (C).

Figure 7

The child in Figure 6 received IV zoledronic acid infusion at every 6-month interval until 2 years, and the lesion healed up with mineralization (A). Four years later, the child presented with femoral shaft fracture (but not in the lesion area) after a fall while playing football (B), and it was treated with open reduction internal fixation with a plate (C). The X-ray around the knee showed multiple Harris growth arrest lines (zebra stripe sign) (D).