Outcomes of zoledronic acid use in paediatric conditions

Angelina Lim; Peter Simm; Simon James; Margaret Zacharin

doi:10.1530/boneabs.6.P030

Objectives: Intravenous bisphosphonates have been used in children for various primary and secondary bone fragility disorders for three decades but beyond osteogenesis imperfecta, there is very limited information published in relation to outcomes. We report the experience at the Royal Children’s Hospital (RCH), Melbourne using Zoledronic acid (ZA), describing outcomes based on the underlying condition for which treatment was given, with the aim of informing future protocols and guidelines for bisphosphonate use.

Methods: A retrospective review of all RCH patients administered at least one dose of intravenous ZA from 2002–2015 was undertaken. All outcome data was collected from existing hospital medical records.

Results: In the 13 years of ZA use, 325 children had at least one dose of ZA; 12 of these were excluded from study inclusion due to either missing documentation regarding use of ZA or indications of extreme prematurity, renal osteodystrophy or intra-arterial calcification. Children included in this review were not taking any other bisphosphonates. Of the 313 patients, Table 1 describes preliminary data outcomes grouped for each condition; more analysis is currently being done on changes per year and after first year of treatment. Mild to moderate first dose acute phase reaction occurred in most with symptomatic acute day 2 hypocalcaemia in several who had steroid induced osteoporosis.

Table 1
Indication for ZA use	n	Outcomes
Bone abnormality indications
Avascular necrosis (AVN)	36	3/36 collapse within 12 months
Bone metastases	8	4/8 significant pain relief
Fibrous dysplasia	11	8/11 significant pain relief, no lesion size change
Non-union	3	2/3 complete union within 6 months, 1/3 partial healing at 12 months
Massive sacral bone erosion by neurofibroma	1	Significant pain relief but no size change
Aneurysmal bone cysts	4	2/4 significant reduction in lesion size after 12 months
Chronic recurrent multifocal osteomyelitis (prior to availability of biology)	3	2/3 significant pain relief and no major change in lesion size
Other indications
Osteogenesis imperfecta	117	Median 73.4% (Interquartile range 35%, 97%) increase in lumbar spine bone mineral density from baseline after 1–12 years of treatment
Osteoporosis inclusive of steroid dependent non DMD neuromuscular diseases	57	Median 44.2% (Interquartile range 23%, 72%) increase in lumbar spine bone mineral density from baseline after 1–10 years of treatment
Duchenne Muscular Dystrophy (DMD)	16	Median 21% (Interquartile range 11%, 32%) increase in lumbar spine bone mineral density from baseline after 1–7 years of treatment
Immobility	55	Median 39% (Interquartile range 24%, 57%) increase in lumbar spine bone mineral density from baseline over 1–10 years of treatment
Hypercalcaemia	2	Normalization of serum calcium, with reactive hypocalcaemia for 24–48 hours 2–4 days post dose

Conclusion: Zoledronic acid demonstrated a good efficacy profile, with improved bone density for osteoporotic conditions, significant pain relief in all treated bone abnormality indications, and stabilization of lesion size with reduced incidence of bone collapse in AVN.

Disclosure: The authors declared no competing interests

Bone Abstracts

P030