Outcomes following intravenous bisphosphonate infusion in pediatric patients: A 7-year retrospective chart review

• Published in: Bone (New York, N.Y.) Vol. 121; pp. 60 - 67
• Main Authors: Nasomyont, Nat, Hornung, Lindsey N., Gordon, Catherine M., Wasserman, Halley
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2019
• Subjects: Administration, Intravenous; Bisphosphonate; Bone Density - drug effects; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - therapeutic use; Child; Child, Preschool; Children; Diphosphonates - adverse effects; Diphosphonates - therapeutic use; Female; Fractures, Bone - prevention & control; Humans; Infant; Male; Osteoporosis; Osteoporosis - drug therapy; Pediatrics; Retrospective Studies; Osteoporosis; Pediatrics; Bisphosphonate; Children
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2019.01.003

Intravenous bisphosphonates (IV BP) have been used to treat children with osteoporosis for many years. Favorable side effect profile and improvements in bone mineral density (BMD) have been demonstrated in patients with osteogenesis imperfecta (OI), a primary form of osteoporosis in pediatrics. Less is known about the safety of IV BP in children with secondary osteoporosis or glucocorticoid-induced osteoporosis (GIO). We aimed to determine the prevalence of both acute and long-term side effects and assess the efficacy of IV BP treatment to increase bone mineral density in pediatric patients with varying presentations of compromised bone health.
We conducted a retrospective chart review of pediatric patients (<21 years old) treated for osteoporosis with intravenous pamidronate (PAM) or zoledronic acid (ZA) at Cincinnati Children's Hospital Medical Center from 2010 to 2017. Patient demographics, diagnosis, infusion type and dose, acute phase reactions (APR), electrolyte abnormalities, and bone density measurements were collected from the electronic medical records. Diagnoses were grouped into 3 categories: primary osteoporosis, secondary osteoporosis, and GIO. Descriptive characteristics and adverse events were compared among categories. Change in bone mineral density (BMD) over time was compared among groups.
123 patients (56% male) received 942 infusions (83% PAM and 17% ZA). APR was reported in 7% of all infusions and more common in secondary osteoporosis (16%, p < 0.0001). There was a higher percentage of acute adverse events after the first infusion (27% vs 5%, p < 0.0001). Hypocalcemia following IV BP infusions occurred in 7% (27/379) of infusions and was significantly associated with ZA use (p = 0.04). Severity of hypocalcemia was generally mild, requiring intravenous calcium in 3% (13/379) of infusions. Hypophosphatemia occurred frequently, however rarely required intravenous supplementation. In 468 patient years of IV BP exposure, there were no reports of osteonecrosis of the jaw (ONJ) nor atypical femoral fracture (AFF). Lumbar spine (LS) aBMD Z-score 1 year after IV BP initiation increased overall for all groups (p < 0.0001) but did not significantly differ for those who did or did not fracture following IV BP treatment.
APR due to intravenous BP treatment for pediatric osteoporosis were infrequent and generally mild. APR were more likely to occur in patients with secondary osteoporosis, a group who may require closer monitoring. A higher proportion of hypophosphatemia occurred in the patients with GIO. Long-term serious adverse events including ONJ and AFF were not identified in our patient population. LS aBMD Z-score increased following initiation of IV BP. However, the change in BMD was not associated with risk of fracture during the follow-up interval. These data provide reassurance and suggest that IV BP can be safely used in pediatric patients with osteoporosis.
•Acute adverse events following intravenous bisphosphonate, although generally mild, were more common in secondary osteoporosis group•There were no reports of osteonecrosis of the jaw or atypical femur fracture in 468 patient years of bisphosphonate exposure•Increases in bone mineral density at trabecular sites (lumbar spine) were noted one year following initiation of bisphosphonate therapy•Frequency of fracture following initiation of bisphosphonate therapy was not associated with a change in BMD Z-score