Elsevier

Bone

Volume 121, April 2019, Pages 60-67
Bone

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

https://doi.org/10.1016/j.bone.2019.01.003Get rights and content

Highlights

  • 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

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusions

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.

Section snippets

Background

Low bone mineral density and fractures are increasingly recognized as complications of chronic pediatric medical conditions. Impaired mobility, chronic inflammation, inadequate nutrition, hormone disruption, and medication use (e.g., glucocorticoids, anti-epileptics and immunosuppressive agents) are all factors that affect bone size and microarchitecture and impair bone mineralization in children with chronic disease, potentially leading to the diagnosis of osteoporosis [1]. Treatment is first

Study design

We conducted a retrospective chart review of patients < 21 years of age at initiation of IV BP therapy for treatment of osteoporosis at a large tertiary medical center (Cincinnati Children's Hospital Medical Center). We utilized the electronic medical records (EMR) to identify all instances of intravenous pamidronate (PAM) or zoledronic acid (ZA) infusion at our hospital between January 2010 and July 2017. A total of 1141 infusions from 169 unique patients were reviewed. Our aim was to study

Patients characteristics

One hundred twenty-three patients (56% male) were followed for an average of 3.8 years following first IV BP infusion at CCHMC. One hundred patients (81%) met the ISCD criteria for the diagnosis of pediatric osteoporosis. Eight patients (7%) had low BMD with a history of one long bone fracture prior to IV BP infusion. The remaining 15 patients (12%) were started on bisphosphonate therapy without a history of fragility fracture prior to first IV BP. The decision to initiate treatment in these

Discussion

Favorable efficacy and safety profiles for IV BP therapy have been well described in patients with primary osteoporosis; however, less is known about the safety and efficacy of IV BPs in children with secondary osteoporosis or GIO. This study reviewed the use of IV BP therapy at a tertiary care center in a diverse cohort of patients with impaired bone mineralization. We aimed to add to the available literature on the safety and efficacy in children with secondary bone disease. In our cohort,

Conclusion

In pediatric patients with osteoporosis, adverse events due to IV BP treatment were mild and generally would not require inpatient management. APR and electrolyte abnormalities were more likely to occur in patients with secondary osteoporosis, a group who may require closer monitoring. Long-term serious adverse events including ONJ and AFF were not identified in 468 patient years of monitoring our cohort. IV BP treatment increased aBMD of trabecular bone but change in LS aBMD Z-score at one

Funding

No external funding.

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