Zoledronic acid in pediatric metabolic bone disorders

Bowden, Sasigarn A; Mahan, John D.

doi:10.21037/tp.2017.09.10

Cited by 28 publications

(18 citation statements)

References 78 publications

(86 reference statements)

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“…BPs were classically viewed as a first line treatment for patients with osteoporosis [7], Paget’s disease [8] and hypercalcemic disorders [9]. Zoledronate or zoledronic acid (zol), is a third-generation nitrogen-containing BP, and the most potent BP described so far.…”

Section: Introductionmentioning

confidence: 99%

Low-dose zoledronate for the treatment of bone metastasis secondary to prostate cancer

et al. 2019

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BackgroundBisphosphonates (BPs) including zoledronate (zol) have become standard care for bone metastases as they effectively inhibit tumor-induced osteolysis and associated pain. Several studies have also suggested that zol has direct anti-tumor activity. Systemic administration at high doses is the current approach to deliver zol, yet it has been associated with debilitating side effects. Local therapeutic delivery offers the ability to administer much lower total dosage, while at the same time maintaining sustained high-local drug concentration directly at the target treatment site. Here, we aimed to assess effects of lower doses of zol on bone metastases over a longer time.MethodsProstate cancer cell line LAPC4 and prostate-induced bone metastasis cells were treated with zol at 1, 3 and 10 µM for 7 days. Following treatment, cell proliferation was assessed using Almarblue®, Vybrant MTT®, and Live/Dead® viability/cytotoxicity assays. Additionally, cell migration and invasion were carried out using Falcon™ cell culture inserts and Cultrex® 3D spheroid cell invasion assays respectively.ResultsWe show that treatment with 3–10 µM zol over 7-days significantly decreased cell proliferation in both the prostate cancer cell line LAPC4 and cells from spine metastases secondary to prostate cancer. Using the same low-dose and longer time course for treatment, we demonstrate that 10 µM zol also significantly inhibits tumor cell migration and 3D-cell growth/invasion.ConclusionsThis project harnesses the potential of using zol at low doses for longer treatment periods, which may be a viable treatment modality when coupled with biomaterials or biodevices for local delivery.Electronic supplementary materialThe online version of this article (10.1186/s12935-019-0745-x) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Low-dose zoledronate for the treatment of bone metastasis secondary to prostate cancer

et al. 2019

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“…We used a higher dose of zoledronic acid (0.1 mg/kg) based on our previous experience that explains the increased incidence of flu-like symptoms and hypocalcemia. The side effects of the zoledronic acid can be minimized with lower effective dose (0.025 mg/kg) (31).…”

Section: Figure 7 | the Child Inmentioning

confidence: 99%

Response to Zoledronic Acid Infusion in Children With Fibrous Dysplasia

et al. 2020

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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.

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“…Several centers have reported retrospective analyses investigating the safety and efficacy of ZA in clinical pediatric practice [ 7 , 8 ]. The rates of ZA related side effects, effects on bone density and fracture in these reports have varied widely [ 9 ]. Non-standardization of ZA dosing and heterogeneity in patient populations may explain some of these differences.…”

Section: Introductionmentioning

confidence: 99%

A quality improvement project to address the challenges surrounding zoledronic acid use in children

et al. 2021

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Introduction Zoledronic acid (ZA) is an intravenous bisphosphonate used to treat pediatric osteoporosis. Adverse events including hypocalcemia and acute phase reaction (APR) are common following first-infusion. The purpose of this report is to describe implementation of a ZA clinical practice guideline and the subsequent process changes to improve adherence to aspects of the protocol related to safety and efficacy. Methods Quality assurance was evaluated by chart review over a 5-year period to compare the prevalence of hypocalcemia and APR to published data. A quality improvement (QI) initiative consisting of process changes including the addition of an endocrine RN to coordinate infusions and a shift to patient/family self-scheduling of infusions was conducted. The effect of the interventions on safety (completion of pre- and post-infusion bloodwork) and efficacy (receipt of all prescribed infusions) outcomes was evaluated. Results Seventy-two patients received 244 infusions over the period. The frequency of hypocalcemia (22%) and APR (31%) was consistent with prior reports. 99% of patients received pre-infusion bloodwork, 78% received post-first-infusion bloodwork, and 47% received all prescribed infusions. QI initiatives increased the percentage of patients receiving post-first-infusion bloodwork from 67 to 79% and those receiving all infusions from 62 to 74%, but fell short of the goal of 90%. Conclusions The implementation of a standardized protocol for ZA use in children was successful in confirming patient eligibility with pre-infusion bloodwork but failed to ensure that patients obtained post-first-infusion bloodwork and received all prescribed infusions. Further efforts to systematize the management of children on ZA are needed. Supplementary Information The online version contains supplementary material available at 10.1007/s00774-021-01214-5.

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Zoledronic acid in pediatric metabolic bone disorders

Cited by 28 publications

References 78 publications

Low-dose zoledronate for the treatment of bone metastasis secondary to prostate cancer

Low-dose zoledronate for the treatment of bone metastasis secondary to prostate cancer

Response to Zoledronic Acid Infusion in Children With Fibrous Dysplasia

A quality improvement project to address the challenges surrounding zoledronic acid use in children

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