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

Nasomyont, Nat; Hornung, Lindsey; Gordon, Catherine M.; Wasserman, Halley

doi:10.1016/j.bone.2019.01.003

Cited by 64 publications

(46 citation statements)

References 35 publications

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“…Although IV bisphosphonates are the most frequently prescribed agents for pediatric bone fragility, regardless of etiology (46,99,100), they remain off-label worldwide with the exception of neridronate in osteogenesis imperfecta (Italy). Most data on IV bisphosphonates have arisen from the pediatric osteogenesis imperfecta literature, where it has been shown that children receiving IV pamidronate, neridronate, and more recently zoledronic acid, demonstrate improvements in lumbar BMD Zscores, vertebral height ratios, muscle strength, activities of daily living, cortical thickness on trans-iliac biopsies, and reductions in long bone fracture rates (101)(102)(103).…”

Section: Intravenous Not Oral Bisphosphonates Are the Recommended Fmentioning

confidence: 99%

“…While IV pamidronate has historically been the most frequently used bisphosphonate (46,99), in recent years, zoledronic acid has been of interest due to the numerous indications for its use in adults, a shorter infusion time, and a longer duration of action compared with pamidronate. IV zoledronic acid is the most potent bisphosphonate available, approved globally to treat osteoporosis in men, in postmenopausal women, in adult GIO, and in the prevention of future fractures in adults with a prior history of low-trauma hip fractures.…”

Section: Intravenous Not Oral Bisphosphonates Are the Recommended Fmentioning

confidence: 99%

“…The side effects of IV bisphosphonate therapy are not trivial, especially in children with underlying diseases (99,112). The most frequent is "the acute phase reaction, " most marked following the first dose, consisting of fever, myalgias, arthralgias, bone pain, nausea, and vomiting.…”

Section: Intravenous Not Oral Bisphosphonates Are the Recommended Fmentioning

confidence: 99%

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Glucocorticoid-Induced Osteoporosis: Why Kids Are Different

Ward

2020

Front. Endocrinol.

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Glucocorticoids (GC) are an important risk factor for bone fragility in children with serious illnesses, largely due to their direct adverse effects on skeletal metabolism. To better appreciate the natural history of fractures in this setting, over a decade ago the Canadian STeroid-associated Osteoporosis in the Pediatric Population (“STOPP”) Consortium launched a 6 year, multi-center observational cohort study in GC-treated children. This study unveiled numerous key clinical-biological principles about GC-induced osteoporosis (GIO), many of which are unique to the growing skeleton. This was important, because most GIO recommendations to date have been guided by adult studies, and therefore do not acknowledge the pediatric-specific principles that inform monitoring, diagnosis and treatment strategies in the young. Some of the most informative observations from the STOPP study were that vertebral fractures are the hallmark of pediatric GIO, they occur early in the GC treatment course, and they are frequently asymptomatic (thereby undetected in the absence of routine monitoring). At the same time, some children have the unique, growth-mediated ability to restore normal vertebral body dimensions following vertebral fractures. This is an important index of recovery, since spontaneous vertebral body reshaping may preclude the need for osteoporosis therapy. Furthermore, we now better understand that children with poor growth, older children with less residual growth potential, and children with ongoing bone health threats have less potential for vertebral body reshaping following spine fractures, which can result in permanent vertebral deformity if treatment is not initiated in a timely fashion. Therefore, pediatric GIO management is now predicated upon early identification of vertebral fractures in those at risk, and timely intervention when there is limited potential for spontaneous recovery. A single, low-trauma long bone fracture can also signal an osteoporotic event, and a need for treatment. Intravenous bisphosphonates are currently the recommended therapy for pediatric GC-induced bone fragility, typically prescribed to children with limited potential for medication-unassisted recovery. It is recognized, however, that even early identification of bone fragility, combined with timely introduction of intravenous bisphosphonate therapy, may not completely rescue the osteoporosis in those with the most aggressive forms, opening the door to novel strategies.

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Section: Intravenous Not Oral Bisphosphonates Are the Recommended Fmentioning

confidence: 99%

Section: Intravenous Not Oral Bisphosphonates Are the Recommended Fmentioning

confidence: 99%

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Glucocorticoid-Induced Osteoporosis: Why Kids Are Different

Ward

2020

Front. Endocrinol.

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“…17 The use of IV BPs has been linked to hypocalcemia both in children and adults, [17][18][19][20] but only few studies have been conducted in patients with OI. [21][22][23][24][25][26][27][28][29] In the literature, there is only one study reporting the risk of hypocalcemia in OI patients treated with neridronate. Gatti et al assessed serum calcium levels 3 to 7 days after the neridronate infusion, observing calcium values ranging from 8.1 to 9.2 mg/dL (normal range, 8.5-10.2 mg/dL).…”

Section: Introductionmentioning

confidence: 99%

Hypocalcemia following Neridronate Administration in Pediatric Patients with Osteogenesis Imperfecta: A Prospective Observational Study

et al. 2020

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The use of intravenous bisphosphonates has been linked to hypocalcemia both in children and adults with osteogenesis imperfecta (OI). The aims of this study were: (1) to investigate the incidence of hypocalcemia in the first 48 hours (T48) after neridronate infusion in a pediatric population with OI and (2) to assess any correlation between the baseline values of calcium, vitamin D (25-hydroxyvitamin D) and bone turnover markers, and the postinfusion calcium values. We conducted a prospective observational study on 37 pediatric patients. All patients were treated with a single infusion of neridronate at a dose of 1 to 2 mg/kg. The study provided two postinfusion reassessments: 24 hours (T24) and T48 after neridronate administration. Hypocalcemia was observed in 11% of patients at T24 and in 50% of patients at T48 from neridronate infusion. We observed a positive linear correlation between the baseline vitamin D values and postinfusion calcium values, both at baseline and at T24 and T48. Hypocalcemia was mild and asymptomatic in all cases. Postinfusion calcium levels were related to baseline vitamin D levels. Consequently, low vitamin D levels should be considered a significant risk factor for hypocalcemia and should be carefully investigated and treated before neridronate infusion.

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“…Recently, Nasomyont et al published a study in which they also treated 19% of the patients with intravenous biphosphonate infusion out of the ISCD criteria. 23 One of these indications was low BMD without a history of fractures, another low BMD in association with kidney stones.…”

Section: Discussionmentioning

confidence: 99%

The Ketogenic Diet and Its Effect on Bone Mineral Density: A Retrospective Observational Cohort Study

Draaisma¹,

Hampsink²,

Janssen

et al. 2019

Neuropediatrics

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Background During long-term follow-up of children treated with the ketogenic diet therapy (KDT) have an increased incidence of bone fractures. However, the exact contribution of KDT to a decreased bone mineral density (BMD) remains unclear. Objective This study aimed to evaluate (changes in) BMD in children treated with KDT and to evaluate whether intravenous bisphosphonate therapy may be effective. Design In this retrospective, observational cohort study, all children treated with KDT from 2010 until 2018 at the Radboudumc Amalia Children's hospital were included. Patients who were on KDT for more than 6 months and who had at least two dualenergy X-ray (DXA)-scans were eligible for inclusion for longitudinal analysis. Z-scores of DXA-scans were compared over the course of time.Results In 34 out of 68 patients, one or more lumbar DXA-scans were performed, with a mean lumbar Z-score of À1.32 AE 1.74. Of these 68 patients, 8.8% got a fracture during KDT, and also 8.8% got kidney stones. In 20 patients, more than one DXA-scan was performed. A statistically not significant decrease in BMD (0.22 Z-score/year) was found. However, there was an increase in BMD in the five patients treated with intravenous bisphosphonate therapy. This was statistically significant in comparison to the nonbisphosphonate treated group (p ¼ 0.034). Conclusion Children on KDT have low normal BMD which may decrease further during KDT. For this reason monitoring of BMD is crucial, as is monitoring of kidney stones and hypercalciuria. Intravenous bisphosphonate therapy may have a positive effect, when other therapies have failed.

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

Cited by 64 publications

References 35 publications

Glucocorticoid-Induced Osteoporosis: Why Kids Are Different

Glucocorticoid-Induced Osteoporosis: Why Kids Are Different

Hypocalcemia following Neridronate Administration in Pediatric Patients with Osteogenesis Imperfecta: A Prospective Observational Study

The Ketogenic Diet and Its Effect on Bone Mineral Density: A Retrospective Observational Cohort Study

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