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Pamidronate administration may result in anaemia in children with osteogenesis imperfecta
  1. Izabela Michałus1,
  2. Zuzanna Nowicka2,
  3. Wiktoria Aleksandra Pietras3,
  4. Maja Nowicka4,
  5. Elżbieta Jakubowska-Pietkiewicz1
  1. 1 Department of Paediatrics, Neonates Pathology and Bone Metabolic Diseases, Medical University of Lodz, Lodz, Poland
  2. 2 Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland
  3. 3 Student’s Scientific Association, Department of Pediatrics, Neonates Pathology and Bone Metabolic Diseases, Medical University of Lodz, Lodz, Poland
  4. 4 Department of Clinical Pharmacology, Medical University of Lodz, Lodz, Poland
  1. Correspondence to Dr Izabela Michałus, Department of Pediatrics, Neonates Pathology and Bone Metabolic Diseases, Medical University of Lodz, 36/50 Sporna Street, 91-738, Lodz, Poland; izabela.michalus{at}gmail.com

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Bisphosphonates are regarded as standard of care for severe forms of osteogenesis imperfecta (OI).1 Intravenous administration is well tolerated and short-term adverse effects are mild; however, more severe reactions were occasionally reported.2 Although anaemia is a known side effect of intravenous bisphosphonates in adults,3 it has not been reported in children with OI. Here, we investigated blood parameters changes in patients with OI treated with intravenous pamidronate.

In this retrospective study, we included children with OI treated in our site over April 2014–May 2018 period. Eligible patients had at least one treatment cycle with complete blood morphology data from before the first dose and >12 hours after last infusion. Pamidronate was administered according to the ‘standard protocol’2; it was diluted in 50 or 100 mL of 0.9% sodium chloride and administrated intravenously over 4 hours.4

We obtained data regarding patients’ sex, age, OI type, body mass, height, adverse reactions and laboratory data for each pamidronate administration cycle. Anaemia was defined as the haemoglobin level below the reference range. Normal C reactive protein (CRP) level was defined as below 5 mg/L. For 58 patients, complete data from 294 administration cycles were available (table 1).

Table 1

Demographic and baseline clinical characteristics of the 58 patients included in the study as compared between OI types

Most common adverse effects were hypocalcaemia, fever and elevated CRP; 20/23 cases of fever occurred during the first treatment cycle. Anaemia was observed in 56/294 (19.0%) administration cycles (in 31 patients) following infusion, as compared with 17 (5.9%) before treatment.

After including in the analysis one treatment cycle per child, we observed that median RBC level decreased from 4.7 (minimum 2.7, maximum 5.6) × 1012/L to 4.4 (2.3–5.3) × 1012/L (p<0.001), HGB from 130 (81–182) to 12.6 (73–181) g/L (p<0.001), haematocrit from 38.4 (23.9–52.3) to 36.5 (19.8–53.6)% (p<0.001) and white cell count from 8.65 (3.7–17.6) × 109/L to 7.2 (2.4–19.4) × 109/L (p<0.001) (figure 1). Haemoglobin decreased ≥20 g/L in 30/294 analysed cycles (in 22 children); this change was not associated with the change in CRP level (p=0.122). No symptoms directly attributable to anaemia, besides nausea and dizziness in 5/294 cases, were noted. One patient, however, required blood transfusion after her haemoglobin levels dropped from 97 to 81 g/L following pamidronate administration.

Figure 1

(A) Haemoglobin concentration (g/dL), (B) red cell count (×106/mL), (C) haematocrit (%) and (D) white cell count (×103/mL) at baseline and at the end of cycle. Horizontal line represents median, box represents lower and higher quartiles (25%–75% of data) and whiskers represent minimum to maximum range. All presented changes are significant at p<0.001. HCT, haematocrit; HGB, haemoglobin concentration; RBC, red cell count; WBC, white cell count.

Here, we report that children with OI receiving intravenous pamidronate experience a decrease in blood parameters and, in some cases, anaemia. To the best of our knowledge, this is the first report on such an association.

Anaemia after pamidronate administration was reported as a treatment-related adverse reaction in adults, and the Food and Drug Administration recommends that either haematocrit or haemoglobin levels be monitored in patients treated with pamidronate.3 Our results show 19% of patients with a reduction in haemoglobin significant enough to be classified as anaemia.

While dilution following intravenous infusion may have contributed, all samples were drawn more than 12 hours after the infusion, limiting this effect. Alternative hypotheses include inflammation or haemolysis. Investigation of these mechanisms was, however, beyond the scope of the current study. Blood parameters should be monitored in paediatric patients treated with pamidronate.

References

Footnotes

  • Contributors Study design: IM, ZN, WAP and MN. Data collection: IM, EJ-P, ZN, WAP and MN. Data analysis: ZN. Data interpretation: IM and ZN. Drafting manuscript: IM, ZN, WAP and MN. Revising manuscript content: IM, ZN, WAP, MN and EJ-P. Approval final version of manuscript: IM, ZN, WAP, MN and EJ-P. ZN takes responsibility for the integrity of the data analysis.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Patient consent for publication Not required.