Efficacy and Safety of Zoledronic Acid in Sickle Cell Disease Associated Bone Disorders :Single Centre Experience
Authors: Bhatwadekar Seema , Deshpande Shubhangi , Lakhmapurkar Ujjwala , Kanade Smruti , Bhave Asmita , Bhatwadekar Shrinivas 
Published: December 2024

Introduction

Osteoporosis, osteopenia, avascular necrosis and bone infarcts are common findings in sickle cell disease (SCD).These complications often lead to a chronic state of pain in addition to the more acute painful episodes. Significant bone impairment is secondary to unbalanced increased osteoclastic activity.Zoledronic (ZA) decreases osteoclastic activity and promote osteogenic differentiation. Though ZA acid is not a FDA approved standard of care for SCD, mouse SCD study and few published studies in Paediatrics and Adults have shown its use as therapy to limit bone disease in SCD.In India SCD patients predominantly present with bone pain and AVN which eventually lead to bone deformity,disability and significant morbidity.Hydroxyurea,Folic acid ,Calcium,Vit D3 supplement and vaccination is standard of care (SOC) for SCD in India. Based on encouraging results of human SCD studies on ZA ,we added ZA to SOC treatment at our centre in SCD patients having significant bone pains.

Aim

Retrospective analysis of Efficacy and safety of ZA in SCD.

Method

A single centre retrospective study done on SCD patients who received SOC treatment with ZA at Hemato-oncology Care Centre (HOCC) Vadodara India. Total 116 SCD patients with severe refractory bone pains received ZA 4mg in 100ml NS over 1 hour intravenous as a day care treatment once in 28 days for 6 doses, followed by maintenance every 6 months only in respondents. Vitals monitoring and Complete Blood Count, S, Creatinine, Calcium, Vit D3 reports done prior to each ZA administration. Dose was omitted if any of parameter found abnormal. Telephonic follow up data on adverse events after 24 hrs and day 7 at home noted. Pain score and adverse events assessed at different timeline, at first ZA dose (T1), Third ZA dose (T2), Sixth ZA Dose(T3).

Result

A total 116 patients were analysed, The median age was 29 years. There was male preponderance with Male 80 and Female 36.Bone Pain was assessed on Visual Analog Scale (VAS).Score 0 no pain ,1-3 Mild pain,4-6 Moderate / Severe pain,7-9 Very Severe pain,10 Worst pain possible. Patients of score 4-6 or above received ZA. The frequency distribution of T1,T2,T3 VAS pain score was as follows:

T1: 4-6 score 83 (71.6%), 7-9 score 33(28.4%).

T2: 1-3 score 27 (23.3%), 4-6 score 89(76.7%), 7-9 score 0(0%).

T3: 0 score 4(3.4%), 1-3 score 86 (74%), 4-6 score 26(22.4%), 7-9 score 0(0%)

In our study, N=116 and the T scores categories are ordinal data type, the non-parametric Friedman test is used to find significant differences in these repeated sample data.

As the p-value &lt; 0.001 for the Friedman's test, we conclude that the difference between the mean ranks of T1, T2, and T3 categories are statistically significant.

The mean rank for T1 = 2.67, T2 = 2.02, and T3 = 1.31.

Adverse events observed within 7 days of ZA administration were mild and transient, fever 12(10%), myalgia 14(12%) arthralgia 17(15%), easily manageable with oral paracetamol at home. None of the patients had severe adverse reaction requiring discontinuation of ZA therapy.

Conclusion

ZA in SCD patients with severe bone pains has shown significant improvement in pain. No severe adverse effects observed. It is efficacious and safe supportive therapy option for patients of SCD with bone disease. It is cost effective option meeting the unmet needs in LMIC, however it needs validation of long term data in larger cohort.