Safety and Efficacy of Zoledronic Acid as Add on Therapy to Calcitriol in Patients of Osteoporosis with Liver Cirrhosis: A Prospective Randomized Controlled Trial

ABSTRACT

Background: Hepatic osteodystrophy includes osteoporosis in liver cirrhosis (LC). The presence of osteoporosis has long term impact in patients of LC in both pre-and post liver transplant setting. Zoledronic acid is a third generation bisphosphonate. Compared to oral bisphosphonates, it has added benefit of no risk of esophagitis and intravenous administration on annual basis. Limited data is available on use of zoledronic acid in patients of LC. We evaluated safety and efficacy of zoledronic acid as add on therapy to calcitriol in patients of LC with osteoporosis. Method(s) A prospective controlled randomized, open label clinical trial was conducted at tertiary care center in patients of liver cirrhosis from March 2020 till January 2022. Trial was registered with Clinical trial registry CTRI/2020/03/024247 dated 25.03.2020. Patients of LC were screened with DEXA scan. Diagnosis of osteoporosis was made with z-score <-2.0 and/or t-score <-2.5 at LS-spine and/or hip. At baseline bone mineral density (BMD) at spine and hip and FRAX (fracture risk assessment tool) score major osteoporotic (MO) and major hip (MH) were determined. Patients were divided into group I zoledronic acid (5 mg intravenous single dose) + SMT, Group II standard medical therapy (SMT) (oral calcitriol 0.25 mug BID and calcium 500 mg BID) for 12 months. Primary end points included DELTABMD at spine and hip, DELTAFRAX score MO and DELTAFRAX score MH at 12 months. Secondary end points included any pathological fracture, change in serum calcium, phosphorus, ALP, vitamin D levels and quality of life (QOL) assessment by IOF QoL QUALEFFO-41 at 12 months. Result(s) Out of 117 patients of LC, 58 had osteoporosis. Finally, 49 patients were randomized with 25 patients allocated to group I and 24 to group II. Due to COVID-19 pandemic enrolment was severely affected and 11 patients were lost to follow up. An intention to treat analysis was done. In primary end points, BMD increased from baseline to 12 months in Group I at LS spine (0.742+/-0.016 to 0.93+/-0.02, P<0.001) and right hip (0.744+/-0.019 to 0.923+/-0.039, P<0.02) as compared to group II at LS-spine (0.77+/-0.01 to 0.77+/-0.02, P=0.6) and right hip (0.808+/-0.022 to 0.81+/-0.21, P=0.09) gm/cm3 respectively. The FRAX score MO (3.16 to 1.91, P<0.001) and FRAX score MH (1.47 to 0.55, P<0.001) decreased from baseline to values at 12 months in group I as compared to group II FRAX score MO (2.97 to 2.82, P=0.07) and FRAX score MH (1.3 to 1.19, P=0.17) respectively. In secondary end points, no significant change was seen in presence of any pathological fracture or serum calcium, phosphorus, ALP and vitamin D levels. QUALEFFO score increased by +13.8 (28.7%) which was statistically significant (P<0.001) compared to baseline QUALEFFO score. No significant difference for adverse effects was noted between two groups. Conclusion(s) Zoledronic acid was safe and effective in improving BMD and FRAX score MO and MH, QUALEFFO score at 12 months in patients of LC with osteoporosis as compared to SMT. (Figure Presented).