Background: In individuals with primary hyperparathyroidism (PHPT), the utility of preoperative bisphosphonate administration in prevention of post-curative-parathyroidectomy hungry bone syndrome (HBS) and effects on long-term bone accrual are uncertain.
Objectives: To estimate the effect of preoperative administration of single infusion of zoledronic acid (ZA) on occurrence of HBS and gain in bone mineral density (BMD) at one year in individuals with PHPT undergoing curative parathyroidectomy.
Methods: In this single-centre, randomized (1:1), single-blind, placebo-controlled study (CTRI/2019/10/021762), a total of 48 adults (age > 18 years) with PHPT (serum Calcium ≥ 11 mg/dl) were enrolled. Prior to parathyroidectomy (≤ 2 weeks), participants received either a single intravenous infusion of 5 mg ZA (n=24) or placebo (n=24). Post-curative-parathyroidectomy, participants were monitored for occurrence of HBS until discharge. HBS was defined by the presence of hypocalcemia (Ca< 8.5 mg/dl) and hypophosphatemia (P< 2.7 mg/dl) with rise in alkaline phosphatase (ALP) (>5%) on any day after surgery. BMD (Hologic Discovery 4500) and trabecular bone score (TBS) were assessed at baseline and one year after surgery. In addition, bone turnover markers (CTX, P1NP) were assessed at baseline, first week, 3-, 9- and 12- months post-surgery. Occurrence of HBS was assessed using binary logistic regression model. Changes in BMD and BTM were assessed using linear mixed model for repeated measures.
Results: Forty five out of 48 participants had succesful curative parathyroidectomy. HBS occured in 6 (27.3%) individuals in ZA and 6 (26.1%) in placebo group [OR: 1.06 (0.28 - 3.98);P=0.928]. The odds for developing HBS were comparable after adjusting for baseline severity and serum 25(OH)D levels (P=0.075). Individuals in ZA group had a higher gain in BMD at lumbar spine (7.54%; 95% CI, 0.06 to 15.02; P=0.048), comparable gain at neck of femur (9.74%; 95% CI, - 5.005 to 24.49; P= 0.190) and a fall in BMD at distal radius (3.29% ; 95% CI, -10.17 to 2.31; P=0.008). Rise in TBS was comparable between the two groups (P=0.396). The higher gain in BMD at lumbar spine was paralleled by a higher decline in CTX (27.8%; 95% CI, -48.44 to -7.12; P=0.009) in ZA group while ALP (10.9%; 95% CI, -23.39 to 1.44; P=0.082) and P1NP levels remained comparable (9.50%; 95% CI, -22.36 to 41.37; P=0.360).
Conclusion: In PHPT, preoperative administration of single infusion of ZA is associated with increased bone mineral accrual at lumbar spine without significant effect on occurrence of HBS.
21 May 2022 - 24 May 2022