Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Hypophosphataemia without hypocalcaemia after xgeva denosumab 120mg (#638)

Nupoor Tomar 1 2 3 , Cherie Chiang 1 2 4 , Seah Jas-Mine 1 2 3 5
  1. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
  2. Endocrinology, Austin Health, Heidelberg, VIC, Australia
  3. Endocrinology, Centre for Research and Education in Diabetes and Obesity, Melbourne, VIC, Australia
  4. Endocrinology and Diabetes, Royal Melbourne Hospital, Melbourne, VIC, Australia
  5. Endocrinology, Northern Hospital, Melbourne, VIC, Australia

It is well recognized that Denosumab can cause hypocalcaemia (1). With or following hypocalcaemia,  hypophosphatemia from Denosumab can also occur due to bone specific parathyroid hormone inhibition(2).

We present a case of a 72-year-old woman with triple hormone receptor positive breast cancer with bone oligometastasis managed with paclitaxel, pertuzumab, trastuzumab and palliative radiotherapy. She otherwise has hypertension on hydrochlorothiazide and irbersartan, as well as osteoporosis on Denosumab 60mg bi-annually which she has tolerated well for 6 years. Denosumab 120mg (XGEVA) was commenced in place of 60mg for prevention of skeletal related events. Seven days after XGEVA, she developed asymptomatic hypophosphatemia (PO4 = 0.43 mmol/L ) with normal corrected calcium (2.37 mmol/L), hyperparathyroidism (25.7 pmol/L, RR = 1.6 - 6.0 pmol/L) and normal magnesium (0.84 mmol/L), albumin 32g/L, Vitamin D (72 nmol/L) and eGFR was at baseline (71 ml/min/1.73m²). Calculated tubular maximum resorption of phosphate to GFR (TmP-GFR) was 0.3 mmol/L (RR 0.7 – 1.35) indicating renal phosphate wasting. She had no prior parenteral iron, had never previously been hypocalcaemic or significantly hypophosphataemic, and had no evidence of pan renal tubular dysfunction. Intravenous magnesium and phosphate were required to normalise levels as to poor tolerability of oral phosphate supplements. Her chemotherapy agents are not known to be associated with hypophosphatasemia and no precipitant other than denosumab was identified. Denosumab was ceased and our patient subsequently received Zoledronic acid infusion with normophosphatemia without PO4 supplements.

66b5b3be1ef08-Graph+1+ESA-ANZBMS+Submission.png

 Graph 1: Trend in relevant biochemistry

This case highlights the lesser recognised side effect of hypophosphataemia after XGEVA, occurring much more commonly than after denosumab 60mg or Zolendronic Acid (3). Mechanisms may be due to multiple risk factors of hypophosphataemia in patients with cancer related bone metastases and unrecognised renal tubular dysfunction (4).

 

  1. 2. Megapanou E, Florentin M, Milionis H, Elisaf M, Liamis G. Drug-Induced Hypophosphatemia: Current Insights. Drug Saf. 2020;43(3):197-210.
  2. 3. Nguyen PA, A. Kalis PBJ, R. Sutz PT, D. Jeffers PBK. Development of a Practice Standard for Monitoring Adult Patients Receiving Bone-Modifying Agents at a Community Cancer Center. Journal of the Advanced Practitioner in Oncology. 2018;9(6).
  3. 4. Adhikari S, Mamlouk O, Rondon-Berrios H, Workeneh BT. Hypophosphatemia in cancer patients. Clinical Kidney Journal. 2021;14(11):2304-15.
  4. 1. Dave, V., Chiang, C. Y., Booth, J., & Mount, P. F. (2015). Hypocalcemia post denosumab in patients with chronic kidney disease stage 4-5. American journal of nephrology, 41(2), 129-137.