SUN-514 Severe Hypophosphatemia and Worsening Secondary Hyperparathyroidism Following Treatment with Denosumab

• Published in: Journal of the Endocrine Society 2019-04, Vol.3 (Supplement_1)
• Main Authors: Adepoju, Yewande, Khitan, Zeid, Khthir, Rodhan
• Format: Article
• Language: English
• Subjects: Bone and Mineral Metabolism
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/js.2019-SUN-514

Introduction We present a case of a patient with osteoporosis and chronic kidney disease (CKD)-induced secondary hyperparathyroidism who developed severe hypophosphatemia and increasing parathyroid hormone (PTH) level after receiving Denosumab. Clinical Case 90-year-old male with CKD stage 3 presented for hyperparathyroidism evaluation in 2015. Baseline GFR was 39 - 47 ml/min/1.73 m 2 . PTH was 320 pg/ml (8 - 97 pg/ml) with normal calcium and low vitamin D (25-D) 14 ng/ml (30 - 100 ng/ml). Repeat PTH was 299 pg/ml; 25-D 23 ng/ml and 24-hr urine calcium was 8 mg (100 - 300 mg). Hyperparathyroidism was concluded to be due to CKD and Vitamin D deficiency. Vitamin D was replaced and PTH decreased to 262 pg/ml. With fragility fracture history, dual-energy X-ray absorptiometry (DXA) scan was obtained and resulted with a T-score of -2.8 SD at the femoral neck. Denosumab (60 mg) was started after 25-D normalized in 3/2016. Follow-up laboratory analysis in 8/2016 revealed PTH 512 pg/ml, calcium 8.9 mg/dl (8.5 - 10.1 mg/dl), 25-D 44.7 ng/ml and phosphate 1.3 mg/dl (2.5 - 4.5 mg/dl), previously 2.1 mg/dl. Alkaline phosphate 104 U/l (45 - 117 U/l), calcitriol 63.9 pg/ml (19.9 - 79.3 pg/ml) and fibroblast growth factor 23 (FGF-23) 188 RU/ml (44 - 215 RU/ml). 24-hr urine calcium was 27 mg and phosphate >90 mg/dl. Serum phosphate improved with supplementation and Cinacalcet started for high PTH. After the second Denosumab injection, low phosphate (1.2 mg/dl) recurred and PTH remained high (510 pg/ml). With recurrent effects, Denosumab was switched to bisphosphonate as GFR was stable >40 ml/min/1.73 m 2 . PTH normalized to 78 pg/ml and phosphate stable (2-2.4 mg/dl) on Cinacalcet and off Denosumab. Discussion Hypophosphatemia is a rare side effect of Denosumab, a monoclonal antibody to RANK-L. PTH mildly increase with Denosumab secondary to hypocalcemia. In our patient, there was a significant rise in PTH level and a decline in phosphate following Denosumab administration with no effect on calcium level. There are very few reports of these combined adverse events in the literature. The proposed mechanism is that the irreversible blockade by Denosumab results in low bone turnover which then causes increase in PTH and then increase urinary phosphate excretion. This mechanism can apply to CKD patients with secondary hyperparathyroidism when given a blocking agent like Denosumab, there is a further increase in PTH in the setting of low bone turnover. If not closely monitored,