SUN-749 Denosumab In Combination With Burosumab For A Case Of X-linked Hypophosphatemia Associated With Postmenopausal Osteoporosis

Abstract R.A. Alnajimi: None. A.A. Khan: Other; Self; Amgen Inc, Research Fund. Denosumab in Combination With Burosumab for a Case of X-Linked Hypophosphatemia Associated With Postmenopausal Osteoporosis Background X-linked hypophosphatemia (XLH) is a rare inherited metabolic disorder with multisystem manifestations. This progressive disease is characterized by hypophosphatemia due to excess serum levels of fibroblast growth factor 23 (FGF23) resulting in renal phosphate wasting and reduced 1,25-dihydroxyvitamin D synthesis. Denosumab is effective in reducing fractures in patients with postmenopausal osteoporosis. We report a case of coexisting osteoporosis in a patient with XLH and management with denosumab. Clinical Case A 55-years old female presented with a diagnosis of XLH at 5 years of age. She had presented with bowing of legs. No history of fractures, dental abscesses, osteoarthritis, enthesopathy or renal disease. She had been treated with conventional therapy (phosphate salts and active vitamin D) with intermittent interruption of phosphate between ages 64 and 69, leading to high ALP consistent with osteomalacia. At age 59 years, the patient was diagnosed with hypertension and hyperparathyroidism secondary to chronic kidney disease. PTH remained elevated despite reductions in active vitamin D dose and phosphate. phosphate levels were between 0.59-1.29 mmol/L (RR: 0.8-1.45). At age 64 years, the BMD at total hip site was 0.420 g/cm2 corresponding to T-score -3.0. At the age of 67 years, she developed hypercalcemia with elevations of ionized calcium and PTH, ALP remained high. Calcium creatinine clearance ratio was low at 0.009 attributed to stage 3a CKD. Burosumab was initiated at this stage, the mean PO4 levels remained in the low range at 0.63-0.79 mmol/L with mean TmP/GFR of 0.44-0.78 (RR: 0.96 -1.44). The patient was offered parathyroidectomy but she declined and she also declined cinacalcet to improve parathyroid function. At 69-years of age, she agreed to start 60 mg denosumab 6 monthly for coexisting postmenopausal osteoporosis. She had elevations in ALP ,PTH , persistent hypophosphatemia and renal phosphate leakage. Subsequent evaluation at 70-years of age revealed that with Denosumab and Burosumab, normal ALP and ionized Calcium were restored, despite low PO4 at 0.60 mmol/L in association with hyperparathyroidism as PTH was elevated at 29.4 pmol/l . The BMD at the total hip site showed improvement, measuring 0.852 g/cm2, corresponding to a T-score of -1.2 Conclusion To our knowledge, this is the first case demonstrating the potential role of denosumab in short-term treatment of coexisting postmenopausal osteoporosis in an XLH patient as evidenced by improved BMD. However, the long-term efficacy of denosumab needs to be determined. Sunday, June 2, 2024