Tumour induced osteomalacia: 2 years treatment with burosumab

Ludovica Aliberti; Margherita Pontrelli; Martina Verrienti; Irene Gagliardi; Maria Chiara Zatelli; Maria Rosaria Ambrosio

doi:10.1530/endoabs.81.P288

Introduction: Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome due to an overproduction of fibroblast growth factor 23 (FGF23) by small and benign mesenchimal tumors. FGF23 increase causes hypophosphatemia, osteomalacia and muscle weakness. TIO is usually cured by tumour resection, but neoplasms may be unidentifiable/unresectable or the patient may refuse surgery. In these cases, medical treatment with high doses of oral phosphate and calcitriol is mandatory, even though it is usually insufficient to restore normal phosphate levels and is associated with low compliance. Burosumab is a human monoclonal antibody against FGF23 employed to treat X-linked hypophosphatemia(XLH), recently approved for TIO in USA. Maximum dose of Burosumab in XLH is 90 mg/2 weeks but there are no data on clinical efficacy and safety concerning the use of Burosumab in TIO

Case report: A 65 years old male presented to our attention for multiple non traumatic fractures (femoral neck, ribs, pelvic bone) and low bone mineral density. He was forced to use crutches because of pain and limb weakness, determining low personal autonomy and mobility. Biochemical evaluation showed hypophosphatemia (1.1 mg/dl), normal calcium and PTH, high ALP (514 U/l) and CTX (0.864 ng/ml), normal creatinine and low tubular phosphate reabsorption (80%), whereas c-FGF23 was elevated. After excluding drug-induced and genetic osteomalacia/hypophosphatemia, a 68GaPET was performed, identifying a lesion at the I right rib as cause of TIO. The patient refused surgery, therefore Burosumab therapy was started (initial dose 0.3 mg/Kg, gradually increasing to 60 mg/2 weeks). After 2 years of treatment, biochemical evaluation showed phosphoremia normalization and ALP reduction (138U/l). Patient clinical symptoms improved: Brief Pain Inventory (BPI) scores decreased, indicating reduced pain severity (from 1 to 0,5pt) and pain interference (from 3 to 0,6pt) as well as reduced fatigue (Brief Fatigue Inventory from 35 to 6pt). Sit-To-Stand Test and 6-minute Walking Test also improved (from 14.83s and 372 m to 11.08s and 430 m respectively). No side effects nor tumour progression were reported during follow-up

Table 1
	Basal	2 years of treatment	Reference Range
Phosphoremia	1.1 mg/dl	2.8 mg/dl	2.5-4.5 mg/dl
Calcium	9.8 mg/dl	9.7 mg/dl	8.5-10.5 mg/dl
ALP	514 U/l	138 U/l	30-120 U/l
CTX	0.864 ng/ml	0.55 ng/ml	0,115 - 0,748 ng/ml
1,25(OH)2vitamin D	180 pmol/l	63 pmol/l	36,5 - 216,2 pmol/l
Bone ALP	138 mg/l	72.7 mg/l	3-20,2 mg/l
TmP/GFR	0.85 mg/dL	1.53 mg/dl	2.47-4.18 mg/dl
TRP%	80%	97%	85-95%

Conclusions: Our experience supports efficacy and safety of the use of Burosumab every 2 weeks in TIO

Endocrine Abstracts

P288