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

Osteomalacia is an under-recognised disorder of bone mineralization. We present a case of osteomalacia secondary to Fanconi syndrome triggered by monoclonal gammopathy of unknown significance (MGUS).

65-year-old woman presented with multiple insufficiency fractures detected on bone scan and severe generalised pain with impaired mobility. She had long-standing malabsorption post-oesophagectomy for oesophageal adenocarcinoma (2017) resulting in 40kg weight loss, IgM MGUS (2018), and CKD IIIb. Prior femoral neck stress fracture was treated with hemiarthroplasty, but without anti-resorptives (2020).

Biochemistry revealed persistent hypophosphataemia (0.51-0.76mmol/L), hypouricaemia, elevated ALP 388U/L of bone predominant band, positive coeliac antibodies, generalised aminoaciduria, and renal phosphate wasting, but normal 25-hydroxy-vitamin D and PTH. Renal biopsy was negative for myeloma cast nephropathy. March 2023 BMD demonstrated T-scores of lumbar spine -1.8 and femoral neck -3.4.

She was diagnosed with osteomalacia secondary to Fanconi syndrome from MGUS with contributing malabsorption post-oesophagectomy and coeliac disease. She commenced gluten-free diet, calcitriol, and electrolyte replacement. Denosumab had been recommended prior to osteomalacia diagnosis, and did improve pain and ALP, but caused marked hypocalcaemia. After 12 months of treatment, repeat bone scan showed complete resolution of areas of prior radiotracer uptake. She now mobilises without aids and no longer requires opiate analgesia.

Osteomalacia diagnosis is challenging due to non-specific symptomatology and imaging. Acquired hypophosphataemic osteomalacia may be from Fanconi syndrome, malabsorption, or malnutrition.¹ Fanconi syndrome is a generalised defect of proximal tubular reabsorption resulting in aminoaciduria, hypophosphataemia, and hypouricaemia.² Increased excretion of monoclonal immunoglobulin (e.g., MGUS) can trigger Fanconi syndrome. These immunoglobulins are shown to be resistant to protease degradation and have increased tendency to form crystals accumulating in proximal renal tubules causing impaired reabsorption.³

Osteomalacia secondary to IgM MGUS-associated Fanconi syndrome is extremely rare complication only described in isolated case reports. Management is directed towards treating the underlying cause, and electrolyte replacement.