LAUSR

Osteoporosis affects over 1 million Australians and is due to reduced bone mass and disruption of bone microarchitecture resulting in increased risk of fracture. Osteomalacia may also present with low bone mineral density (BMD) and atraumatic fractures, but is due to reduced mineralisation of bone rather than low bone mass. The commonest cause of osteomalacia worldwide is calcium/ vitamin D deficiency, but it is rare in the developed world. We present a 46-year-old man with delayed healing of an atraumatic stress fracture of the left distal tibia. BMD was reduced at the hip (T-score: −2.5 SD) and screening tests for secondary osteoporosis were negative apart from an elevated alkaline phosphatase (fracture related) and a marginally reduced serum phosphate (0.77 mmol/ L, normal range (NR): 0.80–1.50). At baseline, parathyroid hormone was within the normal reference interval (5.6 pmol/L; NR: 1.3–7.6). After 3 years of bisphosphonate treatment, the BMD remained low, his fracture failed to heal and further fractures of the ribs, left calcaneus, talus and metatarsals were demonstrated on bone scan/magnetic resonance imaging (MRI). He also developed progressive hypophosphataemia (nadir 0.56 mmol/ L) with evidence of urinary phosphate wasting. Fanconi syndrome was excluded as the 24-h urine collection demonstrated phosphaturia and reduced tubular reabsorption of phosphate without accompanying hypercalciuria, aminoaciduria or glycosuria. Despite hypophosphataemia, 1,25-dihydroxyvitamin D level was inappropriately normal at 163 pmol/L (NR: 60–200) and fibroblast growth factor-23 (FGF-23), a phosphaturic renal hormone, was mildly elevated (56 ng/L, NR: 10–54) raising suspicion of ectopic production. Bisphosphonate therapy was suspended and calcitriol was commenced with normalisation of serum phosphate. Whole body imaging with Gallium-68 DOTATATE positronemission tomography (PET)/computed tomography (CT) demonstrated multiple new stress fractures in the bilateral ilia, ribs and medial femoral condyles as well as an octreopeptide-avid 20 × 26 mm sclerotic lesion in the left lateral femoral condyle (Fig. 1). MRI of the lesion suggested bone infarction, however, in the clinical context, tumour-induced osteomalacia (TIO) secondary to a mesenchymal FGF-23 secreting tumour was considered more likely. Histology of the surgically excised lesion confirmed the diagnosis of benign mesenchymal tumour with positive immunohistochemical staining for somatostatin receptor 2A and FGF-23. Post-operatively, FGF-23 levels normalised and the patient experienced resolution of his fractures. TIO results in reduced bone mineralisation due to FGF-23 mediated urinary phosphate wasting. Phosphaturic mesenchymal tumours are almost always benign, and usually very small without focal diagnostic signs.