The first patient, a 71-year-old woman, had been known to have osteoarthritis of the hip, knee and shoulder as well as osteoporosis for 4 years, on the basis of fractures of vertebrae, ribs and foot, and low T-scores (–3 by dual energy x-ray absorptiometry (DXA)), unresponsive to alendronate. She was suffering from severe back pain, increasing muscle weakness and fatigue. Laboratory studies showed progressively low phosphate (as low as 0.23 mmol/litre) found to be due to renal phosphate wasting (‘phosphate diabetes’). Parathyroid hormone (PTH; 117 ng/litre, normal <65) and alkaline phosphatase (286 U/litre, normal <120) were elevated but calcium, creatinine, 25-OH- and 1,25-(OH)2-vitamin D were normal. Treatment with oral phosphate and calcitriol was initiated. A tumour was suspected. Skeletal scintigraphy was consistent with osteoarthritis and fractures at multiple sites and an octreoscan showed an intense uptake at the first toe of the left foot.
The second patient, a 30-year-old man, developed bone pain (right proximal femur and ribs) and progressive proximal muscle weakness. Skeletal scintigraphy showed multiple areas of increased activity (fractures) in the right proximal femur, ribs and in the thoracic spine. Laboratory studies revealed phosphate of 0.48 mmol/litre and an inappropriately low 1,25-(OH)2 vitamin D (19 ng/litre, normal 20–67), despite hypophosphataemia and normal serum creatinine, calcium and 25-OH vitamin D, and high-normal serum PTH (61 ng/litre). Maximal renal tubular reabsorption of phosphate (TmPi/GFR) was low—that is, renal phosphate wasting contributed to hypophosphataemia and, thereby, to osteomalacia. Such biochemical hallmarks of an acquired disorder—that is, hypophosphataemia and low 1,25-(OH)2 vitamin D, suggested tumour-induced osteomalacia. Octreotide scintigraphy revealed an increased uptake in the right foot.