Tumour-induced osteomalacia: symptoms, how it is diagnosed and treatment

The NHS explains that osteomalacia is the adult form of rickets, in which bones become soft and weak, and that it is usually caused by low levels of vitamin D and calcium. Tumour-induced osteomalacia is a different and much rarer route to the same bone problem. The international guidance on TIO describes it as a rare paraneoplastic syndrome caused by mesenchymal tumours that secrete FGF23, a hormone that normally helps control phosphate. Excess FGF23 makes the kidneys lose phosphate in the urine and reduces activation of vitamin D, so bone cannot mineralise properly.

The international guidance says the tumours are typically benign, though malignant tumours can occur. A case report from 2024 says they are often slow-growing and small, that the median size reported is 2.7 cm, that they typically cause no local symptoms, and that approximately 1,700 cases had been reported worldwide at that time. They can sit in soft tissue or bone almost anywhere, including the feet, which makes them hard to find.

The NHS lists the symptoms of osteomalacia as pain in the back, shoulder, ribs, pelvis or legs, changes in walking, tiring more easily, difficulty climbing stairs or getting out of a chair because of weak muscles, tingling, cramping or twitching of muscles, and breaking bones more often or after a minor accident, especially the hips, lower back and feet.

The international guidance says that patients with TIO usually present with a non-specific combination of diffuse bone pain, fractures, fatigue and muscle weakness, which makes the condition difficult to recognise. Symptoms develop gradually and are often attributed to musculoskeletal or rheumatological disease, and the guidance lists misdiagnoses including disc disease, spondyloarthritis, osteoporosis, rheumatoid arthritis, bone metastases and connective tissue disorders. It also notes that primary hyperparathyroidism is a common misdiagnosis because parathyroid hormone can be raised.

The guidance gives several reasons: the condition is rare, the symptoms are vague, serum phosphate is not routinely included in standard chemistry panels and there is often a failure to link low phosphate to the symptoms. It reports an initial misdiagnosis rate of 95 percent in the literature it reviews and a delay of 2.5 years between first presentation and tumour-related treatment.

A 2024 case report published in a BMJ journal illustrates this. A woman in her 40s had leg and hip pain evaluated repeatedly over about three years, was treated with physiotherapy and steroid injections and was advised to take vitamin D, before bilateral femoral neck fractures led to the diagnosis. The report is from Sweden and is cited here as an illustration of the pattern, not as UK practice.

The practical lesson, in the guidance, is to measure serum phosphate in anyone with chronic muscle pain or weakness, fragility fractures or bone pain, and to look at it in the context of vitamin D and kidney function.

The first step is a blood phosphate level taken fasting, together with urine phosphate and creatinine to calculate how much phosphate the kidneys are reabsorbing. The NHS says that in suspected osteomalacia a GP will check vitamin D and calcium levels with blood tests and a urine sample, and may refer to a specialist for more tests such as X-rays and bone scans.

The international guidance recommends priority laboratory tests including fasting phosphate and creatinine, urine phosphate and creatinine for TmP/GFR, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and FGF23 where available. The suspicious pattern is low phosphate, low TmP/GFR, normal or slightly low calcium, raised alkaline phosphatase, normal or raised parathyroid hormone, and an FGF23 that is raised or inappropriately normal. It recommends referral of people with clinical and biochemical suspicion to a specialist centre experienced in rare metabolic bone disease, and genetic testing to exclude hereditary hypophosphataemic disorders when no tumour is found or when onset is in childhood or young adulthood.

Finding the tumour is the hardest step. The guidance recommends functional imaging with a gallium-68 or copper-64 DOTA-peptide PET/CT scan as first-line, followed by anatomical imaging, and, where two lesions are seen, consideration of venous sampling of FGF23 levels to help localise the causative tumour.

The guidance recommends complete resection of the culprit tumour with tumour-free margins as definitive first-line treatment, to achieve cure. In the 2024 case report, phosphate levels normalised quickly after surgery, but recovery was long, with hungry bone syndrome, fracture healing and physical therapy.

When the tumour cannot be resected or located, the guidance recommends oral phosphate salts plus active vitamin D, or burosumab, considering availability, response and side effects, with monitoring every three to four months of calcium, phosphate, creatinine, parathyroid hormone, alkaline phosphatase and kidney ultrasound. Treatment in the UK is delivered by endocrinology and metabolic bone teams; access to burosumab depends on commissioning decisions.

Alongside this, supportive care includes pain control, physiotherapy to rebuild strength, falls prevention and, where fractures have occurred, orthopaedic management.

Outcomes can be very good when the tumour is found and removed. The guidance says early recognition and diagnosis can prevent disease progression, reverse damage already caused by excess FGF23, reduce the risk of permanent deformity and avert the harm of misdiagnosis. Delay is what causes the most harm: fractures, loss of mobility and psychological and financial strain are described in the case literature.

If the tumour cannot be found, symptoms can often still be controlled with medical treatment, but this requires long-term specialist follow-up and monitoring, including annual renal imaging for kidney calcium deposits and stones, as the guidance advises.

See a GP if you have persistent bone pain, muscle weakness that is getting worse, or fractures after minor injuries, and ask whether a serum phosphate has been checked alongside vitamin D and calcium. Seek urgent care through A&E or 999 for a suspected broken hip, severe injury or sudden inability to bear weight.

On the NHS, endocrinology teams, often in regional centres for rare metabolic bone disease, manage TIO, with nuclear medicine and surgical teams involved in localisation and removal. Private endocrinology can arrange blood tests and a second opinion, but specialised functional imaging and surgery are usually delivered through specialist hospital teams, so ensure that results and plans are shared across both.