26th January 2024

Differential diagnoses

The following conditions can be difficult to distinguish clinically from osteoporosis. However, a thorough history, clinical examination and some investigations can be used in order to rule out conditions which can also either lead to bone pain or increase the risk of fractures. 

• Multiple myeloma – can present with bone pain, but patients would most commonly have other associated features such as renal failure or anaemia. This can be ruled out by the presence of Bence Jones proteins on urine electrophoresis or monoclonal gammopathy on serum electrophoresis.
• Osteomalacia – in osteomalacia, there is a normal amount of bone with a low mineral content (in contrast to osteoporosis, where mineralisation levels are unchanged, but there is overall bone loss). It is associated with vitamin D deficiency or resistance. Blood tests in patients with osteomalacia would normally reveal low vitamin D, calcium and phosphate levels and raised alkaline phosphatase and parathyroid hormone (PTH) levels. It can be distinguished from osteoporosis using bone biopsy.
• Chronic renal disease and associated bone and mineral disorders – patients often have poor renal function with elevated serum creatinine and PTH levels. 
• Primary hyperparathyroidism – this can present with features of hypercalcaemia such as constipation, abdominal pain, and psychiatric disturbances in addition to bone pain. Investigations in patients with primary hyperparathyroidism would normally reveal high calcium and alkaline phosphatase levels and low phosphate levels. PTH would be elevated or inappropriately normal. 24-hour urinary calcium levels would be raised. 
• Primary or metastatic bone malignancy – patients may have a known history of cancer or presence of symptoms indicating primary malignancy. DEXA scan may be normal, but CT or radio nuclear bone scans could reveal presence of a tumour. Bone biopsy is the definitive test of differentiation between malignancy and osteoporosis. 
• Vertebral deformities – conditions such as osteoarthritis or scoliosis may be mistaken for osteoporotic vertebral fractures. X-ray and other imaging modalities can be used in cases of diagnostic uncertainty. 

References

• Wilkinson I, Wilkinson IB, Raine T, Wiles K, Goodhart A, Hall C, O’Neill H. Oxford handbook of clinical medicine. Oxford University Press; 2017.
• Compston J, Bowring C, Cooper A, Cooper C, Davies C, Francis R, Kanis JA, Marsh D, McCloskey EV, Reid DM, Selby P. Diagnosis and management of osteoporosis in postmenopausal women and older men in the UK: National Osteoporosis Guideline Group (NOGG) update 2013. Maturitas. 2013 Aug 1;75(4):392-6.