26th January 2024

Ruling out secondary causes of fragility fractures and osteoporosis

In patients who are diagnosed with osteoporosis or sustain a fragility fracture, further investigations are recommended by the National Osteoporosis Guideline Group (NOGG) to exclude disorders that present like osteoporosis, identify causes and risk factors for osteoporosis, assess risk of further fractures and enable appropriate selection of treatment.

The following investigations are recommended by NOGG, in addition to a full history and clinical examination:

• FBC
• ESR or CRP
• Serum calcium – low in osteomalacia, elevated in hyperparathyroidism
• Serum albumin – may be decreased in osteoporosis
• Serum creatinine – to rule out chronic kidney disease-associated bone disorders
• Serum phosphate – low in osteomalacia
• Serum alkaline phosphatase – raised in osteomalacia
• Liver function tests
• Thyroid function tests – to rule out hyperthyroidism as a cause of osteoporosis

Additional procedures are also recommended if there is a suspicion of alternative diagnoses:

• Lateral radiographs of lumbar and thoracic spine – to investigate for fractures
• Protein immunoelectrophoresis and urinary Bence-Jones proteins – in elderly patients with multiple spontaneous vertebral fractures to rule out multiple myeloma
• 25-hydroxy vitamin D – to rule out vitamin D deficiency
• Serum parathyroid hormone – to rule out hyperparathyroidism
• Serum testosterone – should be considered in all young men with osteoporosis – low levels may indicate hypogonadism
• 24-hour urinary cortisol/dexamethasone suppression test – in patients with features suggestive of Cushing’s syndrome
• Endomysial and/or tissue transglutaminase antibodies – if symptoms suggestive of coeliac disease
• Isotope bone scan – if concerned about malignancy
• Biochemical markers of bone resorption and formation can mostly be used to monitor response to treatment rather than diagnosis of osteoporosis.
• Urinary calcium excretion – to rule out chronic kidney disease

Table 5: Biochemical markers of bone formation and resorption

Adapted from Vasikaran S, Eastell R, Bruyere O, Foldes AJ, Garnero P, Griesmacher A, McClung M, Morris HA, Silverman S, Trenti T, Wahl DA. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporosis international. 2011 Feb;22(2):391-420.