26th January 2024

Diagnosis

The assessment of patients with osteoporosis consists of three main stages: assessment of fragility fracture risk, ruling out secondary causes for fragility fractures and osteoporosis, and the diagnosis of osteoporosis via DEXA scan. The overall aim is to assess patients depending on their risk factors and initiate treatment in order to prevent fragility fractures. However, unfortunately, in many patients, the occurrence of a fragility fracture may be the first indicator of an underlying diagnosis of osteoporosis, which is otherwise an asymptomatic condition. 

Assessment of fragility fracture risk 

NICE guidelines recommend the following algorithm for the identification of high-risk patients to assess for risk of developing a fragility fracture:

• All women over the age of 65 and all men over the age of 75
• Women between the ages of 50 and 64 and men between the ages of 50-74 who have at least one of the following risk factors:
  • Personal or family history of osteoporotic fracture 
  • Use of oral glucocorticoids 
  • History of falls 
  • Causes of secondary osteoporosis
  • Low BMI 
  • Smoking
  • Alcohol intake more than 14 units per week for women and more than 21 units per week for men 
  • Secondary cause of osteoporosis, e.g. rheumatological or endocrine conditions 
• Men and women under the age of 50 years with any of the following risk factors:
  • Use of oral glucocorticoids 
  • Untreated premature menopause
  • Previous fragility fracture 
• Men and women under the age of 40 years with any of the following risk factors:
  • Use of oral glucocorticoids equivalent to, or more than, 7.5 mg prednisolone daily for 3 months or more
  • Previous fragility fracture 
• Consider assessing fracture risk for patients taking certain medications, e.g. SSRIs, antiepileptics, aromatase inhibitors, PPIs, and thiazolidinediones.

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.

Calculating fracture risk 

The diagnosis of osteoporosis is mainly based on an assessment of BMD. However, most osteoporotic fractures occur in patients who do not have a T score of less than -2.5; therefore, an assessment of clinical risk factors and the extent to which these can contribute towards risk of fall should be carried out, independently of BMD. According to NICE guidelines, patients who are at high risk of developing osteoporosis should have an assessment of fracture risk prior to arranging a DEXA scan – this can be done by using a validated online risk calculator such as QFracture or FRAX, which predict the absolute risk of hip and major osteoporotic fracture over a 10 year period. The FRAX calculator calculates the probability of people between the ages of 40 and 90 having a major fragility fracture. The following risk factors are taken into account:

• Sex
• BMI
• History of previous fracture
• Parental history of fracture
• Current smoking status
• Use of glucocorticoids
• History of rheumatoid arthritis
• Secondary osteoporosis
• Alcohol intake of 3 or more units per day
• Femoral neck BMD (if result available)

Patients are then classified as being low, intermediate or high risk according to their results, and subsequent NOGG advice is given regarding the need for treatment. The QFracture score is based on UK data and can be calculated for patients aged 30-99 without a value for BMD. In addition to the risk factors calculated in the FRAX score, the QFracture score also includes ethnicity, residence in care home, history of falls, dementia, cerebrovascular disease, chronic liver disease, and whether the patient is on high-risk medications other than glucocorticoids. Those patients who are identified as having a 10-year fracture risk of 10% or more should then be considered for undergoing a DEXA scan. Fragility fracture risk scores should ideally be carried out prior to DEXA scan; however, in patients over the age of 50 years with a history of fragility fracture or patients younger than 40 years with major risk factors for fracture, DEXA can be carried out without the use of FRAX or QFracture scores. 

DEXA scan 

The gold standard method of diagnosis for osteoporosis is a DEXA scan. Although DEXA carries an accuracy of more than 90% at the hip, it is important to note that false-positive results can be caused by conditions such as osteomalacia, osteoarthritis or soft-tissue calcification. A T-score of less than -2.5 on the DEXA indicates osteoporosis; a score of less than -2.5 with the presence of fragility fractures indicates severe osteoporosis. DEXA is the preferred method of diagnosis of osteoporosis; however, NICE guidelines states that for women aged 75 years or older who have one or more independent risk factors, DEXA may not be required if the clinician deems it to be clinically inappropriate or impractical to carry out. In addition, for some patients with vertebral fractures, it may be suitable to commence drug treatment without carrying out a DEXA scan. Other investigations, such as ultrasound measurement of bone at the heel or single-energy x-ray absorptiometry, can be used for the assessment of fracture risk; however, have not been validated for the diagnosis of osteoporosis. Plain x-rays can detect fractures and osteopenia (low bone density but not severe enough to cause osteoporosis) but not osteoporosis. CT scan can be used if DEXA is not available. 

References

• 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.
• Conaghan PG, Dickson J, Grant RL. Care and management of osteoarthritis in adults: summary of NICE guidance. Bmj. 2008 Feb 28;336(7642):502-3.
• 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.
• National Institute for Health and Care Excellence (Great Britain). Osteoporosis: assessing the risk of fragility fracture. National Institute for Health and Care Excellence (NICE); 2017