Approach

A thorough clinical assessment is important in diagnosis as the condition is asymptomatic until fracture occurs. Clinical evaluation is based on a history of risk factors and a plan for screening. A history of prior low-impact fragility fracture is an indicator for this condition. Laboratory tests are carried out to exclude reversible secondary causes of low bone mass.

Clinical evaluation

The key components of the patient's history include age, sex, ethnicity, whether women are postmenopausal, history of immobilisation, and whether the patient has a history of previous fractures.[31]​ Other risk factors include a family history of maternal hip fracture, secondary amenorrhoea, primary hypogonadism, low calcium intake, vitamin D deficiency, diabetes, rheumatoid arthritis, sarcopenia, and hyperthyroidism.[31]​​[41][45][67]

The use of tobacco, alcohol, heparin, anticonvulsants, glucocorticoids, aromatase inhibitors (women) or androgen deprivation treatment (men), proton-pump inhibitors, and drugs associated with an increased risk of falling (e.g., benzodiazepines, antipsychotics, non-benzodiazepine benzodiazepine receptor agonists [also known as z-drugs], antidepressants) should be established.[31]​​​​[51][67]

The patient may report changes in height (specifically kyphosis), body weight, diet, and pain.[31]

The risk of fracture should be assessed and history of prior falls investigated.[68]

Physical examination

The examination may reveal low body mass index or spinal kyphosis due to asymptomatic fracture.

The risk of fall and fracture may be assessed by testing the patient's vision, and assessing balance, gait, and lower-extremity strength.

Imaging

Dual-energy x-ray absorptiometry (DXA)

Measurement of bone mineral density (BMD) using DXA is the gold standard test for diagnosing osteoporosis in patients without an osteoporotic fracture.[3][31]​​​[69][70]​​

DXA screening of patients with risk factors for osteoporosis will identify cases prior to fracture. However, there is some debate regarding the appropriate use of BMD analysis. For example, in the context of assessment for prevention of osteoporotic fractures, guidance from the National Institute for Health and Care Excellence states that for women aged 75 years or older who have one or more independent clinical risk factors for fracture or indicators of low BMD, a DXA scan may not be required if the clinician considers it to be clinically inappropriate or unfeasible.[71] Nonetheless, it is generally agreed that those with fragility fractures (low trauma fracture), oestrogen or testosterone deficiency, height loss, radiographic osteopenia, or rheumatoid arthritis (with or without corticosteroid treatment) and those on oral corticosteroid treatment are eligible for BMD analysis.[72]

Vertebral fracture assessment (VFA)

Moderate or severe vertebral fractures, even when asymptomatic, are strong risk factors for subsequent vertebral and non-vertebral fractures.[24]​ DXA-VFA can be performed during the same session as DXA-BMD analysis to provide images of the lumbar spine. DXA-VFA has moderate sensitivity and high specificity for detecting vertebral fractures compared with spinal radiography, with the advantages of reduced radiation exposure, lower cost, and greater convenience.[62][73]​​​​[74]​ In general, vertebral imaging (with either DXA-VFA or x-ray) should be considered for postmenopausal women and older men with low BMD, height loss, kyphosis, recent or ongoing long-term glucocorticoid treatment, or patients with acute onset back pain and risk factors for osteoporosis.​[24][62]​​​ However, recommended indications for vertebral imaging vary; consult local guidance.

Trabecular bone score (TBS)

TBS is a measure of bone microarchitecture derived from lumbar spine DXA images. TBS is an independent predictor of incident fracture and can be used in conjunction with BMD, clinical risk factors, and/or the Fracture Risk Assessment Tool (FRAX) to enhance the accuracy of fracture risk predictions.[69]​​[75]​ It may be most useful for patients with a BMD T-score or FRAX score close to an intervention threshold.​​[69]​​[75]

Quantitative ultrasound

Quantitative ultrasound (QUS) of the heel can be used as an alternative if DXA is unavailable, but the same diagnostic criteria defined for DXA cannot be applied to this technique.[3][76][77]​​​ QUS is, rather than a method for assessing BMD, a method to measure unknown elements of bone strength. QUS may be a good predictor of population-based fracture, but not individual fractures. Additionally, T-score has been tested only for DXA and cannot be applied to QUS.

X-ray

X-ray may reveal osteopenia and/or fractures (e.g., vertebral fractures), but is not diagnostic of condition.[78] It is used to drive the need for DXA assessment when osteopenia is detected coincidentally. It should be considered in patients with pain in the thoraco-lumbar spine, height loss, or thoracic kyphosis. X-ray is also used in therapeutic trials to assess fracture incidence.[78][Figure caption and citation for the preceding image starts]: Chest x-ray showing marked deformity and volume loss of bony thorax in a patient with osteoporosisBMJ Case Reports 2009; doi:10.1136/bcr.07.2008.0359. Copyright ©BMJ publishing group 2010 [Citation ends].com.bmj.content.model.Caption@7d2bf404

Quantitative CT

Quantitative computed tomography (CT) can be used to measure trabecular bone density if DXA is unavailable.[69][79][80]​​ Quantitative CT may also be useful for assessing patients with severe degenerative spine disease, obesity, or very tall or short patients.​​​[69]​ Projectional quantitative CT can provide hip BMD measurements equivalent to DXA that may be interpreted using World Health Organization (WHO) T-score criteria, but WHO T-score criteria cannot be applied to spine quantitative CT measurements.[69]​​[81]

FRAX

The FRAX was developed by the WHO to assess fracture risk. FRAX integrates clinical risk factors for fracture, with or without BMD scores at the femoral neck, to calculate a 10-year fracture probability for men and women.

FRAX can be used to help assess the need for BMD testing or pharmacological treatment.[24][31]​​[81]​ However, the American College of Obstetricians and Gynecologists highlights that the FRAX tool may be limited due to the inability to input specific amounts, dosage, or duration for alcohol intake, corticosteroid use, smoking, or the number of prior fractures. History of recent falls and spine BMD are not incorporated into the model, both of which increase the risk of osteoporotic fracture, which may lead to an underestimation of risk for these patients.[31]​ The FRAXplus calculator addresses some of these limitations with the introduction of additional variables (e.g., recency of fragility fracture, duration of type 2 diabetes mellitus, number of falls in the past year) to provide a more accurate estimate of fracture risk.[82]​

The American College of Physicians (ACP) notes that many risk assessment tools are available, but suggests an individualised assessment of baseline fracture risk based on bone density, history of fractures, response to prior osteoporosis treatment, and other risk factors.[67]

Laboratory evaluation

Biochemical markers of bone resorption, in conjunction with BMD, can be useful predictors of fracture risk and are typically ordered to aid in the decision whether to start treatment.[3] Bone turnover markers can be used specifically in monitoring response to treatment rather than for the approach to treatment.[83][84]

Laboratory evaluation is performed after diagnosis to ensure that there are no underlying causes of disease for which there is clinical suspicion based on history and physical examination.[2]​ Initial laboratory tests for all patients assess renal function, as well as calcium, albumin, phosphorus, and vitamin D levels. In men, it is also appropriate to check testosterone levels.

Results that suggest an underlying cause of osteoporosis are:[3]

  • Vitamin D deficiency (defined as 25-hydroxyvitamin D levels of <20 nanograms/mL)

  • Testosterone deficiency (in men)

  • Abnormal thyroid hormone levels (could indicate hyperthyroidism)

  • High levels of parathyroid hormone (could indicate hyperparathyroidism)

  • High levels of urinary free cortisol (could indicate Cushing's syndrome)

  • Abnormal serum/urine protein electrophoresis (could indicate myeloma)

  • Low serum 25-hydroxyvitamin D levels, low serum and urinary calcium levels, and low serum phosphate levels in conjunction with high levels of serum PTH and alkaline phosphatase (could indicate a vitamin D deficiency with or without osteomalacia).

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