Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age

Recommendations

Diagnostic investigations

Evidence statement

Two major international guidelines recommend that the diagnostic assessment for osteoporosis consist of medical history, clinical examination, BMD measurement by DXA, and, if applicable, laboratory tests and radiographs of the thoracic and lumbar spine.2,3  The recommended standard procedure for BMD measurement is bone densitometry by DXA.1–3 For some patients at risk, as indicated by history, clinical examination or Z-scores <–2.0, laboratory findings can reveal unsuspected secondary osteoporosis or may influence some aspects of diagnostics and therapy. In patients in whom a specific secondary, treatable cause of osteoporosis is being considered, relevant blood and urine studies should be obtained prior to initiating therapy.2

Grade: A

Recommendation 4
Measure bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) scanning on at least two skeletal sites, including the lumbar spine and hip, unless these sites are unsuitable (eg hip prosthesis).

Grade: D – consensus

Recommendation 5
Diagnostic assessment for osteoporosis should consist of medical history, clinical examination and BMD measurement by DXA. If applicable, laboratory tests and radiographs of the thoracic and lumbar spine should also be performed.

The World Health Organization (WHO) international reference standard for osteoporosis diagnosis is a T-score of –2.5 or less at the femoral neck (FN). The reference standard from which the T-score is calculated is the female, white, age 20–29 years, Third National Health and Nutrition Examination Survey (NHANES III) database or equivalent. Osteoporosis may be diagnosed in postmenopausal women and in men aged 50 and older if the T-score of the lumbar spine, total hip or FN is –2.5 or less. In certain circumstances, the 33% radius (also called one-third radius) may be utilised.1,2 In premenopausal women and in men younger than 50 years of age, as well as in children, the WHO bone mineral density (BMD) diagnostic osteopenia and osteoporosis classifications should not be used. In these patient groups, the diagnosis of osteoporosis should not be made using dual energy X-ray absorptiometry (DXA) criteria alone.1,2

  • Conventional radiographs should not be used for diagnosis or exclusion of osteoporosis.
  • The evaluation of osteoporosis is based on the lower T-score of either the lumbar spine, FN or total hip.1
  • Repeat BMD measurements should only be performed to assess efficacy of treatment and residual fracture risk, or compliance.
  • To reliably compare change in BMD it is recommended to perform repeat BMD tests using the same instrument or at least the same make of instrument (manufacturer and model type) to improve comparability of results in interpreting any change in BMD.1
  • Relevant blood and urine studies should be obtained prior to initiating therapy if the medical history and/or clinical examination is compatible with secondary osteoporosis, or the DXA Z-score is ≤–2.0.2

Dual energy X-ray absorptiometry (DXA) is the current gold standard for the diagnosis of osteoporosis. BMD of the lumbar spine and the proximal femur are the best sites to measure for prediction of future fracture risk. Both sites should be measured (Table 3). DXA is reliable, with a reported precision of about 1%, although in routine clinical practice this is closer to 2%. At this precision level, the least significant change at the lumbar spine would be 5.6% between measurements, with 95% confidence that the change is real.

Each standard deviation (SD) reduction in FN BMD increases the age-adjusted risk of hip fracture by a factor of approximately 2.5 (range 2.0–3.5), while the risk attributable to any minimal trauma fracture is almost the same (range 1.7–2.4). Similarly, each SD reduction in lumbar spine BMD increases the risk of spinal fracture by a factor of approximately 2.3 (range 1.9–2.8). FN and total hip BMD appear to be the best overall predictors of fracture risk. The total hip is the better site for monitoring BMD as it has good precision (less affected by positioning) and is relatively unaffected by osteoarthritis, which can spuriously elevate spinal BMD values, as can vertebral fractures and arterial calcification.1,2

BMD measurements in the initial assessment have the following aims:

  • Determine the patient’s BMD. Fracture risk is multifactorial and may be significantly elevated in individuals outside the osteoporotic range (T-score ≤–2.5). The use of the osteoporotic T-score threshold is, however, the criterion by which healthcare funders define osteoporosis, as well as being consistent with studies in which the anti-fracture effects of anti-osteoporotic drugs have been demonstrated.
  • Determine the precise extent of BMD reduction. This is important for the assessment of individual fracture risk and the extent of the recommended therapeutic measures. Absolute fracture risk algorithms (eg the Garvan Fracture Risk Calculator  or the Fracture Risk Assessment Tool [FRAX]  may be useful in more accurately determining individual fracture risk and assisting the patient in making a treatment decision.4

As a reference for fracture risk calculation in women in Australia, T-scores calculated from the Geelong Osteoporosis Study database are used for the lumbar spine and the proximal femur. Normative data in Australian men are not currently available. Most BMD  assessments currently report hip T-scores for men based on the US NHANES III normative data. There are no standardised reference ranges for spine BMD in men and the only option is the use of reference ranges provided by densitometer manufacturers. These may differ significantly.5

  • For patients with ready access to a BMD measurement, a DXA measurement before commencing therapy is recommended, even in cases of typical minimal trauma fracture. A normal or near normal BMD, despite existing fractures, should always initiate a more extensive diagnostic work-up to exclude other potential causes of fracture. A normal BMD despite typical vertebral fractures also poses a problem with regard to the usefulness of anti-osteoporotic treatments that have not been tested in such a population. Such discrepant findings should be resolved on an individual basis. A past history of high-trauma falls resulting in vertebral fracture can leave evidence of vertebral deformities which may not indicate underlying osteoporosis. In such situations, consultation with a bone health expert (eg endocrinologist, rheumatologist) may be warranted.
  • If radiographs reveal one or more vertebral fractures typical of osteoporosis, BMD measurement may not be essential before starting medical therapy, if this is appropriate to the overall clinical situation. There are a limited number of scenarios in which a meaningful evaluation of BMD is not possible despite fractures typical of osteoporosis (eg in a combination of double-sided hip replacements and several osteoporotic fractures in the lumbar spine region of BMD measurement). In such cases, it should be assumed that BMD measurement would have been low and that therapy is likely to be beneficial. Forearm BMD may be useful; however, its precise value has not been as well characterised as that in the spine and hip.

The use of repeat DXA scans at intervals of two years or longer is appropriate in settings where the efficacy of treatment, risk assessment or decision to change or interrupt treatment is being considered.6,7 Due to limitations in the precision of BMD testing, a minimum of two years may be needed to reliably measure a change in BMD. If BMD is stable and/or individual is at low risk of fracture (normal or mild osteopenia; T-score >–1.5), less-frequent monitoring, up to an interval of 5–15 years, can be considered. Shorter intervals between repeat DXA scans, at intervals of one year, may be appropriate in high-risk individuals (eg patients on corticosteroid therapy or induced hypogonadism). In all cases, the expected rate of change in BMD and fracture risk should guide repeat measurement.8,9

Quantitative computed tomography (QCT) BMD measurement procedures can provide equivalent hip BMD to DXA scans and may be interpreted using the WHO T-score criteria.1 Spinal QCT also provides information on fracture risk, but it is important to note that the WHO T-score osteoporotic criteria cannot be applied in this situation. Fracture risk in QCT of the spine is most commonly interpreted using the criteria of the American College of Radiology.10 There are no data demonstrating reduction of fracture risk by specific anti-osteoporotic treatment chosen on the basis of QCT measurements. However, given the equivalency of hip QCT to hip DXA, there is no reason to doubt the utility of hip QCT in guiding therapy.1 The disadvantage of QCT remains the significantly higher radiation exposure compared to DXA,11 particularly in the hip. DXA of the spine and hip remains the recommended measurement for diagnosis of osteoporosis and baseline BMD assessment. In some patients with moderate to severe osteoarthritic changes, spine QCT may have a particular advantage as it is less affected than DXA by osteoarthritic changes.

Quantitative ultrasound (QUS) of the heel and other sites can provide information on fracture risk. However, QUS has not been demonstrated to provide information on absolute fracture risk and the reduction of fracture risk by a specific anti-osteoporotic treatment. QUS is not recommended as a diagnostic test for osteoporosis.

Increased biochemical markers of bone turnover in the blood and/or urine have been shown in trials to be an independent risk factor for fractures in women and men. Bone turnover markers are useful markers of compliance and response to treatment and may help guide choice of treatments. However, variability in analysis and lack of standardisation reduce the utility of these assessments. The International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine recommend one serum bone formation marker (procollagen type I amino-terminal propeptide, or PINP) and one bone resorption marker (C-terminal telopeptide, or CTX) to be used as reference markers. These should be measured by standardised assays in observational and intervention studies in order to compare the performance of alternatives and to enlarge the international experience of the application of markers to clinical medicine.12 Such standardised Australian reference intervals are now available for serum PINP and CTX in women and men.13

  1. The International Society for Clinical Densitometry. 2015 ISCD official positions – Adult. Middletown, CT: ISCD, 2015 [Accessed 31 January 2017].
  2. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Washington, DC: National Osteoporosis Foundation, 2014.
  3. Watts NB, Bilezikian JP, Camacho PM, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of postmenopausal osteoporosis. Endocr Pract 2010;16 Suppl 3:1–37.
  4. Johansson H, Kanis JA, Oden A, Johnell O, McCloskey E. BMD, clinical risk factors and their combination for hip fracture prevention. Osteoporos Int 2009;20(10):1675–82.
  5. McMahon K, Kalnins S, Freund J, Pocock N. Discordance in lumbar spine T-scores and nonstandardization of standard deviations.J Clin Densitom 2003;6(1):1–6.
  6. Leslie WD, Majumdar SR, Morin SN, Lix LM. Change in bone mineral density is an indicator of treatment-related antifracture effect in routine clinical practice: A registry-based cohort study. Ann Intern Med 2016;165(7):465–72. doi:10.7326/M15-2937.
  7. Austin M, Yang YC, Vittinghoff E, et al. Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures. J Bone Miner Res 2012;27(3):687–93.
  8. Berger C, Langsetmo L, Joseph L, et al. Association between change in BMD and fragility fracture in women and men. J Bone Miner Res 2009;24(2):361–70.
  9. Nguyen TV, Center JR, Eisman JA. Femoral neck bone loss predicts fracture risk independent of baseline BMD. J Bone Miner Res 2005;20(7):1195–201.
  10. American College of Radiology. ACR practice guideline for the performance of quantitative computed tomography (QCT) bone densitometry. Reston, VA: ACR, 2008.
  11. Njeh CF, Fuerst T, Hans D, Blake GM, Genant HK. Radiation exposure in bone mineral density assessment. Appl Radiat Isot 1999;50(1):215–36.
  12. Vasikaran S, Eastell R, Bruyère O, et al. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: A need for international reference standards. Osteoporos Int 2011;22(2):391–420.
  13. Vasikaran SD, Chubb SP, Ebeling PR, et al. Harmonised Australian reference intervals for serum PINP and CTX in adults. Clin Biochem Rev 2014;35(4):237–42.
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