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Guideline

Risk factors, fracture risk assessment and case-finding

Identifying patients to investigate for osteoporosis

Identifying patients to investigate for osteoporosis

Recommendation 1

Grade

All individuals over the age of 50 years who sustain a fracture following minimal trauma (such as a fall from standing height, or less) should be considered to have a presumptive diagnosis of osteoporosis.

A

Recommendation 2

Grade

Conduct a clinical risk factor assessment in postmenopausal women and men over the age of 50 years with one or more major risk factors for minimal trauma fracture to guide BMD measurement and prompt timely referral and/or drug treatment.A

A

Recommendation 3

Grade

A presumptive diagnosis of osteoporosis can be made in a patient with a vertebral fracture or hip fracture in whom there is no history of significant trauma.

Caution regarding diagnosis and treatment should be exercised if only a single mild vertebral deformity (height loss) is detected, especially in a patient under the age of 60 years.

B

A International guidelines recommend fracture risk assessment in post-menopausal women and men aged >50 years.1-4

 

This section provides an overview of non-modifiable and modifiable clinical risk factors for osteoporosis in postmenopausal women and men aged >50 years. More information and specific references related to these risk factors can be found in other sections as highlighted.
 

History of minimal trauma fracture

The most easily-recognised risk factor for osteoporotic fracture is the presence of any vertebral or non-vertebral minimal trauma (fall from standing height or less) fracture. This also applies to vertebral fractures incidentally detected on radiographs. A trauma history may guide interpretation of vertebral deformities. Any minimal trauma fracture in someone aged >50 years prompt bone health assessment.5 DXA may be useful to determine whether the patient has reduced BMD (refer to Section 1.2).

Paternal or maternal history of hip fracture

A paternal or maternal history of hip fracture is the most reliable indicator of genetic risk of minimal trauma fracture. However, family history of other types of minimal trauma fracture should also be considered.

Height loss ≥3 cm and/or back pain suggestive of vertebral fracture

Some loss of height is typical with advancing age and is usually due to disc degeneration and/or scoliosis. The accurate measurement and recording of height are important; a height loss ≥3 cm, as measured by stadiometer, requires exclusion of vertebral deformity or fractures by X-ray. The greater the height loss, in the absence of obvious scoliosis, the greater the likelihood of vertebral fractures.

Sex

In each age group, men are at an approximately 50% lower fracture risk than women. However, once a man has experienced a fracture, his risk of a subsequent fracture is equivalent to that of a woman of comparable age who has also experienced a fracture.

Age

Fracture risk is strongly affected by age for both sexes. With each decade of life, the risk of minimal trauma fracture approximately doubles. Age as a fracture risk is independent of both BMD and clinical risk factors, such as risk of falling, which also increase with age and contribute to fracture risk. People aged <50 years are likely to be at low risk of fracture in the absence of other risk factors.

History of falls

A history of falls increases the risk of peripheral minimal trauma fractures for postmenopausal women and men of comparable age. This applies to falls without external cause that have occurred more than once in the past 12 months. Risk factors for falling include poor quadriceps strength, body sway, vitamin D deficiency, medications, visual impairment and environmental hazards (refer to Section 2.2).

Premature menopause or hypogonadism

Sex hormone deficiency leads to a reduction in bone mass and increased fracture risk. Early menopause (ie before age 45 years) and male hypogonadism (eg due to androgen deprivation therapy [ADT] to treat prostate cancer) are important causes of secondary osteoporosis. Male hypogonadism results in reductions in bone and muscle mass that improve with testosterone supplementation. Menopausal hormone therapy (MHT) in women with premature menopause mitigates the increase in bone resorption and preserves bone mass (refer to Section 3.4).

Low BMD

Relative fracture risk approximately doubles for each unit (SD) decrease in T-score, as measured by DXA. Postmenopausal women and men aged >50 years with osteoporosis (T-score ≤–2.5) are already at increased risk of minimal trauma fracture. Absolute fracture risk increases with both increasing age and decreasing BMD. The absolute risk for fracture is therefore high in postmenopausal women and men aged ≥70 years with a T-score ≤–2.5 (without fracture) and even higher in those with a T-score ≤–3.0. The strongest association between bone density and fracture risk exists when bone density at one site is used to predict the risk for fracture at that site – hence the focus on BMD at the hip, forearm, and spine5 (refer to Section 1.2).

However, any minimal trauma fracture in someone aged >50 years should be used as an opportunity to assess bone health. Because other factors (e.g., age, falls risk, poor vision) also affect fracture risk, the presence of a normal or only mildly low BMD may mean pharmacological therapy to increase BMD may not be required, and management in that person should focus on fall-prevention strategies.

Low body weight or weight loss

Low body weight (body mass index [BMI] <20 kg/m2) doubles the relative risk of a hip fracture in both women and men. An increased risk has also been demonstrated for spine and peripheral fractures. Unintentional weight loss is also associated with an increased risk of minimal trauma fracture. Anorexia nervosa is associated with an increased risk of developing osteoporosis.

Low muscle mass and strength

The gradual loss of skeletal mass and strength that occurs with advancing age is associated with an increased risk of falls and fragility fractures. Hip fracture patients with sarcopenia are 1.8-fold more likely to have osteoporosis than hip fracture patients with normal muscle mass.6 Insufficient protein intake and skeletal muscle inactivity are two important factors that cause skeletal muscle depletion (refer to Section 1.2).

Low physical activity or prolonged immobility

A lack of physical activity is a risk factor for hip and vertebral fractures. Limited mobility, so that the person cannot leave home or do housework, may be associated with, and compounded by, low or no exposure to sunlight and subsequent vitamin D deficiency. The inability to rise from a chair without using the arms (a marker of loss of lower extremity strength and power) is associated with an increased risk of minimal trauma fracture (refer to Section 2.3).

Poor balance

Poor balance increases the likelihood of a trip, slip, or fall and is a risk factor for hip and vertebral fractures. Balance training in isolation does not improve BMD, although it can reduce falls risk (refer to Sections 2.2 and 2.3).

Smoking

For both women and men, smoking is a moderate risk factor for vertebral and non-vertebral (including hip) minimal trauma fractures. Although a dose–response relationship is unclear, smokers generally have a higher fracture risk than non-smokers.

High alcohol intake

Based on general health advice, the National Health and Medical Research Council (NHMRC) currently recommends women and men should drink no more than 10 standard drinks a week and no more than four standard drinks on any one day.6 In addition to increasing falls risk, high alcohol intake appears to have a deleterious effect on bone-forming cells (osteoblasts), although the specific mechanisms are unclear.7

Vitamin D and calcium levels

Suboptimal dietary calcium intake and vitamin D deficiency are important public health problems in Australia. Vitamin D deficiency is associated with a higher risk of falling in older people. Routine screening of serum vitamin D levels should not be conducted. Testing should be restricted to those with suspected or proven osteoporosis, conditions or medications known to decrease vitamin D levels, deeply pigmented skin or severe lack of sun exposure due to cultural, medical, occupational or residential reasons (refer to Section 2.1).

Co-existing medical conditions

Co-existing medical conditions include those that increase bone loss or lead to lower BMD at an earlier age, such as rheumatoid arthritis, Type 1 and 2 diabetes, Cushing syndrome (endogenous or exogenous), hyperparathyroidism, hyperthyroidism (or thyroxine excess), chronic kidney disease, chronic liver disease, premature menopause, male hypogonadism, coeliac disease, inflammatory bowel disease or other malabsorption disorders. These conditions are associated with an increase in the age-specific risk for osteoporosis and minimal trauma fractures.

Pharmacological risk factors include medications that cause bone loss (e.g., ADT for prostate cancer or aromatase inhibitors for breast cancer; refer to Section 5.2).

Medications associated with increased risk of minimal trauma fracture particularly include prolonged glucocorticoids (at least four months cumulative prednisone or equivalent prednisone dose ≥7.5 mg per day). However, other medications associated with increased fracture risk in population-based studies should be considered, such as excessive thyroid hormone replacement8, selective serotonin reuptake inhibitors9, proton pump inhibitors10,11, some antiepileptic drugs12,13 and certain antipsychotics14,15. However, it can be difficult to distinguish medication-related effects on bone health from the effect of the underlying condition that required their use.

Evidence Statement

In patients with a recent minimal trauma fracture, there is a high prevalence of risk factors for osteoporosis that are independent of BMD.16 This suggests that all postmenopausal women and men aged >50 years should undergo a risk factor assessment for osteoporosis. All patients who sustain a minimal trauma fracture should be screened for risk factors, regardless of BMD, so that action may be taken to reduce the risk of subsequent fractures.

There is strong multinational RCT evidence that mild (Grade 1: 20–25% vertebral height loss) vertebral fractures are a significant risk factor for future vertebral fractures.17 The risk of new vertebral fracture increases progressively with grade of the initial vertebral fracture; a severe initial fracture is associated with a sixfold increase in the risk of new vertebral fractures in the following three years.17 A moderate increase in the risk of non-vertebral fractures is also seen following moderate-to-severe vertebral fracture, a finding independent of BMD.17 The Dubbo Osteoporosis Epidemiology Study found that all fracture types, except ankle and rib fractures, are associated with increased subsequent fracture risk, with even a minor initial fracture resulting in an increased risk of major or hip fracture.18 Approximately half of refractures occurred in the first two years, and the risk persisted for up to 10 years.18

Low BMI is an established risk factor for fracture. A meta-analysis of almost 60,000 participants in 12 prospective population-based cohorts worldwide found that the risk of any type of fracture increased significantly with lower BMI, largely independent of age and sex.19 Compared with a BMI of 25 kg/m2, a BMI of 20 kg/m2 was associated with a twofold increased risk of hip fracture, independent of BMD. The association between high BMI and fracture risk is more complex. A meta-analysis of approximately 400,000 women from 25 prospective cohorts worldwide suggested that, at a population level, high BMI (>35 kg/m2) was protective for all types of minimal trauma fracture, except for humeral fracture.20 However, when adjusted for BMD, obesity slightly increased the risk of all fractures. Weight fluctuation also appeared to influence fracture risk. Post hoc analysis of data from over 120,000 women taking part in the Women’s Health Initiative (WHI) observational study and clinical trials demonstrated that both weight gain and weight loss are associated with increased fracture incidence.21 Women who lost more than 5% of baseline body weight over three years had a 65% increased risk of hip fracture than those who maintained stable weight for three years. Significantly, higher rates of spinal fracture were also seen in the former group. A 5% weight gain over three years was associated with a higher incidence of upper and lower limb fractures.21 The relationship between body weight and fracture risk is complex.

Smoking is a well-recognised risk factor for osteoporosis. A meta-analysis of over 59,000 men and women in 10 prospective cohort studies found that current smoking was significantly associated with an increased risk of any fracture compared with non-smokers (RR 1.25; 95% CI: 1.15–1.36). The highest risk was seen for hip fracture.21 A past history of smoking was also associated with significantly increased fracture risk in that analysis. The risk was lower than for current smoking, indicating that risk was attenuated with smoking cessation. Although smokers tended to be thinner than non-smokers, low BMD could only account for 23% of smoking-related hip fractures in this study, indicating a potential direct effect of cigarette smoke toxins on bone metabolism.22

Excessive alcohol intake is also associated with increased fracture risk. A systematic review and meta-analysis of 22 observational studies suggested a significantly increased risk of fracture in men consuming alcohol daily or consuming more than 10 drinks per week (RR 1.28; 95% CI: 1.08–1.53).23 An analysis of three prospective cohorts (approximately 6000 men and 11,000 women) also found a significant increase in hip fracture risk with alcohol intake, although no increased risk was seen in men and women consuming two units or less of alcohol daily.24 Risk was only marginally lower in women than in men.24 These observations were independent of BMD.24 GPs should consult RACGP guidelines that outline preventive health strategies and smoking-cessation interventions.25–27

 

  • Any postmenopausal woman or man aged >50 years that sustains a fracture after minimal trauma (fall from standing height or less) should be considered as having osteoporosis.
  • Bone densitometry can exclude pathological causes of fracture, although it is not always required following hip or vertebral fracture.
  • BMD is helpful for risk stratification and provides a baseline from which to assess pharmacotherapy response.
  • Patients should be assessed for possible vertebral crush fractures if there is well-documented height loss of ≥3 cm (measured by stadiometer), kyphosis, or unexplained back pain. A lateral thoracolumbar X-ray should be performed. If vertebral crush fractures are detected, bone densitometry (DXA) is recommended to determine BMD at the hip and spine.
  1. Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 2014;25(10):2359–81.
  2. Kanis JA, Cooper C, Rizzoli R, Reginster JY; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2019;30(1):3–44.
  3. National Osteoporosis Guideline Group (NOGG). Clinical guideline for the prevention and treatment of osteoporosis. NOGG, 2021 [Accessed 30 October 2023]
  4. Scottish Intercollegiate Guidelines Network (SIGN). Management of osteoporosis and the prevention of fragility fractures. SIGN, 2021 [Accessed 30 October 2023]
  5. McClung MR. The relationship between bone mineral density and fracture risk. Curr Osteoporos Rep 2005;3(2):57–63.
  6. National Health and Medical Research Council (NHMRC). Australian guidelines to reduce health risks from drinking alcohol. NHMRC, 2020 [Accessed 30 October 2023]
  7. Berg KM, Kunins HV, Jackson JL, et al. Association between alcohol consumption and both osteoporotic fracture and bone density. Am J Med 2008;121(5):406–18.
  8. Thayakaran R, Adderley NJ, Sainsbury C, et al. Thyroid replacement therapy, thyroid stimulating hormone concentrations, and long term health outcomes in patients with hypothyroidism: Longitudinal study. BMJ 2019;366:l4892.
  9. Jones JS, Kimata R, Almeida OP, Hankey GJ. Risk of fractures in stroke patients treated with a selective serotonin reuptake inhibitor: A systematic review and meta-analysis. Stroke 2021;52(9):2802–08.
  10. Hussain S, Siddiqui AN, Habib A, Hussain MS, Najmi AK. Proton pump inhibitors’ use and risk of hip fracture: A systematic review and meta-analysis. Rheumatol Int 2018;38(11):1999–2014.
  11. Wei J, Chan AT, Zeng C, et al. Association between proton pump inhibitors use and risk of hip fracture: A general population-based cohort study. Bone 2020;139:115502.
  12. Shiek Ahmad B, Petty SJ, Gorelik A, et al. Bone loss with antiepileptic drug therapy: A twin and sibling study. Osteoporos Int 2017;28(9):2591–600.
  13. Griepp DW, Kim DJ, Ganz M, et al. The effects of antiepileptic drugs on bone health: A systematic review. Epilepsy Res 2021;173:106619.
  14. Wang GH, Man KKC, Chang WH, Liao TC, Lai EC. Use of antipsychotic drugs and cholinesterase inhibitors and risk of falls and fractures: Self-controlled case series. BMJ 2021;374:n1925.
  15. Papola D, Ostuzzi G, Thabane L, Guyatt G, Barbui C. Antipsychotic drug exposure and risk of fracture: A systematic review and meta-analysis of observational studies. Int Clin Psychopharmacol 2018;33(4):181–96.
  16. Di Monaco M, Vallero F, Di Monaco R, Tappero R. Prevalence of sarcopenia and its association with osteoporosis in 313 older women following a hip fracture. Arch Gerontol Geriatr 2011;52(1):71–74.
  17. Johansson H, Odén A, McCloskey EV, Kanis JA. Mild morphometric vertebral fractures predict vertebral fractures but not non-vertebral fractures. Osteoporos Int 2014;25(1):235–41.
  18. Center JR, Bliuc D, Nguyen TV, Eisman JA. Risk of subsequent fracture after low-trauma fracture in men and women. JAMA 2007;297(4):387–94.
  19. De Laet C, Kanis JA, Odén A, et al. Body mass index as a predictor of fracture risk: A meta-analysis. Osteoporos Int 2005;16(11):1330–38.
  20. Johansson H, Kanis JA, Odén A, et al. A meta-analysis of the association of fracture risk and body mass index in women. J Bone Miner Res 2014;29(1):223–33.
  21. Crandall CJ, Yildiz VO, Wactawski-Wende J, et al. Postmenopausal weight change and incidence of fracture: Post hoc findings from Women’s Health Initiative observational study and clinical trials. BMJ 2015;350:h25.
  22. Kanis JA, Johnell O, Oden A, et al. Smoking and fracture risk: A meta-analysis. Osteoporos Int 2005;16(2):155–62.
  23. Drake MT, Murad MH, Mauck KF, et al. Clinical review. Risk factors for low bone mass-related fractures in men: A systematic review and meta-analysis. J Clin Endocrinol Metab 2012;97(6):1861–70.
  24. Kanis JA, Johansson H, Johnell O, et al. Alcohol intake as a risk factor for fracture. Osteoporos Int 2005;16(7):737–42.
  25. The Royal Australian College of General Practitioners (RACGP). Guidelines for preventive activities in general practice. 8th edn. RACGP, 2012.
  26. The Royal Australian College of General Practitioners (RACGP). Smoking, nutrition, alcohol, physical activity (SNAP): A population health guide to behavioural risk factors in general practice. 3rd edn. RACGP, 2015.
  27. The Royal Australian College of General Practitioners (RACGP). Supporting smoking cessation: A guide for health professionals. RACGP, 2014.
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