Calcified Tissue International

, Volume 92, Issue 5, pp 429–436

Incidence of Hip Fracture in Romania and the Development of a Romanian FRAX Model

Authors

    • Carol Davila University of Medicine, National Institute of Endocrinology
  • Alina Sucaliuc
    • Carol Davila University of Medicine, National Institute of Endocrinology
  • Helena Johansson
    • WHO Collaborating Centre for Metabolic Bone DiseasesUniversity of Sheffield Medical School
  • John A. Kanis
    • WHO Collaborating Centre for Metabolic Bone DiseasesUniversity of Sheffield Medical School
  • Eugene McCloskey
    • WHO Collaborating Centre for Metabolic Bone DiseasesUniversity of Sheffield Medical School
Original Research

DOI: 10.1007/s00223-013-9697-7

Cite this article as:
Grigorie, D., Sucaliuc, A., Johansson, H. et al. Calcif Tissue Int (2013) 92: 429. doi:10.1007/s00223-013-9697-7

Abstract

A FRAX® model for Romania calibrated to the total Romanian population was released June 1, 2011. This article describes the data used to develop the Romanian FRAX model and illustrates its features compared to models for other countries. Age- and sex-stratified hip fracture incidence rates and mortality rates for 2010 were extracted from nationwide databases from the age of 40 years. For other major fractures, Romanian incidence rates were imputed, using Swedish ratios for hip to other major osteoporotic fracture (humerus, forearm, and clinically symptomatic vertebral fractures). Fracture incidence rates increased with increasing age: for hip fracture, incidence rates were higher among younger men than women but with a female preponderance from the age of 65 years. The 10-year probability of hip or major fracture was increased in patients with a clinical risk factor (CRF), lower BMI, female gender, higher age, and decreased BMD T score. Of the CRFs, a parental hip fracture accounted for the greatest increase in 10-year fracture probability. The Romanian FRAX tool is the first country-specific fracture prediction model. It is based on the original FRAX methodology, which has been externally validated in several independent cohorts. Despite some limitations, the strengths make the Romanian FRAX tool a good candidate for implementation into clinical practice.

Keywords

FRAX10-year fracture probabilityHip fractureOsteoporotic fractureOsteoporosis

Introduction

Osteoporosis is a skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue with a resulting increase in bone fragility and susceptibility to fracture. Osteoporosis is an important public health issue because the consequent fractures are a major cause of morbidity, mortality, and health expenditure worldwide. In white populations, about 50 % of women and 20 % of men older than 50 years will have a fragility fracture in their remaining lifetime [1]. Fractures of the hip, vertebral body, proximal humerus, and distal forearm (commonly termed “major osteoporosis fractures”) have long been recognized as typical of osteoporosis, though fractures at many other sites are characteristic of osteoporosis [2, 3]. Because of this huge burden, assessment of an individual’s risk of fracture is important so that intervention can be effectively targeted.

Of the risk-assessment tools available, the most widely used is FRAX®. FRAX is a computer-based algorithm (http://www.shef.ac.uk/FRAX) developed by the World Health Organization Collaborating Centre for Metabolic Bone Diseases, first released in 2008. The algorithm, intended for primary care, calculates fracture probability from easily obtained clinical risk factors (CRFs) in men and women [4, 5]. The output of FRAX is the 10-year probability of a major fracture (hip, clinical spine, humerus, or wrist fracture) and the 10-year probability of hip fracture. Probability is calculated from age, body mass index (BMI), and dichotomized risk factors comprising prior fragility fracture, parental history of hip fracture, current tobacco smoking, long-term oral glucocorticoid use, rheumatoid arthritis, other causes of secondary osteoporosis, and excessive alcohol consumption. Femoral neck bone mineral density (BMD) can be optionally input to enhance fracture risk prediction [6]. Fracture probability is computed by taking both the risk of fracture and the risk of death into account.

The risk of hip fracture and probably of other osteoporotic fractures varies markedly around the world [7]. The difference in incidence between countries is much greater than the differences in incidence between sexes within a country. Indeed, a greater than 10-fold difference in hip fracture incidence has been reported in different countries, which is much larger than the errors arising in such studies [7, 8]; and wide variations of this magnitude are reported from prospective studies in Europe using the same methodology [9]. In addition, the risk of death varies between countries. This variation also contributes to the heterogeneity in fracture probability [8]. For this reason, FRAX models are calibrated to those countries where the epidemiology of fracture and death is known. Models are currently available for 45 countries.

Information about the epidemiology of fractures in Romania is sparse. The annual crude incidence of hip fracture appears to have increased between 2005 and 2009 from 184.3 to 214.4 per 100,000 persons in women and from 126.9 to 143.1 per 100,000 persons in men [10]. The aim of the present study was to estimate age- and sex-specific hip fracture rates in Romania for incorporation into a FRAX model.

Methods

Cases of hip fracture were identified from the national hospital discharge register (National School of Public Health), which collects data from all public hospitals in Romania. It is a legal requirement that all public hospitals register anonymous admissions to the National School of Public Health. In Romania, all patients with hip fracture are treated in public hospitals and the vast majority (93 %) are treated surgically as judged by the proportion of admissions in which there was a record of hip surgery. Hip fractures cases, identified by ICD coding, are available from 2005 when the registration system was introduced. For the years 2005–2009, multiple admissions for the same fracture were not excluded, and for this reason we used the data for 2010.

Cases were defined as patients (aged 40+ years) who were hospitalized for a hip fracture (ICD10 code S72.0 [femoral neck], S72.1 [trochanter], S72.2 [subtrochanter]) in 2010 and who had not been hospitalized for a hip fracture in the previous year. We excluded patients with a code S72.9 (unspecified site of femoral fracture) except where a surgical procedure indicated surgery on the hip. We included hip fracture cases irrespective of country of origin or degree of trauma. Cases associated with neoplasia were not excluded. Cases were studied from the age of 40 years since this is the lower age limit used in FRAX. Incidence rates were estimated as the number of men and women in 5-year age intervals with at least one hip fracture in 2010 divided by the age- and sex-specific population of Romania using government estimates for the same year [11].

In contrast to hip fractures, the incidence of osteoporotic fractures could not be determined because a dedicated registry with routinely recorded osteoporotic fractures does not exist in Romania. It was assumed, therefore, that the age- and gender-specific ratios found in Sweden were comparable to those in Romania. This assumption has also been used for many of the FRAX models with incomplete epidemiological information. Available information suggests that the age- and gender-stratified pattern of fracture is very similar in the Western world and Australia, although it should be noted that incidence rates for vertebral fracture as judged by vertebral morphometry are underestimated in data sources [12]. National mortality rates used data from official government sources [11].

The development and validation of FRAX have been extensively described [4, 5]. The risk factors used were based on a systematic set of meta-analyses of population-based cohorts worldwide and validated in independent cohorts with over 1 million patient-years of follow-up. The construct of the FRAX model for Romania required the beta coefficients of the risk factors in the original FRAX model and the incidence rates of hip fracture and mortality rates for Romania. The relative importance of the beta coefficients for death and fracture was assumed to be similar in Romania, as has been shown across several European countries [6]. However, absolute age-specific fracture risk and mortality rates differ from country to country [8]. Consequently, for each age category, the hazard function was calibrated to match the mean risk (both fracture risk and mortality rate) for that specific age group in Romania, without altering the relative importance of the beta coefficients [5].

In order to compare Romanian hip fracture probabilities with those of other regions of the world, the remaining lifetime probability of hip fracture from the age of 50 years was calculated for men and women, as described by Kanis et al. [8]. In the present analysis, values for Romania were compared with those of China (with and without inclusion of Hong Kong), Canada, Denmark, Finland, France, Hungary, Mexico, Poland, Portugal, Spain, Sweden, Turkey, the United Kingdom, and the United States.

Results

Hip Fracture Incidence

A total of 14,852 cases of hip fracture were registered in 2010, 5,445 in men and 9,407 in women, aged between 40 and 105 years. In both sexes, incidence per 100,000 persons increased with age up to 90 years and then decreased (Table 1). Incidence rates were higher in men than in women up to the age of 60 years and thereafter became much higher in women (almost double at age 80–85 years).
Table 1

Hip fracture cases, population at risk, and annual hip fracture rates by age and sex in Romania 2010

Age range (years)

Men

Women

Hip fractures

Population

Incidence/100,000

Hip fractures

Population

Incidence/100,000

40–44

189

844,271

22.4

50

832,093

6.0

45–49

223

613,462

36.4

61

624,305

9.8

50–54

433

728,226

59.5

171

776,890

22.0

55–59

512

671,502

76.2

314

749,830

41.9

60–64

539

509,384

105.8

427

598,618

71.3

65–69

536

396,275

135.3

738

509,613

144.8

70–74

839

382,994

219.1

1,548

547,217

282.9

75–79

870

279,752

311.0

2,104

429,818

489.5

80–84

772

162,052

476.4

2,134

272,024

784.5

85–89

405

61,253

661.2

1,427

116,568

1,224.2

90–94

93

10,587

878.4

338

22,904

1,475.7

95–99

29

4,259

680.9

83

8,595

965.7

100+

5

797

627.4

12

1,700

647.1

Totals

5,445

  

9,407

  

Fracture Probability Without BMD

The 10-year probability of hip fracture increased with age in men and women up to the age of 85 years and decreased thereafter due to the competing effect of mortality on the fracture hazard. The hip fracture probability for men and women with no CRFs is shown in Fig. 1. As expected, probabilities of a major fracture were higher than hip fracture probabilities at all ages (Table 2). As was the case for hip fracture, probabilities decreased after the age of 85 years. Each of the CRFs contributed independently to fracture probability (see Table 2). Smoking and alcohol were relatively weak risk factors as they increased the probability for a major fracture from 8.0 to only 8.9 and 10 %, respectively, in women at the age of 80 years. A parental history of hip fracture was associated with the highest risk (16 % at 80 years). Intermediate increments in probability were associated with long-term use of glucocorticoids, rheumatoid arthritis, and a prior fragility fracture (12, 12, and 13 %, respectively) at the age of 80 years.
https://static-content.springer.com/image/art%3A10.1007%2Fs00223-013-9697-7/MediaObjects/223_2013_9697_Fig1_HTML.gif
Fig. 1

Ten-year probability of a hip fracture according to age in Romanian men and women (FRAX v3.7 without BMD and BMI set to 25 kg/m2)

Table 2

10-year probability of a major fracture (%) in men and women according to the presence of CRFs in the absence of BMD

CRFs

Age (years)

50

60

70

80

90

Men

 None

1.7

2.3

2.9

3.6

3.3

 Alcohol

2.1

2.8

3.7

4.8

4.5

 Rheumatoid arthritis

2.4

3.2

4.2

5.5

5.2

 Glucocorticoids

2.7

3.5

4.5

5.3

4.8

 Smoking

1.8

2.4

3.1

3.9

3.6

 Parental history

3.5

4.4

4.9

8.0

7.9

 Prior fracture

3.8

4.8

5.6

6.0

5.4

 BMI at 20 kg/m2a

1.7

2.3

3.1

3.9

3.6

Women

 None

2.3

3.8

5.9

8.0

6.4

 Alcohol

2.8

4.7

7.4

10

8.4

 Rheumatoid arthritis

3.2

5.3

8.4

12

9.5

 Glucocorticoids

3.9

6.3

9.7

12

9.1

 Smoking

2.5

4.2

6.6

8.9

6.7

 Parental history

4.6

7.3

9.6

16

13

 Prior fracture

5.2

7.9

11

13

11

 BMI at 20 kg/m2a

2.5

4.2

6.8

9.1

6.7

BMI is set at 25 kg/m2 except where indicated

aNo other CRF

Fracture Probability with BMD

The 10-year probability of a major osteoporotic fracture for women without CRFs according to age and T score is shown in Fig. 2. At any given age, fracture probability increased with decreasing T score. By contrast, at any given T score, fracture probabilities rose with age up to the age of 70 or 80 years and thereafter decreased. The decreasing probability at older ages results from the competing effect of BMD on mortality.
https://static-content.springer.com/image/art%3A10.1007%2Fs00223-013-9697-7/MediaObjects/223_2013_9697_Fig2_HTML.gif
Fig. 2

Ten-year probability of a major osteoporotic fracture for women with a BMI of 25 kg/m2 according to age and BMD T score for femoral neck BMD in the absence of other CRFs

At the extreme of T score (−4.0 SD), probabilities decreased progressively with age in men because of the more marked competing effect of the death risk on fracture risk. At younger ages (below 65 years), the fracture probability was similar in men and women. For example, at the age of 55 years with a T score of −2.5 SD, the probability of a major fracture was 5.2 % in men and 5.6 % in women. With advancing age probabilities in men were qualitatively similar to those in women, increasing to 70 years and thereafter decreasing with age.

The 10-year probability of hip fracture in women calculated with the Romanian FRAX model, for a T score at −2.5 SD and no other CRFs, was 1.6 % at the age of 50 years, rose with age to 3.2 % at the age of 80 years, and decreased thereafter. At younger ages (below 65 years), the fracture probabilities were slightly higher in men than in women. For example, at the age of 55 years with a T score of −2.5 SD, the probability of hip fracture was 2.5 % in men and 1.9 % in women.

Intervention Thresholds

In Romania the current threshold for the reimbursement of treatments is based on BMD measurements by dual-energy X-ray absorptiometry (DXA) with a treatment threshold set at −2.5 SD. In Table 3 the probabilities corresponding to this threshold are shown together with those equivalent to women with a previous fragility fracture and compared to women with no CRFs in the absence of BMD.
Table 3

10-year probabilities of a major fracture (hip, clinical spine, humerus, and forearm) and a hip fracture calculated with the Romanian FRAX model for women

 

Age (years)

50

55

60

65

70

75

80

85

90

Major fracture

 No CRFs

2.3

3.0

3.8

4.7

5.9

7.1

8.0

8.0

6.4

 Previous fracturea

5.2

6.5

7.9

9.5

11

13

13

13

11

 BMD T score −2.5 SDa

4.8

5.7

6.6

7.3

7.9

8.2

7.8

6.7

4.8

 Previous fracture + BMD T score −2.5 SD

9.2

10

11

12

12

12

11

9.5

7.0

Hip fracture

 No CRFs

0.2

0.4

0.6

1.0

1.7

2.5

3.5

3.8

2.9

 Previous fracturea

0.8

1.2

1.8

2.6

3.5

4.6

5.4

5.8

4.5

 BMD T score −2.5 SDa

1.6

1.9

2.2

2.4

2.7

3.1

3.2

2.8

1.8

 Previous fracture + BMD T score −2.5 SD

3.5

3.7

3.9

4.1

4.2

4.3

4.2

3.6

2.4

Shown are results for women with BMI of 25 kg/m2

aNo other CRFs

In women aged 50, 60, 70, and 80 years without CRFs and with a BMD T score of −2.5 SD, the 10-year probability of a major osteoporotic fracture was 4.8, 6.6, 7.9, and 7.8 %, respectively. In women with no CRFs and without DXA, the equivalent probabilities were 2.3, 3.8, 5.9, and 8.0 %, respectively. Thus, the BMD criterion for reimbursement using a fixed T score becomes less and less appropriate with advancing age. For example, at the age of 50 years, women with a T score of −2.5 SD had twice the risk of their counterparts with no CRFs. In contrast, at the age of 80 years and older, fracture probabilities were lower in women with osteoporosis than in their counterparts with no CRFs. A similar observation was made when looking at hip fracture probabilities. The explanation is that in the oldest old there is a decrease in the probability of fracture because of the competing effect of death risk plus the decrease in T score with advancing age.

Probabilities were higher in women with a previous fracture than in women at the threshold of osteoporosis and rose progressively with age up to the age of 80 years. This would suggest that a viable threshold for reimbursement might be the probability equivalent of a prior fracture, in the absence of BMD.

Comparison Across Countries

Table 4 gives a sample of the remaining lifetime probability of hip fracture from the age of 50 years in men and women. The country samples include those with very high probabilities (Sweden and Denmark) and those among the lowest. Lifetime probabilities for Romania were among the lowest for Europe, comparable to those in Hungary but somewhat higher than those in Poland.
Table 4

Lifetime probability of hip fracture in the Romanian population compared with selected countries [8]

Country

Lifetime risk at 50 years (%)

Women

Men

Sweden

28.5

13.1

Denmark

16.5

5.8

United States (Caucasian)

15.8

6

Canada

14

5.2

United Kingdom

13.7

4.8

Finland

12.7

5.5

France

12.7

3.6

Spain

12.0

4.2

Portugal

10.1

3.6

Turkeya

8.9

3.5

China (Hong Kong)

8.8

4.1

Mexicob

8.5

3.8

Hungary

7.4

3.5

Romaniac

7.0

3.8

Polandd

4.5

2.0

China

2.4

1.9

aTuzun et al. [13]

bClark et al. [14]

cThis study

dCzerwinski et al. [15]

Discussion

This study characterizes for the first time the hip fracture incidence in Romania from the age of 40 years until the oldest old, based on national data. As expected, in both sexes incidence rates per 100,000 persons increased with age up to 90 years and then decreased. At younger ages, up to 65 years, incidence rates were higher in men than in women; but thereafter they were much higher in women, almost double at the age of 80–85 years. This confirms the general observation that the age-standardized incidence of hip fracture in men is approximately half that noted in women [7]. Based on the age-standardized annual incidence of hip fracture for men and women combined, Romania belongs to the moderate-risk countries for osteoporosis [7]. The majority of hip fractures occurred in men and women aged 70 years or more. Demographic projections indicate that the Romanian population aged 70 years and over will more than double by 2050, so the burden of the disease will increase markedly with time [16].

Notwithstanding the demographic shifts in the future, hip fracture rates in Romania are low. In a recent systematic review of hip fracture rates worldwide [7], Romania had the lowest age-standardized rates in Europe (142 and 198/100,000 in men and women, respectively) with the exception of Croatia (135 and 177/100,000, respectively). The low incidence is reflected in the low 10-year and lifetime probabilities in the present report.

Reasons for the marked variation in hip fracture risk between countries (and in some cases within countries) are conjectural. The secular trends in incidence that are documented in many countries [17] strongly suggest environmental, rather than genetic, factors. Risk factors for hip fracture such as low BMI, low BMD, low calcium intake, reduced sunlight exposure, early menopause, smoking, alcohol consumption, and migration status may have important effects within communities but do not explain differences in risk between communities [9]. The factor that best predicts heterogeneity of risk is socioeconomic prosperity, which in turn may be related to low levels of physical activity or an increased probability of falling on hard surfaces [18]. This is plausible but only a hypothesis. The contrast between ecological and population risk factors is not uncommon and in the context of hip fracture, for example, is noted with calcium intake where countries with higher calcium intakes have greater hip fracture risk [19]. In the case of Romania, patients with osteoporosis have much poorer vitamin status than their nonosteoporotic counterparts [20]. This may account for a component of fracture risk in Romania but not the low national risk.

The present study also describes the FRAX model for the assessment of fracture probability in men and women from Romania. In the absence of BMD, probabilities of a major fracture were higher than hip fracture probabilities at all ages, and both increased with age in men and women up to the age of 85 years and decreased thereafter due to the competing effect of mortality hazard on fracture risk. The 10-year absolute probability of any major osteoporotic and hip fracture in the presence of a single risk factor increased with advancing age in both sexes, being always higher in women than in men. Each of the CRFs contributed independently to fracture probability but with a different weight. Consistent with other country models, the Romanian model identified a parental history of hip fracture as the strongest risk factor: between a 50-year-old woman without risk factors and an 80-year-old woman with a parental history of hip fracture, the individual probability of a major osteoporotic fracture increased almost fourfold (from 4.6 to 16 %). Long-term use of glucocorticoids, rheumatoid arthritis, and a prior fragility fracture were associated with moderate increments in probability.

Fracture probability depends upon the integration of death risks and fracture risks. The present study illustrates the importance of this with regard to BMD. Although fracture probability increases with decreasing T score, the relationship between probability and T score was not linear. Thus, at any given T score, fracture probabilities rose with age up to the age of 70 or 80 years and thereafter decreased in women, an effect more marked in men (see Figs. 2, 3). The declining fracture probability with age is partly mediated by the increased risk of death in the general population, an effect more marked in men than in women. A more important component of the effect is that low BMD is associated with an increased risk of death, which is captured in the FRAX algorithm [4]. This explains why the declining fracture probability with age is much more marked at low T scores.
https://static-content.springer.com/image/art%3A10.1007%2Fs00223-013-9697-7/MediaObjects/223_2013_9697_Fig3_HTML.gif
Fig. 3

Ten-year probability of a major osteoporotic fracture for men with a BMI of 25 kg/m2 according to age and BMD T score for femoral neck BMD in the absence of other CRFs

This effect has implications for practice guidelines. In Romania, as in many countries, the current threshold for the reimbursement of treatments is based on BMD measurements by DXA with a treatment threshold set at −2.5 SD. This study confirms that the BMD criterion for reimbursement using a fixed T score becomes less and less appropriate with advancing age. For example, in Fig. 2 a T score of −3 SD may be associated with a major fracture probability of 6.5 % (at the age of 50 years), 10 % (at the age of 70 years), or 5.7 % (at the age of 90 years). The corresponding 10-year fracture probabilities in men are 6.9, 7.0, and 3.3 %. Over and above this effect, the assessment of BMD and age alone does not capture all determinants of fracture probability which are provided by the additional independent risk factors used in FRAX. For this reason, the use of BMD criteria alone for the reimbursement of treatment is problematic. This has been recognized in the development or the updating of practice guidelines which have taken more account of fracture probability and placed less reliance on the T score for BMD [2128]. The manner in which new guidelines have accommodated probability-based assessment has been heterogeneous, with some adopting a fixed probability threshold [22] often as a component of preexisting guidelines [25, 28] and others an age-dependent threshold equivalent to a fracture threshold [23, 24, 26] or the risks associated with preexisting guidelines for reimbursement [21].

The present study has several strengths and limitations. A strength is that the data on hip fracture rates are based on national, rather than regional, estimates. We were able to minimize the overidentification of cases (double counting) but were not able to exclude pathological fractures or assess the accuracy of reporting or coding of fractures. There are also important limitations in the construct of the FRAX model. For this purpose, information is required on the incidence of major fractures (hip, spine, forearm, and humerus). In contrast to hip fractures, the incidence of other major fractures could not be determined because a dedicated registry with routinely recorded osteoporotic fractures does not exist in Romania. As undertaken for many countries with incomplete information, the incidence of these three types of osteoporotic fractures was imputed from the hip fracture incidence in Romania and the relationship between hip fracture incidence and that of the other sites in Sweden (Malmö) [29]. This assumes that the ratio of hip fracture incidence to the incidence of other index fractures is similar in Romania and Sweden. This assumption, used in the development of some FRAX models, appears to hold true for the several countries where this has been tested [12].

The FRAX tool is the first country-specific fracture prediction model available in Romania. It is based on the original FRAX methodology, which has been externally validated in several independent cohorts. Despite some limitations, the strengths make the Romanian FRAX tool a good candidate for implementation into clinical practice.

Acknowledgments

We are grateful to Professor C. Vladescu, director of the National School of Public Health, Bucharest, for assistance in gathering data on hip fractures.

Copyright information

© Springer Science+Business Media New York 2013