Central European Journal of Medicine

Potential role of FRAX analysis in postmenopausal women with osteopenia

* E-mail: aleksandardimi@yahoo.com

Received 29 November 2010; Accepted 31 December 2010

Abstract: Early diagnosis of osteoporosis and estimation of subjects that are at high risk for fracture, is neccesary for osteoporosis treatment. Dual-energy X-ray absorptometry (DXA) is a modern method for bone mineral density (BMD) evaluation. However, along BMD, clini-cal risk factors may significantly influence fracture development. Therefore, FRAX algorithm was designed for the assessment of a ten-year risk for serious osteoporotic fractures (SOF), as well as hip fractures. In the current study, we tried to evaluate the possible lumbal spine and hip BMD influence on ten year risk for SOF and hip fractures and potential role of FRAX in predicting the therapy in postmenopausal women with osteopenia. We performed the study on 385 postmenopausal women. According to the DXA measure-ments, at the lumbal (L) spine (L1-L4) and hip (femor neck), patients were then classified as normal, osteopenic, or osteoporotic. BMD evaluation included the L spine and the hip (subgroup 1), and only on the L spine (subgroup 2). By filling up the FRAX questionnaire, a ten-year risk for SOF fracture and hip fracture was calculated. BMD evaluation, in complete patient’s group and in subgroup 1, resulted in the highest number of osteoporosis (61.04%, 48.08%, retrospectively), while ospeopenia was a main finding in subgroup 2. In the subgroup 1, a high risk for SOF and hip fracture was detected in 16.45% and with high risk for hip fracture in 11.38% subjects. In sub-group 2, only high risk for hip fracture was observed in 3.16% subjects, indicating the active medicament treatment. Simultaneously, correlation of BMD results with FRAX values for SOF and hip fracture, showed significant negative correlation (p<0.001). Obtained results showed significant role of femur neck BMD evaluation in predicting the future factors, which may, together with FRAX analysis, improve the therapy approach in postmenopausal women with ospeopenia.

© Versita Sp. z o.o.

Keywords: Osteporosis • Osteopenia • Postmenopausal women • FRAX analysis

Institute for Prevention, Treatment and Rehabilitation of Rheumatic and Cardiovascular Diseases ‘’Niska Banja”, 18000 Nis, Serbia

Aleksandar Dimić*, Stojanovic Sonja, Nedovic Jovan, Stankovic Aleksandra, Stamenkovic Bojana, Milenkovic Sasa, Mitic Valentina

Research Article

1. IntroductionOsteoporosis is a skeletal systemic disease, characterized by low bone strength and increased fracture risk. Bone strength is usually determined by bone mineral density (BMD), and also by other skeletal characteristics, including bone size, bone micro architecture, remodeling, mineralization and bone microfractures.

Osteoporotic fracture is an unfavorable result of a traumatic event with reduced bone strength. The intensity of trauma is often minimal including falls from a small height or from a flat surface. Sometimes it appears even without visible trauma, so these fractures are terminologically defined like “fractures to small trauma” or “spontaneous fractures” [1].

Osteoporosis is a contemporary pandemic. According to IOF (International Osteoporosis Foundation) more than 200 million women worldwide suffer from osteoporosis. There is an assumption that the total number of inhabitants will decrease by 2050, but the percentage of the older population, over 50 years of age, will increase. It is well known that one out of three women, and one out of every five men, over 50 years of age, has a fracture as a result of osteoporosis [2]. According to these data it could be assumed that the number of osteoporotic fractures, in the following years, will increase. Based to the IOF data, 1.5 million fractures happen worldwide during one year. Fractures of the hip, spinal vertebra and forearm represent 65-80% of all osteoporotic fractures. Such fractures have important health and socioeconomic magnitude, followed by

Cent. Eur. J. Med. • 6(2) • 2011 • 185-189 DOI: 10.2478/s11536-011-0002-8

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Potential role of FRAX analysis in postmenopausal women with osteopenia

every day life difficulties in patients. Fear, anxiety and depression development, as a result of a functional handicap, are also present [3]. While vertebral bodies fractures are closely related with comorbidity, high degree of mortality is followed by hip fractures, especially during the first six months after the injury [4].

According to the census in 2002, there are 1 684 289 inhabitants in Serbia over 60 years of age. Taking into account that the incidence of osteoporosis is 30-40% [5], the number of persons with osteoporosis in Serbia is 505 000 to 674.000. Having in mind that the risk of osteoporotic fractures is 10% [6], it could be estimated that 3500 to 5500 fractures may occur in Serbia annually.

Due to the fact that osteoporosis develops after fracture occurrences and without any signs and symptoms; diagnosis is difficult. Therefore, early diagnosis of osteoporosis and estimation of subjects that are at high risk for fracture, is neccesary for osteoporosis prevention. Dual-energy X-ray absorptometry (DXA) is a modern method for BMD evaluation. However, it is well known that fractures mainly occur in postmenopausal women with osteopenia, which suggests, that, along BMD, clinical risk factors (RF) may significantly influence fracture development. Based on the current protocols, we should actively look for persons with proven clinical risk factors, estimate the impact of those factors and select the patients for the active treatment. The WHO (World Health Organization) has designed FRAX (Fracture Risk Assessment Tool) algorithm for the assessment of a ten year risk for serious osteoporotic fractures (SOF), as well as hip fractures, referred to non- treated postmenopausal women and men age 40 to 90 [7]. Beside femur neck BMD and demographic characteristics, other clinical risk factors are also important (smoking, alcohol consumption, previous fractures, hip fractures in the family, corticosteroids intake and rheumatoid arthritis). According to current recommendations of NOF (National Osteoporosis Foundation) persons with a ten-year risk for SOF (FRAX results ≥ 20%) and risk for hip fracture (FRAX results ≥ 3%), are candidates for the active medicamentous treatment [8].

Based on the previous findings, the current study was designed to investigate the possible lumbal spine and hip BMD influence on the ten- year risk for SOF and hip fractures, to correlate the obtained DXA findings with the risk assessment (with FRAX values) and, finally, to evaluate the potential role of FRAX in determination the therapy in postmenopausal women with osteopenia.

2. Material and Methods The study was carried out on 385 postmenopausal women (age - 64.04 ± 9.23; length of menopause - 10.36 ± 6.7 years) admitted to the Institute for Prevention, Treatment and Rehabilitation of Rheumatic and Cardiovascular Diseases in Niska Banja, from March to July 2010. Only subjects without any osteoporosis therapy were included in the study. All subjects were evaluated by dual-energy X-ray absorptometry (DXA) with a Hologic Discovery device and results were expressed as g/cm² or like T-scor [9]. The T-score is defined as the difference in patients’ results from the mean results obtained in a young adult population, expressed in units of standard deviation of the young adult population. DXA measurements at the lumbal (L) spine (L1-L4) and hip (femor neck), were performed by a certified physician. According to the WHO criteria [10], the patients were then classified as normal, osteopenic, or osteoporotic by DXA T score applied at L spine and hip. In 183 patients (47.53%) BMD evaluation included the L spine and the hip, while in 202 subjects (52.47%) BMD was performed only on the L spine. By filling up the FRAX questionnaire, in all patients, ten- year risk for SOF fracture and hip fracture was calculated.

Statistical analysis was performed by Pearson’s correlation coefficient analysis which was used to determine the relationship existing between BMD values with FRAX results for SOF and hip fracture.

3. ResultsAnalysing the incidence of the single clinical risk factors included in FRAX, obtained data showed that the most prevalent factor was previous fracture (108 patients; 28.05%), followed by corticosteroid therapy (74 patients; 19.22%), smoking (52 patients; 13.51%), rheumatoid arthritis (40 patients; 10.39%), positive hip fracture in the family (24 patients; 6.23%) and alcohol consumption of more than 3 units daily (5 patients; 1.29%).

Evaluation the BMD findings, in the complete patient’s group, showed that the most common finding was osteoporosis (235 patients; 61,04%), followed with osteopenia (113 patients; 29,35%), while only 37 (9,61%) patients showed normal BMD values, as evaluated by DXA analysis. On the other hand, when L spine and hip BMD analysis was performed, osteoporosis was mainly finding (88 patients; 48,08%). Osteopenia was registered in 79 patients (43,17%) and normal BMD values were detected in 16 (8,75%) subjects. However, performing the BMD analysis only on the L spine,

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resulted with osteopenia (95 patients; 47,03%) and osteoporosis (67 patients; 33,17%) while normal BMD values were detected in 40 (19.8%) postmenopausal women (Table 1).

By analysing the FRAX results, in complete patient’s group, high risk for SOF (FRAX values > 20%) was registered in 20 (5.19%) subjects, while high risk of hip fracture (FRAX values > 3%) was detected in 75 (19.48%) patients. In the subgroup of postmenopausal women where L spine and hip BMD was evaluated, osteopenia was detected in 79 subjects. Among them, in 13 patients (16.45%), was determinated high risk for SOF and hip fracture, while only high risk for hip fracture was detected in 9 subjects (11.38%), according to FRAX results. However, in patients where only L spine BMD was evaluated, osteopenia was shown in 95 postmenopausal women. By using FRAX analysis, high risk for hip fracture was observed in 3 (3.16%) patients while high risk for SOF was not detected.

Correlation of BMD results (presented through T scor and in g/cm2) with FRAX values for SOF and hip fracture, showed significant negative correlation (p<0.001) as showh in Table 2, Table 3 and Figure 1.

4. Discussion Since there has not been conducted any

epidemiological study, with data concerning the osteoporotic fractures for calculating ten year fracture risk, for calculating the FRAX results we have used France as a referential country, due to its similarity to

Figure 1. Correlation of FRAX results for hip fracture with hip BMD (expressed as T-scor).

-4.00 -2.00 0.00 2.00 T-scor (hip)

0.00

10.00

20.00

y = -1.07 + -1.90 R-Square = 0.29 p<0.001

FRAX for hip

Correlation analysis was performed as described in Material and Methods section. Abbreviations: T-scor (hip) – BMD assesed in femur neck and expressed as T-scor; RAX results for hip – FRAX results for ten year hip fracture rick.

Examined group Osteoporosis Osteopenia Normal BMD finding

Complete group 61.04% (235) 29.35% (113) 9.61% (37)

Subgroup 1 48.08% (88) 43.17% (79) 8.75% (16)

Subgropup 2 33.17% (67) 47.03% (95) 19.8% (40)

Table 1. DXA analysis of BMD in postmenopausal women.

DXA analysis, in postmenopausal women, was performed as described in Material and Methods section. Results are given as percentage of subjects and patients number in brackets. Abbreviations: Subgroup 1 - a subropup of patients where lumbar (L) spine (L1-L4) and hip (femur neck) Bone mineral density (BMD) was performed; Subgroup 2 – a subgropup of patients where only L spine (L1-L4) BMD analysis was performed.

Correlation of FRAX results for hip fracture and L spine BMD Correlation of FRAX results for SOF and L spine BMD

r values r values

T-scor -0.36* T-scor -0.37*

g/cm² -0.34* g/cm² -0.36*

Table 2. Correlation of L spine BMD and 10 year fracture risk.

Statistical analysis was performed as described in Material and Methods section. Abbreviations: L spine BMD - Bone mineral density (BMD) assesed in lumbar (L1-L4) spine; FRAX - Fracture Risk Assessment Tool; SOF - Serious osteoporotic fractures; * - p<0.001.

Correlation of FRAX results for hip fracture and hip BMD Correlation of FRAX results for SOF and hip BMD

r values r values

T-scor -0.30* T-scor -0.33*

g/cm² -0.54* g/cm² -0.56*

Table 3. Correlation of hip BMD and 10 year fracture risk.

Statistical analysis was performed as described in Material and Methods section. Abbreviations: hip BMD - Bone mineral density (BMD) assesed in femur neck; FRAX - Fracture Risk Assessment Tool; SOF - Serious osteoporotic fractures; * - p<0.001.

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our country, regarding ethnical characteristics and life habits.

Examined group of postmenopausal women mainly consisted of subjects (317) where BMD was evaluated during ambulatory treatment. However, only 68 patients, during this follow up period, were hospitalized at the Institute for Prevention, Treatment and Rehabilitation of Rheumatic and Cardiovascular Diseases “Niška Banja”, which may explain the high incidence of the corticosteroids administration, and rheumatoid arthritis presence, in the subject’s group, as a risk factors for the fractures. Previous fracture as the most common risk factor for the fracture development, obseved in our study, is in agreement with previous reports [11,12]. Namely, these studies, which prospectively followed up 2631 women with early menopause or in perimenopause, in addition of the fracture in the personal anamnesis, demostrated that the number of pregnancies, as well as the intake of hormonal substitution in the early perimenopause, represents a significant risk factor for the future fractures.

Taking into account that the highest number of DXA findings in the examined group matched osteoporosis, suggests that patient selection, for DXA analysis, was appropriate. The presented results showed that the previous fracture was present in 108 (28,05%) women, indicating that patients were relatively late sent to DXA examination. Late DXA diagnostics is in line with long duration of menopause (10.36 ± 6.7) in subjects, before BMD evaluation, while other studies were conducted in women with early menopause or in perimenopause [11,12]. Analysis of DXA results, in patients where only L spine BMD was evaluated, demonstrated that osteopenia, but not osteoporosis, was the most common DXA finding, indicating that hip BMD evaluation may significantly improve sensitivity of the DXA analysis. These observations are consistent with recent

report [12] which showed the importance of hip BMD evaluation in predicting the future fractures. Further, the study of Ignaszak-Szczepaniak et al. [13] suggested the significance of hip BMD evaluation for the hip fracture prediction, especially in the women aged from 50 to 69.

FRAX analysis demonstrated, in the complete patient’s group, more pronounced hip fracture risk than risk for SOF development. Similar results of markedly increased hip fracture risk compared to the SOF risk, based to the FRAX results, has been reported in previously epidemiologic study [14]. In the subgroup of postmenopausal women, where hip and L spine BMD was assesed, after calculating the FRAX risk, results showed that almost 17% of subjects with osteopenia, need the active medicament treatment. On the other hand, in the subgroup of subjects, where L spine BMD was performed, FRAX results indicated the administration of pharmacological agents in only 3.16% of subjects. Simultaneously, these results are in accordiance with correlation results of FRAX values for ten year rasik for SOF and hip fractures with hip and femur neck BMD findings, expressed as g/cm² or like T-scor, indicating the BMD as independent predictor of facture risk. Therefore we propose the significant role of femur neck BMD evaluation in calulating the FRAX results and in optimal therapy usage. The significance of femur neck T-score in FRAX analysis [15,16] as well as other risk factors [17] has been conirmed in recent studies.

In summary, we have shown that hip and L spine BMD evaluation significantly correlates with a ten year fracture risk, indicating the important role of both, especially hip, BMD evaluation in predicting the future farctures. Further, FRAX anlysis in routine clinical practice may notablly improve the therapy approach in postmenopausal women with ospeopenia.

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