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Prevalence and risk factors of morphometric vertebral fracture in apparently healthy osteopenic postmenopausal Thai women

Wattanachanya, Lalita MD1,2; Pongchaiyakul, Chatlert MD3

Author Information
doi: 10.1097/GME.0000000000001634
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  • Editorial

Abstract

Osteoporotic fractures are one of the major public health problems worldwide, particularly in older populations. Nearly one quarter of older people who have an osteoporotic hip fracture die within the first year and more than half of the survivors live dependently.1,2 The best strategies to reduce fracture burden is to identify people who are at high risk of fractures and consider pharmacologic therapy and lifestyle measures to prevent the first fracture or to minimize the risk of subsequent fractures.

In general practice, patients with osteoporosis, bone mineral density (BMD) T score of −2.5 or less, and patients who have had a history of low-trauma fracture are at high risk for fractures and will be candidates for antiosteoporotic medication.3-6 However, there is evidence that a majority of osteoporotic fractures occur in patients with BMD T score between −1.0 and −2.5 due to the much higher number of people in this group.7 Consideration of osteoporosis treatment in these patients is based upon the presence of fracture or the Fracture Risk Assessment Tool (FRAX) scores above the country-specific intervention threshold.4-6,8

Identifying fracture in patients with osteopenia is crucial for determining those who require pharmacotherapy. The fracture that is commonly missed is vertebral fracture (VF), particularly in asymptomatic cases.8-11 VF is common in older adults and is a strong indicator of subsequent fractures of both vertebral and nonvertebral sties.12-15 The reported prevalence of VF was around 20% to 30% among women over the age of 50 years and reaches 40% in women aged 80 years old.16,17 Besides age, some studies demonstrated that BMD and the presence of secondary causes of osteoporosis was associated with VF.18-22 There are several osteoporosis guidelines that propose recommendations for VF screening. For example, the International Society for Clinical Densitometry (ISCD)23 has suggested VF assessment with lateral spine imaging with standard radiography or densitometric VF assessment in patients with BMD T score less than −1.0 who are aged above 70 years in women and 80 years in men, or for those who have risk factors. In this study, we sought to determine the prevalence of and risk factors for morphometric VF in apparently healthy postmenopausal women with osteopenia.

METHODS

Study design and participants

This cross-sectional study was designed in Srinagarind Hospital, Khon Kaen, Thailand. Postmenopausal women attending the postmenopausal clinic were invited to participate in the study, if interested. Demographic, anthropometric, and medical data of all participants, including reproductive history, traditional risks for osteoporosis and fracture were reviewed. Our study focused specifically on postmenopausal women with osteopenia who were apparently healthy; therefore, women with history of premature or surgical menopause, history of previous low-trauma fracture or parental hip fracture, known underlying diseases (eg, rheumatoid arthritis, type 1 diabetes, uncontrolled thyrotoxicosis), history of current smoking, currently taking medications affecting bone metabolism (eg, corticosteroids, thyroid hormone) were excluded. Women who ever had antiosteoporotic agents, regardless of type, duration, and time since the last medication exposure were also excluded from the study. Postmenopausal women without any osteoporotic risk factors underwent BMD testing, and those who were diagnosed with osteopenia, T score between −1 and −2.5 at the lumbar spine (LS) and/or femoral neck (FN), were recruited in the current study. Morphometric vertebral fractures were assessed in all eligible individuals. FRAX scores with and without BMD were calculated using the Thai reference [https://www.sheffield.ac.uk/FRAX/tool.aspx?lang=th].

BMD measurement

BMD at the LS, FN, and total hip (TH) were measured using dual energy x-ray absorptiometry on a Lunar Prodigy bone densitometer (GE Healthcare, Madison, WI). BMD T scores were analyzed using Asian population reference databases, supplied by the manufacturer. The coefficient of variation for BMD for normal participants ranged from 1.5% to 2.0% for LS and 1.3% to1.5% for FN.

Radiography and vertebral fracture assessment

A lateral thoracolumbar (T-L) x-ray radiograph was taken with a 101.6 cm tube-to-film distance as per standard protocol that included details regarding positioning of the participants and the radiographic technique used. Radiographs were taken in the left lateral position centered at L1 level. Vertebral bodies from T4 to L4 levels were assessed by three blinded and independent radiologists, to define morphometric VF using the Genant semi-quantitative method.24 The fractures were graded as grade 1 (mild fracture: reduction of 20%-25% of vertebral height), grade 2 (moderate fracture: reduction of 25%-40% of vertebral height), and grade 3 (severe fracture: reduction of 40% or greater of vertebral height). The kappa coefficient among radiologists was 0.64 (95% CI 0.54-0.76) that was considered a moderate agreement.25 Any difference in the assessment of a joint (among the readers) was resolved by consensus. The study was reviewed and approved by the Ethics Committee of Srinagarind Hospital, Khon Kaen, Thailand. Written informed consent was obtained from all individual participants included in the study.

Statistical analyses

Continuous variables are presented as mean and standard deviation and categorical variables as observed number and percentage. Prevalence was expressed as a percentage according to age group and severity of osteopenia. Comparisons of dependent variables between study groups were made using independent t test or ANOVA, where appropriate. A univariate logistic regression was used to determine the associations between patient characteristics (age, BMI, BMD, and FRAX score) and the prevalent vertebral fracture. Because FRAX scores were calculated from age, BMI, and BMD (FRAX with BMD), it clearly shows that there was a theoretical correlation among them. Also, Pearson's correlation analyses showed significant correlations among variables (data not shown). Therefore, we decided not to conduct a multivariable logistic regression analysis. Statistical significance was defined as a P value <0.05. All data analyses were performed using SPSS, version 17 for Windows Evaluation Software (SPSS Inc. Chicago, IL).

RESULTS

Four hundred ninety postmenopausal women with osteopenia were enrolled in the study. Mean age of the participants was 59.9 ± 7.8 years and mean BMI was 24.3 ± 3.4 kg/m2. BMD results and FRAX with and without BMD are summarized in Table 1. The overall prevalence of morphometric VF established by T-L spine x-ray was 29% (142/490) (grade 1: 62.0%, grade 2: 19.3%, and grade 3: 18.7%). Of these, 4.9% were aged 50 years or less, 40.1% were aged 50-59 years, 38% were aged 60-69 years, and 16.9% were aged over 70 years. Fracture prevalence increased with age, which was about twofold higher in women aged over 70 years compared to women aged less than 50 years and 50-59 years. Forty-two of the 142 women (26.6%) had VF at more than one level (Fig. 1). However, we found no differences in fracture prevalence among those with various degrees of osteopenia (Fig. 2).

TABLE 1 - Characteristics, BMD, and FRAX scores of participants (N = 490)
Age (y) 59.9 ± 7.8
Weight (kg) 57.3 ± 8.2
Height (cm) 153.5 ± 5.7
BMI (kg/m2) 24.3 ± 3.4
BMD (g/cm2)
 Lumbar spine 0.91 ± 0.09
 Femoral neck 0.72 ± 0.08
 Total hip 0.81 ± 0.09
10-y probability of major osteoporotic fracture (%)
 With BMD 4.8 ± 2.7
 Without BMD 5.4 ± 3.6
10-y probability of hip fracture (%)
 With BMD 1.0 ± 1.3
 Without BMD 1.5 ± 2.0
All data are expressed in mean ± standard deviation.BMI, body mass index; BMD, bone mineral density; FRAX, Fracture Risk Assessment Tool.

FIG. 1
FIG. 1:
Prevalence of morphometric vertebral fracture by age group. VF, vertebral fracture; VF ≥ 1, one or more vertebral fractures; VF ≥ 2, two or more vertebral fractures; VF = 1, one vertebral fracture.
FIG. 2
FIG. 2:
Prevalence of morphometric vertebral fractures by osteopenic site and classification of osteopenia (Mild: T score −1.0 to −1.49, Moderate: T score −1.5 to −1.99, Advanced: T score −2.0 to −2.49). VF, vertebral fracture; VF ≥ 1, one or more vertebral fractures; VF = 1, one vertebral fracture; VF ≥ 2, two or more vertebral fractures.

Compared to women without fracture, those with morphometric VF had significantly higher FRAX scores for both major osteoporotic and hip fractures, regardless of whether or not BMD was included. Further analyses using the LS BMD for calculating FRAX in women with only vertebral osteopenia showed similar results (Table 2). Logistic regression analysis showed that age and FRAX scores, calculated with or without BMD, were positively associated with morphologic VF (P < 0.05) (Table 3). Sixty-three (12.9%) and 23 (4.7%) women had Thai FRAX scores above the intervention thresholds for hip fracture (3%) calculated without and with BMD, respectively. Only three (0.6%) women had FRAX scores above the intervention threshold of major osteoporotic fracture (20%) calculated without BMD, whereas none of them met the threshold when BMD was included.

TABLE 2 - Ten-year probabilities of major osteoporotic fracture and hip fracture using FRAX in women with and without morphometric vertebral fractures
Women with VF Women without VF Mean difference (95% CI)
Osteopenia at lumbar spine and/or femoral neck N = 142 N = 348
 10-y probability of MOF (%)
  With BMD 5.3 ± 3.2 4.6 ± 2.5 0.70 (0.17-1.23) a
  Without BMD 6.1 ± 4.3 5.2 ± 3.2 0.93 (0.24-1.63) a
 10-y probability of hip fracture (%)
  With BMD 1.3 ± 2.0 0.9 ± 0.9 0.45 (0.19-0.70) b
  Without BMD 2.0 ± 2.9 1.3 ± 1.4 0.68 (0.30-1.06) b
Osteopenia at lumbar spine N = 137 N = 327
 10-y probability of MOF (%)
  With BMD 6.5 ± 5.2 5.1 ± 3.0 1.45 (0.66-2.23) b
  Without BMD 6.6 ± 5.4 5.3 ± 3.7 1.32 (0.47-2.17) a
 10-y probability of hip fracture (%)
  With BMD 2.1 ± 4.0 1.2 ± 1.6 0.87 (0.36-1.37) b
  Without BMD 2.3 ± 4.2 1.5 ± 2.1 0.84 (0.27-1.42) a
Osteopenia at femoral neck N = 143 N = 319
 10-y probability of MOF (%)
  With BMD 6.1 ± 3.4 5.4 ± 2.7 0.61 (0.03-1.19) a
  Without BMD 6.8 ± 4.5 5.9 ± 3.8 0.83 (0.03-1.63) a
 10-y probability of hip fracture (%)
  With BMD 1.7 ± 2.0 1.3 ± 1.3 0.37 (0.07-0.67) a
  Without BMD 2.4 ± 3.0 1.8 ± 2.4 0.58 (0.07-1.08) a
Data are expressed in mean ± standard deviation.BMD, bone mineral density;MOF, major osteoporotic fracture; VF, vertebral fracture.
aP < 0.05.
bP < 0.001.

TABLE 3 - Factors associated with morphometric vertebral fracture in apparently healthy postmenopausal women with osteopenia
Variables Coefficient (β) SE Odds ratio (95% CI) P
Age (every 5 y) 0.203 0.064 1.23 (1.08-1.39) 0.001
BMI (kg/m2) 0.014 0.029 1.01 (0.96-1.07) 0.629
Lumbar spine BMD (g/cm2) −0.522 1.150 0.59 (0.06-5.66) 0.650
Femoral neck BMD (g/cm2) −2.291 1.253 0.10 (0.01-1.18) 0.067
Lumbar spine T score −0.011 0.145 0.99 (0.75-1.31) 0.940
Femoral neck T score −0.162 0.148 0.85 (0.64-1.14) 0.274
FRAX with BMD (hip) 0.258 0.088 1.29 (1.09-1.54) 0.003
FRAX without BMD (hip) 0.167 0.054 1.18 (1.06-1.31) 0.002
FRAX with BMD (MOF) 0.089 0.035 1.09 (1.02-1.17) 0.011
FRAX without BMD (MOF) 0.068 0.027 1.07 (1.02-1.13) 0.010
BMD, bone mineral density; BMI, body mass index; MOF, major osteoporotic fracture; SE, standard error.

DISCUSSION

The present study evaluated the prevalence of morphometric VF in apparently healthy postmenopausal women who had a BMD in the osteopenic range. The prevalence of VF in our study was 29%, which was higher than expected. In western countries, the overall prevalence of VF in a wide range of BMD values among women aged over 50 years was about 20%.16 Prevalence rates in Asia were more heterogeneous and depended on different patient characteristics, sample size, as well as methods and diagnostic criteria of VF, with the highest rates in Vietnam (26.5%)26 and the lowest rates in Japan (9.5%).27 In subgroups of women age over 70 years, the fracture rate in the present study (43%) was also higher than a previous report by Lau et al,28 which found that VF rate was 29.9% in Chinese women aged 70-79 years. In our study, we chose only postmenopausal women with osteopenia. All study participants had relatively low clinical risk factors for fracture because women with history of premature menopause, low-trauma fractures, parental hip fracture, current smoking, and known diseases or taking medications that affected bone metabolism were excluded. Therefore, we expected that the prevalence of morphometric VF should be lower than what has been reported, which included participants with any fracture risks. One possibility that may explain our high prevalence of VF is that we included mild VF (Genant grade I) in the analyses, however, other studies that applied the same criteria had reported lower VF prevalence (4.7%-12%).27,29,30

Previous prevalence rates in women from Thailand's capital city, Bangkok, also differed markedly from 12.8% (age ≥ 65 y old)31 to 23.6% (age ≥ 50 y old).32 However, diagnostic criteria of VF used in these studies differed from ours and BMD was not performed in the latter study. It was not clear why prevalence of VF in our participants was quite high. It could probably be due to participants being genetically prone to fracture or perhaps, they had some occult secondary causes of low BMD such as vitamin D deficiency. We did not have any laboratory testing to confirm our hypothesis, nonetheless, vitamin D deficiency is prevalent worldwide33-38 and might not explain our findings.

Several studies consistently demonstrated that age was a strong predictor for VF.18-22 We found that women aged over 70 years had the highest fracture risk, which was about twofold compared to younger women. Besides age, lower BMD T score, multiple clinical risk factors, previous low-trauma fracture, historical height loss, diabetes, and glucocorticoid use were predictors of VF.18-22 A few women (11%) had a loss of height of at least 3 cm, however, it was not correlated with the prevalent fracture. This may be explained by the small number of women having height loss, inaccuracy of recalled height, or they might have had other causes rather than fracture, such as disc degeneration. We found that FRAX scores, which were mainly calculated based on age and BMI with and without BMD, were significantly higher in women with VF, however, the absolute differences were small. In addition, FRAX scores may underestimate fracture risk because we could only conduct the analysis based on risk factors and did not include genetic factors that may contribute to the susceptibility of fracture. We could not demonstrate the significant association between BMD values or BMD T score and the presence of morphometric VF. Prevalence rates were similar among those with various degrees of osteopenia. Studies that reported such correction included a wide range of BMD values,18,19,21 whereas we chose only women with osteopenia that may explain the result discrepancy.

It has been accepted that identification of osteoporotic VF is very important because it is a strong predictor of subsequent fractures,12-15 however, it is something that physicians often miss, especially in asymptomatic cases. VF in osteopenic individuals determines the need for pharmacologic treatment. Currently, there are no guidelines for screening of T-L spine fractures in postmenopausal women in Thailand. In 2014, the US National Osteoporosis Foundation3 suggested that spine imaging should be considered for women aged ≥70 years and men aged ≥ 80 years if their T score at the LS, FN, or TH was −1.0; for women aged 65-69 years or men aged 70-79 years with a T score of ≤ −1.5; and for postmenopausal women and men aged 50 years with risk factors. The 2019 ISCD official position recommended lateral spine imaging for adults with T score of ≤−1.0 with at least one of the following criteria: women age ≥70 years or men ≥age 80 years, historical height loss >4 cm, self-reported prior VF, or glucocorticoid therapy equivalent to ≥5 mg of prednisone or equivalent daily for ≥ 3 months.23 According to our data, among 142 women who had morphometric VF, 38.7% and 16.9% met the criteria for VF screening by the US National Osteoporosis Foundation and ISCD, respectively. Application of these guidelines in postmenopausal Thai women with osteopenia would underdiagnose a large number of women who need antiosteoporosis medication. Therefore, we suggest VF screening in postmenopausal women with BMD T score less than −1.0 should be done at an earlier age than the current recommendations. Our study has some limitations. First, a self-reported height loss was subject to recall bias. Second, our study population came from only the Northeastern part of Thailand and might not be representative of the entire Thai population or women of a different race or ethnicity. Third, we did not collect biochemical data, therefore, some occult conditions may have been missed. Fourth, a modest agreement among radiologists, as indicated by the kappa statistic, could result in fracture misclassification, even though any differences among radiologists were resolved by consensus. Last, being a cross-sectional study, our data did not prove the causal relationship between having prevalent morphometric VF and future fracture occurrence, so a larger prospective trial would be required to draw conclusions about whether VF screening should be done in all postmenopausal women with osteopenia, whether or not they have additional risk factors for facture, and to test its cost effectiveness.

CONCLUSIONS

In conclusion, morphologic VF was common in apparently healthy postmenopausal women with osteopenia, and that advancing age and higher FRAX scores were associated with greater prevalence of morphometric VF.

Acknowledgments

The authors thank the patients for their participation. We also thank the radiologists of the Department of Radiology, Faculty of Medicine, Khon Kaen University for radiograghic interpretation and the technician for BMD measurement. The authors also thank Assistant Professor Anupol Panitchote and Professor Tuan V Nguyen for statistical analyses.

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Keywords:

Asia; Osteopenia; Postmenopausal women; Vertebral fractures

© 2020 by The North American Menopause Society