Proximal Femoral Cortical Thickness Index as a Predictor of Osteoporosis in Women Aged Over 65 Years Old

Background: Osteoporosis is a systemic condition characterized by loss of bone mass. The gold standard for diagnosing osteoporosis is bone mineral density (BMD) examination. Measurement of proximal femoral Cortical Thickness Index (CTI) can be considered as a predictor of osteoporosis. This research was conducted to prove proximal femoral CTI as a predictor of osteoporosis in women aged over 65 years.

Methods: This research is a cross-sectional study including a correlation test, mean difference test, and diagnostic test for numeric variables. The study population were women aged over 65 years who underwent x-ray and BMD examination at Prof. Dr. IGNG Ngoerah General Hospital from 2021 until October 2023. Samples were taken by consecutive sampling. The subjects were measured for proximal femoral CTI, correlation analysis, mean difference between two groups, and receiver operating characteristic (ROC).

Results: Among 34 research subjects, a weak and significant correlation was found between the proximal femoral CTI and BMD (r = −0.387, p = 0.024). The mean of CTI in the osteoporosis group was lower compared with the group without osteoporosis (p = 0.021). The ability of CTI to predict osteoporosis is quite good (AUC > 0.7). The CTI cut-off point of <0.62 is not proven as a predictor of osteoporosis. The most optimal cut-off point of proximal femoral CTI as a predictor of osteoporosis is <0.57 with 70.59% sensitivity, 76.47% specificity, 82.4% positive predictive value (PPV), and 58.8% negative predictive value (NPV).

Conclusion: Proximal femoral CTI can be considered a predictor of osteoporosis in women aged over 65 years old.

Introduction

Osteoporosis is defined as a systemic condition of the bones characterized by loss of bone mass along with changes in its microarchitecture. This condition will reduce bone strength and increase the risk of pathological fractures. It is estimated that 9 million cases of pathological fractures caused by osteoporosis occur every year worldwide [1]. Detection of osteoporosis in the early stage is difficult, hence a quick and accurate diagnosis method is critical to be able to detect osteoporosis and provide adequate treatment immediately to prevent the emergence of various complications [2].

The current standard procedure for osteoporosis diagnosis is a bone mineral density (BMD) examination. BMD examination is a method that measures the levels of inorganic material of the bone [3]. The problem is that not every health service center provides this examination for osteoporosis diagnosis, especially in Indonesia. BMD examination is only provided by referral center hospitals. On the other hand, not all the district hospitals have access to this examination, especially with the high operational cost. One of the methods that could act as a predictor of osteoporosis is plain radiographs (X-rays), especially plain radiographs of the hip in the AP position [4].

Plain radiographs can be a modality that may help diagnose osteoporosis, but plain radiographs in general can only provide a qualitative picture of bone mass loss [2]. Some parameters that reflect bone mass loss more quantitatively can be measured from plain antero-posterior (AP) hip radiographs. One of these indicators is the Cortical Thickness Index (CTI) of the proximal femur [5].

Previous studies found that proximal femur CTI has a significant correlation along with sufficient sensitivity and specificity for diagnosing osteoporosis, but with various cut-off points. It was stated that proximal femur CTI has a strong correlation with the T-score and has the best sensitivity and specificity in diagnosing osteoporosis, as the proximal femur is likely to experience osteoporosis if the CTI value of the proximal femur is 0.49 or higher [6]. Hadidi et al. [2] also found a similar result that shows a significant difference of proximal femur CTI between osteoporosis and non-osteoporosis patients. Similarly, Sah et al. [5] also found that proximal femur CTI has a positive correlation with osteoporosis with the best cut-off point of 0.40 (0.85 sensitivity, 0.79 specificity). Proximal femur CTI is easily obtained as it only requires plain radiographs that are provided by all types of hospitals. This will serve as a helpful predictor of osteoporosis that allows further evaluation and early detection followed by immediate treatment. It is proposed that proximal femur CTI can be considered a relatively practical and efficient predictor of osteoporosis so that it will help the diagnosing of osteoporosis in women over 65 years old.

Methods

This research is a cross-sectional study using a correlation test design, mean difference between two groups, and a numerical variable diagnostic test. Samples were taken by consecutive sampling methods until the sample size was met. First, the proximal femur Cortical Thickness Index (CTI) from all subjects was assessed, then correlation analysis was done, followed by the mean difference between the two groups, and receiver operating characteristic (ROC) to obtain the sensitivity and specificity, test 0.62 as the best cut-off point and positive predictive value and negative predictive value from that cut-off point by using bone mineral density (BMD) examination as the standard.

Aims

To prove that a proximal femur CTI value of less than 0.62 is a predictor of osteoporosis in women aged over 65 years with a significant correlation with BMD.

Population and Period

The research will be carried out during the period October 2023 to December 2023 at the Orthopedics and Traumatology Polyclinic and the Radiology Installation at the Prof. Dr. IGNG Ngoerah Central General Hospital, Denpasar, Bali.

The target population in this research is all women aged over 65 years. Meanwhile, the population covered by this research are women aged over 65 years who underwent x-ray and BMD examinations at the Radiology Installation of Prof. Dr. IGNG Ngoerah Hospital in the period 2021 to October 2023.

Samples

The sample size was calculated automatically by using medical software for areas under ROC studies. In calculating the sample size, the values α = 0.05 and β = 0.20 are used. For the area under the ROC curve, the value is set at 0.80 with a null hypothesis value = 0.50. The area under the ROC curve value of 0.80 is based on a previous study by Yeung et al. [6].

Meanwhile, the sample size ratio of negative to positive cases is 57/35 based on a previous study by Köse et al. [4].

Based on the calculations, 29 subjects were required for the research. Based on these results, an additional 10% was added to anticipate dropout, resulting in a final sample size of 32 research subjects.

Eligibility Criteria

The inclusion criteria consist of female patients over 65 years old who previously underwent BMD examination at the Radiology Installation of Prof. Dr. IGNG Ngoerah Denpasar Hospital between 2021 and 2023, and had their BMD data stored in an electronic database (SIMRS) at Prof. Dr. IGNG Ngoerah Hospital Denpasar. Additionally, these patients must have X-ray data of the antero-posterior (AP) hip position stored in the same electronic database (SIMRS) at Prof. Dr. IGNG Ngoerah Hospital Denpasar.

The exclusion criteria for this study include several specific conditions. Participants with a history of steroid consumption for more than one week within the past month are excluded. Additionally, those who have been treated with bisphosphonates for more than one year are not eligible. Individuals with a history of autoimmune diseases, such as systemic lupus erythematosus or rheumatoid arthritis, are also excluded. The study further disqualifies participants with a history of bone infection in the lower extremities, malignancy, or congenital/inherited diseases affecting the bones, such as osteogenesis imperfecta.

The drop-out criteria for the study include several scenarios. Firstly, if the patient dies during the study period, making it impossible to collect complete data, they will be considered a drop-out. Secondly, if patients suddenly refuse to continue participating in the research before the data collection is complete, they will also be categorized as drop-outs. Lastly, if the BMD data or plain AP hip radiographs are damaged, erroneous, unusable, or unsuitable for analysis during the study period, the affected patients will be dropped from the study.

Procedure

The data collection process begins with retrieving information from the visit register of the Amertha Wing Radiology Installation at Prof. Dr. IGNG Ngoerah Hospital in Denpasar. Research subjects are selected based on the availability of X-ray and BMD data, adhering to specific inclusion and exclusion criteria until the required sample size is achieved. Next, the phone numbers of potential research subjects are identified. These individuals are then contacted via telephone or chat application to explain the research procedures and ascertain their willingness to participate. Those who agree to participate sign an informed consent form. Following consent, researchers collect anamnesis data and conduct a physical examination, particularly measuring body weight and height, with results recorded on a paper or table. Subjects are also provided with counselling and education about their clinical condition, the results of supporting examinations, and recommendations for management and lifestyle modifications to prevent complications or worsening of their condition. Finally, the research subjects are allowed to go home.

Data collection on plain radiography (X-rays) of research subjects in the hospital electronic database (SIMRS). Interpretation of plain radiograph data to measure CTI of the proximal femur through measurements in the hospital’s electronic management system. Access and recording of previous BMD data from research subjects. The interval between BMD examination and x-ray examination in this research should not be more than 1 year. After data collection and recording have been completed, statistical analysis is carried out using SPSS 22 and STATA v.13 software which includes descriptive analysis, using the proportion difference test (Chi-Square test or Fisher Exact test) and the mean difference test (independent T-test. or Mann Whitney). Determination of correlation strength between CTI of the proximal femur and bone mineral densitometry (BMD) using the Spearman Correlation Test. Normality test (Shapiro-Wilk) and Homogeneity Test. Test the difference between the means of two groups (using the independent T-test if the data is normally distributed, or the Mann-Whitney test if the data is not normally distributed). Testing the value of 0.62 as the cut point for proximal femur CTI in predicting osteoporosis, as well as determining the sensitivity and specificity of proximal femur CTI using ROC analysis (by looking at the area under the curve (AUC) of the ROC curve and its significance through the p-value with significance limit α = 0.05). Determination of the cut-off point with the most optimal sensitivity and specificity results for the proximal femur CTI variable as a predictor of osteoporosis by looking at the highest correctly classified value. Calculation of the Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of the proximal femur CTI as a predictor of osteoporosis using the optimal cut-off point (obtained through cross-tabulation).

Results

Based on the search results of the data register for visits to the Amertha Wing Radiology Installation at Prof. Dr. IGNG Ngoerah Denpasar Hospital from 2021 to 2023, a total of 34 research subjects were obtained (consisting of 17 subjects with osteoporosis and 17 people without osteoporosis) (Table I).

Table I. Characteristic of Study Arrangement of Channels

General characteristic variables	Bone mineral densitometry status		p-value
	Subject with osteoporosis (n = 17)	Subject without osteoporosis (n = 17)
Mean age (years ± SD)	71.35 ± 4.401	71.35 ± 5.623	1.0
History of calcium supplement consumption (%)	Regular consumption = 1 (5.9%)	Regular consumption = 1 (5.9%)	1.0
	No regular consumption = 16 (94.1%)	No regular consumption = 16 (94.1%)
History of vitamin D supplement consumption (%)	Regular consumption = 1 (5.9%)	Regular consumption = 1 (5.9%)	1.0
	No regular consumption = 16 (94.1%)	No regular consumption = 16 (94.1%)
Regular exercise history (%)	Regular exercise = 1 (5.9%)	Regular exercise = 2 (11.8%)	1.0
	No regular exercise = 16 (94.1%)	No regular exercise = 15 (88.2%)
History of lower extremity fracture (%)	There is a history = 5 (29.4%)	There is a history = 5 (29.4%)	1.0
	No history = 12 (70.6%)	No history = 12 (70.6%)
Age at last menstruation (years ± SD)	52.41 ± 2.002	52.76 ± 1.786	1.0
Body mass index (kg/m2 ± SD)	22.22 ± 4.87	23.75 ± 4.47	0.085

Correlation Between Cortical Thickness Index (CTI) of the Proximal Femur and Bone Mineral Densitometry Status

Next, a Spearman correlation test was carried out to see whether there was a correlation between the proximal femur CTI value and bone mineral densitometry status (osteoporosis/no osteoporosis). Spearman correlation test results between proximal femur CTI values and bone mineral densitometry status (Table II).

Table II. Pearson Correlation Test

	Bone mineral densitometry status
Proximal femur CTI values	r = −0.387
	p = 0.024
	n = 34

This negative correlation coefficient indicates that the lower proximal femur CTI value is related to osteoporosis, with a weak correlation strength (correlation coefficient/r value between 0.2–0.4). The p-value = 0.024 indicates that the proximal femur CTI value has a statistically significant correlation with bone mineral densitometry status (p < 0.05) [7].

Difference in Mean of Cortical Thickness Index (CTI) of the Proximal Femur between Subjects Group with Osteoporosis and the Subjects Group Without Osteoporosis

Next, a test of the difference in the mean CTI value of the proximal femur was carried out between the group of subjects with osteoporosis and the group of subjects without osteoporosis. Before statistical tests were carried out, tests were carried out for normality and homogeneity of the proximal femur CTI variables. The normality test was carried out using the Shapiro-Wilk test for sample sizes <50, while the homogeneity test was carried out using the Levene test (Tables III and IV).

Table III. Normality Test Using Saphiro-Wilk

Variable	Group	N	p-value	Remarks
Proximal femur CTI	Osteoporosis	17	0.140	Normal distribution
	No osteoporosis	17	0.346	Normal distribution

Table IV. Homogenecity Test Using Levene Test

Variable	N	p-value	Remarks
Proximal femur CTI	34	0.599	Homogeneous

With variable data that was normally and homogeneously distributed, a test of the difference in mean proximal femur CTI between the group of subjects with osteoporosis and the group of subjects without osteoporosis was carried out using the unpaired T-test (independent T-test) (Table V).

Table V. T-Test Unpaired

Variable		Group		p-value	IK 95%
		With osteoporosis (N = 17)	No osteoporosis (N = 17)
Proximal femur CTI	Mean ± SD	0.51 ± 0.09	0.59 ± 0.10	0.021	0.012–0.145

The results of the unpaired T-test showed a p-value of 0.021, which means that there was a statistically significant difference in the mean CTI of the proximal femur between the group of subjects with osteoporosis and the group of subjects without osteoporosis (p-value < 0.05).

Ability and Cutting Points of the Cortical Thickness Index (CTI) of the Proximal Femur as a Predictor of Osteoporosis in Women Over 65 Years of Age

To see the significance of the proximal femur CTI value in predicting osteoporosis in female subjects over 65 years old, ROC analysis and AUC assessment were carried out. The results of the ROC analysis of the proximal femur CTI variable with bone mineral densitometry status as the standard (Table VI and Fig. 1).

Table VI. ROC Analysis Results

	Bone mineral densitometry status
CTI value proximal femur	AUC = 0.723
	p = 0.026
	n = 34

Fig. 1. ROC curve for proximal femur CTI variables with bone mineral densitometry as standard.

An AUC area of 0.723 was obtained, which is above 0.7, which indicates that the ability of CTI of the proximal femur in predicting osteoporosis is quite good. The p-value of 0.026 (<0.05) indicates that the ability of proximal femur CTI to predict osteoporosis is statistically different from bone mineral densitometry examination which is the diagnostic standard (Fig. 1). Based on the ROC tabulation results above, it was found that at the proximal femur CTI cut point <0.62, the sensitivity of proximal femur CTI in predicting osteoporosis was 41.18% with a specificity of 88.24%. This point is not the most optimal cut point from the results of this research analysis in predicting osteoporosis. The most optimal cut point for the proximal femur CTI value in predicting osteoporosis is <0.57 which has the highest correctly classified value (73.53%) as well as the highest likelihood ratio (+)/likelihood ratio (−) value (7.8003). At this cut point, CTI of the proximal femur had a sensitivity of 70.59% and a specificity of 76.47% in predicting osteoporosis. If a cross-tabulation is carried out between the proximal femur CTI value with a cut point of <0.62 with bone mineral densitometry status as the standard for osteoporosis diagnosis, the positive predictive value (PPV) and negative predictive value (NPV) of the proximal femur CTI in predicting osteoporosis were 82.4% and 23.5%. Meanwhile, at the cut point for proximal femur CTI < 0.57, the positive predictive value (PPV) and negative predictive value (NPV) of proximal femur CTI in predicting osteoporosis were 82.4% and 58.8%, respectively. (Tables VII, VIII).

Table VII. ROC Tabulation Between Proximal Femur CTI Values at the Cut Point <0.62 With BMD as the Diagnostic Standard

Proximal femur CTI status (With cut point <0.62)	Bone mineral densitometry status (Default standard)		Total
	Osteoporosis	No osteoporosis
Osteoporosis (CTI < 0.57)	14	13	27
No osteoporosis (CTI ≥ 0.57)	3	4	7
Total	17	17	34
Positive predictive value (PPV)		82.4%
Negative predictive value (NPV)		23.5%

Table VIII. Cross Tabulation Between Proximal Femur CTI Values at the Cut Point <0.57 with BMD as the Diagnostic Standard

Proximal femur CTI status (With cut point <0.57)	Bone mineral densitometry status (Default standard)		Total
	Osteoporosis	No osteoporosis
Osteoporosis (CTI < 0.57)	14	7	21
No osteoporosis (CTI ≥ 0.57)	3	10	13
Total	17	17	34
Positive predictive value (PPV)		82.4%
Negative predictive value (NPV)		58.8%

Discussion

This research involved 34 research subjects, all of whom were women aged equal to or above 65 years who had bone mineral densitometry data and hip X-rays at Prof. Dr. IGNG Ngoerah General Hospital Denpasar from 2021 to October 2023. The research subjects consisted of 17 subjects with osteoporotic bone mineral densitometry results (T-score < −2.5 SD) and 17 subjects with non-osteoporotic bone mineral densitometry results (T-score ≥ −2.5 SD). The results of the correlation test between the proximal femur CTI value and bone mineral densitometry status (osteoporosis/not osteoporosis) showed a weak and statistically significant correlation between the proximal femur CTI value and bone mineral densitometry status (r = −0.387, p = 0.024).

This result is parallel with various studies that have been conducted previously. A study conducted by Yeung et al. suggested that various hip X-ray parameters have varying correlations with bone mineral densitometry and osteoporosis status. Canal bone ratio (CBR) and morphological cortical index (MCI) have a fairly good correlation with bone mineral densitometry, but other parameters such as canal-to-calcar ratio (CCR) and canal flare index (CFI) show a weak correlation with bone mineral densitometry [6]. Research done by Hadidi et al. [2] also found that the CTI of the proximal femur showed a significant correlation with the T-score of bone mineral densitometry. Sah et al. [5] and Nguyen et al. [8] also found that the CTI of the proximal femur showed a positive correlation with the T-score and mineral densitometry bones and can be considered a good predictive factor for osteoporosis. Similar results were also obtained by Köse et al. [4] who found that there was a significant correlation between CCR and CTI of the proximal femur on bone mineral densitometry. In this study, it was found that CCR has a very weak correlation (r = −0.129) and is not statistically significant (p = 0.467) with bone mineral densitometry in diagnosing osteoporosis.

In this study, there was a significant difference in the mean CTI of the proximal femur between the groups of research subjects with osteoporosis and without osteoporosis, where the mean CTI of the proximal femur in the group of subjects with osteoporosis was lower than in the group of subjects without osteoporosis (p = 0.021). Theoretically, this is caused by the thinning of the cortex and widening of the medullary canal in the proximal region of the femur, which is one of the effects of osteoporosis [9]. These results are also in accordance with various previous studies. Hadidi et al. [2] also found that there was a significant difference in the mean CTI of the proximal femur between the group of patients with osteoporosis and the group of patients without osteoporosis. The same results were also obtained by Köse et al. [4] who found that there was a significant difference between the mean CCR and proximal CTI femur between groups of subjects with osteoporosis and without osteoporosis. The results of the correlation test and analysis of mean differences indicate that there is a fairly strong relationship between the CTI value of the proximal femur and bone mineral densitometry status (osteoporosis status). Meanwhile, for the CCR variable, there was no significant difference in mean CCR between the groups of research subjects with osteoporosis and without osteoporosis (p = 0.468).

In this study, it was found that the ability of CTI of the proximal femur to predict osteoporosis in female research subjects aged over 65 years was quite good (AUC area above 0.7), but it still could not match the bone mineral densitometry examination which is the standard (p-value < 0.05) Previous research from Nguyen et al. [8] revealed that in a population of Japanese women aged over 50 years, the best cut point for CTI of the proximal femur in predicting osteoporosis was <0.62 with a sensitivity of 95.6%. However, this study obtained different results. Based on the results of the ROC analysis in this study, the CTI value of the proximal femur with a cut point <0.62 only had a sensitivity and specificity of 41.18% and 88.24% respectively, with a positive predictive value (PPV) and negative predictive value (NPV), respectively of 82.4% and 23.5%. In this study, the cut point for the most optimal proximal femur CTI value as a predictor of osteoporosis in the population of women aged over 65 years is <0.57 (as evidenced by the highest correctly classified value and likelihood ratio (+)/likelihood ratio (−)) with sensitivity and specificity was 70.59% and 76.47%, respectively, and positive predictive value (PPV) and negative predictive value (NPV) were 82.4% and 58.8%, respectively.

The results of various previous studies involving research subjects from various races indicate that CTI of the proximal femur is one of the radiological parameters that can be considered as a predictor of osteoporosis, but with quite varying results. Yeung et al. [6] through their study found that based on AUC analysis of Chinese cadaver research subjects, CBR (which uses the same dimensions as CTI) showed the best ability in diagnosing osteoporosis, followed by MCI, CFI, and CCR. Köse et al. [4] through their study with research subjects of 92 Turkish women aged over 60 years found that CTI proximal femur <0.3 or CCR <0.47 was able to reflect osteoporosis with a sensitivity of 100% and specificity of 98%. Regarding CCR parameters, in this study, it was found that the ability of CCR to diagnose osteoporosis is not very reliable (wide AUC = 0.574). Sah et al. [5] through their research involving 32 postmenopausal Caucasian women, showed that the proximal femur CTI cut point ≤0.40 could diagnose osteoporosis with a sensitivity of 85% and a specificity of 79% in this population.

The results of this study and various previous studies concluded that the CTI value of the proximal femur can be used as a predictor of osteoporosis [2], [4]–[6]. For the population of women over 65 years, the authors recommend a CTI value of the proximal femur of less than 0.57 as a predictive factor for osteoporosis compared to the cut point. CTI of proximal femur <0.62. Proximal femur CTI measurements <0.57 in the population of women aged over 65 years require further evaluation and bone mineral densitometry examination to establish a diagnosis of osteoporosis and determine treatment as early as possible to obtain optimal clinical results while preventing complications.

As a shortcoming and weakness in this research, it has a limited subject scope, namely that it can only be generalized to the population of women aged over 65 years. This research cannot yet be applied to men or populations aged 65 years and under. Additionally, some variables such as genetic factors and errors in positioning when collecting X-ray data are confounding factors that are difficult to control and have the potential to cause bias in the results of this study. The results of this research also cannot be applied to certain conditions such as genetic/congenital disorders, chronic inflammation/infection, and malignancy.

Conclusion

There is a correlation between the proximal femoral Cortical Thickness Index (CTI) and Body Mass Index (BMI). Studies have shown that the mean CTI of the proximal femur in women over 65 years of age with osteoporosis is lower than in women of the same age group without osteoporosis. However, it has not been proven that a proximal femur CTI value of less than 0.62 can be used as a reliable predictor of osteoporosis in women over 65 years of age.