Keywords
osteoporosis - DXA scan - osteopenia - telopeptide - fracture
Osteoporosis is a silent disease until it is complicated by trivial fall fractures.
These fractures causes enormous financial, medical, and personal burden to the patients
and to the nation. Osteoporosis not only affects woman but affects men also. Osteoporosis
in men is underrecognized and thus undertreated.[1] Till now, the gold standard for diagnosing osteoporosis is dual-energy X-ray absorptiometry
(DXA) scan. DXA is a costly method to assess bone mineral density. Present scenario
needs a simpler and more cost-effective method for diagnosing osteoporosis. There
is an increasing interest within the orthopaedic community in the noninvasive cost-effective
measurement of the bone mineral density. The aim of the study is to assess whether
urinary N-telopeptide level can be a new diagnostic tool in diagnosing osteoporosis.
Subjects and Methods
This prospective study was done at Sri Ramachandra Medical Centre (SRMC) hospital
from October 2015 to October 2017. The study was conducted among patients who comes
to SRMC as inpatient or outpatient with suspected osteoporosis and underwent DXA scan
and urinary N-telopeptide. The sampling method in this study is probability sampling.
Ethics committee approval was obtained from SRMC institutional ethics committee. The
inclusion criteria were women aged 65 or older, women aged less than 65 with risk
factors, younger postmenopausal women with one or more risk factors, men aged 70 or
older, men less than 70 with risk factors, and any earlier group patients who comes
within 24 hours following trivial fall fractures.[2]
[3]
[4] The exclusion criteria were pathological fracture, history of any illness affecting
bone metabolism such as renal failure, hepatic failure, active malignancy, thyroid
abnormalities, and drugs that affect bone metabolism such as steroids, anticonvulsants
etc. The patients who meet the inclusion criteria were enrolled into the study. Prior
informed consent was obtained from all patients.
DXA scan was done using GE healthcare Prodigy pro-DXA machine. DXA scan for right
hip was done for all patients. If the patient is having fracture or operation done
in the right hip, DXA scan was done in left hip or spine. In cases were DXA scan was
done for hip and spine and any one area reported as normal and other as osteoporosis/osteopenia,
then the patient was excluded from the study. Twenty-four hours urine was collected
in a sterile plastic container. The collected specimen was sent to the centralized
laboratory in SRMC. Urine sample was analyzed by enzyme-linked immunosorbent assay
(ELISA) technique using Osteomark kit. The inter- and intra-assay coefficients of
variation of Osteomark urinary N-telopeptide kit are 4.0 and 7.6%, respectively.
The results from DXA scan were taken as gold standard against urinary N-telopeptide.[5]
[6] Then the patients were divided into two groups control and study. The control group
contains patients who had normal DXA, while study group contains patients having either
osteopenia or osteoporosis. Routine bone profile investigations such as serum calcium,
phosphorus, alkaline phosphatase, serum albumin was done for all patients.
Based on our inclusion and exclusion criteria, 110 persons were included in the study.
We had 60 study and 50 controls patients. We had 88 females and 22 males. The results
obtained were statistically analyzed. The collected data were analyzed with IBM SPSS
statistics software 23.0 version. To describe about the data descriptive statistics
frequency analysis, percentage analysis was used for categorical variables, and the
mean and standard deviation were used for continuous variables. To find the significant
difference between the bivariate samples in independent groups, the unpaired sample
t-test was used. To find the significance in categorical data, chi-square test was
used. In both the earlier statistical tools, the probability value of 0.05 is considered
as significant level.
Results
In our study, we had 18.2% osteopenic and 36.4% osteoporotic patients as evident from
[Table 1]. The mean value of urinary N-telopeptide in control was 49.8 and in case was 182.5.
The standard deviation of urinary N-telopeptide value in case was 159.9 from [Table 2]. From [Table 3], the independent sample test for urinary N-telopeptide clearly shows significance
association with osteoporosis/osteopenia. We had totally 53 patients associated with
fracture out of which 47 were cases and 6 were controls.
Table 1
Results of DXA scan
|
DXA scan
|
Study
|
Control
|
Percentage (%)
|
|
Normal
|
0
|
50
|
45.5
|
|
Osteopenia
|
20
|
0
|
18.2
|
|
Osteoporosis
|
40
|
0
|
36.4
|
Abbreviation: DXA, dual-energy X-ray absorptiometry.
Table 2
Mean values of urinary N-telopeptide
|
Groups
|
N
|
Mean
|
Standard deviation
|
Standard error mean
|
|
Study
|
60
|
182.540
|
159.968
|
20.6518
|
|
Control
|
50
|
49.839
|
31.3343
|
4.4313
|
Table 3
Independent sample test for NTx
|
NTx value
|
Levene's test for equality of variances
|
t-test for equality of means
|
|
F
|
Significance
|
T
|
df
|
Significance (two tailed)
|
Mean difference
|
Standard error difference
|
95% Confidence interval of the difference
|
|
Lower
|
Upper
|
|
Equal variance assumed
|
29.076
|
0.000
|
5.770
|
108
|
0.000
|
132.7006
|
22.9983
|
87.1140
|
178.2872
|
|
Equal variances not assumed
|
|
|
6.283
|
64.394
|
.0005
|
132.7006
|
21.1219
|
90.5097
|
174.8915
|
Discussion
DXA scan will give us the quantity of bone; however, it does not give evaluation of
patients bone quality. The factors that may alter or change the DXA scan results are
artifacts, anatomy, machinery, location, varying technicians, and positioning of patients.
Wherever there is radiation, there is always a chance of danger related to that. Any
accidental exposure of radiation can cause drastic implications. However, if this
is carefully done, the advantages of DXA outweigh its risk. Moreover, maximum permissible
limit of precision error of technician doing DXA is around 1.7% for lumbar spine and
1.3% for femoral neck.[7] A major disadvantage of DXA is that currently, there is a lack of standardization
in bone and soft tissue measurements.[8] DXA scan reports tend to vary based on hydration status of patients, tissue thickness,
and soft tissue composition in bony regions. It is evident that it is close to impossible
to control all factors involved, and therefore, there are significant limitations
to the current “gold standard.”[9] Immunoassays for biochemical markers of bone resorption were emerging that appear
to be sufficiently specific and convenient for clinical use.[10] The need for them arises because the impact of osteoporosis on the aging population
increases and better tools to aid in risk prediction and prevention of osteoporosis
was mandatory.
Bone resorption markers are important indicators of disease activity in patients with
osteoporosis. Normalized results of these indicators are helpful in establishing the
disease and its managements. Urinary N-telopeptide has been used for monitoring treatment
for osteoporosis for a long time, but now, clinicians are using it to predict the
onset of osteoporosis. The new ELISA immunoassay for the urinary excretion of cross-linked
collagen peptides is a reliable and specific biochemical marker of bone resorption.[11] The telopeptides are from Type I collagen which forms 90% of organic bone matrix
and are cross-linked at N and C terminal ends of the molecules to form the basic fabric
and tensile strength of the bone tissue. Urinary N-telopeptide is a sensitive and
specific marker of bone resorption.[11] NTx is the stable degradation end product, which can be measured both in serum and
urine. The NTx sequence is generated by osteoclastic activity and proteolysis. Hence
it does not requires further breakdown or metabolism by kidney or liver for its production.[12] Urinary N-telopeptide value does not significantly vary between male and female,
and its range is pretty much same once the patient attains menopause. The urinary
excretion is not affected by diet, and therefore shows less variation than the conventional
markers.[13]
From [Table 3], the independent sample test for urinary N-telopeptide clearly shows significance
association with osteoporosis/osteopenia. There is statistical significance of urinary
N-telopeptide in study group when compared with the control considering DXA scan as
a gold standard. Similarly, urinary N-telopeptide values are significantly higher
in the patients who had an associated fracture. The implication from [Tables 4] and [5] is that fracture is more common in the patients having osteoporosis/osteopenia.
Chi-square test for fracture association in the study group is also statistically
significant. Serum calcium, serum phosphorus, and serum alkaline phosphatase did not
show significant correlation with urinary N-telopeptide value between study and control
groups.
Table 4
Study group patients association with fracture
|
Groups
|
Total
|
|
Study
|
Controls
|
|
Associated with fracture
|
No
|
Count
|
13
|
44
|
57
|
|
% Within groups
|
21.7%
|
88.0%
|
51.8%
|
|
Yes
|
Count
|
47
|
6
|
53
|
|
% Within groups
|
78.3%
|
12.0%
|
48.2%
|
|
Total
|
Count
|
60
|
50
|
110
|
|
% Within groups
|
100.0%
|
100.0%
|
100.0%
|
Table 5
Chi-square test for fracture association with study group
|
Value
|
df
|
Asymptotic significance (two sided)
|
Exact significance (two sided)
|
Exact significance (one sided)
|
|
Pearson chi-square
|
48.065
|
1
|
0.0005
|
|
|
|
Continuity correction
|
45.445
|
1
|
0.000
|
|
|
|
Likelihood ratio
|
52.936
|
1
|
0.000
|
|
|
|
Fisher's exact test
|
|
|
|
0.000
|
0.000
|
|
N of valid cases
|
110
|
|
|
|
|
The N-telopeptide is specific to bone due to its unique amino acid sequence. Bone
density as measured by DXA provides a static snapshot of bones and does not distinguish
if bone loss is ongoing or not. But urinary N-telopeptide is a dynamic measurement
of what is actually happening in bone at any given time. There is considerable research
ongoing to find a better study to replace the DXA scan. Considering financial parts
of the investigations urinary N-telopeptide assessment is being cheaper than DXA.
The cost of single region DXA scan is around 2,500 rupees, while urinary N-telopeptide
ELISA kit is around 25,000 rupees for 100 patients. If urinary N-telopeptide test
were done more frequently, then the kit can be purchased in a much cheaper rate. Moreover,
cost of installing DXA, maintaining, and day-to-day running were enormously high compared
with a simple urine test such as N-telopeptide. As urinary N-telopeptide is cheap,
it can be considered as a screening test also. If we suspect osteoporosis, it is better
to go for urinary N-telopeptide and those who test positive can go for current gold
standard DXA scan. Thus, combination of these two diagnostic tests could be useful
to improve the identification of high risk for fracture.
Conclusion
Urinary N-telopeptide can give reproducible results and be able to assist in the evaluation
of quality of bone and osteoporosis and be a good judge of someone's risk of fracture.
Hence, urinary N-telopeptide can be considered as a new diagnostic tool for diagnosing
osteoporosis.
