Keywords
osteoporosis - hormones - estradiol - calcitonin - parathyroid hormone
Introduction
Osteoporosis results from an imbalance in normal bone metabolism between osteoblasts
and osteoclasts.[1] Osteoclasts seem more active than osteoblasts in bone resorption processes.[2]
[3] Studies indicate that hormones may play an important role in imbalanced bone formation,[4] since parathyroid hormone apparently induces osteocytes differentiation into osteoclasts.[5] Likewise, hormones such as estradiol and testosterone are supposedly important,[6]
[7]
[8] and testosterone acts by inhibiting osteoblast apoptosis.[9] On the other hand, estrogen seems critical to bone remodeling both in males and
females, since it apparently stimulates calcitonin release and activates intestinal
vitamin D receptors, resulting in endocrine and immune functions during bone metabolism.[10]
[11] Calcitonin and vitamin D help to maintain adequate serum concentrations of calcium
to allow normal bone mineralization. In addition, vitamin D is required for bone growth
and remodeling by osteoblasts and osteoclasts.[12]
The increase in life expectancy resulted in a considerable increase in diseases associated
with hormonal changes, including osteoporosis, warranting the focus on studies to
clarify these interactions.
The present study aims to evaluate the influence of hormonal serum levels of vitamin
D, calcitonin, testosterone, estradiol, and parathyroid hormone in patients with fractures
attributed to osteoporosis in comparison with young patients with fractures resulting
from high-impact accidents.
Materials and Methods
The present project was approved by the Ethics Committee under protocol number 51827515.4.0000.5145.
Study Group
Blood samples were collected from 30 elderly patients with fractures attributed to
osteoporosis (T-score ≤ -2.5) (osteoporotic group), and from 30 young patients with
fractures resulting from high-impact accidents (control group). Patients with other
bone conditions, nonosteoporotic fractures, immunosuppression, malignant neoplasms,
or liver disorders were excluded from the study, along with those who did not agree
to participate in it. Serum collected from these patients was used for hormone measurement.
Blood Collection
Venous blood collection was always performed in the morning, 1 day after the bone
reconstruction surgery indicated by the orthopedist. A blood sample was obtained by
venipuncture, using three vacuum collection tubes containing a clot activator and
separating gel. Thirty minutes after collection, the samples were centrifuged at 5,000
rotations per minute (rpm) for 10 minutes to obtain serum.
Hormonal Analysis
Serum obtained after blood samples centrifuging was sent for hormonal analysis. Measurement
of 1,25-hydroxyvitamin D (Kit Diasorin, Saluggia, Italy), calcitonin (Kit Siemens,
Tarrytown, NY, USA), testosterone, estradiol, and parathyroid hormone (Kit Beckman
Couter, Indianapolis, IN, United States) was performed using a chemiluminescence technique,
a chemical reaction that generates luminous energy. Chemiluminescence reagents are
transformed into electrically excited intermediate states and release the absorbed
energy as light when becoming less excited.
Statistical Analysis
Data were inserted into a Microsoft Excel (Microsoft Corp., Redmond, WA, USA) spreadsheet
and analyzed using Statview statistical software. Results showing non-normal distribution
were analyzed with nonparametric methods. The Mann-Whitney test was applied for group
comparison, and a Spearman test correlated hormonal levels. Statistical significance
was set at p < 0.05.
Results
The present study measured hormones in 30 patients with osteoporosis and in 30 control
subjects, totaling 60 people.
The mean age of the patients was 58.8 ± 22.61 years old, and all analyzes compared
gender and subjects with or without osteoporosis. [Table 1] shows the number of patients and the mean age from each group.
Table 1
|
Mean Age (years old)
|
Number of Patients (n)
|
Minimal Age (years old)
|
Maximal Age (years old)
|
|
Female control subjects
|
39.5
|
08
|
18
|
58
|
|
Male control subjects
|
39.6
|
22
|
19
|
58
|
|
Women with osteoporosis
|
80.05
|
18
|
64
|
98
|
|
Men with osteoporosis
|
74.9
|
12
|
60
|
88
|
|
Total
|
58.8
|
60
|
18
|
98
|
In the control group, serum vitamin D levels were significantly higher in females
when compared with males (Mann-Whitney test; p = 0.0169). Comparing both groups (osteoporosis and control subjects), serum vitamin
D levels were significantly higher in women from the control group than in women with
osteoporosis (p = 0.0275). There was no significant difference between males and females from the
osteoporosis group ([Figure 1A]).
Fig. 1 Hormonal measurement using chemiluminescence in female and male patients diagnosed
with osteoporosis and control subjects. (A) Vitamin D, *p = 0.0169 and **p = 0.0275; (B) Testosterone, *p = 0.0023 and **p = 0.0046; (C) Estradiol, p = 0.047; (D) Parathyroid hormone, p = 0.0065; (E) Calcitonin (Mann-Whitney test).
Significantly higher free testosterone levels were observed in males when compared
with females in both the control and osteoporotic groups (Mann-Whitney test; *p = 0.0023 and **p = 0.0046). There was no significant difference in free testosterone levels between
males from the control and osteoporotic groups ([Figure 1B]).
Estradiol levels were significantly lower in women with osteoporosis compared with
those of the control group (Mann-Whitney test; p = 0.047). There was no significant difference in estradiol levels between men and
women from the control group and the osteoporotic group ([Figure 1C]).
Parathyroid hormone levels were significantly higher in men with osteoporosis when
compared with the control group (Mann-Whitney test; p = 0.0065). There was no significant difference between women from the control group
and women with osteoporosis. No significant difference was observed in parathyroid
hormone levels when comparing males and females with or without osteoporosis ([Figure 1D]).
There was no significant difference in calcitonin levels between the control and osteoporotic
groups, regardless of gender. In addition, there was no significant difference when
comparing men and women from both groups ([Figure 1E]).
Discussion
Osteoporosis results from an imbalance of bone remodeling potentially caused by hormonal
factors. In addition, more recent studies show that immunological factors also play
a role in the pathophysiology of the disease. The present study evaluated hormonal
levels in patients with osteoporosis and compared gender-related differences.
Our study revealed significant differences in vitamin D, estradiol, and parathyroid
hormone levels. Osteoporotic women and young men had significantly lower levels of
vitamin D compared with young women. Studies show that vitamin D deficiency is associated
with muscle weakness, bone loss, falls and fractures.[13] In line with the literature, our data suggest that a decrease in vitamin D in older
women may contribute to osteoporosis. The present study also showed that reduced estradiol
levels are related to the onset of osteoporosis in women > 60 years old, which is
consistent with other works, showing that bone health is inversely related to lower
estradiol concentrations.[7]
[8]
[14] Estradiol deficiency was also linked to osteoporosis in men > 64 years old,[15] although this association was not observed here.
Bone remodeling is also stimulated by parathyroid hormone. A study with elderly women
showed a significant increase in parathyroid hormone levels in women with osteoporosis.[16] In the present study, significantly higher levels of parathyroid hormone were found
in men with osteoporosis, showing that it contributes to the onset of the disease
in men > 60 years old; in contrast, women present no differences in parathyroid hormone
levels.
Testosterone was not a limiting factor for the onset of osteoporosis in our patients.
This hormone seems to be more related to differences between males and females. However,
a study showed that testosterone deficiency in men > 64 years old is associated with
rapid bone loss, leading to osteoporosis.[15] Even though the literature showed that calcitonin acts by inhibiting bone resorption,[17] we found no significant differences in calcitonin levels between groups and genders.
Conclusion
The present study suggests that women with osteoporosis had significantly lower levels
of estradiol and vitamin D compared with young women without the disease, whereas
men with osteoporosis had significantly higher levels of parathyroid hormone compared
with men without the disease. These findings show the importance of hormones and vitamin
D in the development of osteoporosis. Although lower testosterone levels are associated
with osteoporosis, our study does not show its impact on the disease, except for a
significant gender-related difference, regardless of age and of the presence of osteoporosis.
