Narjis Hasan Ahmed1, Haider Salih Jaffat2, Mohauman Mohammed Alrufaie3
Authors affiliations:
Background & objective: Osteoporosis is a chronic progressive disease, characterized by decreased bone mass and damage to the microstructure of bone tissue, leading to decreased bone strength and increased risk of fractures. The main serious consequence of osteoporosis is fragility fracture. This case-control study was conducted to know the prevalence of osteoporosis in Iraqi postmenopausal women.
Methodology: One hundred female patients visiting Al-Sader Teaching Hospital in Al-Najaf province of Iraq, were included in the study. To determine the percentage of their bone density we used a dual energy x-ray absorptiometry (DEXA). Blood samples were taken after diagnosing the disease. In addition, serum estrogen and vitamin D3 were measured by enzyme linked immune sorbent assay (ELISA), while alkaline phosphatase was measured by spectrophotometer. Data were gathered by direct interviews with the women. The study excluded those who had chronic diseases.
Results: This study showed a significant increase (P < 0.05) in the concentration of sclerostin and alkaline phosphatase and non-significant differences in vitamin D3 concentrations between patients and healthy group.
Conclusion: Increased serum sclerostin and alkaline phosphatase levels in postmenopausal women with osteoporosis play an important role in the development of primary osteoporosis.
Key word: Osteoporosis; Sclerostin; DEXA
Citation: Ahmed NH, Jaffat HS, Alrufaie MM. Dual role of sclerostin and other parameters in postmenopausal women with osteoporosis. Anaesth. pain intensive care 2023;27(6):745−749; DOI: 10.35975/apic.v27i6.2349
Received: August 22, 2023; Revised: August 29, 2023; Accepted: September 11, 2023
Osteoporosis is a serious public health concern that affects people all over the globe. The rise in osteoclast activity, which outweighs the increase in osteoblast activity, results in a decline in bone mass density in people over 30 y.1 Women lose bone more rapidly, particularly during the first 5-10 y after menopause due to estrogen deficiency. Estrogen is a major sex-stimulating hormone in women, mostly produced in the ovaries; during menopause, estrogen levels rapidly decline.2 Osteoporosis traditionally is classified as a primary disease, which is common in postmenopausal women due to decline in estrogen levels, and secondary type, which is caused by exogenous drugs or systemic disease affecting bone metabolism.3 Bone mineral density (BMD) is used to express the amount of mineral matter per square centimeter in different bone segments, usually forearm, lumber spine and femur.4 The most commonly used method of measuring BMD is dual energy x-ray absorptiometry (DEXA). Sclerostin is a glycoprotein encoded by the Sclerostin (SOST) gene, is mainly produced by mature osteocytes and is a critical regulator of bone formation through its inhibitory effect on Wnt signaling.5 Wnt signaling is a main regulator of skeletal development and homeostasis, so sclerostin negatively regulates osteogenic differentiation and bone formation, and promotes osteoclastogenesis and bone resorption.6 Physiologically, alkaline phosphatase (ALP) in bones adheres to osteoblastic cell membrane with only small amount released in serum. Its concentration in serum rises only in cases of increased remodeling of bone while vitamin D is a steroid hormone classically involved in the calcium metabolism and bone homeostasis.7,8 Clinically, it has been recognized that vitamin D deficiency leads to osteomalacia or osteoporosis in adults.9
This study was conducted in Al-Sader Teaching Hospital in AL-Najaf province from DEXA unit in the Radiology Department and Fractures and Joints Department. Serum specimens were collected from 70 postmenopausal female patients with osteopenia and osteoporosis in addition to 30 healthy women (n=30) as a control group. The age of studied postmenopausal women patients was 50-65 y.
2.1. Collection of blood sample
Five milliliters of blood were taken from a vein using aseptic technique. Sample was placed in a labelled gel tube to enable blood to clot at room temperature for 10 min. The samples were centrifuged @6000 rpm for 15 min, and then serum was separated and frozen at −80 ºC until time to perform the laboratory analysis for study.
2.2. Dual Energy X-ray Absorptiometry (DEXA)
The measurement of bone density (defined as the amount of bone mineral divided by the area of the bone).10 BMD is reported using 2 scores based on SD measurements: - the Z score and the T score.
The statistical system SPSS v.24 was used, and the analysis of variance by using T-test for the comparison between the groups was done. P < 0.05 was considered statistically significant.
The results reveal statistically significant differences of postmenopausal women with osteoporosis and osteopenia compared with the Control group. There was significantly decreased (P < 0.001) BMD and t-scores in patients compared with the Control group in postmenopausal women, while the age showed a significant difference when compared between patients and control group in postmenopausal women (P = 0.009). The result of the same Table indicates that there was no significant difference (P = 0.06) in BMI between control and patient groups.
3.1. Comparison of biomarkers
There was a significant increase (P < 0.001) in serum levels of SOST, ALP between osteopenia / osteoporosis patients compared with control postmenopausal women, while, there was a significant decrease in serum estrogen (P < 0.001) (Table 2).
There was no significant difference (P = 0.18) in vitamin D3 between patients group compared with the control group (Table 2).
3.2. Sclerostin
The levels of sclerostin (SOST) influenced by a variety of factors, including the environment, age, sex, body mass index, and total body fat contents. Increased sclerostin production in osteocytes, followed by a decrease in Wnt-catenin signaling in bone cells, is associated with declining bone mass with aging.10 Sclerostin negatively regulates canonical Wnt signaling pathways by binding to low-density lipoprotein receptor-related protein (LRP) 5/6 so that it is crucial to both bone development and regulation of bone mass.11,12 Recent studies have reported that serum estradiol levels are inversely associated with serum levels of the key inhibitor of Wnt signaling produced by osteocytes, sclerostin, and estrogen treatment of postmenopausal women reduces circulating sclerostin levels.13 As estrogen levels decline at menopause the result of this study indicated, that there was a significant positive correlation(r = 0.540 & P = 0.002) between age and SOST concentrations in postmenopausal women. Studies showed that vitamin D is one of the most important vitamins for bone metabolism and mineralization, according to the same study vitamin D deficiency has been related to osteoporosis, poor bone mineral density, and muscle problems.14
3.3. Correlation Study
Results of the association indicate:
Both osteoporosis and osteopenia are considered dangerous indicators, as they lead to fractures and other complications which may even lead to death. In addition to DEXA scan method, osteoporosis can be clinically confirmed by several methods including measurement of some parameters such as sclerostin, estrogen, ALP, vitamin D3.
5. Data availability
The numerical data generated during this research is available with the authors.
6. Acknowledgement
We gratefully thank staff and Faculty of Medicine, DEXA unit in the Radiology Department and Fractures and Joints Department, Al-Sader Teaching Hospital in AL-Najaf province for their valuable help, as well as the patients who consented to participate in this study.
7. Conflict of interest
The study utilized the hospital resources only, and no external or industry funding was involved.
8. Authors’ contribution
NHA: Writing the manuscript
HSJ: Conduct of the study work and manuscript editing
MMMA: Final evaluation and sending the manuscript
Authors affiliations:
- Narjis Hasan Ahmed, Department of Biology, Faculty of Science, University of Kufa, Najaf, Iraq; E-mail: jww7gdef7@gmail.com
- Haider Salih Jaffat, Department of Biology , Faculty of Science, University of Kufa, Najaf, Iraq; E-mail: hayder.alshafie@uokufa.edu
- Mohauman Mohammed Alrufaie, Department of Chemistry, Faculty of Science, University of Kufa, Najaf 54001, Iraq; E-mail: muhaimin.alrufaie@uokufa.edu.iq
ABSTRACT
Background & objective: Osteoporosis is a chronic progressive disease, characterized by decreased bone mass and damage to the microstructure of bone tissue, leading to decreased bone strength and increased risk of fractures. The main serious consequence of osteoporosis is fragility fracture. This case-control study was conducted to know the prevalence of osteoporosis in Iraqi postmenopausal women.
Methodology: One hundred female patients visiting Al-Sader Teaching Hospital in Al-Najaf province of Iraq, were included in the study. To determine the percentage of their bone density we used a dual energy x-ray absorptiometry (DEXA). Blood samples were taken after diagnosing the disease. In addition, serum estrogen and vitamin D3 were measured by enzyme linked immune sorbent assay (ELISA), while alkaline phosphatase was measured by spectrophotometer. Data were gathered by direct interviews with the women. The study excluded those who had chronic diseases.
Results: This study showed a significant increase (P < 0.05) in the concentration of sclerostin and alkaline phosphatase and non-significant differences in vitamin D3 concentrations between patients and healthy group.
Conclusion: Increased serum sclerostin and alkaline phosphatase levels in postmenopausal women with osteoporosis play an important role in the development of primary osteoporosis.
Key word: Osteoporosis; Sclerostin; DEXA
Citation: Ahmed NH, Jaffat HS, Alrufaie MM. Dual role of sclerostin and other parameters in postmenopausal women with osteoporosis. Anaesth. pain intensive care 2023;27(6):745−749; DOI: 10.35975/apic.v27i6.2349
Received: August 22, 2023; Revised: August 29, 2023; Accepted: September 11, 2023
1. INTRODUCTION
Osteoporosis is a serious public health concern that affects people all over the globe. The rise in osteoclast activity, which outweighs the increase in osteoblast activity, results in a decline in bone mass density in people over 30 y.1 Women lose bone more rapidly, particularly during the first 5-10 y after menopause due to estrogen deficiency. Estrogen is a major sex-stimulating hormone in women, mostly produced in the ovaries; during menopause, estrogen levels rapidly decline.2 Osteoporosis traditionally is classified as a primary disease, which is common in postmenopausal women due to decline in estrogen levels, and secondary type, which is caused by exogenous drugs or systemic disease affecting bone metabolism.3 Bone mineral density (BMD) is used to express the amount of mineral matter per square centimeter in different bone segments, usually forearm, lumber spine and femur.4 The most commonly used method of measuring BMD is dual energy x-ray absorptiometry (DEXA). Sclerostin is a glycoprotein encoded by the Sclerostin (SOST) gene, is mainly produced by mature osteocytes and is a critical regulator of bone formation through its inhibitory effect on Wnt signaling.5 Wnt signaling is a main regulator of skeletal development and homeostasis, so sclerostin negatively regulates osteogenic differentiation and bone formation, and promotes osteoclastogenesis and bone resorption.6 Physiologically, alkaline phosphatase (ALP) in bones adheres to osteoblastic cell membrane with only small amount released in serum. Its concentration in serum rises only in cases of increased remodeling of bone while vitamin D is a steroid hormone classically involved in the calcium metabolism and bone homeostasis.7,8 Clinically, it has been recognized that vitamin D deficiency leads to osteomalacia or osteoporosis in adults.9
2. METHODOLOGY
This study was conducted in Al-Sader Teaching Hospital in AL-Najaf province from DEXA unit in the Radiology Department and Fractures and Joints Department. Serum specimens were collected from 70 postmenopausal female patients with osteopenia and osteoporosis in addition to 30 healthy women (n=30) as a control group. The age of studied postmenopausal women patients was 50-65 y.
2.1. Collection of blood sample
Five milliliters of blood were taken from a vein using aseptic technique. Sample was placed in a labelled gel tube to enable blood to clot at room temperature for 10 min. The samples were centrifuged @6000 rpm for 15 min, and then serum was separated and frozen at −80 ºC until time to perform the laboratory analysis for study.
2.2. Dual Energy X-ray Absorptiometry (DEXA)
The measurement of bone density (defined as the amount of bone mineral divided by the area of the bone).10 BMD is reported using 2 scores based on SD measurements: - the Z score and the T score.
- Osteoporosis: T-score −1 to −2.5; Severe osteoporosis: T-score ≤ −2.5 plus the presence of at least one fracture.
- Osteopenia: Is a BMD T-score between −1 and −2.5
- Normal bone density: Is a BMD less than −1
The statistical system SPSS v.24 was used, and the analysis of variance by using T-test for the comparison between the groups was done. P < 0.05 was considered statistically significant.
3. RESULTS AND DISCUSSION
The results reveal statistically significant differences of postmenopausal women with osteoporosis and osteopenia compared with the Control group. There was significantly decreased (P < 0.001) BMD and t-scores in patients compared with the Control group in postmenopausal women, while the age showed a significant difference when compared between patients and control group in postmenopausal women (P = 0.009). The result of the same Table indicates that there was no significant difference (P = 0.06) in BMI between control and patient groups.
| Table 1: Comparisons of age, BMI, BMD and T-score between two groups | |||
| Parameter | Patients Group
(n = 70) |
Control Group
(n = 30) |
p-value |
| Age (y) | 60.7 ± 7.60 | 54.2 ± 7.25 | 0.009 |
| BMI (kg/m2) | 28.01± 4.33 | 30.38± 3.82 | 0.06 |
| BMD (g/cm2) | 0.73 ± 0.09 | 0.97 ± 0.08 | < 0.001 |
| T-score | -2.44 ± 0.72 | 0.05± 0.82 | < 0.001 |
| Data presented as mean ± SD; P ≤ 0.05 considered significant; BMI: body mass index; BMD: bone mineral density | |||
3.1. Comparison of biomarkers
There was a significant increase (P < 0.001) in serum levels of SOST, ALP between osteopenia / osteoporosis patients compared with control postmenopausal women, while, there was a significant decrease in serum estrogen (P < 0.001) (Table 2).
There was no significant difference (P = 0.18) in vitamin D3 between patients group compared with the control group (Table 2).
| Table 2: Comparison of biomarkers in patient with osteoporosis, and control group in postmenopausal women | |||
| Biomarkers | Patients Group
(n = 70) |
Control Group
(n = 30) |
p-value |
| Sclerostin (pg/ml) | 2870 ± 160 | 2500 ± 83.84 | < 0.001 |
| Estrogen (pg/ml) | 14.3 ± 3.53 | 22.3 ± 1.78 | < 0.001 |
| ALP (U/l) | 177.5 ± 50.08 | 110.13 ± 13.42 | < 0.001 |
| Vit-D3 (ng/ml) | 23.08 ± 4.77 | 26.77 ± 9.74 | 0.18 |
| Data presented as mean ± SD; P ≤ 0.05 is significant; ALP- Alkaline phosphatase. | |||
3.2. Sclerostin
The levels of sclerostin (SOST) influenced by a variety of factors, including the environment, age, sex, body mass index, and total body fat contents. Increased sclerostin production in osteocytes, followed by a decrease in Wnt-catenin signaling in bone cells, is associated with declining bone mass with aging.10 Sclerostin negatively regulates canonical Wnt signaling pathways by binding to low-density lipoprotein receptor-related protein (LRP) 5/6 so that it is crucial to both bone development and regulation of bone mass.11,12 Recent studies have reported that serum estradiol levels are inversely associated with serum levels of the key inhibitor of Wnt signaling produced by osteocytes, sclerostin, and estrogen treatment of postmenopausal women reduces circulating sclerostin levels.13 As estrogen levels decline at menopause the result of this study indicated, that there was a significant positive correlation(r = 0.540 & P = 0.002) between age and SOST concentrations in postmenopausal women. Studies showed that vitamin D is one of the most important vitamins for bone metabolism and mineralization, according to the same study vitamin D deficiency has been related to osteoporosis, poor bone mineral density, and muscle problems.14
3.3. Correlation Study
Results of the association indicate:
- Figure 1 indicates, there was a significant negative correlation (r = -0.841) between SOST and estrogen concentrations in postmenopausal women.
- Figure 2 indicates that there was a significant positive correlation (r = 0.270) between estrogen and vitamin D3 concentrations in postmenopausal women.
- Figure 3 indicates that there was a significant negative correlation (r = -0.422) between BMD and SOST concentrations in postmenopausal women.
- Figure 4 indicates that there was a significant positive correlation (r = 0.593) between BMD and estrogen concentrations in postmenopausal women.
- Figure 5 indicates that there was a significant positive correlation (r = 0.540) between age and SOST concentrations in postmenopausal women.
4. CONCLUSION
Both osteoporosis and osteopenia are considered dangerous indicators, as they lead to fractures and other complications which may even lead to death. In addition to DEXA scan method, osteoporosis can be clinically confirmed by several methods including measurement of some parameters such as sclerostin, estrogen, ALP, vitamin D3.
5. Data availability
The numerical data generated during this research is available with the authors.
6. Acknowledgement
We gratefully thank staff and Faculty of Medicine, DEXA unit in the Radiology Department and Fractures and Joints Department, Al-Sader Teaching Hospital in AL-Najaf province for their valuable help, as well as the patients who consented to participate in this study.
7. Conflict of interest
The study utilized the hospital resources only, and no external or industry funding was involved.
8. Authors’ contribution
NHA: Writing the manuscript
HSJ: Conduct of the study work and manuscript editing
MMMA: Final evaluation and sending the manuscript
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- Jean G, Souberbielle JC, Zaoui E, Lorriaux C, Mayor B, Hurot JM, et al. Total and bone-specific alkaline phosphatases in haemodialysis patients with chronic liver disease. Clin Biochem. 2012 Apr;45(6):436-9. [PubMed] DOI: 1016/j.clinbiochem.2012.01.018
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- Mödder UI, Hoey KA, Amin S, McCready LK, Achenbach SJ, Riggs BL, et al. Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res. 2011 Feb;26(2):373-9. [PubMed] DOI: 1002/jbmr.217
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- Mirza FS, Padhi ID, Raisz LG, Lorenzo JA. Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab. 2010 Apr;95(4):1991-7. [PubMed] DOI: 1210/jc.2009-2283
- Hadi SM, Ouda MH, Alboaklah HKM. Association of vitamin D3 deficiency and osteoporosis. Review. Kerbala J Pharm Sci. 2022;1(20). [FreeFullText]