|Year : 2016 | Volume
| Issue : 1 | Page : 143-149
Depressive symptoms and bone mineral density in menopause and postmenopausal women: A still increasing and neglected problem
Abdulbari Bener1, Najah M Saleh2, Dinesh Bhugra3
1 Department of Biostatistics and Medical Informatics, Cerrahpaşa Faculty of Medicine, Istanbul University, Istanbul, Turkey; Department of Evidence for Population Health Unit, School of Epidemiology and Health Sciences, University of Manchester, Manchester, UK
2 Department of Obstetrics and Gynecology, Women's Hospital, Hamad Medical Corporation, Doha, Qatar
3 Department of Evidence for Population Health, Section of Cultural Psychiatry, Institute of Psychiatry, King's College London, Maudsley Hospital, UK
|Date of Web Publication||24-Jun-2016|
Department of Biostatistics and Medical Informatics, Cerrahpa?a Faculty of Medicine, Istanbul University, 34098 Cerrahpasa-Istanbul
Source of Support: None, Conflict of Interest: None
Background: The association between depression and loss of bone mineral density (BMD) has been reported as controversial. Objective: The objectıve of the current study was to investigate whether an association exists between depression and low BMD during the menopausal and postmenopausal period. Materials and Methods: A cross-sectional descriptive study was used to generate menopause symptoms experienced by Arabian women at the Primary Health Care Centers in Qatar. A multi-stage sampling design was used, and a representative sample of 1650 women aged 45-65 years were included during July 2012 and November 2013. This prospective study explored the association between bone density and major depressive disorder in women. Bone mineral densitometry measurements (BMD) (g/m 2 ) were assessed at the BMD unit using a lunar prodigy DXA system (Lunar Corp., Madison, WI). Data on body mass index (BMI), clinical biochemistry variables including serum 25-hydroxyvitamin D were collected. The Beck Depression Inventory was administered for depression purposes. Results: Out of 1650 women 1182 women agreed to participate in the study (71.6%). The mean age and standard deviation (SD) of the menopausal age were 48.71 ± 2.96 with depressed and 50.20 ± 3.22 without depressed (P < 0.001). Furthermore, the mean and SD of postmenopausal age were 58.55 ± 3.27 with depression and 57.78 ± 3.20 without depression (P < 0.001). There were statistically significant differences between menopausal stages with regards to a number of parity, and place of living. There were statistically significant differences between menopausal stages with regards to BMI, systolic and diastolic blood pressure, Vitamin D deficiency, calcium deficiency and shisha smoking habits. Overall, osteopenia and osteoporosis and bone loss were significantly lower in postmenopausal women than in menopausal women (P < 0.001). Similarly, T-score and Z-score were lower with depression menopause and postmenopausal women (P < 0.001). The multivariate logistic regression analyses revealed that the depression, the mean serum Vitamin D deficiency, calcium level deficiency, less physical activity, comorbidity, number of parity, systolic and diastolic blood pressure and shisha smoking habits were considered as the main risk factors associated with bone mineral loss after adjusting for age, BMI and other variables. Conclusion: Depression is associated with low BMD with a substantially greater BMD decrease in depressed women and cases of clinical depression. Depression should be considered as an important risk factor for osteoporosis.
Keywords: Bone mineral density, depression, depressive disorders, disease, menopause, physical activity, postmenopausal
|How to cite this article:|
Bener A, Saleh NM, Bhugra D. Depressive symptoms and bone mineral density in menopause and postmenopausal women: A still increasing and neglected problem. J Family Med Prim Care 2016;5:143-9
|How to cite this URL:|
Bener A, Saleh NM, Bhugra D. Depressive symptoms and bone mineral density in menopause and postmenopausal women: A still increasing and neglected problem. J Family Med Prim Care [serial online] 2016 [cited 2021 Apr 17];5:143-9. Available from: https://www.jfmpc.com/text.asp?2016/5/1/143/184640
| Introduction|| |
Menopause is the cessation of a woman's reproductive ability, the opposite of menarche and it is usually a natural change; it typically occurs in women in midlife, during their late 40 s or early 50 s, signaling the end of the fertile phase of a woman's life. ,,,, The transition from a potentially reproductive to a nonreproductive state is normally not sudden or abrupt, occurs over a number of years, and is a consequence of biological aging. ,,,, Many women are likely to live more than 30 years after menopause, spending about one-third of their lives in a state of estrogen deficiency.  Age at natural menopause is an important research issue because of the suspected links between it and risk for certain diseases. ,
In the last decade, researchers have begun studying the relationship of decreased bone mineral density (BMD) to mood variables, such as depression, anxiety, and stress. ,,,,, Literature documenting the relationship of anxiety and stress response to osteoporosis is limited.  Most of these studies have focused on the psychological effects of coping with the disease, including pain, difficulties in the ability to function and fractures - which may occasionally require surgery and prolonged rehabilitation. ,, Several studies have suggested a strong link between depression and low BMD ,,,,,,,,, and other studies found no such relationship. ,, Most recent meta-analyses supported a significant correlation of depression with low BMD or osteoporosis. , This situation may explain a condition characterized in an increase in an individual's anxiety level. However, there is no information available on depression during menopause and postmenopause in the State of Qatar. The reported association between depression and loss of BMD have been controversial. ,,,,,,,,,,, The objective of this study was conducted to investigate whether an association exists between depression and low BMD during the menopausal and postmenopausal period.
| Materials and Methods|| |
This is a cross-sectional Primary Health Care (PHC) Centres based study conducted in the State of Qatar. The survey was conducted among Qatari Nationals and Arab women aged 45-65 years who had ceased menstruation for 2-5 years, who had not had a hysterectomy, and who had not used hormone therapy during the preceding 6 months. Similar to other reported studies, ,, women were excluded with contraindications to estrogen use and women who had a current unstable medical or social problem.
Questionnaire and interview
The entry criteria for the study were to be: (1) 45-65 years of age; (2) diagnosis of major depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4 th Edition (DSM-IV); (3) moderate to severe depression according to the 21-item Beck Depression Inventory (BDI) (1-63) score; (4) no current use of homeopathic treatment for depression or antidepressants or anxiolytic drugs for 3 months prior to study entry; (5) no use of psychotherapy for at least 3 months before screening; (6) no intake of estrogens or other medications known to affect ovarian function for at least 3 months before screening; (7) early transition to menopause, defined by a change in cycle length of 7 days or longer in either direction from the participant's own baseline for at least two cycles; (8) postmenopausal stage defined by 12 months or more of amenorrhea; and (9) capability and willingness to give informed consent and to comply with the study procedures.
The BDI-II was a 1996 revision of the BDI,  developed in response to the American Psychiatric Association's publication of the DSM-IV, which changed many of the diagnostic criteria for major depressive disorder. The BDI is a widely-used, self-evaluation depression scale. The long form of the BDI, used in this study, comprises of 21 questions or items, each with four possible responses. Each response is assigned a score ranging from 0 to 3, indicating the severity of the symptom.  Items 1-13 assess symptoms that are psychological in nature while items 14-21 assess more physical symptoms. The sum of all BDI item scores indicates the severity of depression. A score of 21 or above represents depression. Scores from 1 to 10 are considered normal; 11 to 16 considered mild mood disturbance; 17 to 20 considered borderline clinical depression; 21 to 30 considered moderate depression; 31 to 40 considered severe depression; finally, scores over 40 are determined extreme depression.
Bone mineral densitometry measurements
BMD (g/m 2 ) was assessed at the BMD unit using a lunar prodigy DXA system (Lunar Corp., Madison, WI). The anteroposterior lumbar spine (L2-L4) and the mean of the proximal right and left femur (including total femur, neck, Ward's triangle, and the trochanter) were be measured by two technologists and then reviewed by one radiologist using methods described. ,,, Quality control of the DXA scanner included daily calibration and duplicate measures of a sample of the participants.
T-score and Z-score
The T-score is the most significant parameter for the assessment of osteoporosis, which compares BMD of the subject with average BMD of the young normal population. BMD was categorized according to the World Health Organization criteria based on the T-score. ,, Values between −1.0 and −2.5 were classified as osteopenia, a T-score of −2.5 or below as osteoporosis, and a T-score of −1.0 and above as normal. ,, T-score lower than −2.5 is osteoporotic which is an indication of the risk of fracture. Z-score compares BMD of the subject with average BMD of a population of the same age. This comparison determines whether the subject deviates from the normal pattern for her age.
Stiffness index (SI) which represents BMD, combines broadband ultrasound attenuation (BUA) and speed of sound (SOS) into a single clinical measure that has a lower precision error than either variable alone. This index is formulated by normalizing BUA and SOS through subtracting the lowest observable values (50 dB/MHz and 1380 m/s) from each other and then scaling the resultant values. The SI is the sum of the scaled and normalized BUA and SOS values. The resultant formula is empirically derived such that the index has 50% contribution due to SOS and 50% contribution from BUA. 
SI = ([0.67 × BUA] + [0.28 × SOS]) − 420
The SI is scaled in such a way to make the young adult value equal to 100. The normalized and scaled BUA and SOS values contribute about equally to the resulting SI over the adult age range. SI results expressed as T-score and Z-score are used to assist physicians in the diagnosis of osteoporosis.
Data collection took place from July 2012 to November 2013. The sample size was determined on a priori presumption that the prevalence rate of postpartum depression in Qatar would be more or less similar to rates found in other countries in the Arab Gulf Counties, ,, where the reported prevalence of depression to be 25-30%, with the 95% confidence interval for 2% error of estimation, a sample size of 1650 subjects would be required for this study. Of the 22 PHC Centers available, we have selected 12 health centers, of these, 10 were located in urban and 2 in semi-urban areas of Qatar. Finally, subjects were selected systematically 1-in-2 using a sampling procedure. Each participant was provided with brief information about the study and was assured of strict confidentiality. A multi-stage sampling design was used, and a representative sample of 1650 women aged 45-65 years were included. Incomplete questionnaire or nonresponse subjects were excluded from the total required sample size. The survey instrument was initially tested for validation on 75 patients who visited the health centers through face to face interviews, and those women were excluded from the analysis. The Cronbach's alpha score was 0.87 for internet BDI scales respectively, confirming a high level of consistency among the different Likert items in both of these scales.
Data were analyzed using IBM SPSS Inc. Statistical Software Window Version # 21, Chicago, IL 60611, USA. Sum of scores were calculated for BDI. Proportion with percentage was calculated for categorical variables and mean with standard deviation (SD) for continuous scale variables. Student's t-test was used to ascertain the significance of differences between mean values of two continuous variables and confirmed by nonparametric Mann-Whitney test. The Chi-square and Fisher's exact tests (two-tailed) were performed to test for differences in proportions of categorical variables between two or more groups. Multivariate regression analysis using the forward inclusion and backward deletion method was used to assess the relationship between dependent and independent variables and to adjust for potential confounders and orders the importance of risk factors (determinants) for BMD loss among menopausal women. The level P < 0.05 was considered as the cut-off value for significance.
| Results|| |
Of 1650 women, 1182 women agreed to participate (71.6%) and responded to the study. The mean age and SD of the menopausal age were 48.71 ± 2.96 with depression and 50.20 ± 3.22 without depression (P < 0.001). The median age of natural menopause in the present study was 49 years. Furthermore, the mean and SD of postmenopausal age were 58.55 ± 3.27 with depression and 57.78 ± 3.20 without depression (P < 0.001). [Figure 1] shows the distribution of depression in menopausal and postmenopausal women; there were statistically significant differences between menopausal stages with regards to depression.
|Figure 1: The distribution of depression in menopausal and postmenopausal women|
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[Table 1] shows the sociodemographic characteristics of the studied subjects by menopausal and postmenopausal status. There were statistically significant differences between menopausal stages with regards to the number of parity and the place of living.
|Table 1: The sociodemographic of studied subject by menopause and postmenopausal according to depression (n=1182) |
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[Table 2] shows the lifestyle characters of the studied subjects by menopause and postmenopausal according to depression. There were statistically significant differences between menopausal stages with regards to body mass index (BMI), systolic and diastolic blood pressure, Vitamin D deficiency, calcium deficiency, and sheesha smoking habits.
|Table 2: The lifestyle characters of studied subject by menopause and postmenopausal according to depression (n=1182) |
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[Table 3] presents BMD loss regarding osteopenia, osteoporosis SI in with depression and without depression in menopause and postmenopausal women. Overall, osteopenia and osteoporosis and bone loss were statistically significant and lower in postmenopausal women than in menopausal women (P < 0.001). Similarly, T-score and Z-score were lower among women with menopause and postmenopausal depression (P < 0.001).
|Table 3: Bone mineral density indices in menopause and postmenopause women according to the presence of depression* |
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[Table 4] gives multivariate logistic regression analyses with bone mineral densities. The depression, mean serum Vitamin D deficiency, mean calcium deficiency, less physical activity, comorbidity, the number of parity, systolic and diastolic blood pressure and sheesha smoking habits were considered as the main risk factors associated with the bone mineral loss after adjusting for age, BMI and other variables.
|Table 4: Multivariate logistic regression analyses for predictors of bone mineral loss (n=1182)* |
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| Discussion|| |
Menopause produces very complex changes during this stage of life which include other changes such as psychological and social changes. , More recently, a study in Finland showed that due to postmenopausal depression the predicted bone loss increased.
Depression has been implicated as a possible risk factor for low BMD. However, there is still no solid evidence that could connect these two different illnesses. This research examined the association between depression and low BMD in menopausal and postmenopausal women. The loss of BMD with aging is a result of the complex interactions of hormonal, environmental, nutritional, and genetic factors. In recent years, psychological status has been identified as another factor possibly related to the loss of BMD. ,,,,,,,,,,, In clinics with depression populations, significantly lower BMD has been found compared to without depression controls. ,,, Lower BMD in with depression populations could be related to depression itself or to other behavioral disturbances that occur as a result of depression. Factors sometimes associated with depression such as lower levels of physical activity, changes in body weight, lower calcium compliance, or use of antidepressant medications have been postulated as underlying causes of bone loss. ,,,
The current study data suggest that there is a strong association between depression symptoms and rates of bone loss in menopause and postmenopausal women: The greater the number of depressive symptoms, the higher the rate of bone loss. These findings are consistent with some previous cross-sectional studies that have reported lower BMD in subjects with depression than in those without depression loss. ,,,,
Furthermore, it is very clear that the depression and osteoporosis share a biological pathway, or one is a consequence of the other, there are some common risk factors such as unhealthy lifestyle ,,,,,,, or co-morbidity. ,, We, therefore, considered current smoking (only for men), at-risk drinking, regular exercise, and co-morbidity as covariates as well as age, BMD, and current hormone use (only for women).
The current study showed that women with major depression had lower T-scores and Z-scores at the menopause and postmenopause stages. These findings suggest that depressed patients may be at risk for higher rates of bone loss, and clinicians might consider depression as a factor when deciding when to screen women for low bone density. This is confirmative with the most recent Korean study. 
In the present community-based cross-sectional study, menopause and postmenopause women with depression had a lower BMD and a correspondingly 2 times higher probability of having osteoporosis, compared to those without depression. This is consistent with the previously reported studies. ,,,,,,,,,,,,,
In the United Arab Emirates,  the study was conducted to identify the prevalence of physical, psychological, and menopause-related symptoms and their association with minor psychiatric disorders in menopause, and postmenopausal women, fatigue was the most frequent complaint in all groups of menopause, and postmenopausal women, respectively. This is consistent with the current and previous reported studies. ,,,,,,,,, These findings suggest that depressed patients may be at risk for higher rates of bone loss, and clinicians might consider depression as a factor when deciding when to screen women for low bone density.
Limitations and strengths
There are several limitations of this study. First, this is cross-sectional study and, thereby, subjects might be misclassified in this analysis. Second, the study sample was based on PHC Clinics visits. Third, the majority of the study sample was Arab women and of relatively high socioeconomic and education status; hence, the results are not generalizable to the population of all midlife women. Furthermore, since this is a cross-sectional study, we evaluated the association between factors and quality of life. We were unable to evaluate the impact of these factors on the change in the quality of life over time. Despite these limitations, this study had a number of strengths. This study based on a large representative's sample. The information obtained for the biochemistry variables were based on the latest medical records.
| Conclusion|| |
The current study is consistent with previous findings of diminished BMD in people with depression and suggests that depressive symptoms may be a risk factor for reduced BMD in menopause or postmenopause women. A large number of factors were associated with experiencing menopausal symptoms and that had negative effects on the quality of life and BMD among Arabian women. Depression should be considered as an important risk factor for osteoporosis.
AB was involved in data collection, statistical analysis, interpretation of data and writing the manuscript. NMS was involved in data collection, interpretation of data, and editing the manuscript. DB was involved in the interpretation of data, writing and editing the manuscript. All authors approved the final version.
The authors would like to thank the Hamad Medical Corporation for their support and ethical approval (HMC RC No. 8222/08).
Financial support and sponsorship
Conflicts of interest
There is no conflicts of interest.
| References|| |
Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al.
Executive summary of the stages of reproductive aging workshop + 10: Addressing the unfinished agenda of staging reproductive aging. J Clin Endocrinol Metab 2012;97:1159-68.
Gerber LM, Bener A, Al-Ali HM, Hammoudeh M, Liu LQ, Verjee M. Bone mineral density in midlife women: The study of women's health in Qatar. Climacteric 2015;18:316-22.
Bener A, Falah A. A measurement-specific quality-of-life satisfaction during premenopause, perimenopause and postmenopause in Arabian Qatari women. J Midlife Health 2014;5:126-34.
Oppermann K, Fuchs SC, Donato G, Bastos CA, Spritzer PM. Physical, psychological, and menopause-related symptoms and minor psychiatric disorders in a community-based sample of Brazilian premenopausal, perimenopausal, and postmenopausal women. Menopause 2012;19:355-60.
Michelson D, Stratakis C, Hill L, Reynolds J, Galliven E, Chrousos G, et al.
Bone mineral density in women with depression. N Engl J Med 1996;335:1176-81.
Spangler L, Scholes D, Brunner RL, Robbins J, Reed SD, Newton KM, et al.
Depressive symptoms, bone loss, and fractures in postmenopausal women. J Gen Intern Med 2008;23:567-74.
Cizza G, Primma S, Coyle M, Gourgiotis L, Csako G. Depression and osteoporosis: A research synthesis with meta-analysis. Horm Metab Res 2010;42:467-82.
Erez HB, Weller A, Vaisman N, Kreitler S. The relationship of depression, anxiety and stress with low bone mineral density in post-menopausal women. Arch Osteoporos 2012;7:247-55.
Sabia S, Fournier A, Mesrine S, Boutron-Ruault MC, Clavel-Chapelon F. Risk factors for onset of menopausal symptoms: Results from a large cohort study. Maturitas 2008;60:108-21.
Mezuk B, Eaton WW, Golden SH. Depression and osteoporosis: Epidemiology and potential mediating pathways. Osteoporos Int 2008;19:1-12.
Yirmiya R, Bab I. Major depression is a risk factor for low bone mineral density: A meta-analysis. Biol Psychiatry 2009;66:423-32.
Bosworth HB, Bastian LA, Kuchibhatla MN, Steffens DC, McBride CM, Skinner CS, et al.
Depressive symptoms, menopausal status, and climacteric symptoms in women at midlife. Psychosom Med 2001;63:603-8.
Cizza G, Ravn P, Chrousos GP, Gold PW. Depression: A major, unrecognized risk factor for osteoporosis? Trends Endocrinol Metab 2001;12:198-203.
Wu Q, Magnus JH, Liu J, Bencaz AF, Hentz JG. Depression and low bone mineral density: A meta-analysis of epidemiologic studies. Osteoporos Int 2009;20:1309-20.
Furlan PM, Ten Have T, Cary M, Zemel B, Wehrli F, Katz IR, et al.
The role of stress-induced cortisol in the relationship between depression and decreased bone mineral density. Biol Psychiatry 2005;57:911-7.
Yazici KM, Akinci A, Sütçü A, Ozçakar L. Bone mineral density in premenopausal women with major depressive disorder. Psychiatry Res 2003;117:271-5.
Milliken LA, Wilhelmy J, Martin CJ, Finkenthal N, Cussler E, Metcalfe L, et al.
Depressive symptoms and changes in body weight exert independent and site-specific effects on bone in postmenopausal women exercising for 1 year. J Gerontol A Biol Sci Med Sci 2006;61:488-94.
Bener A, Kamran S, El-Rufaie OF, Georievski AB, Sabri S, Farooq A, et al
. Disability, depression and somatization in low back pain patients. APLAR J Rheumatol 2006;9:257-63.
Hammoudeh M, Al-Khayarin M, Zirie M, Bener A. Bone density measured by dual energy X-ray absorptiometry in Qatari women. Maturitas 2005;52:319-27.
Beck AT, Steer RA, Ball R, Ranieri W. Comparison of beck depression inventories -IA and -II in psychiatric outpatients. J Pers Assess 1996;67:588-97.
Holi MS, Radhakrishnan S, Swaranamani S, Jayavelan NA. Quantitative ultrasound technique for the assessment of osteoporosis and prediction of fracture risk. J Pure Appl Ultrason 2005;27:55-60.
Schweiger U, Deuschle M, Körner A, Lammers CH, Schmider J, Gotthardt U, et al.
Low lumbar bone mineral density in patients with major depression. Am J Psychiatry 1994;151:1691-3.
Jacka FN, Pasco JA, Henry MJ, Kotowicz MA, Dodd S, Nicholson GC, et al.
Depression and bone mineral density in a community sample of perimenopausal women: Geelong osteoporosis study. Menopause 2005;12:88-91.
Yirmiya R, Goshen I, Bajayo A, Kreisel T, Feldman S, Tam J, et al.
Depression induces bone loss through stimulation of the sympathetic nervous system. Proc Natl Acad Sci U S A 2006;103:16876-81.
Oh SM, Kim HC, Ahn SV, Rhee Y, Suh I. Association between depression and bone mineral density in community-dwelling older men and women in Korea. Maturitas 2012;71:142-6.
Bener A, El Ayoubi HR. The role of Vitamin D deficiency and osteoporosis in breast cancer. Int J Rheum Dis 2012;15:554-61.
Lyles KW. Osteoporosis and depression: Shedding more light upon a complex relationship. J Am Geriatr Soc 2001;49:827-8.
Bener A, Rizk DE, Shaheen H, Micallef R, Osman N, Dunn EV. Measurement-specific quality-of-life satisfaction during the menopause in an Arabian Gulf country. Climacteric 2000;3:43-9.
[Table 1], [Table 2], [Table 3], [Table 4]