Key findings:

The study found that 18% of postmenopausal Iraqi women with osteoporosis had major depressive disorder, with a significant association between depression and osteoporotic vertebral fractures. However, no significant association was found between major depressive disorder and bone mineral density. This suggests a need for further research to understand the complex relationship between depression, osteoporosis, and fractures in this population.

What is known and what is new?

Osteoporosis is a condition characterized by decreased bone mineral density, leading to increased fracture risk. Major depressive disorder (MDD) is a common mental health condition that can impact quality of life and mortality. New is in his study explores the prevalence of MDD in postmenopausal Iraqi women with osteoporosis and its relationship with osteoporotic vertebral and other mild stress fractures. It found a significant association between MDD and osteoporotic vertebral fractures but not with bone mineral density.

What is the implication, and what should change now?

Implication of the study suggests that screening for depression may be important in postmenopausal women with osteoporosis, especially those with vertebral fractures, to improve overall management and outcomes. Healthcare providers should consider assessing and managing depression in postmenopausal women with osteoporosis, particularly those with vertebral fractures, to provide comprehensive care and potentially improve treatment outcomes.

Osteoporosis is a medical condition that is characterized by a decrease in bone density and deterioration of the bone structure, resulting in increased vulnerability to fractures [1]. The issue at hand represents a significant public health concern, as it is linked to heightened rates of illness and death, specifically in relation to fractures occurring in the hip and vertebrae. These fractures place a substantial strain on the healthcare system due to the considerable financial expenses associated with their treatment and the resulting disabilities they give rise to (Al-Mukhtar et al., 2013) [2]. According to the World Health Organization (WHO), fractures are the primary clinical characteristic of osteoporosis. Osteoporotic fractures are characterized by being the result of trauma that would not typically produce a fracture in healthy bone.  To clarify, a fragility fracture may occur as a consequence of little stress, such as a fall from a height equivalent to standing or lower [3]. The manifestation of vertebral fractures in a clinical setting includes symptoms such as back discomfort, restricted range of motion in the spine, reduction in height, and functional impairment. Individuals may have challenges in activities such as, climbing stairs, rising, bending, dressing as well as a decrease in walking speed, diminished independence, or reliance on assistive devices [4]. According to the cited source (Cauley et al., 2007) [5], the occurrence of vertebral fractures significantly amplifies the likelihood of subsequent vertebral fractures by a factor of four to five, as well as the risk of other fragility fractures by a factor of two to four. During the initial year following fracture, hip fractures have more pronounced functional, economic, and health-related implications compared to vertebral fractures. Nonetheless, in the long run, vertebral fractures have an equivalent impact in terms of extended mortality and diminished quality of life (QOL) [6]. Other common sites for fragility fractures are the distal radius, proximal humerus, ribs, pelvis, clavicle, femur and tibia [7]. The semi-quantitative grading (SQ) method is commonly utilized in epidemiology studies and pharmaceutical trials to determine the prevalence and incidence of vertebral fractures. This method is particularly prevalent in evaluating the effectiveness of new osteoporosis treatments (Figure 1) [8].

Figure 1: The semiquantitative method of grading of Genant et al.

Epidemiology

Osteoporosis is a significant concern within the realm of public health. According to the National Osteoporosis Foundation (NOF), it is estimated that osteoporosis affects around 10.2 million individuals in the United States, with an additional 43.4 million individuals having low bone mass. Annually, the United States experiences a prevalence of over 2 million fractures associated with osteoporosis, with a significant majority of these fractures, exceeding 70%, affecting the female population [9,10]. In Iraq the Prevalence of Osteoporosis in Post-Menopausal Iraqi Women was 22.8%. Distribution of the study sample was 65.6% for age group 50-60 years, 29.2% for age group 61-70 years, 5.2% for age group>70 years [11].

Risk factor

Numerous factors were recognized as contributing to the increased danger of osteoporosis and/or fragility fractures. Among these factors female gender and increasing age, stand out as particularly significant risk factors. However, additional prevalent and potentially modifiable risk factors encompass chronic inflammatory disease, long-term corticosteroid therapy, untreated premature menopause, and malabsorption and [12]. Numerous factors have been noted to be contributors to the heightened susceptibility to osteoporosis and/or fragility fractures. Among these factors, female gender and advancing age are recognized as particularly significant risk factors [13]. Nevertheless, additional prevalent and potentially modifiable risk factors involve chronic inflammatory disease, long-term corticosteroid therapy, and untreated premature menopause malabsorption. Estrogen deficiency induced imbalance between bone formation and resorption such that resorption predominates over formation [14].

Diagnosis

Dual-energy x-ray absorptiometry (DEXA) is the most applicable method to assess bone mineral density (BMD), it is highly accurate x-ray technique [15]. One significant benefit of Dual-energy X-ray absorptiometry (DEXA) is its ability to subject the patient to radiation levels that are roughly 90% lower compared to those of a conventional chest radiograph [16].  As per the standards established by the World Health Organisation (WHO), osteoporosis is characterised by a Bone Mineral Density (BMD) that falls 2.5 standard deviations (SD) or more below the mean value observed in young, healthy women (equivalent to a T score of less than -2.5 SD) [17]. The AACE concurs with the recommended clinical diagnosis put out by the National Bone Health Alliance, which suggests that osteoporosis may be diagnosed in individuals with osteopenia and a heightened risk of fractures by employing FRAX® country-specific criteria [18], appendix 1).Other diagnostic procedures include : high resolution peripheral quantitative computed tomography (HR-pQCT), quantitative computed tomography (QCT), quantitative ultrasonography , magnetic resonance imaging (MRI) and biochemical bone turnover markers (BTM) [19].

Treatment

Bisphosphonates are extensively utilised in pharmaceutical medication for the treatment of skeletal disease. Generally, these medications are well tolerated, with serious adverse events being rare. The risk-benefit profile in osteoporotic patients is overwhelmingly favourable, making them a preferable option [20]. While it is important to undergo appropriate bone mineral density screening and receive medication treatment, it is worth noting that osteoporosis can be prevented through proper management of diet, lifestyle, and interventions aimed at preventing falls [21].

Major depressive disorder (MDD)

This mental disorder is quite widespread, impacting around 16% of the adult population in the United States [22]. The incidence of major depressive episodes in the general population of Iraq was found to be 12% among individuals aged 50-64 years and 13% among those aged 65 years and above [23]. It is characterized by a sleep abnormality, anhedonia, sustained depressive mood, social behaviors, and alongside a number of motivational [24]. According to the World Health Organisation, severe depression has been identified as the primary contributor to global disability.  Depression causes decreases life quality, suffering, and impairment in occupational and social functioning. The condition is associated with escalated healthcare expenditures, as well as elevated prevalence rates of several chronic medical ailments [25]. The presence of a depressed mood does not always indicate the presence of mental disorders. It is plausible that such a response may be considered within the realm of typical reactions to specific life circumstances, indicative of particular physiological ailments, or an outcome of pharmaceutical interventions or medical procedures.

Population-based clinical investigations have observed a higher occurrence of Major Depressive Disorder (MDD) during the perimenopausal phase in comparison to both the premenopausal and postmenopausal stages. The available evidence indicates a correlation between fluctuations and decline in hormone levels and the reported rise in risk for severe depressive illness [26].

Osteoporosis and depression

The presence of osteoporosis can exert a substantial influence on the psychological well-being and health-related quality of life (HRQOL) of individuals. The initial recognition of the coexistence of depression among individuals diagnosed with osteoporosis was documented throughout the latter part of the 1980s through observational investigations conducted within the framework of osteoporosis educational initiatives. When queried about the origins of these despondent emotions, a significant number of participants expressed that the consequences of osteoporosis—chronic pain, failure to meet societal role expectations, deformity, and loss of control resulted in more negative feelings [27]. There is a lack of empirical data supporting a direct causal relationship between osteoporosis and psychological disorders, specifically depression [28]. Osteoporosis, in the absence of concurrent clinical fractures, has been linked to adverse outcomes such as impaired physical ability, deformity, chronic pain, depressed mood, poor well-being, loss of control, and reduced social activity, resulting in a diminished quality of life [29]. The findings of the Multiple Outcomes of Raloxifene Evaluation (MORE) study revealed a higher prevalence of depression in individuals diagnosed with osteoporosis. This association was particularly prominent in postmenopausal women with vertebral fractures, who exhibited a significantly greater occurrence of depressive symptoms and probable depression compared to those without fractures [30]. Fractures, especially vertebral fractures, can be associated with chronic, disabling pain; in addition, fractures can be extremely debilitating [31]. Up to our knowledge, there are no previous reports about Prevalence of Major Depressive Disorder Among postmenopausal Iraqi women with osteoporosis.

Study design

The present study was a cross-sectional investigation that carried out in the Rheumatology Unite in Baghdad Teaching Hospital from October 2017 to April 2018. 

Sample selection

The study included a sample of 100 post-menopausal women from Iraq who had been diagnosed with osteoporosis based on the categorization criteria established by the World Health Organisation (WHO) for osteoporosis and osteopenia (17). Bone mineral density was assessed using T score ( number of standard deviation (SD) from mean bone density value in normal sex matched young adults) of total hip and lumbar spine by using dual energy x- ray absorptiometry (DXA) scan (393 rue Charies Lindbergh , 34130 Mauguio France) by trained radiology technician.

Data collection and entry

The female participants underwent screening for major depressive disorder utilising the diagnostic criteria for depression outlined in the DSM5 (, appendix 2). Additionally, the intensity of their depressed symptoms was evaluated using the Beck Depression Inventory scale, specifically the Arabic version (احمد, 2010) [32], appendix 3). The interview was done in isolated room and lasting for 30-45 minutes.

All women were asked for their ages, marital status, employment status, educational status, house hold crowding index (Persons per room), age of menopause years since menopause and treatment with bisphosphonate. Body mass index (BMI) was measured according the equation BMI=weight/ height2, all women were subjected to thoracolumbar spine x-rays (lateral views). Semi-quantitative (SQ) approach was used to assess osteoporotic vertebral fracture (8). self-reports was utilised to assess history of nonvertebral low trauma fractures (appendix 4).

The following conditions precluded patients from the study:

1-            Chronic physical illness that may contribute to depression.

2-            History of depression or mental illness

3-            Family history of depression

4-            Substance abuse 

5-            Social problems

6-           Premature menopause due to medical interventions, chronic disease or Medication.

All participants gave their informed permission before being included in the study. Ethical approval was obtained from the   Ethics  Committee in   the Medical department-College   of  Medicine-Baghdad University.

Statistical analysis:-

 All data of the study were analysed by utilizing “SPSS software version 26”. Categorical data was presented as frequency and percentage. The numerical data was presented as mean and slandered deviation. Student T test and ANOVA were used to perform comparisons between groups. p <0.05 was considered statistically significant.

The findings regarding sociodemographic and gynecological history revealed that 62% of studied sample was married, 78% was housewife, 45% was illiterate, 46% was obese, 39% with crowding index of more than four, 43% of women ceased menopause within 5-9 years and 18% on bisphosphonate treatment as displaced in table.1.

Table.1; Descriptive characteristics of studied group

BMI=Body Mass Index

The results demonstrated that the prevalence of depression in our osteoporotic patients was 18%, Severity of depression was 77.8% mild, 16.7% moderate and 5.6% severe depression as showed in fig.1 and 2. 

Fig.2; Prevalence of depression among post-menopausal osteoporotic women

Fig3; Prevalence of severity of depression among post-menopausal osteoporotic women

         The findings of current study showed there were no significant association between depression status and each of marital, occupation, education, BMI, years since menopause, age groups statues and treatment with bisphosphonate (p≥0.05 for all).The significant association (p=0.03) was reported between prevalence of depression and house hold crowding index where the results showed that the subject with ≥4 index had higher prevalence of depression in comparison to subject with <4index (61.1 vs.34.1) respectively as showed in table.2.

Table.2 Incidence of depression according to sociodemographic characteristics, years since menopause and bisphosphonate treatment

BMI=Body Mass Index

P value=Probability Value

       The results demonstrated that the status of depression in term of present or absent was significantly (p=0.01) higher among subjects who had spine fracture in comparison to subjects with others type of fractures or no fracture (61.1vs, 26.8, 0.0 vs.6.1, 39.8 vs.67.1%) respectively as seen in table 3.

Table.3; Association of depression status and fracture status

P value=Probability Value 

         Our data indicated there was no significant association between severity of depression and fracture statues (p=0.6) even one case of sever form was reported with the subjects who had fracture but the difference did not reach the significant level as seen in table 4.

Table.4; Association of severity of depression and fracture status

P value=Probability Value

        Our findings indicated there was no significant association between depression status and fracture status when analyzed according to age group where the prevalence of depression nearly equally distributed among patients belonged to age group of   <65 or ≥65 years as seen in table 5.

Table.5; Association between facture and depression status according to age groups

P value=Probability Value

         The results of this study showed that the mean of Total Spine T score, Total RT hips BMD, Total RT hip T score, Total LT hip BMD and Total LT hip T score was -3.1,0.8,-1.9,0.8 and -1.9 respectively as seen in table 6.

Table.6; Mean of T- score of different sites

BMD= Bone Mineral Density

        The results of current study showed that the mean of Total Spine T score, Total RT hips BMD, Total RT hip T score, Total LT hip BMD and Total LT hip T score not differed significantly (p≥0.05 for all)when compared according to depression status  as seen in table 7.

Table.7; Means difference for osteoporotic indictors according to depression status

BMD= Bone Mineral Density

DXA=Dual-energy X-ray Absorptiometry

P value=Probability Value

SD=Standard Deviation

There are few reports available concerning prevalence of depression in postmenopausal osteoporotic women and its association with osteoporotic vertebral fracture .This cross sectional study showed that the prevalence of major depressive disorders among postmenopausal Iraqi women with osteoporosis were 18%. This is close to the results of Drosselmeyer et al study [33], which showed that 11.7 % of osteoporosis patients developed depression after 1 year of follow-up and 33 % of them developed depression after the 5-year follow-up period.

In this study major depressive disorder was significantly (p=0.01) higher among women who had vertebral fracture in comparison to women with history of others type of fragility fractures or no fracture (61.1vs, 26.8, 0.0 vs.6.1, 39.8 vs.67.1%) respectively. Which is similar to the result of  Silverman et al study [31], which showed that women with prevalent vertebral fractures reported a significantly higher mean number of depressive symptoms compared to women without prevalent vertebral fractures (p = 0.001). Additionally we did not find significant association between severity of depression and fracture statues.

 The results of current study showed that the mean of Total Spine T score, Total RT hips BMD, Total RT hip T score, Total LT hip BMD and Total LT hip T score are lower in women with major depressive disorder than women without major depressive disorder but there is no significant difference   (p≥0.05 for all). In compared with Bener et al study [34], which showed that BMD,  T-score and Z-score of lumbar spine and the mean of the proximal right and left femur were lower among women with postmenopausal depression than postmenopausal women without depression with significant difference (P < 0.001).

Osteoporosis with vertebral fracture and major depressive disorder are chronic debilitating diseases with high prevalence, The relationship between them is bidirectional. Osteoporotic vertebral fracture may generate chronic pain, which reduces mobility and consequently the capacity for self-care, often creating a feeling of loss of independence and low self-esteem. All these adversely affect the patients’ quality of life [35. 36], so women with osteoporotic fracture may present significantly with higher levels of depressive symptoms and a corresponding higher prevalence of depression. Additionally, patients with major depressive disorder may cause decrease in bone mineral density and increase risk of fracture by a sedentary lifestyle, low calcium intake diet and physical inactivity [37], depression also leads to excessive activity of the hypothalamic-pituitary-adrenal axis which increase cortisol secretion [38], that have known deleterious effects on bone. 

The findings of this study indicated there was no significant association between depression status and fracture status when analyzed according to age group where the prevalence of depression nearly equally distributed among patients belonged to age group of   <65 or ≥65.

In the current study we found no significant association between depression status and age, in contrast to Silverman et al study (Silverman et al., 2001) [31]vv which found that age associated with increasing numbers of depressive symptoms. This may be related to small sample size of this study.

In this study we found no significant association between depression status and each of BMI, occupation and education which is similar to Bener et al study (Bener et al., 2016) [34] finding.

The study showed that major depressive disorder was insignificantly associated with bisphosphonate treatment (p=0.8). Results revealed that the women who were receiving this medication reported lower prevalence of depression but the difference did not reach a significant level. There is no previous reports to our knowledge that studied the effects of alendronate treatment on major depressive disorder.

Additionally, this study showed significant association between depression status and household crowding index with increase depression prevalence in women with household crowding index ≥4, and insignificant association between depression status and both of marital status and years since menopause. There are no previous studies to compare with our study.

A limitation of this study includes small sample size due to short period of the study. Information about pain, frequency of falls and mobility was not collected in this study; therefore, we cannot assume any causal relationships from this study, only associations. Also this study was cross-sectional therefore we cannot determine which occurred first, osteoporotic vertebral fracture or the major depressive disorder.

The present study reveals that 18% of postmenopausal Iraqi women with osteoporosis had a major depressive disorder with statistically significant association with osteoporotic vertebral fracture. Women with a history of vertebral fractures showed a considerably greater prevalence of major depressive disorder compared to those without or with a history of other types of fragility fractures. There was no significant correlation found between major depressive disorder and osteoporotic women's sociodemographic data, with the exception of the home crowding index, which did show a significant association. In order to evaluate the causal link and identify whether of the two conditions, prevalent vertebral fracture or severe depressive disorders, came about first, research with a larger sample size that was conducted over a longer period of time is required. Physicians who treat significant depression should be sensitive to any indications of fractures, bone loss, or osteoporosis in their patients, and physicians who manage osteoporosis should realize the necessity of looking for depressed symptoms in their patients.

Funding: No funding sources 

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee of Ibn Sina training Hospital, Ministry of Health

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