Anxiety Is Associated With Fracture Risk in Postmenopausal Women


Globally, osteoporosis is a major public health problem, affecting hundreds of millions of people, predominantly postmenopausal women. Bone fracture, due to low bone mineral density (BMD) and impairment of bone microarchitecture, is the main clinical consequence of osteoporosis. Osteoporotic fractures are estimated to affect 1 in 3 women and 1 in 5 men worldwide. In many countries, the frequency of fragility fractures is growing, representing a leading healthcare-cost driver.1

Anxiety disorders are among the most common mental disorders, with a global prevalence between 5.3% to 10.4%, suggesting that approximately 1 in 14 people around the world is living with an anxiety disorder. The potential relationship between anxiety disorders and osteoporosis has been poorly investigated; studies have primarily focused on the psychological effects of handling osteoporosis (eg, pain and impaired ability to perform daily activities due to fracture occurrence), which may affect anxiety.1

Studies have demonstrated that women with osteoporosis have an increased incidence of anxiety symptoms and a decreased quality of life (QoL) compared with healthy women. High anxiety levels may be considered a potential risk factor for low BMD, as low BMD is commonly observed in women with depression and anxiety. Additionally, the effects of anxiety and stress response trigger immunological and endocrinological reactions that may involve bone biology.1

Catalano et al conducted this study to examine the association of anxiety levels with BMD among postmenopausal female outpatients.1

Study Design

This study was a cross-sectional study of white, postmenopausal women consecutively referred to an outpatient osteoporosis clinic in Italy between January and April of 2017. Women who had a self-reported diagnosis of depression or anxiety were excluded from the study. Additional exclusion criteria included cognitive decline; moderate to severe renal or hepatic impairment; cancer; malabsorption; and endocrine disorders of the thyroid, parathyroid, or adrenal glands. Eligible participants were naïve to psychotropic drugs or active bone agents (eg, bisphosphonates, denosumab, selective estrogen receptor modulators, or hormone therapy).1

Enrolled participants were divided into tertiles according to their anxiety levels (Hamilton Anxiety Rating Scale [HAM-A] scores) at study entry. Fracture risk was evaluated by using the Fracture Risk Assessment Tool (FRAX), a computer-based algorithm that calculates the 10-year probability of a major fracture (hip, clinical spine, humerus, or wrist) and the 10-year probability of a hip fracture using select patient characteristics such as age, body mass index (BMI), and dichotomized clinical risk factors (eg, parental history of hip fracture, prior fragility fracture, current tobacco use). The HAM-A was used to assess the severity of perceived anxiety symptoms, and the Beck Depression Inventory, 2nd edition (BDI-II), was used to evaluate depression among study participants. A dual-energy x-ray absorptiometry densitometer was used to asses BMD at the lumbar spine and the femoral neck.1


A total of 192 postmenopausal women were enrolled in the study; 87 enrolled patients were classified in the lower tertile (ie, had the lowest HAM-A scores) (HAM-A 1), 48 in the second tertile (HAM-A 2), and 57 in the highest tertile (ie, had the highest HAM-A scores) (HAM-A 3). Overall, the mean age of participants was 67.5 years, and they began menopause at a mean age of 47.55 years. Additionally, 150 (78%) patients had previous fractures and 87 (45%) had a parent who experienced a hip fracture.1

Participants in the HAM-A 1 cohort had a lower 10-year probability of major osteoporotic fractures when compared with those in the HAM-A 3 cohort (mean ± SD FRAX score, 20.44 ± 9.3 vs 24.94 ± 13.06, respectively; P = .03). Similarly, the probability of osteoporotic fractures was lower in the HAM-A 2 cohort compared with the HAM-A 3 cohort (P = .002).

Additionally, depression severity increased with increasing HAM-A scores; the mean ± SD BDI-II score reported in the HAM-A 1 tertile was 5.93 ± 3.15, while those in the HAM-A 2 and HAM-A 3 tertiles were significantly higher than that in HAM-A 1 tertile (7.06 ± 2.09 and 9.36 ± 2.78, respectively; P <.05 vs HAM-A 1 for both).1

As illustrated in the Table, women in the HAM-A 3 tertile exhibited a lower T-score in lumbar spine and femoral neck BMD than did women in HAM-A 1 tertile.1 The same trend for T-scores was observed when the HAM-A 2 and HAM-A 3 tertiles were compared (P <.05).1

A subsequent multiple regression analysis demonstrated that lumbar BMD was independently negatively associated with HAM-A score (P = .0002) and independently positively associated with BMI (P <.0001).1


This study demonstrated that anxiety levels in postmenopausal women were significantly associated with BMD in the lumbar spine and femoral neck. The authors note that the increasing prevalence of osteoporosis and its significant impact on QoL highlights the need to recognize clinical risk factors and screen at-risk patients for bone fragility. Osteoporosis remains an underdiagnosed and undertreated disease, and the emerging relationship of anxiety and BMD suggests the importance of recognizing fracture risk in women with anxiety.1


1. Catalano A, Martino G, Bellone F, et al. Anxiety levels predict fracture risk in postmenopausal women assessed for osteoporosis. Menopause. 2018;25(10):1-6. doi: 10.1097/GME.0000000000001123.