Osteoporosis (OP) is a systemic skeletal disease characterized by reduced bone mineral density (BMD) and deterioration of bone microarchitecture. OP is estimated to affect over 200 million people worldwide, with one in three women and one in six men likely to suffer the disease during their lifetime.1 OP is a chronic condition which significantly increases bone fragility and susceptibility to fractures from minimal trauma and it is influenced by a complex interplay of biological factors including age, gender, genetics, environmental factors, and lifestyle.2 OP is considered a global public health problem, contributing to decreased quality of life, increased disability and institutionalization, higher mortality and morbidity rates, and substantial healthcare costs. In 2019, the total cost of fragility fractures and pharmacological interventions in Europe was estimated at 56.9 billion euros, representing about 3.5% of the healthcare spending. The total costs and the percentage of healthcare spending increase every year.1

Several studies analysed the relationship between OP and cardiovascular diseases (CVDs),3–9 the leading cause of death.10 Both conditions share common pathophysiological mechanisms regulating bone homeostasis and vascular repair, involving factors like type 1 collagen, proteoglycan, osteopontin, osteonectin, bone morphogenetic proteins, osteoprotegerin, RANKL (receptor activator of nuclear factor kappa-B ligand), phosphate, parathyroid hormone, and vitamins D and K.4,5 Some of the risk factors for both CVD and OP are also shared, with advanced age as a particularly critical factor, but also including family history, oestrogen levels, dyslipidaemia, oxidative stress, inflammation, hypertension, hyperhomocysteinemia, hypovitaminosis D, diabetes mellitus, glucocorticoid intake, and lifestyle factors.4,5

The connection between these conditions might be related to the dependence of skeletal and muscle function on vascular health for blood and nutrient supply, which can be compromised by CVD.4–6 Clinical studies have shown associations between vascular calcification or CVD events and OP, reduced BMD or fracture. For instance, studies have shown that major cardiovascular (CV) events are more common in postmenopausal women with lower BMD.6,11 Similarly, decreased BMD is a predictor of the risk of atherosclerotic vascular disease (AVD),7 with AVD more frequently present in women with OP.12 Moreover, women with low BMD have a 1.9-fold increased risk of stroke,3 and men with OP are at increased risk of CV mortality, whereas women are more prone to CV events but not necessarily CV death.9 Nevertheless, there is a proportional relationship between the severity of OP and the risk of CV events.11 On the other hand, in postmenopausal women, the presence of AVD contributes to the risk of development of OP and hip fractures.13 In this line, a meta-analysis of eight observational studies also linked heart failure with an increased risk of fractures.8 Preliminary studies indicate that some OP treatments may positively impact the CV system.5

Despite the overlapping pathophysiological mechanisms and risk factors between OP and CVD, along with the established scientific evidence linking these conditions, there are very few data analysing the frequency of CVD or CV risk factors in OP patients in clinical practice, or investigating if the presence of these conditions influences the therapeutic management.

The aim of the VASOS (cardioVAScular risk in patients with OSteoporosis) study was to analyse the frequency of comorbidities, with special focus on CVD, as well as the frequency of CV risk factors (CVRF) in patients with OP in Spain in a Rheumatology setting, and if it could influence the osteoporosis therapeutic management of patients.

The VASOS study described the rheumatologist's perception regarding the frequency of comorbidities, CVD and CVRF in patients with OP, and the influence on their OP patient management. To our knowledge, this is the first study conducted in real clinical practice that provides an approximation of the frequency of CVD and CVRF in patients with OP within a Rheumatology setting.

According to the participants, almost 75% of the patients with OP were aged 65 or above. It is well known that the prevalence of OP increases with age.14 Also, aging predispose to CVD, and it is associated with both structural and functional disturbances on the CV system.15 The predominance of women in the VASOS study is also aligned with the female dominance in OP.16 The rheumatologists participating in the study identified age as the most frequent risk factor for OP and fragility fracture, while a sedentary lifestyle was the most frequent CVRF, closely followed by dyslipidaemia and high blood pressure. Although age and sex are non-modifiable risk factors, modifiable lifestyle choices such as physical activity, dietary habits, smoking, and alcohol consumption play a significant role in the onset and prevention of both OP and CVD.17

Inflammatory rheumatic or autoimmune diseases, along with endocrinopathies, were the most frequent comorbidities in patients with OP. As the study was conducted in Rheumatology units, an increased occurrence of rheumatic and autoimmune diseases was anticipated. Patients with rheumatic diseases are more susceptible for OP due to the bone-degrading effects of both inflammation and corticosteroid treatment.18 Moreover, the reduced physical activity often associated with rheumatic diseases may lead to lower mechanical loading on bones, which is essential for preserving BMD and strength.18 Hormonal imbalances, whether a deficiency or excess, can occur in these patients, and can lead to BMD loss.19

Surprisingly, rheumatologists reported that only an average of 15% of patients experienced depression, lower than what has been previously reported, where the majority of patients with OP exhibited mild to moderate depression.20 This discrepancy might be due to patients not reporting depressive symptoms or the limited time available during medical consultations for a comprehensive evaluation of mental health.

According to the participants, one out of six OP patients had a major CVD. It is well known that OP and CVD share overlapping pathophysiological processes and risk factors.4,5 The most prevalent CVDs among patients with OP were heart failure and ischemic heart disease. Heart failure has been linked to a rise in major osteoporotic fractures.8 Various theories have been suggested to explain the relationship between OP and heart failure, such as chronic inflammation and the overstimulation of the renin-angiotensin-aldosterone system.21 Similarly, patients with ischemic heart disease are at an increased risk of fractures due to shared pathophysiological processes, which involve factors that contribute to the formation of calcified vascular plaque and bone turnover.22

The rheumatologists participating in the study indicated that they took CVRF into account before prescribing OP treatments. Patients identified with CVRF were not administered MHT, and the average percentage of patients treated with SERMs and romosozumab was numerically reduced from 0.7 and 1.1 to 0.3 and 0.2 respectively, compared to all patients with OP. Furthermore, the rheumatologists expressed that they tend to avoid these treatments in patients with CVRF.

Some therapies for OP may confer CV benefits.5 Several studies conducted on women with OP suggested that bisphosphonates might protect against atherosclerosis by slowing the progression of calcification in the abdominal aorta, decreasing the thickness of the carotid artery walls, and improving patients’ cholesterol levels.23,24 Despite these findings, a meta-analysis encompassing 58 randomized clinical trials found no substantial link between bisphosphonate use and a reduction in CV events.25 On the other hand, SERMs like raloxifene and bazedoxifene have been linked to an increased risk of venous thromboembolism,26,27 MHT has been found to increase CVD by 22%,28 and the CV profile of romosozumab is unclear.29 Therefore, the presence of CVRF must be meticulously assessed before initiating any OP treatment.16 There is not concern about the CV risk with teriparatide or denosumab, and this is reflected in our results, with the prescription of this drugs not been affected by the presence of CVRF. Although abaloparatide was not commercialized in Spain when the study was conducted, according to a real-world study from US, it seems its cardiovascular profile could be comparable to teriparatide.30

According to most of the participants, there is a need for increased training or education on CV risk and OP. This call to action could improve the knowledge of the link between the two diseases and could impact in a better patient management.

This study had several limitations. The data collected were from the insights of rheumatologists, which could be subject to recall bias and lack of individual patient data. Another limitation is that the study was carried in a Rheumatology setting in Spain, so the results may not be applicable or representative of other settings or countries.

Nonetheless, this study offers a novel insight into the intersection of OP and CVD, highlighting the importance of holistic patient care and the need for further investigation into the interplay of OP, CVD, and associated risk factors. Future research could focus on refining strategies to assess CVRF while determining the most suitable OP treatment for each patient.

In conclusion, the VASOS study provides a survey-based comprehensive characterization of patients with OP in a Rheumatology setting in Spain. Most of these patients seem to be elderly women, with primary OP. However, comorbidities such as inflammatory, endocrine, and CVD are common, with CVRF being present in over half of the patients. In patients with CVRF there is a preference for oral bisphosphonates, followed by denosumab and teriparatide, avoiding the use of MHT, SERMs and romosozumab. This study highlights the need for enhanced education on CV risk to improve the management of OP patients.

This work was funded by Grünenthal Pharma S.A. Medical writing support provided by Evidenze Health España S.L.U., was funded by Grünenthal Pharma S.A.

E. Casado has received funding for travel or speaker fees from Amgen, UCB, Theramex, STADA, Gedeon-Richter, Grünenthal and GP-Pharm.

I. Gómez-Olmedo is an employee of Grünenthal Pharma.