Osteoporosis, characterized by decreases in bone mineral density (BMD) and reduced bone strength, is a prevalent health concern worldwide as the aging population grows (1). In the USA, over 40 million older adults have osteopenia, and in Australia, 66% of adults over the age of 50 have osteoporosis (2, 3). According to data from China’s first osteoporosis epidemiological survey, 32.0% of people over 65 had osteoporosis, while 46.4% of people over 50 had low bone mineral density (4). Osteoporosis is becoming more common in China as the country’s population ages. By 2050, 212 million people in China are expected to have osteoporosis (5). Osteosarcopenia is linked to raised risks of falls, fractures, functional disability, and mortality, according to a population-based prospective cohort investigation conducted in Chile (6). Osteoporosis prevention in older adults is a major public health priority due to the substantial increase in disease burden and healthcare expenditures associated with osteoporosis (7).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for coronavirus disease 2019 (COVID-19), which has over 770 million confirmed cases as of 2025 (8). Bone metabolism is significantly impacted by SARS-CoV-2 infections, as indicated by several studies. Two weeks following SARS-CoV-2 infection, significantly enhanced osteoclastogenesis and bone loss was observed in an animal model (9), while recovering patients showed a variety of skeletal abnormalities, such as osteoporosis and decreased BMD, according to Tangl (10). According to numerous studies, SARS-CoV-2 causes inflammatory cytokine dysregulation, which in turn stimulates osteoclast activity and leads to bone loss and resorption in patients with severe infections, particularly inolder individuals (11–13). With the appearance of immune-evading variants and waning immunity, SARS-CoV-2 reinfections have become increasingly common, affecting millions worldwide, particularly among the older population (14). Previous studies have demonstrated that reinfection significantly amplifies higher rates of severe outcomes (hospitalization, mortality) compared to primary infection (15), with emerging evidence suggesting cumulative damage to musculoskeletal health, indicating that repeated inflammatory insults and cytokine dysregulation from multiple infections could cumulatively impair bone remodeling. It is essential to emphasize the connection between SARS-CoV-2 reinfection and osteoporosis in older populations, as most SARS-CoV-2-infected individuals are of older age (14), who are at a higher risk of reinfection.

Osteoporosis risk is influenced by several factors. Individual characteristics such as advancing age, female sex, particularly postmenopausal status, and Caucasian ethnicity have long been linked to increased likelihood of developing osteoporosis (16). This risk can be amplified by nutritional inadequacies, particularly insufficient consumption of vitamin D and calcium. Regular physical exercise has been shown to strengthen bones and help prevent age-related declines in BMD (16, 17).

Identifying these risk factors is crucial for identifying individuals at high risk, enhancing diagnostic accuracy, informing further evaluations, and implementing timely and effective interventions. However, despite the global prevalence of SARS-CoV-2 reinfection, relatively little is known regarding its association with osteoporosis in older adults. It is thus important to understand the influence of reinfection on bone health among older people. Such insights could contribute to personalized prevention and therapeutic strategies for reinfection-associated osteoporosis, ultimately helping to reduce the growing disease burden worldwide.

The influence of SARS-CoV-2 reinfection and other contributing factors on osteoporosis in adults aged ≥ 55 was investigated through a cross-sectional design. The objective was to elucidate the relationship between SARS-CoV-2 reinfection and osteoporosis in the older population, aim to help identify high-risk individuals, promote early and personalized prevention and treatment strategies, and ultimately contribute to reducing the disease burden of osteoporosis in older individuals with COVID-19.

Despite the global prevalence of SARS-CoV-2 reinfection, relatively little is known regarding its association with osteoporosis in older adults. This investigation was undertaken to further investigated the prevalence of osteoporosis between older individuals with single SARS-CoV-2 infection and those with reinfection, providing a basis for subsequent research on the impact of SARS-CoV-2 on bone health, offering valuable insights into the prevention of osteoporosis among individuals aged 55 years and above. Our findings revealed that 48.3% of older participants with SARS-CoV-2 reinfection were diagnosed with osteoporosis, a significantly higher proportion compared with those who had a single infection, even after adjusting for the other influence factors. Moreover, the prevalence of osteoporosis was consistently higher across all measured skeletal sites in the reinfected group. These results indicate that older adults (≥55 years) who have experienced SARS-CoV-2 reinfection are at a heightened risk of osteoporosis. Given that the older population is particularly susceptible to osteoporosis, we recommend effective prevention and management strategies for older adults who have been infected with SARS-CoV-2, especially for those with reinfection, should be implemented to mitigate its adverse effects on bone health and reduce the broader public health burden.

Earlier studies indicate that infection with SARS-CoV-2 adversely affects bone metabolism, contributing to the development of osteoporosis (19). In 2021, Awosanya et al. demonstrated in a SARS-CoV-2 mouse model that infected mice exhibited a marked increase in osteoclast formation compared with uninfected controls, resulting in significant bone loss following infection (9). Similarly, it was found that recovering patients exhibited skeletal abnormalities, such as decreased bone density and osteonecrosis (10). A recent study revealed that the ongoing impact of the COVID-19 pandemic had led to an overall downward trend in BMD (20). Consistent with these findings, our study revealed that osteoporosis was more prevalent in individuals infected with SARS-CoV-2 compared with data from the China Osteoporosis Prevalence Study in older populations (21). This bone loss may be explained by cytokine dysregulation induced by SARS-CoV-2, as proinflammatory factors not only induce differentiation of osteoclasts within bone but also promote inflammation in the skeletal system, thereby enhancing osteoclastogenic activity (11–13).

The so-called “cytokine storm” in COVID-19 is considered a major contributor to disease severity, characterized by increased production of cytokines, such as IL-1, IL-6, IL-17, and TNF-α (11, 22). Among these, IL-1 is a well-characterized inflammatory mediator that stimulates osteoclast formation and suppresses bone synthesis through direct activation of the RANK-mediated signaling pathway, resulting in extensive bone and cartilage degradation (23, 24). TNF-α serves as a positive regulator of osteoclastogenesis by inhibiting osteoblastic activity and promoting osteoclastic proliferation and differentiation (25). IL-6 also contributes to bone resorption by inducing osteoclast formation and enhancing their activity (25, 26). Moreover, Th17 cells modultate osteoclastogenesis via IL-17-induced upregulation of RANKL and may participate in fracture healing via their modulatory effects on bone cells (27).

A comprehensive cohort investigation of the consequences of SARS-CoV-2 reinfection found that, relative to individuals who were either uninfected or infected only once, those with reinfection showed a significantly higher risk of severe illness (15). Similarly, Elmedany et al. reported that the severity of SARS-CoV-2 infection was inversely correlated with BMD; patients with severe infections experienced a greater reduction in BMD compared with those with mild or moderate disease (28). These findings suggest that repeated SARS-CoV-2 infections may heighten the risk of osteoporosis as disease severity increases, aligning with the results of our study. One potential mechanism involves the marked elevation of osteoprotegerin (OPG), a key regulator of bone remodeling, observed in patients with severe infections (29).

Amid the global prevalence of SARS-CoV-2 reinfections, close monitoring of bone health in older individuals reinfected with SARS-CoV-2 is critical to prevent or mitigate bone loss and reduce the risk of adverse outcomes, such as fractures associated with osteoporosis.

It is well established that advanced age, female sex, inadequate consumption of calcium and vitamin D, and limited physical activity are major risk factors for osteoporosis (16, 30, 31). It is well-documented that the prevalence of osteoporosis and other bone metabolism disorders increases with age, and that females, regardless of age group, are disproportionately affected (32). The development of osteopenia or osteoporosis in postmenopausal women is also a consequence of estrogen deficiency (33). Consistent with previous research, our study also demonstrated that female participants with SARS-CoV-2 infection had more than a fivefold higher risk of developing osteoporosis compared with males. These results demonstrate the vital role of closely monitoring bone health in older adults, particularly among women.

Moreover, there are several reports of a modest but meaningful link between low calcium intake and reduced BMD (34). Vitamin D deficiency is also associated with a greater risk of osteoporosis, primarily through mechanisms such as increased bone turnover, impaired calcium absorption, secondary hyperparathyroidism, and compromised immune regulation, all of which contribute to bone mass loss (35, 36). Furthermore, insufficient physical activity has been positively correlated with an elevated likelihood of osteoporosis in multiple studies (37).

In agreement with these findings, a higher prevalence of osteoporosis was observed among participants with vitamin D deficiency, inadequate calcium intake, or less than 30 min of daily physical activity. Importantly, even among those with SARS-CoV-2 reinfection, regular calcium supplementation and engaging in at least 30 min of daily physical activity remained protective against osteoporosis. Therefore, maintaining optimal vitamin D levels, ensuring adequate calcium intake, and adopting a physically active lifestyle, along with sufficient exposure to sunlight, are all essential strategies for preventing osteoporosis.

This study has several limitations. First, all individuals were enrolled from the single-center hospital, selection bias may over represent individuals with health issues. Second, information regarding SARS-CoV-2 infection history, lifestyle habits, and dietary intake was collected through face-to-face questionnaires, which made the data susceptible to recall bias. Thirdly, osteoporosis is a multifactorial condition influenced by numerous variables; however, not all potential confounders identified in previous studies were addressed in the present analysis, potentially affecting the results. Finally, the lack of baseline BMD data before infection and hormonal or inflammatory biomarker measurements (e.g., IL-6, estrogen, OPG), which limits mechanistic insight. Future studies should include longitudinal follow-up to determine the causal relationship between SARS-CoV-2 reinfection and osteoporosis progression, integrate inflammatory and hormonal biomarkers to clarify mechanisms, and evaluate targeted interventions such as vitamin D supplementation and exercise rehabilitation in this population.

In summary, it has been found that patients with repeated SARS-CoV-2 infections had a significantly higher frequency of osteoporosis compared to the single-infected individuals. These findings offer valuable insights into the prevention of osteoporosis among older adults who have been affected by SARS-CoV-2 reinfection. Amid the ongoing COVID-19 pandemic, it is essential to closely monitor bone health in this population, particularly among older and female individuals. Maintaining adequate vitamin D levels, ensuring sufficient calcium intake, engaging in regular physical activity, and obtaining appropriate sun exposure remain key strategies for preventing osteoporosis, regardless of SARS-CoV-2 infection status.