Introduction
Osteoporosis (OP) is an age-increasing disease with osteopenia and destruction of bone microstructure, and its serious consequence is osteoporotic fracture ( Su et al., 2024 ). According to the results of the 2018 China Epidemiological Survey on Osteoporosis, osteoporosis has become an important health problem for people over 50 years old in China, with a prevalence rate of 19.2% and a low bone mass rate of 46.4% ( National Health Commission of the People’s Republic of China, 2018 ). According to China’s Seventh Population Census, China has the largest elderly population in the world ( Chen, 2023 ; Zhen, 2023 ). As the population ages, these rates will rise rapidly. At present, the pathogenesis of osteoporosis is not fully understood, but aging and menopause are two important influencing factors of osteoporosis ( Lane, Russell & Khan, 2000 ). Therefore, there is an urgent need to focus on bone health in people over the age of 50.

Generally, the indicators of bone metabolism in blood will be tested clinically to evaluate the status of bone metabolism, and can be used as a short-term monitoring tool to evaluate the efficacy of OP. The level of bone turnover markers (BTMs) is usually used to measure the strength of osteogenesis and osteoclastic activity. BTMs include bone formation markers ( e.g. , P1NP, etc .) and bone resorption markers ( e.g. ,  type I collagen carboxy-terminal peptide ( β -CTX), etc .) ( Zhen, 2023 ).

Plasmapheresis is the collection of plasma components by centrifugation of whole blood in an extracorporeal circuit, and the remaining blood components are returned to the donor ( Okafor et al., 2010 ). Citrate is the standard anticoagulant used in the plasmapheresis process ( Lee & Arepally, 2012 ). In China, the concentration of anticoagulant used and the ratio to whole blood were 4% and 1:16, with a dose of approximately 70–90 ml per donor per time. Acute side effects of citrate ( e.g. , perioral numbness and even hypocalcemia) have been reported ( Lee & Arepally, 2012 ; Hegde et al., 2016 ; Sigler, Lee & Srivaths, 2018 ). After acute citrate infusion, the average decrease in calcium ion levels in the body can reach 25%–35% ( Hester et al., 1983 ), and in severe cases, hypocalcemia may occur. After citrate is chelated with calcium, it is excreted in the urine. Therefore, it can cause partial calcium loss with urine. Skeletons are the body’s calcium reservoir, storing 99% of the body’s calcium ( Peacock, 2010 ). When the body encounters a decrease in serum calcium levels, parathyroid hormone (PTH) will be secreted in a timely manner and act on multiple organs in the body, including bones. An increase in PTH enhances the activity of osteoclasts in the bone, thereby releasing calcium ions into the bloodstream to maintain blood calcium levels ( Chen et al., 2011 ). Overall, it is to maintain blood calcium levels by mobilizing calcium in the bones. However, it is currently unknown whether long-term and frequent decreases in serum calcium levels will affect bone health. At present, the results of studies on the effect of repeated plasmapheresis donors on bone are inconsistent. Amrein et al. (2010) found that the apheresis group had a higher rate of low bone mass compared with the non-apheresis group, and there was a statistically significant difference in lumbar BMD between the two groups. However, a prospective study by Bialkowski et al. (2019) showed that apheresis did not cause a significant difference in BMD. The frequency of donation, volume of anticoagulant used per time vary between countries ( National Health Commission of the People’s Republic of China, 2022 ). These findings do not necessarily reflect the status of the Chinese donors. The 46-60-year-old group accounted for 84.4% of the total plasmapheresis population ( Sun et al., 2021 ). With the growth of plasmapheresis donor population, the number of women donor in China is now about twice that of men. There is a high degree of overlap between this population and those at high risk of osteoporosis. There’s no study to date on the bone health of plasmapheresis donors in China.

In recent years, an increasing number of studies have suggested a close relationship between iron metabolism and bone metabolism ( Wang, 2018 ; Cheng et al., 2019 ). In the preliminary research of our research group, we found that plasmapheresis has two different health effects on iron metabolism. Plasma donation increased the risk of iron deficiency in women, while alleviated the risk of iron accumulation in men. Therefore, apheresis may also have a certain correlation with bone metabolism and BMD through its impact on iron metabolism.

Therefore, this article investigates the relationship between bone mineral density (BMD), bone metabolism indicators, and plasmapheresis donation behavior among some high-risk plasmapheresis donors for OP in China, and further explores the mediating factors through reasonable statistical methods, providing a certain theoretical basis for ensuring the health and safety of Chinese plasmapheresis donors.