Study: Vitamin D linked to reduced mortality in osteoarthritis patients

The well-established roles of Vitamin D in the calcium metabolism of bone make Vitamin D a highly influential factor that can be used for the prevention and management of the common musculoskeletal disorder osteoarthritis (OA).

Additionally, Vitamin D has been shown to have benefits in many non-skeletal diseases​, such as cardiovascular disease (CVD), diabetes, and cancers, via its effects of reducing inflammation, anti-proliferative activity, anti-oxidative activity, etc.

Although the benefit of Vitamin D in mortality reduction has been reported in the general population and diabetic patients, there have only been a few studies that have focused on such a relationship for OA patients.

The current study therefore aimed to evaluate whether serum 25(OH)D concentrations were associated with all-cause and cause-specific mortality in OA patients from NHANES III (National Health and Nutrition Examination Survey in the US) and the newly released NHANES 2001–2018 database.

This study concludes that OA patients with sufficient serum 25(OH)D were significantly associated with a decreased risk of all-cause and CVD mortality than those at lower 25(OH)D levels, which suggested a beneficial role of Vitamin D on a long-term basis.

"In addition, relatively lower hazard ratios (HRs) were observed in men than in women, highlighting the need of developing gender-personalized therapeutic strategies for OA patients, especially postmenopausal women," ​the report states.

Results

There were 4570 OA patients included in this analysis, with a median follow-up of 7.6 years. Approximately 65.53% of the patients were female and the mean age was 61.82 ± 12.94 years old.

A total of 16.54% of the patients were Vitamin D deficient (<50 nmol/L), and 48.15% were Vitamin D insufficient (<75 nmol/L). By the census day of 31 December 2019, 1388 OA patients died, including 427 (30.8%) from CVD, 268 (19.3%) from cancer, and 693 (49.9%) from other causes.

On a continuous scale an L-shaped association was found for all-cause mortality, and the concentration of serum 25(OH)D related to the lowest all-cause mortality risk was approximately 84.50 nmol/L. An inverse association was found for CVD-specific mortality.

However, such associations were not significant for cancer-specific mortality. 

Methods

The  NHANES is a large-scale and periodic program that harvests nationally representative health-related data of non-institutionalized citizens in the United States. 

Here, the data from NHANES III (from 1988 to 1994) and NHANES 2001–2018 were used and only respondents (aged > 18 years) with self-reported OA were included. 

The authors gathered all serum 25(OH)D data and corresponding mortality information.

The authors note several limitations of the study. Firstly, due to the lack of repeated Vitamin D measurements, they could not ascertain the associations of dynamic Vitamin D status with mortality. Secondly, the inclusion of OA patients was based on a simple question, “Doctors ever told you had OA”, as opposed to medical records. Another limitation was the limited statistical power for detecting the associations between 25(OH)D and cancer-specific mortality, given the low frequency of cancer deaths.

Additionally, studies showed that the role of Vitamin D in cancer incidence and survival and in different sites of cancer might be different. Therefore, when feasible, future studies that evaluate the effect of Vitamin D on different sites of cancer are warranted. Finally, due to the study design, the authors could not directly deduce the causality of Vitamin D with mortality in OA patients.

"Theoretically, this question can be addressed with the utilization of randomized controlled trials and Mendelian randomization analyses," ​the report states, "which unfortunately we were not able to perform in this study. Future studies that evaluate the potential casual associations are of vital use in elucidating the effect of Vitamin D on a long-term basis (such as mortality reduction) on OA patients."​

The role of Vitamin D

Bone diseases are a major cause of death in the elderly [24​], and it is widely known that vitamin D helps the body to absorb and use calcium, protecting the bones [25​].

Serum vitamin D is first converted into hormone calcitriol (known as “active Vitamin D”), which can promote the absorption of calcium, for example, by acting on the nuclei of small intestinal mucosal cells [26​]. Calcium is subsequently combined with other minerals to form hard crystals, giving bones strength and structure.

Additionally, calcium also has benefits in other body systems, such as reducing blood pressure and cholesterol levels, preventing tooth loss, and etc. [27​].

The benefits mentioned above, whether relative to the bones, or endocrine or dental, have an essential impact on the reduction in mortality in later life. On the contrary, in the situation of Vitamin D deficiency, the body has to take calcium from its stores in the skeleton. Weakened existing bone leads to a less favorable survival [24​].

Source: Nutrients​

https://doi.org/10.3390/nu14214629 (registering DOI)

"Vitamin D Status and Risk of All-Cause and Cause-Specific Mortality in Osteoarthritis Patients: Results from NHANES III and NHANES 2001–2018"​

Wang, J.; Fan, J.; Yang, Y.; Moazzen, S.; Chen, D.; Sun, L.; He, F.; Li, Y.