A Clinical Analysis of Vitamin D Status in Patients Before Spinal Surgery

Vitamin D, an important fat-soluble vitamin, plays an important role in maintaining normal functions of skeletal muscles. It primarily maintains homeostasis of calcium and phosphate metabolism in the body, and thus ensures normal mineralization of bones. 1,25-dihydroxyvitamin D3 [1,25(OH)₂ D3], the metabolite of vitamin D, is the most active form of vitamin D in the body and maintains homeostasis of bone formation and resorption by regulating the functions of osteoblasts and osteoclasts. Low levels of vitamin D (≤9 ng/mL) will reduce the intestinal absorption of calcium, cause compensatory increases of parathyroid hormone, disrupt homeostasis of bone formation and resorption, and thus result in osteoporosis and osteomalacia disease, impair functions of skeletal muscles, and increase the risk of fractures and its associated kyphosis.^1–3

In recent years, a large number of studies have shown that increased incidence of diseases associated with vitamin D deficiency has become a global issue.^4,5 Currently, approximately 10 million people worldwide have vitamin D insufficiency or deficiency.⁵ The degree of deficiency is affected by many factors mainly including the duration of sunshine, dietary supplements, age, gender, race/ethnicity, etc. Since vitamin D levels are important for homeostasis of bone formation and resorption, vitamin D deficiency in orthopedic surgery patients has attracted more and more attention. A recent study showed that 43% of 723 orthopedic surgery patients had vitamin D deficiency,⁶ whereas the rate of vitamin D deficiency in another study on 313 spinal surgery patients was 27%.⁷ The incidence of vitamin D deficiency may substantially vary due to several reasons including living environment, physiological condition, lifestyle, etc.⁴Although there is controversy about the incidence of vitamin D deficiency in orthopedic patients, it has been confirmed that vitamin D deficiency affects surgical approach and prognosis of orthopedic surgery, especially spinal surgery. Studies have shown that vitamin D promotes fracture healing in humans.⁸ Osteoporosis caused by vitamin D deficiency will result in reduced vertebral bone density, trabecular thinning, and reduced holding power of screws at bone interface. Complications of screw loosening and prolapse may occur in patients undergoing spinal fusion surgery due to factors associated with vitamin D deficiency, whereas adequate vitamin D levels are conducive to bone fusion after spinal fusion surgery by enhancing the stability of pedicle screws. Therefore, severe osteoporosis is a relative contraindication to a pedicle screw fixation surgery. Moreover, studies have shown that vitamin D deficiency affects the prognosis of patients with spinal surgery. An assessment of postoperative vitamin D status in female patients with spinal stenosis showed that patients with vitamin D deficiency had lower Oswestry Disability Index (ODI) score, and European Quality of Life-5 Dimensions (EQ-5D) scores compared with the other patients.⁹ Therefore, preoperative vitamin D screening should be reinforced in spinal surgery patients and vitamin D should be replenished in case of vitamin D deficiency.

Previous research described already cannot accurately reflect the current situation of vitamin D deficiency in our country due to the differences in living environment, physiologic condition, lifestyle, etc. between foreign and domestic patients. Currently, no relevant research has been performed on preoperative vitamin D status in domestic spinal surgery patients. Vitamin D is critical for maintaining the normal functions of skeletal muscles, and its deficiency may influence the choice of surgical approach and outcomes. Therefore, it is very important to study the incidence of vitamin D deficiency in domestic spinal surgery patients, which is very helpful for spinal surgeons to make an early treatment plan for vitamin D deficiency and ultimately improve therapeutic efficacy of the surgery.

Materials and Methods

Results

Basic medical data of patients

A total of 503 patients were enrolled in this study including 275 females (54.7%) and 228 males (Table 1). The mean age was 58.2 ± 14.1 years, and 356 patients were over the age of 50 (70.8%). Mean BMI was 24.2 ± 2.9 kg/m with 214 overweight (42.5%) and 43 obesity patients (8.5%). Only 31 out of all 503 patients (6.2%) patients had history of vitamin D supplementation. A total of 101 patients (20.1%) had smoking history, which includes only 1 female smoker. Among 206 patients undergoing bone densitometry, 72 had osteoporosis, 64 showed osteopenia, and 70 were normal.

Table 1  General medical data of patients

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The number of cases in spring, summer, fall and winter were 113, 141, 161, and 88, respectively. The number of cases for each disease was as follows: 91 cases of cervical spondylosis, 228 cases of lumbar degenerative disease, 125 cases of osteoporotic vertebral compression fracture, 28 cases of spinal fracture, 21 cases of recurrent lumbar disc herniation, and 10 cases of spinal tumors.

Analysis of risk factors identified

The correlation between vitamin D deficiency with age, sex, BMI, BMD, smoking history, history of vitamin D supplementation, season, and type of disease (Table 2) was studied by univariate analysis. Results showed that no significant difference in vitamin D levels (P = 0.364) of patients among the 3 age groups. Female patients had a significant lower level of vitamin D compared with male patients (P < 0.001). BMI was correlated with vitamin D levels in that obese patients had significantly lower levels of vitamin D compared with nonobese patients (P = 0.009). Since there was only 1 female smoker in this study, the impact of smoking on vitamin D levels was analyzed in male patients. In 228 male patients, vitamin D levels of smokers were statistically lower than those of nonsmokers (P < 0.001). it was also revealed that patients with previous vitamin D supplementation had significantly higher levels of vitamin D compared with patients without history of supplementation (P = 0.009). No correlation between vitamin D levels and BMD or T scores of lumbar spine was identified in the analysis of 206 patients undergoing bone densitometry (P = 0.316). As shown in Fig. 1, the highest rate of vitamin D deficiency was observed in January (90.6%), and the lowest in September (44.8%). Additionally, the lowest level of vitamin D was observed in winter (13.0 ± 6.0 ng/mL), whereas the highest in fall (18.7 ± 8.9 ng/mL; P < 0.05). As shown in Fig. 2, patients in recurrent lumbar disc herniation group had the highest incidence of vitamin D deficiency (80%), followed by cervical spondylosis (74.7%) and lumbar degenerative disease group (73.2%). The lowest rate of vitamin D deficiency (61.9%) was observed in patients in spinal tumor group. Multivariate logistic regression analysis revealed that female, smoking history and winter were potential risk factors for vitamin D deficiency (Table 3).

Table 2  Univariate analysis of potential risk factors of vitamin D deficiency

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Table 3  Multivariate regression analysis of potential risk factors associated with vitamin D deficiency (<20 ng/mL)

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Discussion

As an important fat-soluble vitamin, vitamin D is crucial for maintaining normal functions of skeletal muscles by maintaining homeostasis of calcium and phosphate metabolism in the body, and thus ensuring normal mineralization of bones.

Low levels of vitamin D (≤9 ng/mL) will reduce the intestinal absorption of calcium, cause compensatory rise of parathyroid hormone, lead to excessive absorption of bones, and thus result in osteoporosis and osteomalacia disease, impair functions of skeletal muscles, and increase the risk of fracture and its associated kyphosis.^1–3 Although research in other parts of the world has reported the incidence of vitamin D deficiency and its associated risk factors, no studies have been conducted on vitamin D status of spinal surgery patients in China. The current study investigated the vitamin D levels of 503 spinal surgery patients admitted in the First Affiliated Hospital of Nanjing Medical University. The rates of vitamin D insufficiency and deficiency were 23.9% and 71.4%, respectively. While no correlation was identified between vitamin D levels and age or BMD, factors including gender, BMI, smoking, vitamin D supplementation, and season were found to be related with vitamin D deficiency. Multivariate analysis suggested that being female, smoking, and winter were potential risk factors for vitamin D deficiency.

In a study of vitamin D levels in 313 patients with spinal surgery by Geoffrey E. Stoker et al, the incidences of vitamin D insufficiency and deficiency were 57% and 27%,⁷ which were lower than those of this study. This may be associated with preoperative vitamin D supplementation in the research by Geoffrey E. Stoker, during which approximately 25% of patients had history of vitamin D supplementation. In contrast, a higher incidence of vitamin D deficiency in this study was probably due to a much lower rate of patients with preoperative vitamin D supplementation, suggesting that patients with vitamin D deficiency should be supplemented with vitamin D as soon as possible. Additionally, no significant difference was identified between female and male groups in the research by Geoffrey E. Stoker, whereas this study showed that female patients had much lower levels of vitamin D compared with male patients (P < 0.001). Supplementation of calcium and vitamin D is often neglected in elderly patients due to the lack of attention on the prevention of osteoporosis in China. Moreover, reduced bone mass and severe bone osteoporosis are common in perimenopausal women with reduced estrogen levels due to recession of ovarian functions,^14,15 which might be the main reason for higher incidence of vitamin D deficiency of female patients compared with male patients in China.

The main way to get vitamin D for humans is by exposing to sunlight, during which 7-dehydrocholesterol (7-DHC) in the skin is converted to a precursor of vitamin D, and then is converted to vitamin D3 under the effect of ultraviolet light (mainly UVB).¹⁶ The amount of vitamin D3 produced in the body depends on the latitude and sunshine hours received.¹⁷

In this study, the highest rate of vitamin D deficiency was observed in January (90.6%), and the lowest in September (44.8%). In addition, the lowest level of vitamin D was observed in winter (13.0 ± 6.0 ng/mL), whereas the highest was observed in fall (18.7 ± 8.9 ng/mL; P = 0.001). These results are similar to the findings in research of seasonal characteristics of vitamin D levels by Amy K. Kasahara et al, which shows that vitamin D levels of Americans reach the highest peak in late summer (August), and come to the lowest peak in late winter (February).¹⁸ Both studies suggest that plenty of sunshine can increase levels of vitamin D in the body.

Previous research has proven that vitamin D levels are correlated with BMD. Clinical studies have shown that lumbar spine BMD of patients with osteoporosis caused by immunosuppression increases after a long-term 1,25(OH)₂D3 treatment.¹⁹ Animal experiments performed by Duque et al have demonstrated that 1,25(OH)₂D3 dramatically increases BMD and bone mass of SAM P/6 mice by adjusting the balance between bone formation and resorption.²⁰ However, some other studies suggest that vitamin D levels are not correlated with BMD. A study of 206 patients performed by Kruavit has revealed no significant difference (P = 0.577) in mean lumbar spine BMD of vitamin D deficiency (0.869 ± 0.191 g/cm²), insufficiency (0.898 ± 0.199 g/cm²), and normal group (0.994 ± 0.082 g/cm²).^21,22 In a study of menopausal women by O. Sahota et al, hip BMD of patients with vitamin D deficiency (≤30 nmol/L) and secondary hyperparathyroidism is lower than the other patients, whereas no significant difference in lumbar spine BMD has been identified among all patients.²³ The accuracy of lumbar spine BMD measurement is often affected by degenerative calcification and osteophyte formation around lumbar spine, and inflammatory changes of lumbar facet joints in elderly patients.²⁴ Moreover, in the study by Kruavit, patients with vitamin D deficiency and insufficiency are 154 (74.8%) and 48 patients (23.3%), respectively, whereas only 4 patients (1.9%) have normal levels of vitamin D. Such low proportion of patients with normal vitamin D levels may be another factor contributing to the conclusion that vitamin D levels are not correlated with lumbar spine BMD. Although the correlation between vitamin D levels and BMD remains controversial, it has been confirmed that vitamin D supplementation can increase BMD. Therefore, it is especially important for patients with osteoporosis to replenish vitamin D.

Among different groups of patients in this study, the group of recurrent lumbar disc herniation had the highest rate of vitamin D deficiency (80%), followed by a group of cervical spondylosis (74.7%) and lumbar degenerative disease (73.2%).

Previous study has shown that vitamin D can promote fracture healing in humans.⁸ Vitamin D deficiency can cause osteoporosis and result in reduced vertebral bone density, trabecular thinning, and reduced holding power of screws at bone interface. Vitamin D deficiency may cause complications of screw loosening and prolapse in patients undergoing spinal fusion surgery, whereas adequate vitamin D levels are conducive to bone fusion after spinal fusion surgery by enhancing the stability of pedicle screws. Therefore, patients with vitamin D deficiency should be replenished with vitamin D, and the degree of osteoporosis of these patients should be systematically evaluated before surgery to choose an appropriate surgical approach.

Geoffrey E. Stoker et al found out that preoperative NDI and lumbar ODI scores were suitable indicators for vitamin D status.⁷ Byung Ho Lee et al have shown that over 50% of patients with lumbar spinal stenosis exhibit vitamin D deficiency, and vitamin D levels are correlated with surgical outcomes (ODI and EQ-5D index). Such deficiency in vitamin D in these patients may be related to their limited outdoor activities.⁸ In this study, NDI scores of 91 patients with cervical spondylosis and ODI scores of 228 patients with degenerative lumbar spine were measured before surgery, and results have shown that increased NDI/ODI scores were significant correlated with vitamin D deficiency (P < 0.05).

The results of this study demonstrate that the incidences of preoperative vitamin D insufficiency (23.9%) and deficiency (71.4%) are very common in spinal surgery patients in China. Low levels of vitamin D may be related to lifestyle (sunshine duration, smoking, vitamin D supplementation) and reduced activity. Since vitamin D is very important for maintaining normal functions of skeletal muscles, vitamin D deficiency may influence the choice of surgical approach and prognosis. Therefore, preoperative screening of vitamin D in spinal surgery patients should be reinforced and patients with vitamin D deficiency should be subject to early intervention to facilitate prognosis and to reduce the incidence of long-term complications. Although this retrospective study may possibly have bias, and the prognosis of patients with vitamin D deficiency needs a long-term follow-up observation, the results of this study are still clinically significant.