Several studies in developed countries have reported a decreasing trend in hip fracture incidence.[1234] However, studies in Korea show that a two-fold increase in the total number of hip fractures, and the incidence rate of hip fracture in women increased steeply during a 10-year study period.[5] Hip fractures in elderly patients are the most serious because of high mortality, loss of independence, lower quality of life, and the high socioeconomic burden.[67] Although most risk factors, such as ageing, sex, and medical comorbidities, are inevitable, aging is the most important risk factor for hip fractures; thus, identifying modifiable risk factors is extremely important. Among these modifiable risk factors, vitamin D deficiency is a known modifiable risk factor for hip fracture.[8] A cohort study in Norway reported that patients in the lowest quartile of 25hydroxy-vitamin D (25-[OH]D) level had a 38% increased risk of hip fracture compared with those in the highest quartile 25-(OH)D level.[9]

According to a multi-national study, Korea has the highest prevalence (92.1%) of vitamin D insufficiency (25-[OH]D<30 ng/mL), followed by Japan (90.4%), Lebanon (84.9%), Turkey (76.7%), UK (74.5%), Germany (68.0%), Mexico (67.1%), and Spain (64.7%).[10] Song et al.[11] determined the prevalence of vitamin D deficiency in an urban Korean population of 8,976 participants (3,587 men and 5,389 women) aged ≥50-year-of-age. They reported 59.7% and 86.5% prevalence rates of vitamin D deficiency (25-[OH]D <20 ng/mL) in men and women, respectively. Therefore, vitamin D deficiency is a general phenomenon in Korean elderly subjects.[11] However, no study has investigated the association between vitamin D deficiency and mortality in patients with hip fractures.

The purpose of this study was to assess the prevalence and relationship between mortality and vitamin D deficiency among hospitalized patients aged ≥50-year-of-age 50 with hip fractures.

A total of 489 patients (489 hips) aged ≥50-year-of-age who was diagnosed with a femoral neck or intertrochanteric fracture from January 2010 to December 2014 were include in this study. Of them, 10 patients had a contralateral hip fracture and were excluded.

The follow-up period was a minimum of 12 months after discharge. There were 146 men (146 hips) and 343 women (343 hips). Demographic datas including age at the time of admission, diagnosis, body mass index (BMI), American Society of Anesthesiologist (ASA) score,[12] T-score (osteoporosis, osteopenia, and normal),[13] pre-fracture ambulatory status using Koval's categories,[14] serum 25-(OH)D₃ level, and type of management were obtained by reviewing the medical records (Table 1).

Blood sampling of all patients at the admission date, after fasting for 8 to 12 hr, was performed by experienced laboratory technicians. Detailed information on the 25-(OH)D assay was provided previously.[15] Briefly, of serum 25-(OH)D levels were assayed with a radioimmunoassay (RIA) kit (Siemens Healthcare, Erlangen, Germany).

Routine follow-up visits were scheduled at 6 weeks, and 3, 6, 9, 12 months, and every year thereafter. Patients who had not returned for regularly scheduled visits were contacted by telephone.

Osteoporosis was defined as a T-score ≤-2.5, osteopenia was defined as a T-score between -1 and -2.5, and normal was defined as a T-score ≥-1.0.[13]

Activity levels were defined as follows: I-independent community ambulator, II-community ambulator with cane, III-community ambulator with walker/crutches, IV-independent household ambulator, V-household ambulator with cane, VI-household ambulator with walker/crutches, and VII-nonfunctional ambulatory.[14]

According to the Holick [16] classification, vitamin D deficiency was considered at a vitamin D level <20 ng/mL, vitamin D insufficiency was 21 to 29 ng/mL, and normal ≥30 ng/mL. In addition, severe vitamin D deficiency was <10 ng/mL.[17]

Mortality was determined by the hospital records and/or by interviewing the patient's family. A systemic search for death certificates at the National Statistical Office was conducted for patients lost to follow-up.

The mean vitamin D level at admission was 15.7 ng/mL. The prevalence of vitamin D deficiency was 76.5%, 12.3% of patients were vitamin D insufficient, with 11.2% had normal vitamin D levels. Of them, severe vitamin D deficiency was present in 41.7% (204/489 patients) (Fig. 1).

During the minimum 1-year follow-up period, 114 of 489 patients (23.3%) died. Of them, 54 died within 1 year, 32 within 2 years, 11 within 3 years, and 17 within 5 years.

The univariate analysis showed that mortality was associated with vitamin D deficiency (P=0.012), age (P<0.001), BMI (P<0.001), type of management (P<0.001), ASA score (P=0.009), pre-fracture ambulatory status (P<0.001), and osteoporosis (P<0.001). However, no significant association was found between mortality and sex (P=0.489) or diagnosis (P=0.626) (Table 2). The adjusted multivariate analysis revealed that ASA score (HR 12.220; 95% CI 3.314-45.063, P=0.001) and pre-fracture ambulatory status (HR 1.681; 95% CI 1.104-2.558, P=0.011) were significant associated with death after hip fracture.

Our results show a high prevalence of hypovitaminosis D and mortality in patients with hip fracture. In total, 89% of patients were vitamin D deficient or insufficient, and 1-year mortality after hip fracture was 11%. Although vitamin D deficiency was a possible risk factor for death after hip fracture, we did not find any strong evidence for vitamin D deficiency as risk factor for death after hip fracture. Medical comorbidities and preoperative ambulatory status were important risk factors for mortality after hip fracture in this study.

Although the mean vitamin D insufficiency (<30 ng/mL) rate was 63.9% in a multinational study of 18 countries that evaluated 2,606 postmenopausal women with osteoporosis, South Korea had the highest rate (92.1%) of vitamin D insufficiency (<30 ng/mL) among the 18 countries.[10] Choi [18] evaluated the 2008 Korea National Health and Nutrition Examination Survey IV data that included 6,925 subjects in the general population and reported vitamin D deficiency (<20 ng/mL) prevalence rates of 47.3% in men and 64.5% in women and those for vitamin D insufficiency (<30 ng/mL) were 86.8% in men and 93.3% in women. In this study, vitamin D insufficiency (<30 ng/mL) and deficiency (<20 ng/mL) were present 88.8% and 76.5% of subjects, respectively. The reason for the high vitamin D insufficiency rate in Korea may be due to the indoor lifestyle and protection from ultraviolet light.[18]

The relationship between vitamin D deficiency and mortality in elderly subjects has been reported in several studies.[192021] However, serum vitamin D concentrations and mortality rates in elderly patients with hip fractures are rarely reported.[2223] Although our univariate analysis found that vitamin D deficiency was an independent risk factor for mortality after hip fracture, it was not associated with mortality after adjusting for age (P<0.001), BMI (P=0.041), type of management (P<0.001), ASA score (P=0.009), pre-fracture ambulatory status (P<0.001), and osteoporosis (P<0.001) in the multivariate analysis. This finding is similar to a previous study. Gumieiro et al.[22] assessed whether serum vitamin D concentration is associated with gait status and mortality among 87 elderly patients with fractures of the proximal femur 6 months after suffering the fracture. They reported that serum vitamin D concentration was not related to gait status or mortality among patients with fractures proximal femur.[22] Madsen et al. [23] performed a case control study of 562 patients aged ≥70 years with hip fractures and found that serum parathyroid hormone serum calcium levels were significantly associated with mortality, whereas serum 25-(OH)D level was not.

Risk factors for mortality after hip fracture have been reported in several studies.[2425262728] The known risk factors for mortality after hip fracture are race, old age, dementia, male sex, low BMI, low handgrip strength, preoperative activity, preoperative delirium, and medical comorbidities, such as chronic renal failure, congestive heart disease, and chronic obstructive pulmonary disease.[62526272829] In that study, the patient's medical condition according to the ASA score and preoperative functional status by the Koval's classification were important risk factors for mortality after hip fracture. In a previous Jeju cohort study, Lee et al.[6] performed mid-term follow-up after hip fracture in patients >50 year old. After adjustment for covariates, age, woman sex, and medical comorbidities were significantly associated with the risk for mortality after hip fracture.[6] However, preoperative functional activity was not associated with the risk for mortality. Karademir et al.[29] reported no significant association between ASA score and mortality after hip fracture in patients >75-year-old. The reason for these discrepancies might be related to cohort size, sex distribution, and patient age or other demographic characteristics.

This study had several limitations. First, it was a retrospective review of prospectively collected data, and no control group was used. Second, a single blood 25-(OH)D measurement is an imperfect surrogate as a long-term indicator of 25-(OH)D. Finally, serum 25-(OH)D levels were measured at baseline by radioimmunoassay. Therefore, further study is necessary to evaluate the real-time effect of vitamin D.

In conclusion, we did not find a relationship between serum 25-(OH)D level and mortality after hip fracture, although we observed high prevalence of vitamin D deficiency and a significant association with mortality in a univariate analysis.