Assessment of vitamin D levels in association with clinical determinants in females with hip fracture.

Background: Vitamin D deficiency is associated with an increased risk of falls and hip fractures in older adults. Risk factors are suboptimal sunlight exposure and the lower cutaneous synthesis of vitamin D, reduced dietary intake of D2 (ergocalciferol) and D3 (cholecalciferol), impaired intestinal absorption, and impaired hydroxylation in the liver and kidneys. The present study's objective was to determine the frequency of vitamin D levels in females with hip fractures presenting to a tertiary care facility in Karachi, Pakistan. Methodology: A cross-sectional study was conducted at the Orthopaedic Surgery Department of Jinnah Postgraduate Medical Center, Karachi, from 17 May to 16 November 2016. A total of 123 females with Hip fracture of ≤ 4 weeks were included in this study. Patient's age, occupation, education level, and comorbidities like diabetes mellitus (DM), hypertension (HTN), and Vitamin D levels were observed. The patient was labeled with vitamin D sufficiency, insufficiency, and deficiency on the basis of Vitamin D levels. Stratification was done, and the post-stratification Chi-square test was applied. Results: The mean age of study participant was 60.32 ± 9.14 years and the mean duration of fracture was 12.27 ± 5.84 days, Body Mass Index (BMI) was 24.57 ± 2.77 kg/m, vitamin D level was 18.28 ± 8.10 ng/ml. Only 8.9% were found with sufficient vitamin D levels. Insufficiency was found in 28.5% of patients. Vitamin D deficiency was found in 62.6% of patients. Conclusion: Vitamin D deficiency is common in elderly female patients with hip fractures and is associated with age and DM. This initial work warrants further larger-scale studies of vitamin D variations.


Introduction
Vitamin D deficiency is associated with increased muscle weakness and pain leading to reduced strength, balance, and function 1 ; increased bone turnover 2,3 , and increased risk of falls and hip fractures in older adults 4 . Elderly people are at greater risk of vitamin D deficiency because of risk factors such as suboptimal sunlight exposure and the lower cutaneous synthesis of vitamin D, reduced dietary intake of D2 (ergocalciferol) and D3 (cholecalciferol), impaired intestinal absorption, and impaired hydroxylation in the liver and kidneys 1 . In Western countries, Vitamin D deficiency occurs especially in the early spring due to reduced cutaneous synthesis during winter months 5,6 in housebound individuals 7 , and medical inpatients 8 .
A Turkish study had shown that patients living in old age homes had a higher risk of vitamin D deficiency than those living in their own homes. The same study found that clothing habits and exposure to sunlight were also associated with a higher risk of vitamin D deficiency 9 . The prevalence of vitamin D deficiency is even higher in elderly patients with fragility fractures (varying from 55 % to 91.6%) 6,10-13 , that was 57.5% among hospitalized elderly patients with hip fracture 14 . In 2000, there were an estimated 1.6 million hip fractures worldwide, and mortality in the year following a hip fracture is estimated at 20-30 % 13,14 . The social and economic burden of hip fractures worldwide is expected to increase significantly over the next 50 years due to aging populations, especially within developing countries [15][16][17] . Identifying interventions that can prevent hip fractures remains a key research priority, and vitamin D is an appealing therapy to fulfill this role.
In the face of the continuing uncertainty and the need for firm evidence to guide practice, up to date and broader quantitative examination of the evidence regarding vitamin D and fracture is warranted. Shrier et al. suggest that the advantages of examining different levels of evidence by including observational studies with Randomized control trials in meta-analyses may outweigh the disadvantages 18 . In a community-based study of 901 mother and offspring pairs, researchers found that maternal vitamin D deficiency (serum 25hydroxyvitamin D < 50 nmol/L) at 18 weeks' pregnancy was associated with impaired lung development at age 6 in offspring, neurocognitive difficulties at age 10, increased risk of eating disorders in adolescence, and lower peak bone mass at age 20 12-14 . There is a paucity of data on the prevalence of vitamin D levels in female patients with hip fractures. Numerous studies are available where sun exposure is scarce; however, in countries where sun exposure is abundant, data is deficient. Although females were found to have more Vitamin D deficiency than males, there was no statistically significant difference observed. In our part of the world, females with full-body coverage tend to be at home in the majority of the cases, so our study's result may differ compared to other countries. Therefore, the present study's objective was to determine the frequency of vitamin D levels in females with hip fractures presenting to a tertiary care facility in Karachi, Pakistan.

Methodology
A cross-sectional study was conducted in the Department of Orthopaedic Surgery, Jinnah Postgraduate Medical Center, Karachi, for six months from 17th May to 16th November 2016. Ethical approval was obtained from the College of Physicians & Surgeons of Pakistan and the Ethical Review Committee of JPMC. Informed consent was obtained from patients. The study's objective, procedure, risk, and benefit were explained to participants and confidentiality was assured and maintained throughout the study.
Consecutive female patients with the age between 45-75 years with duration of fracture ≤ 04 weeks admitted through the emergency department of JPMC meeting the inclusion criteria were included in the study while Patients with End-Stage Renal Disease (ESRD) requiring Renal Replacement Therapy (RRT) (GFR < 15) and high-impact injuries were excluded from the study. Patient's demographics like age, occupation, education level, and comorbidities like DM, HTN, and Vitamin D levels were sent to the institutional laboratory.
The patient's vitamin D profile along with the demographics was noted and entered in the study record sheet.
Data were entered into SPSS version 20.0. Quantitative variables like age, vitamin D level, the weight of the patient, height, and BMI were given as mean and standard deviation. Frequencies and percentages were expressed for qualitative variables i.e. marital status, residence background (rural/urban), menstrual phase (premenopausal /postmenopausal), cause of fracture (Fall/RTA), housing, clothing (Burqa/Abaya), occupation, educational level, comorbidities like DM, HTN, and Vitamin D sufficiency, insufficiency and deficiency.
Stratification was done to see the effect of the modifiers on the outcome variable. Poststratification Chi-square test was applied and, a pvalue < 0.05 was taken as significant.

Results
Out of 123 study subjects, 79.7 % were from urban areas, while 20.3 % were from rural areas. It was also observed that 63.4 % of study subjects were living in cemented houses while the rest of 36.6 % were living in non-cemented houses and, most of the females (84.6 %) were in the postmenstrual phase.
Around 62.6 % were of average weight, 33.3 % were overweight, and 4.1 % were obese. The mean duration of fracture was 12.27 ± 5.84 days, and the leading cause of fracture in most patients was Road Traffic Accidents (RTAs). DM was found in 47.2 % of patients, whereas 54.5 % were suffering from HTN. It was found that only 8.9 % of patients had sufficient vitamin D level, insufficiency was found in 28.5 % while 62.6 % of patients were observed with Vitamin D deficiency (Table 1).

Discussion
Vitamin D deficiency is common in the elderly, especially in patients with hip fracture. Older adults infrequently stay outside in the sunshine, and nutrition is deficient in vitamin D. Also, the hydroxylation of vitamin D into active metabolites decreases with age. Vitamin D deficiency ultimately leads to osteomalacia, but in an earlier stage, it causes secondary hyperparathyroidism, which is accompanied by increased bone turnover and cortical bone loss. Along with these pathways, vitamin D deficiency may contribute to the pathogenesis of hip fractures 19 .
Vitamin D supplementation is widely considered an essential therapy for preventing fracture, and use for this purpose is both widespread and recommended, with and without calcium [20][21][22] . A study showed that hypovitaminosis D is common in older patients presenting with hip fractures. In our study of patients with hip fracture, 62.6 % had vitamin D deficiency and 28.5 % had vitamin D insufficiency with only 8.9 % of patients with hip fracture having sufficient vitamin D levels which are almost similar to Ramason et al according to which 57.5 % had vitamin D deficiency and 34.5 % vitamin D insufficiency, with only 8 % of patients with hip fracture having sufficient vitamin D levels 14 . This is also comparable to deficiency and insufficiency levels found in Western patients with hip fracture 11,23,24 . The predominance of female patients with hip fractures also mirrors that seen in Western countries 25 & Ramason et al. study 14 . The finding that the housebound state carried a significantly greater risk of vitamin D deficiency compared to previously community ambulant elderly patients with hip fracture has also been previously reported 25 . This group of frailer housebound patients is more likely to have less sun exposure as they are not only confined indoors due to reduced physical activity but are also likely to have other risk factors, such as the reduced dietary source of vitamin D as well as coexisting illnesses (such as the liver and renal impairment) that could contribute to vitamin D deficiency.
Interestingly, patients with hip fracture previously residing in nursing homes before admission were not significantly associated with vitamin D deficiency. We postulate that the small sample size could explain this unexpected finding. A Turkish study had shown that patients living in old age homes had a higher risk of vitamin D deficiency than those living in their own homes. The same study found that clothing habits and exposure to sunlight were also associated with a higher risk of vitamin D deficiency 9 .
In the literature, we found the levels of vitamin D deficiency to be 90.5 % in Malay patients with hip fracture compared to 55% of Chinese and 61.1% Indian patients with hip fractures. Darker skin pigmentation is associated with low vitamin D levels, and the presence of genetic factors may have resulted in increased 24-hydroxylase activity in Indians. We postulate that this could be related to the religious-cultural practice of dressing style (long sleeves, headdress for Muslim-Malay females). This avoidance of sunlight by the Malays could account for the lower vitamin D levels. Similar findings of Malays being at greater risk of vitamin D deficiency than the Chinese were also shown in a recent study in Singapore by Hawkins 26 , although this was in a younger population. Studies have shown a high prevalence of vitamin D deficiency (49.4 %-100 %) in healthy young women in the Middle East despite abundant sunlight, and conservative clothing style has been identified as a risk factor 27,28 . This is an exciting finding that merits further study for vitamin D genetic polymorphisms, environmental factors, and clothing habits, accounting for the ethnic differences observed. In our study, clothing (Burqa/Abaya) was used by 43.1 % of females.
The actual definition of vitamin D deficiency is also not universally agreed upon, and cutoffs have been known to vary from 12 to 30 µg/L. The Institute of Medicine has defined serum vitamin D levels of 20 µg/L as adequate and less than 12 µg/L as deficient 29 . Holick and the Endocrine Society Clinical Practice Guideline has defined vitamin D deficiency as <20 µg/L and insufficiency as 21 to 29 µg/L 30 . In this study, we took <20 µg/L to be vitamin D deficient, which is also similar to Ramason et al. study 14 .
Hip fracture is the most severe outcome of osteoporosis and an important and increasing health problem. It is common amongst older individuals and is associated with significant morbidity and mortality. In 2000, an estimated 1.6 million hip fractures world-wide 31 and mortality in the year following a hip fracture was estimated at 20-30 % 32 . The social and economic burden of hip fractures worldwide is expected to increase significantly over the next 50 years due to aging populations, especially within developing countries [33][34][35] . Identification of interventions that can prevent hip fractures remains a key research priority, and vitamin D is an appealing therapy to fulfill this role.

Conclusion
This is an observational study and lacks randomization. The present study's main limitations include a single-center experience, a small sample size, and data collected from the urban environment only. Therefore, the results might not be generalizable to larger populations. In conclusion, this study confirms that vitamin D deficiency is common in elderly female patients with hip fractures and is associated with age and DM. This initial work warrants further larger-scale studies of vitamin D variations.

Conflicts of Interest
None.