|Year : 2022 | Volume
| Issue : 3 | Page : 173-179
Vitamin D deficiency in proximal femur fractures: An observational, cross-sectional study
Utkarsh Singh, Punit Tiwari, Navneet Singh, Guncha Kalia, Bhupinder Singh Brar
Department of Orthopaedics, Maharishi Markandeshwar Medical College and Hospital, Solan, Himachal Pradesh, India
|Date of Submission||22-Mar-2022|
|Date of Decision||28-Jun-2022|
|Date of Acceptance||07-Jul-2022|
|Date of Web Publication||1-Sep-2022|
Department of Orthopaedics, Maharishi Markandeshwar Medical College and Hospital, Kumarhatti, Solan, Himachal Pradesh
Source of Support: None, Conflict of Interest: None
Introduction: A proximal femur fracture is the most serious complication of osteoporosis, due to the high mortality and morbidity associated with it. Its risk in the elderly is a function of multiple factors, including bone mineral density, muscle strength, and balance, all of which have been related to Vitamin D status and function. Materials and Methods: This was a prospective hospital-based study conducted over 2 years in the hilly state of Himachal Pradesh, India, to evaluate any correlation between Vitamin D levels and proximal femur fractures (PFFs). We also studied the influence of age and sex on Vitamin D levels in PFFs. Results: In our study, the female patients had lower Vitamin D levels (19.85 ± 5.28) as compared to males (20.436 ± 9.36), but this decrease was not found to be statistically significant (P = 0.2374). There was an average decrease of Vitamin D levels in patients of higher age group (20.770 ± 6.57 vs. 19.692 ± 8.40), but this was not statistically significant (P = 0.613). Thirty-four patients, i.e., 68%, had hypocalcemia, while 16 patients, i.e., 32%, had normal levels of serum calcium. Similarly, 30 patients, i.e., 70%, had hypomagnesemia, while 20 patients, i.e., 40%, had normal serum magnesium levels. The mean level of alkaline phosphatase in PFF was found to be 116.36 IU/L, i.e., within normal limits. The average Vitamin D level in our patients who were adequately exposed to sunlight was 22.5 ± 8.80 ng/ml, while the average Vitamin D level in patients who were inadequately exposed was 16.925 ± 5.98 ng/ml. The mean Vitamin D levels in vegetarian and nonvegetarian patients were 19.17 ± 6.05 ng/ml and 19.83 ± 9.56 ng/ml, respectively. We found that vitamin levels were relatively low (19.46 ng/dL) in patients from high altitudes as compared to patients from low altitudes (22.62 ng/dL), but the difference was insignificant (P = 0.3925). Conclusion: In our study, almost all patients (96%) were suffering from hypovitaminosis D (Vitamin D levels <30 ng/ml), and 38% of our patients had Vitamin D deficiency (Vitamin D levels <20 ng/ml). However, we were unable to find any significant difference in Vitamin D levels when patients of various ages, sex, and altitude were compared with each other.
Keywords: Osteoporosis, proximal femur fracture, Vitamin D
|How to cite this article:|
Singh U, Tiwari P, Singh N, Kalia G, Brar BS. Vitamin D deficiency in proximal femur fractures: An observational, cross-sectional study. J Orthop Dis Traumatol 2022;5:173-9
|How to cite this URL:|
Singh U, Tiwari P, Singh N, Kalia G, Brar BS. Vitamin D deficiency in proximal femur fractures: An observational, cross-sectional study. J Orthop Dis Traumatol [serial online] 2022 [cited 2022 Dec 3];5:173-9. Available from: https://jodt.org/text.asp?2022/5/3/173/355244
| Introduction|| |
Fracture of the proximal femur is the most serious complication of osteoporosis, due to the high mortality and morbidity associated with it, as well as the significant social, economic, and welfare cost it warrants. These types of fractures continue to be the most common reason for admission to the orthopedics ward. A majority of these patients (90%) are aged above 50 years and most of these fractures are a result of low-energy trauma. The incidence of proximal femur fractures (PFFs) is 2–3 times more in females as compared to the male population. It has been projected that with the rise in the aging population, the incidence of these fractures will rise. Pertrochanteric and neck of femur (NOF) fractures together account for 90% of the PFF and the remaining 5%–10% are subtrochanteric (ST) fractures.
PFF secondary to bone fragility have been correlated with a significant reduction in independence and the mortality rates relating to it are very high and may range from 14% to 47% over the 1st year after their occurrence. NOF fractures and pertrochanteric fractures account for almost equal incidence and together account for about 90% of the PFFs and the remaining are subtrochanteric fractures.
Proximal femur fracture risk in the elderly is a function of multiple factors, including bone mineral density (BMD), muscle strength, and balance, all of which have been related to Vitamin D status and function. Osteoporosis is characterized by a decrease in bone mass with increasing age, which further contributes to the decrease in bone strength. It is biologically reasonable that slowing the progressive bone loss by the use of Vitamin D and calcium supplementation may reduce the fracture rates. There is probably a consistent relationship between neuromuscular function and Vitamin D plasma concentrations. Patients who have lower Vitamin D levels have a slower walking time and often take a long time to stand up.
It has been shown that elderly people with a low dietary intake of calcium and Vitamin D, low cutaneous production of Vitamin D, and reduced renal production of calcitriol (1,25(OH) 2 D) may be at risk of falls and fractures owing to myopathy caused by Vitamin D deficiency (VDD) and secondary hyperparathyroidism. Vitamin D is crucial for intestinal calcium absorption and for maintaining calcium homeostasis and skeletal integrity. It has been also studied that VDD and low calcium cause long-standing secondary hyperparathyroidism, which leads to increased bone turnover causing osteoporotic fractures.
Because of the correlation of PFFs with osteoporosis, and the implication of deficiency of Vitamin D in the prevention of osteoporosis, it was decided to conduct a study with an aim to study the Vitamin D levels in PFFs.
The objectives set were:
- To evaluate any correlation between Vitamin D levels and PFFs and compare this to historical controls
- To study the influence of age and sex on Vitamin D levels in PFFs
| Materials and Methods|| |
This hospital-based study was conducted in the orthopedics department of a medical college situated in the hilly state of Himachal Pradesh, India, over 2 years (from 2019 to 2021).
It was a prospective study conducted on the 50 consecutive patients who suffered proximal femur fracture and were willing to undergo study and fulfilled the inclusion and exclusion criteria and reported to the emergency and outpatient department of the orthopedics department.
Fifty consecutive patients who suffered a proximal femur fracture, who fulfilled the inclusion and exclusion criteria, and who reported to the department of orthopedics were included in the study. Patients were interviewed after checking their suitability as per the inclusion and exclusion criteria irrespective of their religion, income, occupation, socioeconomic status, and place of residence.
The study was conducted according to the Good Clinical Practice guidelines (an Amended version of Schedule Y, 2005, Declaration of Helsinki, International Conference on Harmonization – Good Clinical Practice, and Indian Council of Medical Research guidelines on research on human subjects, 2006) after permission of the institutional ethical committee. The ethics committee reviewed the protocol in view of the rights, safety, well-being, health state, adverse event management, and confidentiality of study subjects (enrolled patients).
All patients with proximal femur fractures which included the following:
- Intertrochanteric fractures
- Subtrochanteric fractures
- Fractures of the neck of the femur including pertrochanteric, subcapital, and transcervical fractures.
The above could be:
- Patients of either sex
- Patients above 50 years of age
- Patients willing to undergo study
- Patients of any religion.
- Patients not giving consent
- Subjects suffering from various diseases affecting the proximal femur bone health such as malignancy, metastasis, rheumatoid arthritis, and osteoarthritis hip
- Patients with active infections
- Patients suffering from secondary osteoporosis
- Patients below 50 years of age
- Patients who were not ambulant before the fracture.
All patients who sustained a proximal femur fracture were initially placed on skin traction and given pain relief for the alleviation of their symptoms. Subsequently, all these patients were worked up for surgery including routine blood count, urine analysis, electrocardiogram, X-ray chest, echocardiogram, and pulmonary functions wherever applicable. Blood samples were also drawn for the evaluation of the patient's Vitamin D levels as elucidated in the technique below. Additional samples were also sent for the evaluation of serum calcium, serum magnesium, phosphate, and alkaline phosphatase.
- Patients were primarily divided into two groups, male and female, and Vitamin D levels were compared between the two sexes to seek any correlation between Vitamin D levels, PFFs, and gender
- Patients have also been divided additionally into two groups, one between 50 and 64 years of age and another above 64 years of age. Vitamin D levels between these two groups were also compared to observe if age had any correlation to Vitamin D levels
- Patients were also distributed into three groups according to their socioeconomic status based on the Kuppuswamy socioeconomic status scale
- Patients were also assessed according to their sun exposure. According to Food and Agriculture Organization/World Health Organization, expert consultation patients were divided into two groups (adequately exposed and inadequately exposed).
Method of Vitamin D estimation
Chemiluminescence immunoassay of Vitamin D estimation
At our facility, Vitamin D testing is carried out using chemiluminescence immunoassay (CLIA) technology in a fully automated analyzer, Advia Centaur. CLIA is a quantitative immunoassay method used for the determination of 25(OH) D in serum or plasma on a fully automated platform.
Kuppuswamy socioeconomic scale
The modified Kuppuswamy scale is commonly used to measure socioeconomic scale in urban and periurban communities.
- Nominal data (such as gender and complications) were presented as numbers and percentages
- Continuous data (such as age, alkaline phosphatase, and Vitamin D) were expressed as mean, standard deviation, and range
- Unpaired t-test was applied as appropriate for comparison of nominal data
- P ≤ 0.05 was considered statistically significant.
Limitations of the study
- Small sample size and time constraint. A larger number of patients may have given the better strength of association.
- Age, dietary history, compliance, and intersubject variability may be confounding factors.
| Results|| |
Out of the total of 50 patients above 50 years of age suffering from PFFs, 31 (62%) patients were above 64 years of age, whereas the remaining were between 50 and 64 years of age. Our study was designed to evaluate the relationship between Vitamin D and osteoporosis. We recruited an equal number of consecutive male and female (25 each) patients with PFF for this study to obviate any selection bias. We found 48 of our patients to have abnormal Vitamin D levels, i.e., 96% of the total number of patients. Out of them, 23 of our patients had a deficiency of Vitamin D (38%) and 23 had insufficiency (58%).
The distribution of the total number of patients with proximal femur fracture as per their sex and Vitamin D level is summarized in [Table 1]. In our study, the female patients had lower Vitamin D levels (19.85 ± 5.28) as compared to males (20.436 ± 9.36), but this decrease was not found to be statistically significant (P = 0.2374). There was an average decrease of Vitamin D levels in patients of higher age group (20.770 ± 6.57 vs. 19.692 ± 8.40), but this was not statistically significant (P = 0.613).
|Table 1: Distribution of the total number of patients with proximal femur fracture as per their sex and Vitamin D level|
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Out of 50 study participants, 34 patients, i.e., 68%, had hypocalcemia, while 16 patients, i.e., 32%, had normal levels of serum calcium. Similarly, 30 patients, i.e., 70%, had hypomagnesemia, while 20 patients, i.e., 40%, had normal serum magnesium levels. [Figure 1] depicts the number of patients with PFFs as per their serum magnesium levels. The distribution of patients with proximal femur fracture according to their serum calcium levels is shown in [Figure 2] and according to their levels of alkaline phosphatase [Figure 3]. The mean level of alkaline phosphatase in PFF was found to be 116.36 IU/L, i.e., within normal limits.
|Figure 1: Patients with proximal femur fractures as per their serum magnesium levels|
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|Figure 2: Patients with proximal femur fractures as per their serum calcium levels|
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|Figure 3: Estimation of alkaline phosphatase levels in patients with a proximal femur fracture|
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[Table 2] evaluates the average Vitamin D levels and standard deviation among patients with proximal femur fracture according to their sex, whereas [Table 3] demonstrates the average Vitamin D levels and their standard deviation in patients with proximal femur fracture according to the age groups. The average Vitamin D level in our patients who were adequately exposed to sunlight was 22.5 ± 8.80 ng/ml, whereas the average Vitamin D level in patients who were inadequately exposed was 16.925 ± 5.98 ng/ml.
|Table 2: Evaluation of average Vitamin D levels and standard deviation among patients with proximal femur fracture according to their sex|
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|Table 3: Evaluation of average vitamin D levels and their standard deviation in patients with proximal femur fracture according to the age groups|
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In our study, 70% of patients were vegetarians and only 30% of patients were nonvegetarians. The mean Vitamin D levels in vegetarians and nonvegetarian patients were 19.17 ± 6.05 ng/ml and 19.83 ± 9.56 ng/ml, respectively, as shown in [Table 4]. In our study, we found that vitamin levels were relatively low (19.46 ng/dL) in patients from high altitudes [Table 5] as compared to patients from low altitudes (22.62 ng/dL), but the difference was insignificant (P = 0.3925).
|Table 4: Distribution of patients with proximal femur fracture as per their diet|
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|Table 5: Evaluation of average Vitamin D levels and standard deviation among patients with proximal femur fracture according to altitude|
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| Discussion|| |
PFFs in the elderly are common in orthopedic practice. Most of them are associated with osteoporosis. VDD has been implicated in the causation of osteoporosis in these patients.
Vitamin D, a fat-soluble vitamin that also functions as a steroid hormone, is one of the necessary fat-soluble vitamins. Endocrine, paracrine, and autocrine actions are all present in it. Its primary purpose is to boost calcium absorption efficiency in the small intestine. As a result, it is critical for calcium homeostasis and bone health maintenance. As per literature, when Vitamin D levels are over 32 ng/ml, intestinal calcium absorption is at its peak, and when Vitamin D levels fall below 30 ng/ml, parathyroid hormone (PTH) levels begin to diminish. Therefore, a level of Vitamin D between 21 and 29 ng/ml is considered indicative of relative insufficiency, and a level >30 ng/ml is considered sufficient. Previous studies have shown that Vitamin D toxicity does not occur until the Vitamin D concentration is >150 ng/ml. Vitamin D is also necessary for the proper absorption of phosphates from the small intestine, which is essential for effective bone mineralization. The maturation of osteoclasts is the second important function of Vitamin D. It works by stimulating osteoblasts to generate receptor activator of nuclear factor kappa beta, as well as stimulating osteoclastogenesis and activating resting osteoclasts for calcium resorption from the bones. Further, in the presence of low calcium levels, there is an increase in serum PTH level, which promotes the tubular absorption of calcium in the kidneys and resorption from the bones at the cost of lowering BMD. In the long term, this leads to the weakening and softening of bones that break easily. As 40%–60% of the total bone mass is accumulated during childhood and adolescence, VDD during this period leads to rickets in children, and its chronic deficiency in adults results in osteomalacia, osteoporosis, and muscle weakness resulting in the increased risk of falls.
Despite being a tropical country and having abundant sunlight, VDD is common in India in both urban and semiurban Indians, pregnant females, postmenopausal women, school-going children, and even newborns.
VDD has been recognized as an important risk factor for the causation of osteoporotic fracture in almost every age group, especially in the elderly. In adults, its deficiency can either precipitate or aggravate osteopenia and osteoporosis and may also lead to osteomalacia, muscle weakness, and increased fracture risk. Studies by Lips and Delmas have suggested Vitamin D supplementation as a protective measure in the treatment of osteoporosis. People with VDD have characteristic muscle weakness, particularly in hip extensors, muscle pains, and disability in getting up and climbing stairs. In a study by Bischoff et al., it was stated that there is a significant correlation between Vitamin D levels in elderly persons of age >65 years and leg extensor power. It has been reported that VDD affects mainly the weight-bearing muscles of the lower limb, which are essential for walking and maintaining balance. Studies have shown that 90% of the PFFs are sustained due to a fall and Vitamin D status is associated with the risk of falling.
Elderly people are more prone to develop VDD because of various risk factors such as low dietary intake, inadequate sunlight exposure, reduced skin thickness, decreased intestinal absorption, and impaired hydroxylation in the liver and kidneys. Studies have stated that the cutaneous production of Vitamin D decreases with age due to the associated reduction in the 7-dehydrocholesterol concentration. Moreover, elderly people stay indoors for longer periods and have limited physical activity due to multiple comorbidities, leading to inadequate sun exposure. As seen in darker skin, the color of the skin also interferes with the cutaneous production of Vitamin D. Moreover, medications such as Dilantin, rifampicin, and phenobarbital can induce hepatic P450 enzymes which accelerate the catabolism of Vitamin D and thus lead to its deficiency. Other causes of VDD are a high fiber diet containing phosphates and phytates in diet, repeated and unplanned pregnancies in females, people suffering from hepatic, renal, dermatological disorders, alcoholics, and inflammatory rheumatological conditions, etc.
The first PFF study in India was undertaken by Dhanwal et al. In a study of 541 patients in Rohtak District (Haryana), they discovered that females aged 55 and above had a greater PFF incidence rate than males. However, they limited their study to incidence and Vitamin D levels have not been studied by them. O'Neill et al. found that women over the age of 50 were more than three times more likely than men of the same age to fall on their hip.
VDD causes softening, thinning, and brittleness of bones, leading to an increased incidence of fractures. Studies by Bischoff-Ferrari et al. have shown that hypovitaminosis D is commonly associated with PFFs in the elderly and they occur either due to decreased production or low dietary intake of Vitamin D. Replacement of Vitamin D has been used successfully to reduce such types of fractures and falls among the elderly. Vitamin D receptors are located on the fast-twitch muscle fibers, which are the first to respond in a fall. It is known that Vitamin D may increase muscle strength, thereby preventing falls. PFF risk in the elderly is a function of multiple factors including BMD, muscle strength, and balance, all of which have been related to Vitamin D status and function.
It will be more cost-effective to implement aggressive nationwide programs for Vitamin D supplementation and food fortification rather than testing Vitamin D levels individually, in such a huge population with a high prevalence of VDD. Mg is required for Vitamin D metabolism; therefore, consuming excessive dosages of Vitamin D can cause severe Mg depletion. Magnesium supplementation should be regarded as a critical component of Vitamin D therapy.
Our study shows that the incidence of PFF was higher in the elderly age group (more than 64 years of age) as compared to those between 50 and 64 years. In our study, to avoid any bias, we have taken an equal number of male and female patients.
Further, we have also distributed the patients according to the type of fracture they sustained. In our study of 50 patients with a PFF, 88% of patients sustained intertrochanteric (IT) and NOF fracture, while only 12% of patients presented with subtrochanteric fracture. Similar results were found by Gallagher et al. A study found that there is almost an equal incidence of NOF fracture and pertrochanteric fractures and these fractures together account for about 90% of the total PFF and the remaining 5%–10% were subtrochanteric fractures. In the current study, 66% of fractures were caused by a fall, and nearly all patients had low Vitamin D levels.
A study by Sharma et al. reported that postmenopausal women with fractures had low serum Vitamin D levels. In our study, there was a decrease in the average value of Vitamin D in females, but this was not statistically significant too (P = 0.2374). This may be due to the fact the number of patients in our series was less and probably more patients are required to increase the power of the study.
We had divided our patients into two age groups (50–64 years and >64 years) to evaluate if there is any correlation between age and Vitamin D levels in patients with PFFs. The statistically insignificant (P = 0.613) decrease of Vitamin D levels in patients of higher age group is similar to the results obtained by Guerra et al. who studied Vitamin D levels in 341 patients with PFF and distributed them according to different age groups. They found that there were no significant differences between the age groups regarding the serum levels of 25(OH) D for the age ranges of 60–65 years (P = 0.327), 66–70 (P = 0.417), and 76–80 (P = 0.095). Another study by Simonelli et al. reported that the mean Vitamin D levels in elderly patients with PFFs are low, but they were not significantly associated with the age and sex of the patients.
As most of the patients in our study presented within a week after they sustained a fracture, the average within normal limits level was not surprising. Hosking et al. in Nottingham found that alkaline phosphatase activity remained considerably unchanged before a week after a fracture. We found a significant relationship between sunlight exposure and average Vitamin D levels (P = 0.0142). Alagöl et al. have also found similar results and they concluded that there is increased subclinical VDD in participants who wear concealed clothing.
The percentage of hypocalcemia and hypomagnesemia in PFFs of our study was about 70%, which is quite similar to Hoikka et al. Statistically insignificant (P = 0.775) difference of Vitamin D levels between the vegetarian and nonvegetarian participants of our study is not in concordance with an EPIC-Oxford study which had reported that vegetarians had the lowest mean intake of Vitamin D (0.88 μg/dl), a value one-fourth the mean intake of omnivores.
The overall observations of our study match with other studies conducted upon Indian population. About three-fourths of hip fracture patients had VDD in the study by Dhanwal et al. A pilot study conducted at PGIMER Chandigarh found the high prevalence of VDD (74.2%) and osteoporosis in patients with fragility fractures of hip. Khadgawat et al. at AIIMS New Delhi too found the very high prevalence (96.7%) of VDD in Asian-Indian patients with fragility hip fracture. The sample size of these studies done at PGIMER (66 patients) and AIIMS (43 patients) was comparable to ours.
As our study was time bound, we had a few limitations. The sample size was small and this was a single-center study, the results of which cannot be extrapolated to the entire population.
| Conclusion|| |
In our study of 50 consecutive patients with PFF and age above 50 years, almost all patients (96%) were suffering from hypovitaminosis D (Vitamin D levels <30 ng/ml), and 38% of our patients had VDD (Vitamin D levels <20 ng/ml). However, we were unable to find any significant difference in Vitamin D levels when patients of various ages (50–65 years vs. above 65 years), sex (male vs. female), and altitude (high vs. low) were compared with each other.
We acknowledge the help of all the participants of this study who spared some time and without whose cooperation this study could not have been completed. The role of our secretary Mrs. Poonam Chauhan was indispensable throughout the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]