https://orcid.org/0009-0003-5699-4577
Figures
Abstract
Background
Hip fractures are highly prevalent in the elderly, with intertrochanteric (IT) fractures of the femur constituting about half of the fractures in this region. We aimed to evaluate the levels of serum calcium and vitamin D in patients with stable or unstable IT fractures to study their contribution to the severity of IT fracture.
Materials and methods
Using a prospective cross-sectional design, we enrolled patients with IT fractures admitted to two referral orthopedic centers in 2022. Unstable IT fracture was defined as those with reverse obliquity or a trans-trochanteric pattern of fracture, a large or comminuted posteromedial fragment, and subtrochanteric extension of the fracture. Serum 25 (OH) vitamin D and calcium levels were the main study variables assessed by lab tests and compared among the two study groups: stable and unstable IT fractures.
Results
A total of 286 patients with a mean age of 70.5 ± 7.3 years and a female predominance (60.4%) were included in the final analysis. Among the patients, 139 (48.6%) had stable IT fractures, and 147 (51.4%) had unstable IT fractures. The mean serum level of vitamin D was significantly higher in the stable group (30.3 ± 7.0) compared to the unstable group (26.5 ± 6.1) (P-value = 0.007). Increasing age was associated with a decreasing level of serum vitamin D; however, the association was weak and not statistically significant (P-value = 0.319). The mean serum calcium level was higher among stable cases (8.6 ± 0.7) compared to unstable cases (8.4 ± 0.9); however, the difference was not statistically significant (P-value = 0.540). Vitamin D and calcium levels were almost similar among males and females.
Citation: Alijanpour K, Afzal S, Alijanpour A, Barati H, Gholinia H, Tavassoli M (2024) Analysis of serum vitamin D and calcium levels in elderly patients with stable and unstable intertrochanteric fractures: A multi-center prospective study. PLoS ONE 19(11): e0313023. https://doi.org/10.1371/journal.pone.0313023
Editor: Satabdi Mitra, KPC Medical College and Hospital, INDIA
Received: August 14, 2023; Accepted: October 17, 2024; Published: November 22, 2024
Copyright: © 2024 Alijanpour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: Data cannot be shared publicly because of legal restrictions. Data are owned by Ethics Committee of Babol University of Medical Sciences. Data are available from the Ethics Committee of Babol University of Medical Sciences (contact via research@mubabol.ac.ir) for researchers who meet the criteria for access to confidential data.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Hip fractures are one of the most prevalent types of fractures among the elderly, and with increasing life expectancy and aging populations globally, their incidence has shown an upward trend in recent decades [1]. While there are variations in the epidemiology of hip fractures based on geographical locations and population characteristics worldwide, the increasing trends have been concerning in nearly all countries and regions [2]. Intertrochanteric (IT) fractures of the femur constitute approximately half of the hip fractures in the elderly population, who are vulnerable to frailty, osteoporosis, and a higher risk of falls [3, 4]. In addition to the clinical epidemiology and burden, IT fractures also account for almost half of the economic burden associated with hip fractures, posing a significant strain on healthcare systems and patients affected by this injury [5]. These fractures present various challenges, particularly unstable fractures, which are associated with higher post-operative complications such as non-union, leading to increased mortality and morbidity rates [6]. Unstable IT fractures generally refer to those with a reverse obliquity or trans-trochanteric pattern of fracture, a large or comminuted posteromedial fragment, and subtrochanteric extension of the fracture [7].
The management of IT fractures involves various surgical methods, including intramedullary nails and sliding hip screws, each with its advantages and disadvantages [8]. A study from Iran reported high post-operative complications following the treatment of IT fractures in the elderly population, outcomes associated with factors including instability and the quality of the fractured bone undergoing fixation [9]. Investigations into the factors associated with the incidence and outcomes of IT fractures have led researchers and clinicians’ attention to serum elements contributing to bone health, which may determine the severity of fractures and the success of surgical treatment [10]. Among these elements, vitamin D and calcium play pivotal roles in bone health through various pathophysiological pathways, and studies suggest that appropriate supplementation with these elements can prevent hip fractures and facilitate fracture union [10–12].
Previous literature has examined the association between serum levels of vitamin D and calcium and the severity of hip fractures, indicating that lower serum calcium levels and deficient or insufficient serum vitamin D levels are associated with more severe hip fractures [13, 14]. This finding has prompted consideration of vitamin D supplementation alongside calcium to prevent severe osteoporotic hip fractures in the elderly [14]. However, evidence on the severity of IT fractures, particularly stable and unstable types, is limited, with available literature reporting an association between low vitamin D and calcium levels and unstable IT fractures [15–17]. Nevertheless, these findings are based on small sample sizes and retrospective study designs, making definitive conclusions challenging [15, 16]. Therefore, we designed a study to analyze serum levels of vitamin D and calcium among patients with IT fractures at two referral orthopedic surgery centers in Iran, aiming to investigate the association between serum levels of these elements and the stable or unstable types of IT fracture. The findings of this study may contribute to the existing body of evidence on vitamin D and calcium supplementation in the elderly to prevent severe fragility fractures in this vulnerable population.
Materials and methods
Study design and population
This study was designed as a prospective cross-sectional investigation on patients with IT fractures admitted to two referral orthopedic centers, namely Shahid Yahya Nezhad Hospital and Shahid Beheshti Hospital, both affiliated with Babol University of Medical Sciences in Babol, Iran, during the period from January 1st to December 31st, 2022. Inclusion criteria comprised individuals aged over 55 years with any type of IT fracture, including both stable and unstable cases, admitted to the study centers during the specified timeframe. Exclusion criteria encompassed patients with femoral head or neck fractures, those who did not provide informed consent, individuals with laboratory test failure, and patients diagnosed with neurological, psychiatric, or metabolic diseases due to their potential impact on surgical and treatment outcomes and the bone healing process. Unstable IT fractures were characterized by reverse obliquity or a trans-trochanteric pattern of fracture, a large or comminuted posteromedial fragment, and subtrochanteric extension of the fracture [6, 7]. The required sample size for this study was determined to be 300 cases of IT fractures. Quota sampling was used to select participants, equally distributing them between stable and unstable fracture categories based on the prevalence of this fracture type in Iran [18].
Data collection and study variables
Data collection for this study involved the enrollment of patients based on the inclusion criteria at the time of admission, with laboratory values assessed in the pre-operative stage. The main study variables were serum vitamin D and calcium levels, assessed by drawing 5 cc of venous blood and separating serum by centrifugation after coagulation of the blood cells. The 25 (OH) Vitamin D level was determined using an ELISA kit produced by Ideal Tashkhis Atieh Company (Iran), with a normal value range defined as 30–70 ng/ml. Serum total calcium was assessed using the Arsenazo III calcium-sensitive dye and photometric method by the Pars Azmoon kit (Iran), with the normal range for its value defined as 8.6–10.3 mg/dl. Patients’ age and sex were demographic variables used to compare study outcomes across different stratifications based on the type of IT fracture (stable/unstable).
Statistical analysis
Quantitative variables were presented as mean with standard deviation (±SD), while qualitative variables were summarized in terms of frequency and percentages. The associations between different categorical and quantitative variables were assessed using the chi-squared test and independent samples T-test. Pearson correlation coefficient was employed to evaluate the degree of association between two quantitative variables. To ensure the robustness of the study findings, a post-hoc power analysis was conducted based on the mean values of serum levels of vitamin D and calcium as continuous endpoints of the study, with the sample size distributed across two study groups as the two independent samples, and considering a type I error of 0.05. A P-value <0.05 was deemed statistically significant for all tests conducted. Data analysis was performed using IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; Armonk, NY: IBM Corp.).
Ethical considerations
This study obtained ethical approval from the ethical committees at Babol University of Medical Sciences, Babol, Iran (IR.MUBABOL.REC.1400.211). All patients provided informed written consent before participating in the study and agreed to the publication of results. Study investigators were dedicated to safeguarding the privacy of patients throughout the process of data collection, analysis, and reporting.
Results
General findings
A total of 300 patients with IT fractures were initially enrolled for this study. However, 14 patients were excluded due to pre-determined exclusion criteria, resulting in a final sample size of 286 patients included in the analysis. Among these patients, 173 (60.4%) were female, while 113 (39.6%) were male. The mean age of the patients was 70.5 ± 7.3 years. In terms of fracture pattern, 139 (48.6%) were classified as stable IT fractures, while 147 (51.4%) were categorized as unstable IT fractures (Table 1).
Vitamin D and calcium assessments
The mean serum vitamin D level was significantly higher in the stable group (30.3 ± 7.0) compared to the unstable group (26.5 ± 6.1), with the difference reaching statistical significance (P-value = 0.007). Vitamin D levels were similar between males (28.7 ± 6.7) and females (28.2 ± 6.8) (P-value = 0.727). Increasing age was weakly associated with a decrease in serum vitamin D levels; however, this association was not statistically significant (Pearson correlation coefficient: -0.106, P-value = 0.319).
Regarding serum calcium levels, the mean level was higher in stable cases (8.6 ± 0.7) compared to unstable cases (8.4 ± 0.9), but the difference was not statistically significant (P-value = 0.540). Calcium levels were also similar between males (8.4 ± 0.8) and females (8.3 ± 0.9) (P-value = 0.417). The association between age and serum calcium level was weak and inversely related but not statistically significant (Pearson correlation coefficient: -0.038, P-value = 0.722) (Fig 1).
Power analysis
The post-hoc power analysis revealed a power of 99.8% for the results of vitamin D, which exhibited a significant difference between study groups, and 55.7% for the results of calcium, showing non-significant differences between study groups. However, it is important to acknowledge that post-hoc power analysis has limitations and should be interpreted cautiously. While it offers insights into the adequacy of sample size and the likelihood of detecting significant effects, it is not considered the best practice for assessing the strength of a study.
Discussion
This study investigated the levels of serum vitamin D and calcium and their association with the severity of IT fractures. The findings indicated significantly higher levels of vitamin D in patients with stable IT fractures compared to unstable cases. Although calcium levels were also higher in stable cases with IT fractures, the difference did not reach statistical significance. Additionally, age and sex were not notable predictors of the type of IT fractures regarding the assessed biomarkers in this study.
The findings presented in this study were comparable to similar literature. In a retrospective study on IT fractures in patients aged ≥60 years, including 21 cases of stable fracture and 36 cases of unstable fracture, with an overall mean age of 81.93 ± 9.58 years and females comprising 71.9% of the patients, the level of 25 (OH) vitamin D was significantly higher in the stable group (27.01 ± 15.75) compared to the unstable group (17.52 ± 8.65) (P-value = 0.010), which was similar to our study. However, in that investigation, the calcium level was also remarkably higher in the stable group (8.48 ± 0.45) rather than the unstable cases (8.19 ± 0.43) (P-value = 0.019), which was different from our findings [15].
Another cross-sectional study that included 114 patients with IT fractures, with 47.7% of them being male and an average age of 66 ± 16.67 in males and 71 ± 14.29 in females, categorized the IT fractures based on the Boyd & Griffin classification into four types. The results indicated a strong statistical association between the degree of vitamin D deficiency and the type of IT fracture based on the assumed classification [16]. In the mentioned study, different levels of vitamin D deficiency were observed in type Ⅱ fractures followed by type Ⅲ fractures; for example, severe vitamin D deficiency was only observed in these two types, with 66.7% of them having type Ⅱ fractures and 33.3% having type Ⅲ fractures [16].
In a series of 196 hip fracture cases, including 101 with femoral neck fractures and 95 cases with femoral IT fractures, female patients constituted the dominant proportion in both groups, comprising 80.20% of the first group and 57.89% of the second group. The mean age of patients with femoral neck fractures was 73.85 ± 11.88, and for the IT group, it was 76.27 ± 11.93. Serum calcium levels were assessed at the time of admission, post-operation, and discharge. The results indicated significantly higher values among patients with femoral neck fractures compared to IT cases in the admission (2.19 ± 0.12 vs. 2.13 ± 0.15, P-value = 0.002) and discharge phases (2.15 ± 0.13 vs. 2.10 ± 0.16, P-value = 0.019), but not in the post-operation assessment (2.01 ± 0.12 vs. 2.01 ± 0.14, P-value = 1.000) [17]. The authors of this study suggested that serum calcium preservation and restoration in patients with femoral neck fractures might be better than those with IT fractures based on their findings, and they proposed that low serum calcium might predispose patients to femoral IT fractures [17].
Other studies related to the theme of our investigation were found to compare the findings with a wider scope of patients, mostly focused on overall patients with hip fractures [13, 14, 19–22]. A recent prospective study on an elderly population aged > 50 years, which included 120 patients with a male dominance of 56.7%, found the most common type of fracture to be IT fracture (59.2%), followed by femoral neck fracture (29.2%) and subtrochanteric fracture (11.7%). The study assessed levels of serum calcium and vitamin D based on different types of hip fractures and their severity. The authors concluded that the more deficient the calcium and the more deficient/insufficient the vitamin D level, the more severe type of fracture was observed in each location [13]. The study found the mean level of serum calcium to be 8.83 mg/dl and vitamin D to be 21.85 ng/dl among patients with IT fractures, with a decreasing pattern of both biomarkers observed from type Ⅰ to Ⅳ of the Boyd & Griffin classification, with overall significant differences (P-value = 0.001) [13].
A cross-sectional study of 324 patients aged > 65 years, with a mean age of 83 ± 7 years and a female predominance (80%), found that vitamin D deficiency was more frequent and severe in patients with severe femoral neck fractures (Garden III–IV types) and IT fractures (Kyle III–IV) compared to those with less severe fractures (frequency: 74% vs. 57%, 25 (OH) vitamin D3 level: 20 ± 15 vs. 26 ± 21) [14]. The investigators of that study suggested vitamin D supplementation in the elder population to prevent severe femoral neck and IT fractures, as the reported findings were indicative of an association between vitamin D deficiency and the severity of osteoporotic hip fractures [14].
A study on the prevalence of vitamin D deficiency in Asian-Indian patients with fragility hip fractures reported a high prevalence, with 96.7% having vitamin D deficiency, and found significantly lower bone mass density (BMD) in these patients compared to age- and sex-matched healthy controls [19]. Another investigation on 1319 subjects aged 65–88 years old revealed overall higher BMD values in groups with higher serum 25 (OH) vitamin D levels and suggested a cut-off of 50–60 nmol/liter for this element, where values higher than this range might be associated with improved bone health and physical activity [20]. In a prospective study on 360 patients with fragility hip fractures, with a mean age of 84.7 ± 8.2 years and mostly being female (77.8%), vitamin D was insufficient (<30 ng/mL) in 93.9% and deficient (<20 ng/mL) in 7.17% of the patients, with the values of serum 25 (OH) vitamin D being higher in the younger population [21].
Vitamin D deficiency might be associated with lower BMD, which is important in the prevention of fragility fractures of the hip [23]. However, it is proven in the literature that vitamin D supplementation in the prevention of hip fractures risk is only effective if calcium supplementation is prescribed for patients [10, 11, 24]. Additionally, low vitamin D serum levels have been associated with an increased risk of non-orthopedic complications in patients with hip fractures, including the risk of delirium, refractures of the hip, and readmissions due to other medical complaints [12]. Compiling the findings of the referred studies could suggest vitamin D supplementation as a preventive measure against fragility fractures and more severe types of fractures, specifically in IT fractures as a common type of hip fracture with a high burden in the elder population (Table 2).
In addition to reducing the incidence of intertrochanteric fractures as reported in the literature, our findings indicate that adequate vitamin D levels can mitigate fracture severity and the risk of unstable fractures. Therefore, screening and maintaining normal vitamin D levels through supplementation is crucial.
The current study had some limitations. Lack of multiple assessments of serum calcium and vitamin D levels, lack of evaluation of other related biomarkers like parathyroid hormone, lack of data on patients’ comorbidities and drug histories. Additionally, the study’s limitations were compounded by the non-random selection of patients and its conduct in only two centers, which could have introduced laboratory variations and biases into the results. On the other hand, this study had major strengths and achievements as it was among the first efforts to study this notion in Iran and via a multicenter design. Future similar studies are suggested to validate the findings of this study and provide evidence for future possible trials to prove the efficacy and safety of calcium and vitamin D supplementation for the prevention of severe hip fractures, including IT fractures. Regarding the potential of serum vitamin D and calcium supplementation for IT fracture prevention, further research is warranted to explore this aspect comprehensively. However, our study lays a foundation for future investigations in this area.
Conclusions
Findings of this study showing higher levels of serum calcium and vitamin D in patients with stable IT fractures compared to unstable cases suggest these two elements as possible effective and protective agents against more severe IT fractures, as a common type of hip fractures.
References
- 1. Marks R. Hip fracture epidemiological trends, outcomes, and risk factors, 1970–2009. Int J Gen Med. 2010;3:1–17. pmid:20463818
- 2. Rapp K, Büchele G, Dreinhöfer K, Bücking B, Becker C, Benzinger P. Epidemiology of hip fractures: Systematic literature review of German data and an overview of the international literature. Z Gerontol Geriatr. 2019;52(1):10–6.
- 3. Ahn J, Bernstein J. Fractures in brief: intertrochanteric hip fractures. Clin Orthop Relat Res. 2010;468(5):1450–2. pmid:20195807
- 4. Nieves JW, Bilezikian JP, Lane JM, Einhorn TA, Wang Y, Steinbuch M, et al. Fragility fractures of the hip and femur: incidence and patient characteristics. Osteoporos Int. 2010;21(3):399–408. pmid:19484169
- 5. Adeyemi A, Delhougne G. Incidence and Economic Burden of Intertrochanteric Fracture: A Medicare Claims Database Analysis. JB JS Open Access. 2019;4(1):e0045. pmid:31161153
- 6. Babhulkar S. Unstable trochanteric fractures: Issues and avoiding pitfalls. Injury. 2017;48(4):803–18. pmid:28284469
- 7. Knobe M, Gradl G, Ladenburger A, Tarkin IS, Pape HC. Unstable intertrochanteric femur fractures: is there a consensus on definition and treatment in Germany? Clin Orthop Relat Res. 2013;471(9):2831–40. pmid:23389806
- 8. Werner BC, Fashandi AH, Gwathmey FW, Yarboro SR. Trends in the management of intertrochanteric femur fractures in the United States 2005–2011. Hip Int. 2015;25(3):270–6. pmid:25907393
- 9. Sarrafan M, Nasser , Dashtbozorg M, Ahmad , Mehdinassab M, Seyed Abdolhossein, Afshin Azma M. Outcome of Surgical Fixation of Intertrochanteric Hip Fracture. Iranian Journal of Orthopedic Surgery. 2020;8(1):9–13.
- 10. Nowson CA. Prevention of fractures in older people with calcium and vitamin D. Nutrients. 2010;2(9):975–84. pmid:22254066
- 11. Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab. 2007;92(4):1415–23. pmid:17264183
- 12. Ingstad F, Solberg LB, Nordsletten L, Thorsby PM, Hestnes I, Frihagen F. Vitamin D status and complications, readmissions, and mortality after hip fracture. Osteoporos Int. 2021;32(5):873–81. pmid:33201249
- 13. Hublikar AA, Nayak AR, Kenganal PB, Kulkarni S, Bagewadi RM, K BM, et al. Association of Serum Vitamin-D and Calcium Levels With the Severity of Hip Fragility Fractures in the Elderly: A Prospective Study. Int J Acad Med Pharm. 2023;5(3):1697–702.
- 14. Larrosa M, Gomez A, Casado E, Moreno M, Vázquez I, Orellana C, et al. Hypovitaminosis D as a risk factor of hip fracture severity. Osteoporos Int. 2012;23(2):607–14. pmid:21394494
- 15. Hwang S-M, Hwang S-H, Kim Y-H. Association of Serum Vitamin D and Calcium Levels With the Severity of Intertrochanteric Fractures in the Elderly: A Retrospective Study. ResearchSquare. 2020.
- 16. Jamal AB, Hasan Khan MN, Sadiq M. Intertrochanteric Hip Fractures And Vitamin D Deficiency; A Significant Association. J Ayub Med Coll Abbottabad. 2021;33(2):257–61. pmid:34137541
- 17. Li PF, Lin ZL, Pang ZH, Zeng YR. Does serum calcium relate to different types of hip fracture? A retrospective study. Chin J Traumatol. 2016;19(5):275–7. pmid:27780507
- 18. Maharlouei N, Khodayari M, Forouzan F, Rezaianzadeh A, Lankarani KB. The incidence rate of hip fracture in Shiraz, Iran during 2008–2010. Arch Osteoporos. 2014;9:165. pmid:24424876
- 19. Khadgawat R, Brar KS, Gahlo M, Yadav CS, Malhotra R, Guptat N, et al. High prevalence of vitamin D deficiency in Asian-Indian patients with fragility hip fracture: a pilot study. J Assoc Physicians India. 2010;58:539–42. pmid:21391372
- 20. Kuchuk NO, Pluijm SM, van Schoor NM, Looman CW, Smit JH, Lips P. Relationships of serum 25-hydroxyvitamin D to bone mineral density and serum parathyroid hormone and markers of bone turnover in older persons. J Clin Endocrinol Metab. 2009;94(4):1244–50. pmid:19158198
- 21. Niikura T, Oe K, Sakai Y, Iwakura T, Fukui T, Nishimoto H, et al. Insufficiency and deficiency of vitamin D in elderly patients with fragility fractures of the hip in the Japanese population. J Orthop Surg (Hong Kong). 2019;27(3):2309499019877517. pmid:31554468
- 22. Vellingiri K, Ethiraj P, S NJ, Shanthappa AH, J KS. Assessment of Vitamin D Levels and Its Correlation With Osteoporosis and Fracture Site Comminution in Osteoporotic Hip Fractures in Tertiary Care Hospital. Cureus. 2021;13(1):e12982. pmid:33654639
- 23. Alkhenizan A, Mahmoud A, Hussain A, Gabr A, Alsoghayer S, Eldali A. The Relationship between 25 (OH) D Levels (Vitamin D) and Bone Mineral Density (BMD) in a Saudi Population in a Community-Based Setting. PLoS One. 2017;12(1):e0169122. pmid:28046015
- 24. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. Jama. 2005;293(18):2257–64. pmid:15886381