Keywords vitamin D - vitamin D deficiency - osteoporosis - hip fractures - fracture healing
Introduction
The study of vitamin D (VIT D) and the consequences of its deficiency in the body
are relatively new topics, and they became known after the Industrial Revolution,
when the rural population migrated to the urban centers.
The main known function of VIT D is to keep calcium and serum phosphorus concentrations
within normal physiological limits to maintain most metabolic functions, neuromuscular
transmission, and bone mineralization. Most often, the changes due to VIT D deficiency
are subclinical.[1 ]
Hypovitaminosis D (HVD) leads to decreased mineralization of the bone matrix, which
can lead to rickets in childhood and osteomalacia in adults, as well as worsening
of cases of osteoporosis. Vitamin D plays a fundamental role in the metabolic pathway of calcium, and its supplementation
is associated with increased bone mineral mass and the prevention of fractures. Fractures
due to osteoporosis result in high costs, with a treatment comparable to those for
cardiovascular diseases.[2 ]
Approximately one third of the world's population has levels of 25-hydroxyvitamin
D (25[OH]D) lower than 20 ng/mL, which may not be ideal to maintain good bone health.[3 ] There is evidence that HVD is the most common nutritional deficiency in the world.[4 ] Traditionally, Brazil was considered a place where there were no cases of HVD, because
it is a tropical, sunny country, with wide exposure of the population to the sun.
However, recent studies have demonstrated the lack of VIT D in the most diverse age
groups and places in the country.[5 ]
[6 ]
[7 ]
[8 ]
[9 ]
[10 ] Hypovitaminosis D, which plagues the world population and even Brazil may have occurred
due to changes in habits such as protection against the sun protection, the use of
sunscreen, the season of the year and lower exposure to the sun in cold regions, as
well as food shortages.
It is well established in the literature that HVD predisposes to bone fragility and
influences postural and dynamic balance, favoring the occurrence of fractures. However,
until the beginning of the present study, no studies on the dosage of VIT D in the
population of our region (the southern part of the state of Minas Gerais, Brazil)
had been found, nor studies on the influence of VIT D on the occurrence of fractures
in the Brazilian population. The aim of the present study was to measure the levels
of VIT D in fractured patients and evaluate its relationship with fractures.
Methods
A primary, analytical, cross-sectional, non-interventional, observational, controlled
study was conducted in humans. We consecutively selected 49 patients with fractures
(study group) (1 patient in the study group was excluded due to renal alteration)
with surgical indication, and 50 patients without fractures (control group), older
than 18 years of age, without any restrictions regarding color or gender, who agreed
to participate in the study. The patients in the study group were selected consecutively
to their hospitalization in the orthopedics and traumatology ward of our institution;
and the tests were collected along with routine preoperative blood tests. The patients
in the control group were selected from the outpatient clinics of the various specialties
in the same hospital, provided they had any outpatient indication of blood collection.
We excluded: patients hospitalized for more than 24 hours; undergoing VIT D replacement;
with endocrine, genetic or metabolic diseases capable of altering the normal metabolism
of VIT D (osteogenesis imperfecta, Paget disease); with acute or chronic renal failure;
with pathological fractures of neoplastic origin or under neoplastic treatment; with
malnutrition; with psychiatric eating disorders (bulimia and anorexia); those undergoing
bariatric surgery or bowel resection; those with small bowel diseases, biliary or
hepatic tract disease, and intestinal exocrine pancreatic insufficiency that interfere
with fat absorption (sprue, amyloidosis, etc.); and patients using medications that
hinder the resorption of fat (orlistat, cetilistat and the like).
All patients who spontaneously agreed to participate in the study signed a free and
informed consent form. The study was approved by the Ethics Committee under CAAE 94612618.6.0000.5102.
The patients were initially submitted to sociodemographic data collection, body weight
and height (in meters) measurements, and filled out a questionnaire on habits of protection
against the sun and smoking. Next, they were submitted to peripheral venous puncture
and blood collection for dosage of 25(OH)D, parathyroid hormone (PTH), total and ionized
serum calcium, phosphorus, magnesium and albumin. The 25(OH)D and PTH were dosed by
the chemiluminescence method. Hypovitaminosis was characterized according to the current
position of the Brazilian Society of Clinical Pathology and Laboratory Medicine (Sociedade
Brasileira de Patologia Clínica e Medicina Laboratorial, SBPC/ML, in Portuguese) and
the Brazilian Society of Endocrinology and Metabology (Sociedade Brasileira de Endocrinologia
e Metabologia, SBEM, in Portuguese).[11 ] Thus, evels of 25(OH)D > 20 ng/mL were considered the normal value for a healthy
population (aged up to 60 years); between 30 ng/mL and 60 ng/mL, the recommended value
for risk groups such as: elderly, pregnant women, osteoporosis patients, those with
a history of falls and fractures, and patients with secondary causes of osteoporosis
(diseases and medications); levels > 100 ng/mL were considered risk of intoxication.
The data were tabulated in Microsoft Excel 2016 (Microsoft Corp., Redmond, WA, US)
spreadsheets and submitted to statistical analysis. Central trend measurements were
used for the quantitative variables, and absolute and relative frequencies were used
for the categorical variables. The Minitab (Minitab, LLC, State College, PA, US) software,
version 18.1, and the Statistical Package for the Social Sciences (SPSS, IBM Corp.,
Armonk, NY, US) software, version 22.0, were used. The significance level adopted
for the statistical tests was of 5% (p < 0.05).
Results
The groups were similar in terms of body mass index (BMI), age and gender ([Tables 1 ] and [2 ]). In the study group, there were 15 (30.61%) elderly (aged > 60 years) patients,
and 14 of them (93.33%) had VIT D levels < 30 ng/mL. In the control group, there were
18 (36%) elderly people, and 5 of them (27.77%) had VIT D levels < 30 ng/mL.
Table 1
Group
N
Mean
Standard deviation
Minimum
Maximum
p
Age
Control
50
50.40
21.3
20
89
0.983
Study
49
50.30
21.5
18
90
Body mass index
Control
50
26.13
3.69
18.39
35.1
0.289
Study
49
27.10
5.19
18.13
45.49
Table 2
Group
Male
Female
Total
p
Study
31 (63%)
18 (37%)
49 (100%)
0.150
Control
25 (50%)
25 (50%)
50 (100%)
There was also a similarity between the skin color of the groups, which was predominantly
white in more than 80% of the population studied (82% of white subjects in the control
group, and 87.75% in the study group).
The groups also resembled each other in degree of skin protection, smoking and exposure
to the sun ([Table 3 ]).
Table 3
Protection against the sun
Control
Study
p
No
23
23
Sunscreen and/or clothing
27
26
1
Only sunscreen
0
0
Total
50
49
Smoking
Yes
10
12
No
40
37
0.483
Total
50
49
Exposure to the sun
Daily
37
32
Occasional
13
19
1
Total
50
49
The mean level of PTH of the control group was of 39 ( ± 23.70) pg/mL, and that of
the study group was pf 44.60 ( ± 21.80) pg/mL (VN = 18.5 pg/mL to 88 pg/mL). Evaluating
both groups, only two cases of hyperparathyroidism secondary to HVD were observed.
FA total of 54 fractures were observed in 49 patients, and 53.68% of them occurred
in the lower limbs ([Figure 1 ]). The mean level of 25(OH)D of the groups can be observed in Table [4 ]. In total, HVD was present in 30 (61.22%) patients with fractures (study group),
and in 5 (10%) patients in the control group.
Table 4
Groups
N
Mean (ng/mL)
Standard deviation
p
Study
49
23.78
8.01
0.00*
Control
50
37.52
9.21
Fig. 1 Distribution of fractures (low- and high-energy traumas).
The distribution of fractures according to the intensity of the energy of the trauma
is demonstrated in [Figure 2 ], and its relationship with the degree of sufficiency of 25(OH)D is shown in [Figure 3 ]. The correlation between HVD and the occurrence of fractures is found in [Table 5 ].
Table 5
N (STUDY + CONTROL)
Spearman r
p
99
0.668
0.00*
Fig. 2 Distribution of trauma energy (percentage of patients).
Fig. 3 Distribution of fractures according to trauma intensity and degree of vitamin D sufficiency
(Fischer exact test). Note: *Statistical significance.
Discussion
Studies, including Systematic reviews[12 ]
[13 ]
[14 ]
[15 ]
[16 ] evaluated the dosage of VIT D in fractures and evidenced the importance of HVD in
their occurrence (prevalence: between 40% and 100% of the cases).[12 ]
[13 ]
[14 ]
[15 ]
[16 ] In the present study, HVD was observed in 30 (61.22%) patients with fractures. There
was a statistically significant difference regarding the dosage of VIT D between the
groups, which enabled us to speculate that HVD was a facilitating agent for fractures
([Tables 4 ] and [5 ]). Most studies mainly evaluate the elderly and postmenopausal women, who are populations
at risk for osteoporosis;[7.9 ] therefore, these studies evaluate low-energy fractures, because they represent the
highest percentage of fractures.[12 ]
[13 ]
[16 ] Fractures resulting from low-energy trauma tend to be spontaneous, due to falls
from standing height, or to tortional mechanisms, and they mainly occur in the proximal
femur, distal radius and spine,[12 ]
[16 ]
[17 ] especially in the elderly, among whom an episode within their own home is frequent.
They are commonly unique lesions and are the ones that mostly require surgical treatment.[13 ] In studies that exclusively evaluated low-energy fractures, a higher frequency of
fractures of the proximal femur [12 ]
[16 ] or wrist was found.[15 ] The present study evaluated all fractures that arrived consecutively in the emergency
room, that is, low- and high-energy fractures, which were included in the study as
long as they had a surgical indication. On the one hand, this could be a limiting
factor of the present study, since fractures without surgical indication were not
catalogued; however, it venous punctures that for the exclusive purpose of the present
study were avoided. Low-energy fractures were also predominant in the present study
([Figure 2 ]), but, unlike other publications[12 ]
[15 ]
[16 ], the highest incidence of low energy fractures occurred in the ankles (8 cases;
14.81% of the fractures). This discrepancy may be justified by the fact that, in the
present study, unlike other studies[12 ]
[13 ]
[15 ]
[16 ], the male population composed most of the sample (63% of the cases), and also because
the mean age (50.30 years) was much lower than that found in other studies. Therefore,
the sample of the present study was composed of a majority of patients of the male
gender and of an age group in which proximal fractures of the femur are less frequent.
High-energy fractures are usually due to accidents that occur outside the home, such
as car accidents; they are less evaluated, but these patients also tend to have a
very high HVD index.[14 ] In the fractures caused by high-energy trauma in the present study, there were 29.41%
of cases of HVD ([Figure 3 ]).
Although the effect of VIT D on a fracture that already occurred is unknown and there
is no concrete evidence that VIT D accelerates the consolidation process, its effect
of increasing the vascularization of the bone callus,[18 ]increaseing bone strength and mineral density, as well as increasing the volume of
the bone callus, is undeniable.[10 ]
[14 ] In addition, a study reported[19 ] HVD in 83% of the cases of pseudarthrosis and consolidation delays.[19 ] In a retrospective study, Gorter et al.[15 ] evaluated 617 patients with fractures (40% of prevalence of HVD) and observed that
fracture consolidation was influenced by the status of VIT D at the time of the fracture.
It is customary that, in the case of fractures, the levels of VIT D fall sharply due
to their consumption in the focus of the fracture, especially if the initial level
is already low. This fall occurs between oneand three weeks after the fracture.[14 ] The initial levels of VIT D fall around 20% at the end of the first week.[20 ] This detail is considered a major factor in studies on HVD prevalence in fractures,
but a significant part of the studies[12 ]
[13 ]
[15 ]
[16 ] does not mention the exact moment the levels of 25(OH)D were assessed. In the prsent
study, this assessment occurred within 24 hours of the fracture. This detail also
has importance in order to supplement more rigorously the patient with HVD who suffers
a fracture.
Falls represent a marker of morbidity and mortality, especially in the elderly, and
in about 10% of the times they cause fractures.[21 ] In Brazil, osteoporosis mainly affects women from metropolitan regions.[22 ] There is a high prevalence of HVD, especially among the elderly. In the present
study, we observed that 93.33% of the elderly with fractures presented HVD. Fractures
resulting from falls, especially in the hip, lead to death in about 20% of the cases
and, in 50% of the non-fatal cases, they lead the elderly to become dependent.[23 ] The treatment of HVD in the elderly reduces falls by 20%, and in every 15 patients
treated, a fall is prevented.[24 ] Adequate levels of VIT D reduce the risk of fractures by 20%.[25 ] It was also observed that the associated use of VIT D and calcium decreased by 15%
the chance of developing fractures in general, and decreased hip fractures by 30%.[26 ]
The orthopedic surgeon should be prepared to recognize HVD and know how to track and
treat it, or give the patient a referral.[27 ] In the daily practice, patients who are hospitalized with fractures to undergo surgical
treatment have preoperative tests that usually do not involve the measurement of VIT
D. Given the importance of VIT D in muscle strength and balance, and its role in fracture
consolidation (although questionable), it is suggested that, whenever possible, the
measurement of the levels of VIT D (a relatively expensive examination, not covered
by the Brazilian Unified Health System [SUS, in Portuguese]), should be part of the
preoperative routine, especially in the elderly or postmenopausal women with fractures,
as well as its replacement, if necessary. Hypovitaminosis D is present in all age
groups and population groups, especially among the Brazilian elderly, who depend on
skin synthesis to obtain sufficiency.[5 ]
[6 ] Although exposure to the sun can increase the levels of VIT D, this organic management
for the sufficiency of VIT D has been shown to be unfavorable in view of the potential
carcinogenic effects of ultraviolet rays and changes in habits (protection against
the sun), and also because the seasons and geographic latitude may prevent appropriate
exposure to sunlight. Therefore, dietary supplementation has been the preferred method
to manage VIT D levels. A study[24 ] conducted with healthy young adults showed that the use of VIT D is safe and does
not have severe side effects, even in doses that are ten times greater than the recommended
dose. The policy of supplementation of foods such as milk, orange juice and butter
with VIT D proved to be efficient to increase the plasma concentrations of 25(OH)D
in the countries in which it is enforced.[6 ] Similar policies could also be used in Brazil, with potential benefits for our geriatric
population. Given the low cost, safety and demonstrated benefit of higher concentrations
of 25(OH)D, VIT D supplementation should be a public health priority.[28 ] Although VIT D supplementation is considered inexpensive in food, in Brazil it is
addded to specific foods that are not part of the routine feeding of the elderly.
Until a broader VIT D supplementation becomes a reality in Brazil, traumatologists
have a duty to know and correct HVD, especially in the elderly treated with fractures.
The events of intoxication by VIT D are rare. It should be considered that, in selected
cases, supplementation, although somewhat indiscriminate (it is not always possible
to dose VIT D), can bring benefits that would overcome the risks of its deficiency
and the high costs related to fractures.
Conclusion
Hypovitaminosis D was found in a significant percentage (61.22%)of the patients who
suffered fractures. Further studies on the subject are needed to better understand
the influence of HVD on the occurrence of fractures and the benefits of VIT D supplementation
in these patients.
