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Abstract

Background:

Missile-related blood lead elevations and toxicity are well documented in the literature but reports on its associated risk factor(s) are few.

Objective:

To determine if bone fracture(s) contribute to an elevated lead blood level.

Method:

This is a prospective study of subjects with retained pellets in the craniomaxillofacial region following gunshot injuries who met the inclusion criteria. Blood samples were collected from the test subjects and their corresponding control subjects via venipuncture. Collected blood samples were used for blood lead measurement by the wet method of the atomic absorption spectrophotometry. Using appropriate statistical tests, p < 0.05 was considered significant.

Results:

A total number of 48 subjects were studied. The mean blood lead levels (BLLs) of the study population were 6.88 ± 1.17 µg/dl while that of the control group was 1.52 ± 0.87 µg/dl and the mean difference was statistically significant (p = 0.03). The mean and standard deviation of BLL of subjects with fractures were 4.77 ± 0.9, 5.08 ± 1.0, and 5.22 ± 1.0 µg/dl at days 3, 21, and 42 postinjury, respectively, while for those without bone fractures were 3.07 ± 1.4, 3.70 ± 0.8, and 4.33 ± 1.7 µg/dl. The difference was statistically significant (p = 0.04).

Conclusion:

Subjects with bone fractures were found to have higher BLLs than those without bone fractures, where pellets were retained in their bodies.

Keywords

Blood lead level bone fracture(s)retained lead pellets craniomaxillofacial region gunshot wounds

Introduction

Missile-related blood lead elevations and toxicity are well documented in the literature.^1

–7 Lead toxicity following occupational and environmental exposures has reduced drastically following the regulation of the use of lead in most industries and the ban on the use of lead gasoline in some countries, respectively.⁸ While much attention has been given to the reduction in occupational and environmental lead exposures, there seem to be little or no attention given to the reduction in lead toxicity following missile retention after injury.⁹

It was initially reported that only pellets located in the joints can result in an elevated blood level but, recently, blood lead elevations have been reported in extraarticular missile retention.¹⁰ It has been suggested that conditions that increase metabolic stress, such as surgery, fracture, hyperparathyroidism, infection, illicit drug abuse, alcohol abuse, pregnancy, and lactation, increase the mobilization of lead from the extraarticular missiles.^2,3,11 Other risk factors associated with elevated blood lead levels (BLLs) that have been documented in the literature are the number of retained pellets, duration of missiles retention, and the number of fractures.¹²

Several case reports^1,2 and cohorts studies^{3,6

–12} have demonstrated a relationship between missiles and blood lead elevation, and these are well documented in the literature. However, studies on the risk factors of elevated BLLs following missile retention are few in the literature.¹² Therefore, the purpose of this study is to determine whether BLLs are higher in patients with bone fracture than in those without bone fracture following pellets retention after gunshot injury.

Methods

This is a prospective cohort study at the Department of Oral and Maxillofacial Surgery of the University of Benin Teaching Hospital, Benin, Edo, Nigeria, from September 2010 to November 2016. The institution’s Ethics and Research Committee approval was obtained before the commencement of the study (ADM/E22/A/VOL V11/162). Each subject also signed informed consent for the study.

Subjects

The test subjects were individuals who presented in our hospital for gunshot injuries in the craniomaxillofacial region and had retained pellets. The control subjects were those with craniomaxillofacial bone fracture(s) from other causes other than gunshot. They were matched for age, sex, socioeconomic status, and abode. As the prevalence of retained pellets after gunshot injuries are unknown, the sample size was extrapolated from the work of Farrell et al., who compared BLLs in 15 subjects with retained missiles to BLLs in 15 patients without retained missiles.¹² All the study populations were consecutively selected. The subjects with retained pellets were divided into two groups on the basis of their estimated number of retained pellets as group A (those with pellets less than 30) and group B (those with pellets greater than 30) with the aid of clear orthopantomographs. This categorization was based on a previous study that demonstrated lead intoxication 4 weeks after injury with approximately 30 lead shots.¹³ The group A was further subdivided into groups A1 (without bone fracture(s)) and A2 (with bone fracture(s)) and this was also applied to group B as groups B1 and B2. All study subjects had retained pellets at the site of injury for the entire follow-up period, which was confirmed by history, clinical examination, and radiographs.

Specifically excluded from the study were subjects with the following problems: previous history of fracture, history of other hypermetabolic conditions (surgery, ketoacidosis, infection, illicit drug use, alcohol abuse, pregnancy) in the past 30 days, previous history of missile retention prior to the study, pellets retention and bone fractures in other parts of the body, and comorbid illness (seizures, anemia, renal disease, liver disease, Paget’s disease, diabetes, hypertension).

Radiograph

Orthopantomographs were used to verify the presence or absence of retained pellets and the number of pellets and bone fractures. They were used to divide the subjects into two groups, those with bone fractures and those without bone fractures. Where there were limitations with the plain radiographs, computed tomography was used for pellets and fracture assessments. The radiographs of participants were reviewed to verify the presence or absence of retained pellets and fragmentation of pellets and bone fractures. They were used to divide the subjects into two groups, those with bone fractures and those without bone fractures. Where there were limitations with the plain radiographs, computed tomography was used for pellets and fracture assessments.

Blood lead determination

BLLs were determined in the Laboratory of the Nigerian Institute for Oil Palm Research using the atomic absorption spectrophotometry with graphite furnace. Quality control data have previously been published.¹⁴ The BLLs of every participating individual were measured at 3 days, 3 weeks, and 6 weeks postinjury. The increased metabolic rate during bone healing enhances increased osseous calcium redistribution that inhibits bone lead deposition causing an elevated lead in the circulation. Complete bone consolidation can occur at 3 weeks postoperatively in the craniomaxillofacial region due to the elaborate vascularization. Blood lead measurement was based on the healing period of craniomaxillofacial bones. Three-day postoperative measurement was done at the prehealing phase of bone, 3-week postoperative measurement at the healing phase, while the 6 weeks measurement was done at the posthealing phase of bone. The timing of the blood lead measurements was based on information from the previous study.¹⁰

Health and risk questionnaires

The administered questionnaires were closed-ended and face-to-face interviewer type with simple “yes/no” pattern. Exposure to lead at the time of presentation or previously from environmental sources (occupational, residential, and recreational) was determined with the questionnaire. History of comorbid conditions, the experience of other hypermetabolic conditions, and any symptoms of lead toxicity were also determined. The usefulness of these questionnaires has been documented in published lead studies.¹⁵ The information from the questionnaires was not for analysis but to rule out cofounders.

Data management

The collected data for analysis were biodata, number of retained pellets, duration of retention, BLL of patients with bone fractures (s), and those without bone fracture(s). The data were tabulated and expressed in mean, standard deviation, and percentage. The data were entered into a computer and analyzed with the statistical package for social sciences (SPSS, Version 17). One-way analysis of variance was used to compare the means of BLL of the four groups of patients while the paired student’s t-test was used for the means of BLLs between the control group and the patients. In multivariate analysis, the association between BLL and the number of retained pellets was tested with Pearson correlation coefficient while the point-biserial correlation was used to examine the relationship between the presence or absence of bone fracture and BLL. Using a two-tailed test, a p value of <0.05 was considered significant.

Results

A total of 48 subjects were studied comprising 24 patients with retained pellets and 24 matched individuals. There were six subjects in each group of A1, A2, B1, and B2. The age range was 19–65 years for both subjects and controls (Table 1). The mean age and standard deviation of the study and control subjects were 38.0 ± 11.6 years and 39.2 ± 10.4 years, respectively. The mean difference was not statistically significant (p = 0.34; Table 1). All the recruited individuals were males. The minimum and maximum number of lead pellets recorded was 15 and 47, respectively. The average number of pellets recorded was 32.6 ± 1.50. Though there were widespread of pellets in the muscles and subcutaneous tissues, no pellets were seen in the joints, fracture site, bone, and nerves.

Table 1.

Age distribution of patients and their matched individuals (n = 24 each).

Age (years)	Patients	Percentage (%)	Control	Percentage (%)
Age (years)	No. (n)	Percentage (%)	No. (n)	Percentage (%)
11–20	2	8.33	1	4.17
21–30	4	16.67	5	20.83
31–40	9	37.50	10	41.67
41–50	4	16.67	3	12.50
51–60	5	20.83	5	20.83
61–70	0	0.00	0	0.00
Total	24	100.00	24	100.00

Table 2 shows that the mean BLLs of the study population were 6.88 ± 1.17 µg/dl while that of the control group was 1.52 ± 0.87 µg/dl and the mean difference was statistically significant (p = 0.03). No test subjects had BLL above toxicity prescribed by the Center of Disease Control (CDC).

Table 2.

Blood lead levels of patients and their matched individuals (µg/dl).^a

BLL (µg/dl)	Controls		Patients
BLL (µg/dl)	Range	Mean ± SD	Range	Mean ± SD
BLL1	0.13–2.62	1.39 ± 0.80	4.91–7.93	6.53 ± 1.00
BLL2	0.79–2.21	1.54 ± 0.50	5.02–8.29	6.82 ± 1.10
BLL3	0.21–3.21	1.36 ± 1.30	5.13–9.32	7.29 ± 1.41

SD: standard deviation; BLL: blood lead level; BLL1: blood lead level at 3 days postinjury; BLL2: blood lead level at 3 weeks postinjury; BLL3: blood lead level at 6 weeks postinjury.

^at = −35.210, df = 2, p = 0.01.

In the group with pellets less than 30, the mean BLLs of those with bone fracture were 5.02 ± 0.97 µg/dl while those without bone fracture were 3.70 ± 1.00 µg/dl and the difference was statistically significant (p = 0.02; Table 3). For the groups with pellets greater than 30, those with bone fracture has a mean BLLs of 6.88 ± 1.13 µg/dl while those without bone fracture had BLL of 5.70 ± 1.03 µg/dl and the difference was statistically significant (p = 0.04; Table 3).

Table 3.

Blood lead levels of individuals with versus without bone fractures (µg/dl).

BLL	Group A				Group B
	Group A1		Group A2		Group B1		Group B2
	Range	Mean ± SD	Range	Mean ± SD	Range	Mean ± SD	Range	Mean ± SD
BLL1	0.25–4.73	3.07 ± 1.4	3.62–6.03	4.77 ± 0.9	3.20–6.34	5.07 ± 1.0	4.91–7.93	6.53 ± 1.0
BLL2	2.32–5.01	3.70 ± 0.9	3.80–6.98	5.08 ± 1.0	4.31–6.92	5.40 ± 1.0	5.02–8.29	6.82 ± 1.0
BLL3	3.51–5.13	4.33 ± 1.7	3.91–7.10	5.22 ± 1.0	4.51–7.91	6.62 ± 1.1	5.13–9.32	7.29 ± 1.4

SD: standard deviation; BLL: blood lead level; BLL1: blood lead level at day 3 postinjury; BLL2: blood lead level at 3 weeks postinjury; BLL3: blood lead level at 6 weeks postinjury; group A: subjects with pellets less than or equal to 30; group B: subjects with pellets greater than 30; group A1: subjects with pellets less than or equal to 30 without bone fracture; group A2: subjects with pellets less than or equal to 30 with bone fracture; group B1: subjects with pellets greater than 30 without bone fracture; group B2: subjects with pellets greater than 30 with bone fracture.

The mean BLLs of the population with pellets greater than 30 and those with pellets lesser than 30 were 6.30 ± 2.43 and 4.36 ± 1.62 µg/dl, respectively. In the multivariate analysis, there was a positive significant association between BLLs and the number of lead pellets in the body (r = 0.52, p = 0.04). There was a positive and statistically significant correlation between BLL and bone fracture (r = 0.38, p = 0.03).

As shown in Table 3, the mean BLLs of the study subjects at 3 days, 3 weeks, and 6 weeks postinjury were 6.53 ± 1.00, 6.82 ± 1.10, and 7.29 ± 1.41 µg/dl, respectively, and the differences were statistically significant (p = 0.02).

Discussion

The purpose of the present study is to determine if bone fracture(s) contributes to elevated BLLs by comparing the BLLs of those with bone fractures with those without bone fractures following lead missiles retention.

All the 24 gunshot patients in this study were wounded by shotguns such that only the subjects with retained pellets were recruited unlike other studies, where the missiles were bullets and shrapnel.^{2

–9,16} This could be due to the more prevalence of shotguns in our environment than in the western world, where handguns are more common.^17,18 Although some studies recorded a disproportion between both male and female subjects sustaining gunshot injuries,¹⁹ the present study recorded only males.

The mean BLL of the study subjects was higher than that of their control counterpart (Table 2). This result is similar to the findings of Araújo et al.,¹⁵ Nguyen et al.,¹⁷ Moazeni et al.,²⁰ and Farrell et al.¹² Following the absence of occupational and environmental exposure of both the patients and their control subjects, the only possible explanation for the higher levels of lead among the patients is undoubtedly the presence of retained missiles.

The high and low figures of lead concentration that were respectively seen in the study and control populations were generally lower than 10.0 µg/dl, which is the reference limit set by CDC. This was similarly reported in previous studies except the study by Moazeni et al.²⁰ that reported mean BLL of 29.0 ± 12.8 and 25.3 ± 6.40 µg/dl in the patients and their control individuals. They, however, did not give any reason for the higher level of lead seen in the blood of these controls.

Our study showed a relationship between BLLs and the number of retained pellets in the body. Moazeni et al.,²⁰ in their case-controlled study to review 25 patients with retained pellets in their bodies due to shotgun and 25 volunteers without similar lead exposures, reported a minimum and maximum number of pellets as 1 and 30, respectively, and a mean BLL of 10.5 ± 9.7 µg/dl. Moazeni et al.²⁰ were able to demonstrate that where the number of pellets was up to 30 and above that it can predispose patients to elevated BLLs above the reference value of 10.0 µg/dl and the present study reported a lower BLL possibly due to a fewer number of pellets seen.

The individuals with bone fracture had more lead in their blood than those without bone fracture even though both have approximately the same quantity of missiles retained (Table 3). This was similarly reported by Nguyen et al.¹⁷ that a mean BLL of 9.95 and 6.23 µg/dl was seen in those with and without bone fractures, respectively. The probable explanation in support could be the higher plasma calcium during bone healing, which prevents or reduces deposition of lead in the bone. Another reason for the early onset elevation of lead seen could be that the presence of fracture indicates greater missile fragmentation leading to dissolution of lead from the missiles. To the best of our knowledge, this study is the first attempt to compare BLLs in patients with bone fracture with those without bone fracture following pellets retention from gunshot injuries. The study by Nguyen et al.¹⁷ only recruited individuals with bullets retention in the body. This could be as a result of the preference of steel pellets in the United States¹⁹ in contradistinction to the availability of only lead pellets in the developing countries.²⁰ Furthermore, weapons that fire bullets are commonly seen in the developed countries when compared to developing countries were weapons that fire shots or pellets are commonly seen.⁸

While the previous study^15,16 on fracture-related blood lead elevation risk factor was cross-sectional in nature, the present study uses a prospective cohort design, which obviates errors in measurements.

In conclusion, patients with bone fractures were found to have higher BLLs than those without bone fractures, where pellets were retained in their bodies.

Patients with retained lead pellets from gunshot wounds are not recommended to be the subject of extensive surgery to remove the pellets. However, patients with bone fractures with many retained lead pellets should be considered at risk for lead poisoning and monitored carefully. Furthermore, preoperative precautionary measures are to be taken before the manipulation of the operative sites.

Footnotes

Acknowledgements

We thank our colleagues for allowing us to recruit their patients and other members of staff for their support and cooperation.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

BE Edetanlen

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