The proportional magnitude of rickets and diagnostic utility of radiography in children with cerebral palsy attending neurology clinic at tertiary hospital in a low resource setting: a cross-sectional study

Abstract

Background

Cerebral palsy (CP) remains a significant public health challenge in Africa, compounded by economic burdens and limited healthcare resources. The co-occurrence of rickets in children with CP is poorly understood, particularly in low-resource settings, where its etiology and radiographic features remain unclear. Children with cerebral palsy often stay indoors, have poor nutrition, and low vitamin D due to limited sun exposure. Vitamin D deficiency plays a key role in the development of rickets. It is therefore crucial to investigate the magnitude of rickets in CP, its radiographic features, and associated factors to improve treatment strategies and management protocols for affected populations.

Methodology

This was a hospital-based cross-sectional study of 200 children with CP who were clinically suspected of having rickets. Each participant underwent clinical examination, plain hand X-rays, and blood sampling for laboratory investigations. Data analysis was performed using SPSS V.16, with summary statistics for univariate analysis and chi-square tests for bivariate comparisons. A p-value of less than 0.05 was considered statistically significant.

Results

The study included 200 participants, 72% of whom were male. The mean age was 5.13 (± 3.43) years. The least represented age groups were 6 months to 1 year (2%) and 13 to 15 years (5%), while the majority (39%) were aged 1 to 3 years. Rickets was diagnosed in 49 participants (24.5%). 95% experienced bone soreness or stiffness, and all cases presented with muscle weakness or cramping. Other notable clinical findings included joint thickening (55.06%), skull abnormalities (55.10%), and dental abnormalities (42.86%). Radiographically, 80% of children with rickets exhibited coarse trabeculation, 65.30% showed reduced bone density, and 57.14% had frayed metaphyses. Biochemical analysis showed that 38% of patients had vitamin D deficiency. Among children with radiographic signs of rickets, 64% were vitamin D deficient and had lower serum calcium (p < 0.001). Serum phosphate levels remained unchanged (p = 0.44), while alkaline phosphatase (ALP) was significantly higher in the rickets group (p = 0.018).

Conclusion

This study found that a significant proportion of children with cerebral palsy (CP) exhibited radiographic features of rickets, which were strongly linked to low serum calcium and vitamin D levels. These findings underscore the importance of routinely assessing calcium and vitamin D levels in children with CP at risk for rickets, and of conducting comprehensive radiographic evaluations to confirm its presence.

Introduction

Cerebral palsy (CP) is a disorder of movement and posture caused by non-progressive disturbances in the developing brain. This clinical syndrome results from brain injury or dysfunction [1, 2] and is one of the most prevalent motor disabilities in children. The global prevalence of CP ranges from 1.5 to 4 per 1,000 live births [3]. Patients with CP often experience muscle spasticity, coordination difficulties, and involuntary movements, which can significantly affect mobility and quality of life [3]. CP is considered one of the most expensive chronic conditions, imposing substantial psychological and economic burdens on families and communities caring for affected individuals [4].

On the other hand, rickets is a disease of growing bones that results from a failure of, or a delay in, the calcification of newly formed cartilage at the growth plates of long bones [5]. The primary cause of rickets is vitamin D deficiency, which impairs the absorption of calcium and phosphorus, both essential for healthy bone development. In developing countries, the prevalence of rickets is estimated to increase due to a parallel rise in malnutrition and starvation [5, 6].

The disease has a wide spectrum of presenting features, including bowed legs, skeletal deformities, and bone pain, and severe cases can lead to complications such as fractures and growth delays [2, 7]. The disease is more common in children because it is associated with development and growth [8]. The prevalence of rickets is not well documented, as in some cases it is very difficult to diagnose rickets based solely on skeletal deformities and clinical symptoms. This is also due to the fact that bony deformities may persist even after treatment, and some may become permanent [6].

Rickets can be diagnosed in the active stage through clinical evaluation of bone deformities. This may include: widening of the wrists, knees, and ankles; palpable, enlarged costochondral junctions (the rickety rosary); and deformities of the long bones due to weight-bearing. The relationship between rickets and CP is evident, as children with CP are at higher risk for developing rickets due to immobility, poor nutrition, reduced sunlight exposure, and the use of antiepileptic drugs that interfere with vitamin D metabolism [2, 7]. Vitamin D deficiency in these children can exacerbate bone fragility and deformities, further complicating their physical condition. Early diagnosis and intervention for vitamin D insufficiency are critical to mitigating the impact of rickets on growth and mobility in CP patients [3, 7].

The study aimed to determine the prevalence of rickets among children with cerebral palsy (CP), characterize its radiographic features, and analyze associations between radiographic evidence of rickets and demographic, clinical, and laboratory variables (including vitamin D deficiency) in a low-resource setting. There are research gaps related to these aims. There are few studies quantifying the burden of rickets among children in our low-resource settings, despite the known vulnerability of children with cerebral palsy (CP) to nutritional deficiencies and bone health complications. Little research also exists on the specific radiographic features of rickets in children with CP and how these correlate with clinical and biochemical parameters such as vitamin D, calcium, and phosphorus. The overlap in clinical presentation between CP-related musculoskeletal abnormalities and rickets further complicates diagnosis; thus, the need for detailed investigation using radiographic and laboratory assessments to guide accurate diagnosis and effective management.

In low-resource settings in low- and middle-income countries, children with cerebral palsy (CP) often face challenges, including limited access to specialized healthcare, poor infrastructure, inadequate rehabilitation support, and financial constraints. These conditions, including rickets, can go unrecognized, leading to worsened disability and reduced quality of life. The lack of diagnostic tools in this setting further complicates care for these children.

Methods

Participants

The study received ethical approval from the Institutional Review Board of Muhimbili University of Health and Allied Sciences (MUHAS-IRB Ref. No. DA.282/298/01.C/884). Written informed consent was obtained from the parents or guardians of all participants. Permission to collect data was granted by the Muhimbili National Hospital IRB. This prospective descriptive cross-sectional study included 200 children aged 6 months to 15 years with cerebral palsy (CP) and clinically suspected rickets who attended the pediatric neurology clinic at Muhimbili National Hospital (MNH).

Sample size calculation

The minimum sample size required was calculated using the formula for estimating a proportion in a cross-sectional study.

where:

After adjusting for a 10% non-response rate, the final sample size required was approximately 182. We included 200 participants, exceeding the minimum sample size needed to detect meaningful associations.

Clinical, laboratory and radiographic data

Locally developed, pre-tested, and standardized questionnaires were used to record clinical, laboratory, and radiographic data. The clinical variables assessed included bone soreness or stiffness, muscle weakness or cramping, joint thickening, skull abnormalities, and dental abnormalities. All patients underwent laboratory evaluations to assess serum levels of vitamin D, calcium, alkaline phosphatase (ALP), and phosphate. These laboratory tests were performed on a COBAS INTEGRA 400 + analyzer, manufactured in Germany in 2020, with serial number 420,488.

Image acquisition

All participants underwent wrist X-rays using the PHILIPS XRAY PLATFORM, model Digital Diagnostic C50 (SN: 180173, Class I, Type B), manufactured by PHILIPS HEALTHCARE (SUZHOU) Co., LTD, in 2018 and calibrated in December 2018 according to hospital SOPs. The X-rays were performed by two experienced radiographers, capturing anterior-posterior and lateral views of the distal forearm and hand. Parents or guardians assisted when necessary and were provided with lead coats and gonadal shields for radiation protection. The images were evaluated by the principal investigator (PI) and a radiologist with 10 years of experience. Kappa statistics were used to assess interobserver agreement. Diagnosis of rickets was based on vitamin D deficiency (< 30 nmol/L) or insufficiency (30–50 nmol/L) [9], and radiographic findings of rickets on radiography (metaphyseal cupping, splaying, fraying, coarse trabeculation, and osteopenia) [10].

Data analysis

Data collected in this study were analyzed using SPSS v.16. Univariate analysis was summarized using descriptive statistics, and bivariate comparisons were conducted using the Chi-square test. Statistical significance was set at p < 0.05.

Bivariate analysis: nutritional status vs. rickets

BMI Category	Rickets	No Rickets
Underweight	20	18
Normal BMI	29	133

• Chi-square statistic (χ²): 18.24

• Degrees of freedom: 1

• P-value: 0.0000195 (significant)

Interpretation

There is a statistically significant association between being underweight and having rickets among children with cerebral palsy (p < 0.001). This supports the assertion that poor nutritional status increases the risk of rickets in this population.

Sampling method

A convenience sampling approach was used because of the limited number of eligible children attending the neurology clinic at Muhimbili National Hospital during the study period. All children aged 6 months to 15 years with cerebral palsy and clinical suspicion of rickets who attended the clinic and met inclusion criteria were recruited consecutively until the target sample size of 200 was reached. This approach enabled timely recruitment within the operational constraints of a low-resource tertiary care setting.

Results

A total of 200 children aged 6 months to 15 years with cerebral palsy (CP) and clinically suspected rickets attending the pediatric neurology clinic at Muhimbili National Hospital (MNH) were included in the study. The mean age of participants was 5.13 years (SD ± 3.43), with ages ranging from 6 months to 15 years. The majority were male (143/200, 72%), resulting in a male-to-female ratio of 2.5:1. More than one-third (39%) of participants were aged 1 to 3 years, while the least represented groups were 6 months to 1 year (2%) and 13 to 15 years (5%). Most participants (81%) had a normal BMI, while the remaining 19% were underweight (Table 1).

Table 1.

Demographic characteristics of the study participants

Variable	frequency (N = 200)	Percentage (%)
Age groups
6 months to 1 year	4	2
1 to 3 years	78	39
4 to 6 years	61	30
7 to 9 years	29	14
10 to 12 years	21	10
13 to 15 years	7	5
Sex
Female	57	28
Male	143	72
BMI
Normal	162	81
Underweight	38	19

Clinical features of rickets in children with CP

Among the 49 children diagnosed with rickets, the most common clinical features were muscle weakness or cramps (100%) and bone pain or tenderness (95.92%). Other significant findings included skull deformity or delayed fontanel closure (55.10%), thickened joints in the wrists, knees, or ankles (53.06%), and dental abnormalities or delayed tooth formation (42.86%). Less frequent skeletal deformities included bowed legs or knock knees (22.45%) and bone fractures (22.45%). Rachitic rosary or Harrison’s sulcus was observed in only 2.04% of cases. (Table 2) (Fig. 1).

Table 2.

Percentage distribution of clinical features of rickets in children with CP

Variable
Rickets signs	Frequency (N = 49)	Percentage (%)
Pain/tenderness in the bones	47	95.92
Muscle weakness/cramps	49	100.00
Bowed legs/knock knees	11	22.45
Thickened wrist/knee/ankle	26	53.06
Rachitic rosary/Harrison’s sulcus	1	2.04
Teeth deformity/delayed teeth formation	21	42.86
Skull deformity/delayed closure fontanel	27	55.10
Bone fracture	11	22.45

Fig. 1.

Bar chart showing the percentage distribution of clinical features of rickets in children with cerebral palsy

Radiographic findings of rickets in children with CP

The two observers demonstrated substantial agreement (Cohen’s Kappa = 0.77). Among 200 children with cerebral palsy (CP), 49 (24.5%) exhibited radiographic features of rickets. The most common findings were coarse trabeculation (80%), reduced bone density (65.30%), and metaphyseal fraying (57.14%). Additional notable features were irregular metaphyseal surfaces (49%), widened epiphyseal plates (47%), and splayed metaphyseal ends (32.65%). Less frequent abnormalities included indistinct cortices (30.6%) and metaphyseal cupping (16.3%). (Table 3) (Fig. 2).

Table 3.

Radiographic findings of rickets in children with CP

Rickets radiographic features on x-ray	Frequency (N = 49)	Percentage (%)
Fraying reaction of periosteum (Metaphysis)	28	57.14
Indistinct cortex	15	30.60
Course trabeculation	39	80.00
Loss of bone density	32	65.30
Epiphyseal plate widened and irregular	23	47.00
*Cupping	8	16.30
^Splaying	16	32.65
Irregularity of metaphyseal surfaces	24	49.00

*Concavity of metaphysis

^Widening of metaphyseal ends

Fig. 2.

Pie chart displaying the relative proportions of radiographic features observed in these children

Laboratory findings and radiographic features of rickets

A total of 76 (38%) patients had vitamin D deficiency. A higher proportion of patients with low serum calcium (39%) and vitamin D (64%) levels had radiographic features of rickets (p < 0.001). Nearly all participants had normal serum phosphate and alkaline phosphatase levels, with only two individuals showing elevated serum phosphate despite positive radiographic findings of rickets (Table 4) (Fig. 3).

Table 4.

Comparison of laboratory findings and presence of features of rickets on radiograph

Laboratory variables	Radiographic features of rickets		p-value
	Present (%)	Absent (%)
Serum Calcium level			< 0.001
High (> 13 mg/dL)	1 (14)	6 (86)
Low (< 6 mg/dL)	34 (39)	54 (61)
Normal (6 to 12 mg/dL)	14 (13)	91 (87)
Serum Vitamin D level			< 0.001
Low (< 50 nmol/L))	49 (64)	27 (36)
Normal (> 50 nmol/L)	0 (0)	124 (100)
Serum Phosphate			0.44
High (> 1.5 mmol/L)	2 (4.08))	0 (0)
Normal (0.74–1.54 mmol/L)	47 (95.91)	151 (76.5)
Serum Alkaline-Phosphates			0.018
High (> 150 IU/L)	2 (4.08)	0 (0)
Normal (45–150 IU/L)	47 (95.91)	151 (100)

Fig. 3.

The wrist radiographs of a 1-year-old cerebral palsy patient with rickets show distinct features: Image A and B depict AP and lateral projections, respectively. Fraying, splaying, and cupping of the metaphysis, with reduced bone density, are hallmark radiographic features of rickets, as observed in this case. These findings align with descriptions in the literature, where fraying refers to indistinct metaphyseal margins, splaying indicates widening of the metaphyseal ends, and cupping reflects concavity at the metaphysis due to abnormal mineralization [11, 12]

Discussion

The study aimed to determine the prevalence of rickets among children with cerebral palsy (CP), characterize its radiographic features, and analyze associations between radiographic evidence of rickets and demographic, clinical, and laboratory variables in a low-resource setting. A total of 200 children with CP were studied. There were more males than females, with a male-to-female ratio of 2.5:1, accounting for 72% of cases. This observation aligns with findings from other studies but contrasts with research conducted in Saudi Arabia, where a higher prevalence was noted in females [13, 14]. The increased prevalence in male children may be attributed to genetic factors, such as higher calcium requirements in males, and socio-cultural practices, including prolonged breastfeeding [14].

Rickets primarily affected children aged 1 to 3 years. Similar findings were reported in studies from India [13] and Yemen [15], where children aged 0 to 5 years, particularly those under 3 years, were most affected. This alarming trend underscores the burden of rickets in younger children, with significant impacts on growth and development. One contributing factor may be exclusive breastfeeding without vitamin D supplementation, as breast milk alone does not provide adequate vitamin D [16]. This issue is particularly common in infants, emphasizing the need for maternal and infant vitamin D supplementation and sun exposure [15, 17].

The current study found that muscle weakness or cramps were universally present in the diagnosed children (100%), and bone pain or tenderness was nearly as prevalent (95.92%). These findings align with recent academic literature, which frequently identifies bone pain and muscle weakness as common symptoms of nutritional rickets due to the softening of growing bones [8]. Vitamin D receptors are found in muscle cells, underscoring the link between vitamin D deficiency, a common cause of rickets, and muscle-related symptoms [18]. Other significant findings included skull deformity or delayed fontanel closure (55.10%) and thickened joints in the wrists, knees, or ankles (53.06%). These are well-documented signs of rickets. Delayed fontanel closure and frontal bossing are often early signs, particularly in infants [11, 19]. Widened metaphyses, which manifest as thickened wrists and ankles, are a classic feature resulting from impaired mineralization of the growth plates [19]. Hypophosphatasia, a condition with similar skeletal manifestations, also highlights the importance of proper mineral metabolism for bone health [20].

Dental abnormalities or delayed tooth formation were observed in 42.86% of cases. Delayed tooth eruption and enamel hypoplasia are associated with rickets, especially when the condition develops before enamel formation is complete or during critical periods of tooth development [21, 22].

Less frequent skeletal deformities in our study included bowed legs or knock knees (22.45%) and bone fractures (22.45%). While less common in our cohort, these are recognized as significant consequences of rickets. Bowed legs (genu varum) and knock-knees (genu valgum) are typical leg deformities caused by the softening and bending of bones under weight-bearing stress [23]. Fractures can occur because of compromised bone integrity in rickets [24].

Interestingly, the rachitic rosary or Harrison’s sulcus was observed in only 2.04% of cases in our study. Although these are considered classic signs of rickets, with the rachitic rosary representing enlargement of the costochondral junctions and Harrison’s sulcus a groove at the lower margin of the thorax [11], their lower prevalence in this cohort suggests variability in presentation or that these signs may be more pronounced in certain stages or severities of the disease. Some studies have reported higher prevalence. Collectively, these findings emphasize the diverse clinical spectrum of rickets in children, highlighting the importance of a thorough clinical examination for diagnosis.

Radiography plays a crucial role in diagnosing rickets in children with CP [25, 26], as it can reveal hallmark features such as fraying, cupping, splaying of the metaphyses, reduced bone density, and widening of the growth plates [25–27]. These findings are essential for confirming the diagnosis, especially when clinical symptoms and laboratory tests alone are insufficient. In one study, radiography identified rickets in a significant percentage of children with CP, consistent with the findings of this study, underscoring its diagnostic importance. The high prevalence is linked to factors such as vitamin D deficiency, calcium insufficiency, and limited mobility common among children with CP [28, 29].

Loss of bone density was among the most common radiographic findings in this study, consistent with previous research [27]. Other typical radiographic features of rickets include coarse trabeculation, reduced bone density, metaphyseal fraying, and splaying of the metaphyses, which were also observed in the current study [25–27]. Specific features such as widening of the growth plates, cupping of the metaphyses, and pseudofractures (Looser’s zones) were also observed, further aligning with findings from earlier studies [30, 31]. These radiographic signs are critical for diagnosing rickets and reflect failure of normal mineralization at the growth plates and metaphyseal zones [11, 32]. The observations from this study reinforce the importance of radiographic evaluation in identifying and managing rickets effectively. Radiographic evaluation is particularly useful in detecting both early and advanced stages of rickets, as it provides detailed visualization of bone changes associated with the disease.

Rickets in children with CP is often linked to poor nutrition, which is significantly influenced by economic status and family income [2]. These factors affect access to balanced diets and necessary supplements, which are crucial for proper growth and development. CP is one of the costliest chronic conditions, requiring specialized care, frequent hospital visits, and assistive equipment for daily mobility [33, 34]. As a result, the financial burden may lead some families to prioritize other expenses over nutritional support, contributing to the prevalence of rickets in this population. This study observed that all children with rickets experienced delayed developmental milestones, which could be attributed to both CP and rickets. Rickets is associated with bone and muscle weakness, often leading to delays in sitting and walking in affected children [6, 27].

Our study found significant vitamin D and calcium deficits in all children diagnosed with rickets. This finding is particularly relevant because it highlights the utility of these laboratory tests in diagnosing both clinical and subclinical rickets, especially in settings where radiographic facilities are unavailable. Previous studies have similarly reported vitamin D and calcium deficiencies as major contributors to rickets, often linked to nutritional barriers prevalent in developing countries [2, 31, 35].

Hypocalcemia was also observed in patients with rickets in this study. This condition may result from vitamin D deficiency, which impairs calcium absorption, or from dietary calcium deficiency, both of which play critical roles in the pathogenesis of nutritional rickets [5, 7, 35]. Vitamin D is essential for maintaining calcium and phosphate balance in the body, and its deficiency can lead to weakened bones and delayed growth [36]. Addressing these deficits through supplementation and improved dietary practices is crucial for preventing and managing rickets.

Most participants in the current study had normal serum phosphate levels, a finding consistent with previous studies that emphasize the role of serum phosphate in diagnosing rickets based on laboratory and clinical manifestations in children with CP [8, 12, 37]. Serum phosphate levels are critical for bone mineralization, and alterations in phosphate homeostasis can lead to rickets. However, normal phosphate levels in some cases may reflect the complexity of rickets etiology, which involves multiple factors such as vitamin D and calcium deficiencies. Studies have highlighted that hypophosphatemic rickets is often associated with genetic or renal phosphate-wasting disorders, whereas nutritional rickets typically presents with normal or slightly reduced phosphate levels [12, 38].

Study limitations

Small sample size and the use of descriptive study designs could limit the generalizability of the findings and may not fully capture the complexity of the condition across diverse populations. This was a cross-sectional study, and there were no longitudinal data on laboratory variables or rickets. Longitudinal studies would offer more insight into how these conditions evolve over time.

Conclusion and recommendations

Conclusion

This study found a higher prevalence of radiographic evidence of rickets in children with cerebral palsy (CP), particularly in those aged 1–3 years. A significant proportion of these children had low serum vitamin D levels, indicating that vitamin D deficiency is a primary cause of their bone abnormalities. Hypocalcemia was also observed, but vitamin D deficiency remained the most significant factor. The radiographic findings align with the pathophysiology of rickets, characterized by impaired bone mineralization due to vitamin D deficiency, leading to features such as metaphyseal fraying and reduced bone density [11]. Early detection and intervention are crucial to prevent long-term skeletal deformities and growth impairments in this age group.

Recommendations

The prevalence of radiographic findings underscores the need for routine imaging in children with cerebral palsy (CP) who show signs of nutritional deficiencies or delayed growth and development. Early detection via radiography enables timely interventions, such as vitamin D and calcium supplementation, to mitigate complications [23]. Furthermore, a multicentre longitudinal study is recommended to investigate the multifactorial causes of rickets in children with CP and to monitor the outcomes of management strategies.

Abbreviations

CP

Cerebral palsy

CT

Computed Tomography

IU/L

International units per liter

Mmol/L

Milimole per liter

MNH

Muhimbili National Hospital

MUHAS

Muhimbili University of Health and Allied Science

MRI

Magnetic Resonance Imaging, MS Excel-Microsoft Excel

Authors’ contributions

EF conceived the study concept, protocol, and execution of the study and wrote the manuscript. MS reviewed the manuscript. MCM supervised the study and revised the manuscript. SCM assisted in the laboratory and revised the manuscript. MJ critically reviewed and revised the manuscript. KPM supervised the conception of the proposal, provided technical input throughout the study, and reviewed, revised, and further contributed to the study.

Funding

No funding.

Data availability

The data from this study can be obtained upon request from the first author, Dr. Edward Feksi, at feksie04@gmail.com.

Declarations

Ethics approval and consent to participate

All methods were carried out in accordance with relevant guidelines and regulations, and the study was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Ethics Review Committee of Muhimbili University of Health and Allied Sciences (MUHAS) and the Directorate of Research, Training and Consultancy at MNH. The study was approved by the institutional review board of Muhimbili University (MUHAS-IRB Ref. No. DA.282/298/01.C/884). Individual written consent was obtained from the parents/guardians of participants. Permission to collect data was granted by Muhimbili National Hospital-IRB. Confidentiality was maintained throughout the study by using a study identification number assigned to each participant.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.