Introduction

Rickets is characterized by inadequate mineralization of the growth plates and bone matrix of the skeleton and represents a heterogeneous group of disorders with both acquired and inherited subtypes. Patients with rickets typically present with decreased serum calcium and/or phosphorus levels [1]. In addition to various skeletal deformities, hypocalcemia-related symptoms, such as tetany, convulsions, laryngospasm, and muscle weakness, may also be observed [2]. Although nutritional rickets, caused by insufficient intake of vitamin D or calcium, is the most commonly encountered subtype, recognition of inherited forms, including hypophosphatemic and vitamin D-dependent rickets, is increasing due to advances in molecular genetic diagnostic techniques [3].

Despite the implementation of prophylactic treatment protocols in many countries to prevent rickets, the disease remains a significant public health issue, particularly in developing nations. In 2005, a marked decline in the incidence of rickets was reported in Turkey following the introduction of the “Vitamin D Deficiency Prevention Program” [4,5]. However, recent studies have indicated a resurgence in rickets cases, particularly due to inappropriate or inadequate administration of vitamin D supplementation intended for prophylaxis [6,7]. One major contributing factor to this increase is the insufficient follow-up and treatment of the children of refugees who have migrated to the country for various reasons. Similar challenges have been reported in several other countries as well [8,9].

Although physical examination, medical history, and biochemical analyses provide the primary basis for diagnosing rickets, radiological confirmation is essential [1]. Physical examination alone is insufficient to differentiate between children with active rickets and those in recovery, and it does not allow for distinction between the various subtypes of the disease [10]. Moreover, if skeletal abnormalities are detectable on clinical examination, the disease is often already at an advanced stage. Therefore, reliance solely on clinical signs may lead to overestimation of the prevalence of active rickets and result in unnecessary treatment.

Rickets, which holds significant relevance in orthopedic and traumatology practice, often presents through various skeletal deformities and pathological fractures. Patients with nutritional rickets, in particular, may be evaluated by orthopedic surgeons at any stage of the disease course [11]. The most common reasons for referral to orthopedic and traumatology departments include nonspecific musculoskeletal pain, genu varum, genu valgum, and fractures that occur spontaneously or after minor trauma [12–14].

Rickets is a serious pediatric health concern, and early diagnosis and treatment are crucial to prevent the development of permanent and significant sequelae later in life. Given that different subtypes of rickets require tailored treatment approaches, establishment of an accurate and standardized treatment protocol is essential [15]. This study evaluated the clinical approaches of orthopedic surgeons who frequently encounter patients with rickets and who play pivotal roles in both diagnosis and disease management. The findings of this study may contribute to the development of more accurate and standardized diagnostic and therapeutic strategies for rickets, fostering better collaboration between pediatric endocrinologists and orthopedic surgeons.

Materials and methods

Following a comprehensive review of the literature and previous related studies, an online questionnaire was developed and distributed to orthopedic surgeons who are members of the Turkish Society of Orthopedics and Traumatology and the Pediatric Orthopedics Association. Prior to questionnaire development, a detailed MEDLINE search was conducted, revealing that no similar study had targeted orthopedic surgeons previously. Ethical approval for the study was obtained from the Ankara Bilkent City Hospital Medical Research Ethics Committee (dated February 14, 2024, number 1-24-15). The survey link, hosted on https://docs.google.com/forms, was distributed via email. As of 1 October 2024, the survey link started to be sent to the participants, three reminder e-mails were sent at 3-week intervals to encourage participation, and the survey link activation was terminated on 30 November 2024. With the online link sent to the participating physicians, before starting the survey the detailed information about the purpose and content of the study was given and their online informed consent was obtained.

The questionnaire comprised 14 multiple-choice and open-ended textbox questions designed to assess participants’ sociodemographic characteristics (including institution of employment, years of professional experience, frequency of treating pediatric and rickets patients, and the presence of a pediatric endocrinologist at their institution) as well as their general approach to the diagnosis and management of rickets (S1 Appendix). Prior to distribution, the questionnaire was reviewed by 13 board-certified orthopedic surgeons from various institutions to evaluate its clarity and identify potential issues. Necessary revisions were made based on their feedback.

The first three questions gathered demographic information about the participants. Subsequent questions addressed whether a pediatric endocrinologist was available at each participant’s institution and the frequency with which patients with rickets were encountered in daily practice. Later sections of the questionnaire were designed to evaluate participants’ clinical approaches to suspected rickets cases, including the clinical and radiological findings they anticipated, concerns typically expressed by parents, laboratory tests ordered, treatment strategies employed, and their awareness of potential side effects related to the treatments.

Physicians who did not treat patients aged 0–18 years were instructed not to proceed with the survey. Upon collecting the responses, data analysis was limited to a specific subset of participants, i.e., those who were orthopedic specialists, who regularly treated pediatric patients within the 0–18 age group, and who had completed all survey questions. Responses from individuals who did not meet these criteria, including those who were not orthopedic specialists, who did not treat pediatric patients, or who submitted incomplete responses, were excluded from the final evaluation.

The resulting data were analyzed in detail according to four main parameters: the number of years the respondent had worked as an orthopedic specialist, the frequency of encountering pediatric patients in daily practice, the presence or absence of a pediatric endocrinologist at their institution, and the frequency of encountering patients with rickets.

Results

Among the 257 completed surveys, 198 met the inclusion criteria. Approximately half of the participants had more than 10 years of experience as orthopedic surgeons (n = 111, 56.1%), managed pediatric patients in ≥ 25% of their daily practice (n = 88, 44.4%), and encountered at least one rickets patient per week (n = 78, 39.4%). Nearly half of the respondents reported the presence of a pediatric endocrinologist at their institution (n = 96, 48.5%). Additionally, the majority of participants (n = 139, 70.2%) were affiliated with government healthcare facilities (Table 1).

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Table 1. Demographic data of participants.

https://doi.org/10.1371/journal.pone.0329944.t001

Participants’ responses were analyzed according to years of experience in orthopedic surgery (Table 2). As years of experience increased, the likelihood of requesting serum calcium and 25-hydroxyvitamin D3 (25-OH-vitamin D3) for a diagnosis of rickets significantly increased (p = 0.008). When asked about radiological findings expected in pediatric rickets cases, participants with more than 10 years of experience more frequently reported metaphyseal and growth plate widening, stress fractures, and pelvic deformities as expected findings (p = 0.032, < 0.001, = 0.001, and < 0.001, respectively). While the majority of participants selected > 20 ng/mL (> 50 nmol/L) as the normal 25-OH-vitamin D3 level, no significant difference was observed between experience groups. Experienced surgeons were significantly less likely to refer patients to a pediatric endocrinologist (p = 0.009) and more likely to recommend oral or intramuscular 25-OH-vitamin D3 ampoule treatments (p < 0.001).

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Table 2. Comparison according to the experience in years as an orthopedic surgeon.

https://doi.org/10.1371/journal.pone.0329944.t002

When participants were grouped based on the proportion of pediatric patients seen in daily practice, those who treated < 25% pediatric patients were more likely to refer rickets cases to a pediatric endocrinologist without ordering diagnostic tests (p = 0.011). As the proportion of pediatric patients increased, significant differences emerged regarding the radiological findings reported for rickets cases. Moreover, surgeons treating a higher proportion of pediatric patients more frequently identified > 20 ng/mL (> 50 nmol/L) as the normal value for 25-OH-vitamin D3 (p = 0.027). Those treating < 25% pediatric patients were more inclined to refer rickets patients to pediatric endocrinology without initiating treatment (p = 0.005) (Table 3).

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Table 3. Comparison according to the rate of seeing pediatric patients in daily practice.

https://doi.org/10.1371/journal.pone.0329944.t003

Surgeons working in institutions with a pediatric endocrinologist were significantly more likely to refer suspected rickets cases directly to the endocrinologist without ordering laboratory tests (p = 0.003) or initiating treatment (p = 0.002). These surgeons were also less likely to prescribe oral or intramuscular 25-OH-vitamin D3 ampoules (p < 0.001) (Table 4).

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Table 4. Comparison according to whether there is a pediatric endocrinologist working in the institution.

https://doi.org/10.1371/journal.pone.0329944.t004

Participants who saw ≥ 1 rickets patient per week demonstrated significantly different response patterns concerning expected radiological findings (p = 0.016 and < 0.001). These surgeons also more frequently identified > 20 ng/mL (> 50 nmol/L) as the normal 25-OH-vitamin D3 level (p = 0.042). Conversely, surgeons who encountered < 1 rickets patient per week were more likely to refer these patients to a pediatric endocrinologist rather than initiate treatment themselves (p < 0.001), and were less likely to prescribe oral or intramuscular 25-OH-vitamin D3 (p < 0.001) (Table 5).

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Table 5. Comparison according to the frequency of rickets patient presentation.

https://doi.org/10.1371/journal.pone.0329944.t005

Finally, when asked whether they would inquire whether a patient suspected of having rickets had received vitamin D supplementation from a family physician during infancy (< 1 year of age), significantly more affirmative responses were given by physicians with > 10 years of experience (p = 0.010), those treating ≥ 25% pediatric patients (p = 0.008), and those seeing ≥ 1 rickets patient per week (p = 0.020) (Tables 2–3, and 5).

Discussion

This study used an electronic questionnaire to evaluate the clinical approaches of orthopedic surgeons to patients with suspected rickets. Physicians with more than 10 years of professional experience were less likely to refer such patients to a pediatric endocrinologist and more likely to initiate treatment with oral or intramuscular 25-OH-vitamin D3 ampoules. Conversely, those who managed fewer pediatric patients (< 25% of their caseload) and those working in clinics with an on-site pediatric endocrinologist were more inclined to refer patients to the endocrinologist without conducting further investigations.

It is essential that children with suspected rickets are evaluated by a pediatric endocrinologist to ensure accurate diagnosis and standardized treatment, as rickets remains a significant health issue in many developing countries and includes various subtypes [16]. Orthopedic manifestations of rickets in early childhood can often be resolved with timely and appropriate replacement therapy, or at the very least, optimal pre-treatment can improve surgical outcomes [11]. Thus, effective collaboration between orthopedic surgeons and pediatric endocrinologists is crucial in managing rickets patients.

Diagnosis of rickets relies on a comprehensive evaluation including physical examination, family history, laboratory analyses, and radiological findings. The most frequently observed clinical signs include wrist and ankle widening, genu varum or valgum, thoracic deformities, and prominent costochondral junctions [17]. In this study, while physicians were asked to report common clinical complaints and reasons for hospital visits as noted by families, no significant differences were observed based on their professional experience or the frequency with which they managed pediatric or rickets cases.

For accurate diagnosis and classification of rickets subtypes, laboratory tests such as serum calcium, phosphate, magnesium, alkaline phosphatase, and 25-OH-vitamin D3 levels are essential [1]. Although our study did not find significant differences in test-ordering behavior among physicians overall, those treating fewer pediatric patients were significantly more likely to refer patients to a pediatric endocrinologist without ordering any laboratory tests (p = 0.011).

Radiological evaluation plays a crucial role in diagnosing rickets. Common findings include metaphyseal and growth plate widening, osteopenia of the long bones, stress fractures, and pelvic deformities [18]. Our findings reveal that surgeons who saw ≥ 25% pediatric patients or ≥ 1 rickets patient per week had significantly greater awareness of these radiographic features (p < 0.001), implying that frequent exposure to such cases enhances diagnostic confidence and knowledge.

Although there is some variability in the literature regarding the cutoff for normal 25-OH-vitamin D3 levels, values above 50 nmol/L (> 20 ng/mL) are generally accepted as normal [11]. In our study, while no statistically significant difference was found overall, surgeons who regularly treated pediatric patients or managed ≥ 1 rickets case per week identified the correct threshold value more frequently (p = 0.027 and = 0.042, respectively).

Since the implementation of Turkey’s “Vitamin D Prophylaxis Augmentation Programme” in 2005, there has been a marked decrease in the incidence of rickets [5]. However, due to recent demographic changes, particularly an influx of regular and irregular migrants, monitoring and maintaining optimal vitamin D levels in early childhood have become increasingly challenging, potentially leading to a resurgence of nutritional rickets as a public-health concern [7–9]. Family physicians play a key role in preventing vitamin D deficiency by providing routine oral 25-OH-vitamin D3 supplementation to children under the age of 1 year. In our study, physicians with > 10 years of experience, those treating ≥ 25% pediatric patients, and those who managed ≥ 1 rickets case per week were significantly more likely to inquire about prior vitamin D supplementation in suspected cases (p = 0.010, = 0.008, and = 0.020, respectively), reflecting a higher level of clinical vigilance in these subgroups.

Treatment modalities for rickets due to nutritional deficiencies of vitamin D, calcium, or phosphorus vary significantly depending on the patient’s age and the underlying etiology [2,19]. In cases of rickets caused by vitamin D deficiency, treatment typically involves oral or intramuscular administration of 25-OH-vitamin D3, and calcium supplementation may be required based on the individual patient’s needs [20]. In contrast, calcium-deficiency rickets is primarily managed with calcium replacement, while vitamin D supplementation may be added to facilitate rapid symptomatic improvement in certain cases [21]. For rickets due to nutritional phosphorus deficiency, it is crucial to assess parathyroid hormone levels before initiating treatment. Parathyroid hormone levels are typically elevated in calcium deficiency; however, in phosphorus deficiency, they may be decreased, normal, or elevated, depending on the specific pathophysiological mechanisms involved [1].

Vitamin D-dependent and hypophosphatemic rickets follow different therapeutic protocols compared to nutritional rickets and generally require more complex individualized management strategies [22,23]. As such, a comprehensive clinical evaluation is essential in patients with suspected rickets to guide the development of patient-specific treatment plans.

In our study, we observed that orthopedic surgeons with more than 10 years of professional experience and those who managed pediatric patients in more than 25% of their daily clinical practice were significantly more likely to both diagnose and treat rickets independently (p = 0.009 and = 0.005, respectively). Furthermore, this subgroup demonstrated a greater tendency to recommend oral 25-OH-vitamin D3 ampoule therapy (p < 0.001). However, in our country, the only available formulation of 25-OH-vitamin D3 in ampoule form contains 300,000 IU/mL, which raises concerns regarding accurate dose adjustment and patient compliance, rendering this formulation suboptimal for general use [24].

Although vitamin D deficiency is associated with severe health consequences, inappropriate or unsupervised treatment can lead to equally significant complications. While some adverse effects of excessive vitamin D are mild and manageable, others may result in serious and irreversible outcomes [24]. Toxic doses of vitamin D may induce complications such as nephrolithiasis, cardiac arrhythmias, pancreatitis, and even coma, in addition to more common symptoms such as weakness, fatigue, anorexia, and bone pain. Moreover, in patients with underlying genetic mutations affecting enzymes like vitamin D hydroxylase, severe adverse reactions may occur even at non-toxic doses of vitamin D [25]. Therefore, it is imperative that clinicians prescribing vitamin D therapy are well-versed in appropriate dosing strategies and aware of potential side effects. In our study, no statistically significant differences were found among physicians regarding their knowledge of potential adverse effects associated with uncontrolled vitamin D administration.

Survey-based research is widely used in the medical field to evaluate various aspects, such as disease prevalence and patients’ quality of life [26–28]. Additionally, survey studies are utilized to assess the adequacy of residency training across specific specialties and subspecialties [29]. One of the most prevalent applications of such studies in the literature is the assessment of physician approaches to specific diseases. These evaluations facilitate interdisciplinary communication and help identify educational deficiencies or redundancies [30–33]. In the present study, we examined the clinical approaches of orthopedic surgeons, who are integral to the diagnosis and management of rickets, to elucidate their practices and perspectives regarding this condition.

To the best of our knowledge, this was the first national study in the English-language literature to investigate orthopedic surgeons’ approaches to rickets patients within the context of pediatric endocrinology. A major strength of the study was the exclusive inclusion of board-certified orthopedic surgeons who participated voluntarily and without any conflicts of interest. Additionally, the high proportion of experienced physicians (nearly half with more than 10 years of practice and over 25% of pediatric patients in their daily caseload) contributed to the robustness of the findings. Moreover, the survey was distributed nationally, rather than being limited to a specific geographic region or institution, enhancing its generalizability.

However, several limitations should be acknowledged. First, the exact number of actively practicing orthopedic surgeons in the relevant email groups was unknown, and thus, the response rate to the survey could not be accurately calculated. Second, it is possible that the responses provided in the questionnaire did not fully reflect actual clinical practice, as discrepancies may exist between intended and real-world behavior. Nevertheless, previous research has shown that survey responses are generally consistent with daily clinical practices [34]. Third, this study was descriptive in nature and, therefore, did not allow for causal inference or evaluation of predictive relationships between variables. Fourth, we used self-reported data, which is subject to recall and self-report bias and may have affected our findings.

Supporting information