Prevalence of vitamin D deficiency in pediatric limb lengthening and deformity patients

Oliver C Sax; Ethan A Remily; Nequesha S Mohamed; Philip K McClure; John E Herzenberg

doi:10.4103/jllr.jllr_3_21

ORIGINAL ARTICLE

Year : 2021 | Volume : 7 | Issue : 2 | Page : 114-118

Prevalence of vitamin D deficiency in pediatric limb lengthening and deformity patients

Oliver C Sax¹, Ethan A Remily¹, Nequesha S Mohamed², Philip K McClure¹, John E Herzenberg¹
¹ International Center for Limb Lengthening, Rubin Institute for Advanced Orthopedics, Sinai Hospital of Baltimore, Baltimore, Maryland, USA
² Department of Orthopaedic Surgery, Wake Forest Baptist Health, Medical Center Boulevard, Winston-Salem, NC, USA

Date of Submission	12-Feb-2021
Date of Decision	24-May-2021
Date of Acceptance	24-Jun-2021
Date of Web Publication	30-Dec-2021

Correspondence Address:
Dr. Philip K McClure
Sinai Hospital of Baltimore, 2401 West Belvedere Avenue, Baltimore, Maryland 21215
USA

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/jllr.jllr_3_21

Abstract

Background: Vitamin D deficiency is one of the most common vitamin deficiencies in the world, afflicting over 1-billion children. Currently, there is a shortage of studies evaluating Vitamin D levels in pediatric limb lengthening or deformity correction (LLDC) patients. The purpose of this study is to determine the prevalence of Vitamin D deficiency in pediatric patients undergoing lower extremity osteotomies for LLDC. Materials and Methods: We retrospectively analyzed pediatric patients undergoing a lower extremity long bone osteotomy for lengthening/deformity correction at a single center from 2014 to 2018. Of 214 subjects, 80% had perioperative 25-hydroxyvitamin D (25[OH]D) levels available. Variables included age, sex, race, diagnosis, long bone treated, and perioperative 25(OH) D levels. Most patients were female, Caucasian, had a congenital diagnosis, and averaged 12.7 years old. Results: A single long bone was treated in 138 subjects (80%), while 19 patients (11%) underwent ipsilateral femur and tibial surgery and 15 patients (9%) underwent a bilateral surgery. The mean 25(OH)D level was 28.7 ng/mL. Deficient levels were found in 32% of subjects, and insufficient levels were found in an additional 41%. All patients healed appropriately. Conclusions: LLDC requires optimal bone metabolism for the generation of new bone. This study revealed a high proportion of Vitamin D insufficiency in pediatric limb-lengthening patients. Identifying these patients preoperatively may allow for Vitamin D “prehabilitation” to optimize bone health before limb-lengthening procedures in order to obtain satisfactory outcomes.

Keywords: Limb lengthening, pediatric limb lengthening and deformity correction, Vitamin D, Vitamin D deficiency

How to cite this article:
Sax OC, Remily EA, Mohamed NS, McClure PK, Herzenberg JE. Prevalence of vitamin D deficiency in pediatric limb lengthening and deformity patients. J Limb Lengthen Reconstr 2021;7:114-8

How to cite this URL:
Sax OC, Remily EA, Mohamed NS, McClure PK, Herzenberg JE. Prevalence of vitamin D deficiency in pediatric limb lengthening and deformity patients. J Limb Lengthen Reconstr [serial online] 2021 [cited 2022 Aug 8];7:114-8. Available from: https://www.jlimblengthrecon.org/text.asp?2021/7/2/114/334376

Introduction

Vitamin D (25-hydroxyvitamin D [25(OH)D]) deficiency is among the most common pediatric vitamin deficiencies in the world, afflicting over 1 billion children.^[1] The United States is not impervious to this condition, as an estimated 7.6 million children and adolescents are Vitamin D deficient and another 50.1 million are Vitamin D insufficient.^[2] Certain factors, such as ethnicity and obesity status, appear to predispose individuals to this condition, as African-Americans and obese patients are 21.9 and 1.9 times likelier to suffer from Vitamin D deficiencies, respectively.^[2],[3] Furthermore, preventing deficiencies in Vitamin D is important, as literature has suggested that the condition may create an increased susceptibility to childhood fractures and decreased bone mass later in life.^[4],[5] As the pervasiveness and lasting implications of Vitamin D deficiency have necessitated expansive research, the vitamin has been found to play an essential role in several processes throughout the body, including bone metabolism.

Several studies have highlighted the importance of Vitamin D in fractures, concluding that the vitamin plays a part in all four stages of fracture repair.^[6] In particular, Vitamin D has been demonstrated to upregulate various proteins, such as inflammatory cytokines, receptors, and growth factors, to stimulate growth and differentiation of cells in the stages of callus formation and remodeling.^[6],[7],[8] This knowledge can be translated to limb-lengthening (distraction osteogenesis), as the process, although not identical, employs many of the same principles.^[9],[10] Distraction osteogenesis consists of three phases: lLatency (initial hematoma and inflammation), distraction (stretching of callus), and consolidation (remodeling and healing).^[9],[10] During the distraction phase, many of the aforementioned factors increase to stimulate osteogenesis.^[10] Moreover, in the consolidation phase, receptor activator of nuclear factor kappa-B ligand increases, which is an essential component in bone remodeling dependent on Vitamin D concentrations.^{[11],[12],[13]} The importance of Vitamin D in bone healing has long been documented, although little information exists on whether low Vitamin D levels play a role in limb lengthening or deformity correction (LLDC) patients.

Although several studies have examined the incidence of Vitamin D deficiency in the general pediatric population, there have been few studies reporting on Vitamin D status in pediatric patients undergoing LLDC. Therefore, this study performs a retrospective analysis specifically assessing incidence and demographics of Vitamin D levels in pediatric patients undergoing LLDC procedures from 2014 to 2018.

Materials and Methods

Patient selection

This retrospective study analyzed pediatric patients under the age of 17 years undergoing correction osteotomy or limb lengthening at a single referral center between January 01, 2014 and December 31, 2018. Patients were identified by screening case logs for osteotomy procedures, followed by acute deformity correction and fixation, placement of a circular external fixator, or insertion of an intramedullary lengthening nail. After screening, there were 214 identified subjects that underwent these procedures. However, 42 were excluded as they lacked perioperative 25(OH) D levels, giving us a final total of 172 LLDC patients for the study. This retrospective study did not receive any funding and was deemed exempt from the institutional review board approval.

Variables

Variables collected were age, sex, race, diagnosis, location of long bone treated, and perioperative 25(OH)D levels. Vitamin D levels were measured either the day before or the day of surgery. In accordance with the Endocrine Society,^[14] patients with serum 25(OH)D levels ≥30 ng/mL were considered adequate for bone health, while Vitamin D levels from 29 to 20 ng/mL were considered insufficient, and levels <20 ng/mL were considered deficient.

Statistical analysis

Data were summarized with descriptive statistics including means and standard deviations for continuous variables, and the number of subjects and percent in each category for categorical variables. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 25.0 (IBM Corporation, Armonk, New York, United States).

Results

Patient demographics

More LLDC subjects were female (93/172, 54%) with a mean age of 12.7 ± 3.7 years [Table 1]. The most common ethnicity was Caucasian (108/172, 63%), followed by African-American (44/172, 25%), Asian (12/172, 7%), and “Other” (8/172, 5%). Congenital diagnoses were most common (79/172, 46%) followed by miscellaneous diagnoses (48/172, 28%), dwarfism (21/172, 12%), posttraumatic growth arrest (15/172, 9%), and postinfectious growth arrest (9/172, 5%). A singular long bone was treated in 138 subjects (80%), whereas 19 patients (11%) underwent ipsilateral femur and tibial surgery and 15 patients (9%) underwent bilateral surgery.

Table 1: Demographics for patients undergoing limb-lengthening surgery

Click here to view

Vitamin D levels

The mean 25(OH) D level was 28.7 ± 17.4 ng/mL (range 9.1–103.5 ng/mL) [Table 2]. Deficient levels were found in 55/172 (32%) of subjects and insufficient levels were found in 70/172 (41%) of subjects. A minority of subjects (47/172, 27%) had adequate 25(OH) D levels. All patients were supplemented with Vitamin D postoperatively, regardless of measured level, to ensure appropriate healing, and the desired final outcome was achieved in all patients (172/172, 100%).

Table 2: Vitamin D outcomes

Click here to view

Discussion

Vitamin D deficiency has become one of the most common vitamin deficiencies in the United States pediatric population.^[1] A deficiency in Vitamin D has lasting effects, as this condition has been associated with increased fracture risk and poor bone health.^[4],[5] Furthermore, pediatric patients who present with fractures are often concomitantly diagnosed with deficits in Vitamin D.^[15] This deficiency is not exclusive to pediatric fracture patients, as patients with other musculoskeletal conditions may also be at risk for this nutritional deficit. As such, this study aimed to determine the Vitamin D status of pediatric patients undergoing LLDC surgery. Our findings demonstrated that 41% of LLDC patients presented with insufficient Vitamin D levels and 32% had deficient Vitamin D levels. Although consistent with the general pediatric population, these levels among LLDC patients may be cause for concern if not preemptively corrected.

This study is not without limitations. Although we identified over 200 patients with our inclusion criteria, several patients could not be included due to the absence of Vitamin D levels during chart review. However, this proportion was a small minority, and the included patients comprised an accurate representation of pediatric LLDC population. Another limitation was that this study only assessed the perioperative Vitamin D status of pediatric patients and the levels were not trended over time. To better characterize the degree of hypovitaminosis D, it would have been preferable to test Vitamin D status months before surgery to allow for early detection and mitigation. However, most surgeons do not routinely measure perioperative Vitamin D, and our study was intended to quantify perioperative levels of Vitamin D to create awareness regarding the ubiquity of Vitamin D deficiencies in these pediatric LLDC patients. Finally, these results were obtained from the patient population of a single institution. However, patients are referred to our center from around the world, providing a very diverse population of LLDC patients. Nonetheless, this is the first study to assess Vitamin D deficiency in this subset of patients and may incline surgeons to supplement their pediatric patients before this procedure.

When both insufficient and deficient Vitamin D LLDC patients are taken into consideration, the overall percentage of patients with low Vitamin D levels was 73%. In comparison to the entire pediatric population of the United States, the proportions found in the present study are comparable. In a National Health and Nutrition Examination Survey performed by Kumar et al.,^[2] the authors determined that 70% of pediatric patients were below the normal threshold for Vitamin D (<30 ng/mL). Despite the similarities, appropriately comparing our findings to the general pediatric population may be difficult, as many factors such as geographical location, time of year, time spent indoors, and ethnicity affect the incidence of Vitamin D deficiency.^[2],[16] To date, no studies have specifically examined the incidence of Vitamin D deficiency in distraction osteotomy patients, although a study performed by Parry et al.^[16] did retrospectively analyze Vitamin D levels in patients undergoing long bone osteotomies and spinal fusions over a 10-month period. The authors ascertained that 90% of their patients undergoing these procedures were below normal levels (<32 ng/mL). Furthermore, a retrospective study performed by Mayes et al.^[17] examined Vitamin D levels in pediatric scoliosis patients. In this study, the authors discovered that 75% of patients possessed Vitamin D levels below normal serum levels (<32 ng/mL). Both of these studies reveal a higher prevalence of low Vitamin D levels similar to the present study. Yet, the resemblance between the high proportions of these studies may indicate that orthopedic patients with musculoskeletal deformities experience low serum Vitamin D levels at a similar or higher frequency than the general population. These patients arguably demonstrate a higher need for supplementation, as they are actively undergoing procedures requiring extensive bone healing. This is the reason all our patients received Vitamin D supplementation postoperatively regardless of Vitamin D status, as it was determined to be detrimental to withhold supplementation given the high prevalence of hypovitaminosis D among pediatric patients.

The abundance of literature demonstrating the purpose of Vitamin D in bone metabolism has led to the exploration of Vitamin D supplementation and its effect on bone. A meta-analysis performed by Winzenberg et al.^[18] analyzed six studies involving pediatric patients receiving varying amounts of Vitamin D supplementation, ranging from 132 international units (IU) to 14,000 IU/week over 1–2 years. The authors concluded that individuals with low serum Vitamin D levels may benefit from Vitamin D supplementation, as a 21% increase in total body bone mineral content was observed after treatment in these patients. Furthermore, in a randomized, double-blinded, placebo-controlled study performed by Ghazal et al.,^[15] the authors analyzed the effect of weekly high-dose (14,000 IU) versus low-dose (1400 IU) Vitamin D supplementation in pediatric patients at 12- and 24-month postsupplementation initiation. The authors observed significant differences in bone mineral content changes of the hip in females receiving high-dose supplementation at 12 and 24 months when compared to low-dose supplementation (12.9% vs. 7.2% at 12 months; 21.8% vs. 13.9% at 24 months). Both of these studies illustrate a potential benefit for patients, and particularly Vitamin D deficient patients, as they may experience increased bone mineral content from Vitamin D supplementation.

Although the literature has demonstrated a positive effect of Vitamin D supplementation in those with low levels, only a small number of studies have examined and incorporated fracture healing as an end point of their study. In a randomized, double-blinded, placebo-controlled Dutch study performed by Doetsch et al.,^[19] the authors enrolled thirty elderly osteoporotic or osteopenic females (mean age: 77.7 years) who underwent nonoperative treatment with nondisplaced proximal humerus fractures. For 12-week postinjury, one cohort received a placebo and the other received 800 IU of Vitamin D plus 1 g of calcium. Over the course of the study, patients receiving Vitamin D and calcium experienced a higher level of bone mineral density than those who did not, with 6-week peak density levels being significantly different (0.623 g/cm² ^vs. 0.570 g/cm²; P = 0.006). Furthermore, fracture dislocation rates were not significantly different from the placebo group. In another prospectively randomized, double-blinded, placebo-controlled study performed by Haines et al.,^[1] the authors enrolled 100 adult patients who sustained long bone fractures (15 humeri, 50 femurs, and 35 tibias) and possessed Vitamin D levels <30 ng/mL. Patients were then stratified into a treatment group receiving a single dose of 100,000 IU oral Vitamin D or a placebo group. The union rates observed in the treatment group was higher, although this was not statistically significant (93% vs. 90.7%; P = 0.693). While both of these studies present encouraging outcomes, both of these studies have small sample sizes and are underpowered, limiting the ability to detect true differences between groups. Furthermore, these studies are performed in adult populations, which may not be relatable to pediatric patients. Although the present study repleted Vitamin D for all LLDC patients to prevent complications with bone healing, more research is needed in pediatric populations with sufficient sample sizes to draw meaningful conclusions about Vitamin D's effect on bone healing.

Conclusions

The United States continues to experience high number of pediatric patients with low Vitamin D levels. This study similarly revealed a high proportion of below normal Vitamin D levels in pediatric LLDC patients. Limb lengthening and deformity correction require optimal bone metabolism for the generation of new bone, and many studies have demonstrated the extensive role Vitamin D has in bone metabolism. Therefore, identifying these patients preoperatively may allow for Vitamin D “prehabilitation” to optimize bone health before LLDC procedures in order to obtain satisfactory outcomes. Further research is needed to elucidate the role of Vitamin D in limb-lengthening patients, specifically regarding its potential impact on regenerate healing. Regardless, we recommend that all pediatric patients undergoing orthopedic procedures receive Vitamin D screening in the perioperative period, as the majority will likely have below normal levels that could impact bone healing.

Financial support and sponsorship

PKM is a consultant for DePuy Synthes Companies, Novadip, Orthofix, and Smith+Nephew. JEH is a clinical advisor for Bonus BioGroup and a consultant for NuVasive Specialized Orthopedics, Orthofix, OrthoPediatrics, OrthoSpin, Smith+Nephew, and WishBone Medical. The following organizations supported the institution of OCS, EAR, PKM, and JEH: Biocomposites, DePuy Synthes Companies, MHE Coalition, Orthofix, OrthoPediatrics, Pega Medical, Smith+Nephew, Stryker, and Zimmer Biomet.

Conflicts of interest

There are no conflicts of interest.

References

1.	Haines N, Kempton LB, Seymour RB, Bosse MJ, Churchill C, Hand K, et al. The effect of a single early high-dose vitamin D supplement on fracture union in patients with hypovitaminosis D: A prospective randomised trial. Bone Joint J 2017;99-B: 1520-5.
2.	Kumar J, Muntner P, Kaskel FJ, Hailpern SM, Melamed ML. Prevalence and associations of 25-hydroxyvitamin D deficiency in US children: NHANES 2001-2004. Pediatrics 2009;124:e362-70.
3.	Rovner AJ, O'Brien KO. Hypovitaminosis D among healthy children in the United States: A review of the current evidence. Arch Pediatr Adolesc Med 2008;162:513-9.
4.	Winzenberg T, Jones G. Vitamin D and bone health in childhood and adolescence. Calcif Tissue Int 2013;92:140-50.
5.	Gorter EA, Oostdijk W, Felius A, Krijnen P, Schipper IB. Vitamin D deficiency in pediatric fracture patients: Prevalence, risk factors, and vitamin D supplementation. J Clin Res Pediatr Endocrinol 2016;8:445-51.
6.	Gorter EA, Hamdy NA, Appelman-Dijkstra NM, Schipper IB. The role of vitamin D in human fracture healing: A systematic review of the literature. Bone 2014;64:288-97.
7.	Gurlek A, Pittelkow MR, Kumar R. Modulation of growth factor/cytokine synthesis and signaling by 1α, 25-dihydroxyvitamin D3: Implications in cell growth and differentiation. Endocr Rev 2002;23:763-86.
8.	van Leeuwen JP, van Driel M, van den Bemd GJ, Pols HA. Vitamin D control of osteoblast function and bone extracellular matrix mineralization. Crit Rev Eukaryot Gene Expr 2001;11:199-226.
9.	Ai-Aql ZS, Alagl AS, Graves DT, Gerstenfeld LC, Einhorn TA. Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis. J Dent Res 2008;87:107-18.
10.	Hvid I, Horn J, Huhnstock S, Steen H. The biology of bone lengthening. J Child Orthop 2016;10:487-92.
11.	Runyan CM, Gabrick KS. Biology of bone formation, fracture healing, and distraction osteogenesis. J Craniofac Surg 2017;28:1380-9.
12.	Flanagan AM, Stow MD, Kendall N, Brace W. The role of 1,25-dihydroxycholecalciferol and prostaglandin E2 in the regulation of human osteoclastic bone resorption in vitro. Int J Exp Pathol 1995;76:37-42.
13.	Atkins GJ, Kostakis P, Pan B, Farrugia A, Gronthos S, Evdokiou A, et al. RANKL expression is related to the differentiation state of human osteoblasts. J Bone Miner Res 2003;18:1088-98.
14.	Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911-30.
15.	Ghazal N, Al-Shaar L, Maalouf J, Nabulsi M, Arabi A, Choucair M, et al. Persistent effect of vitamin D supplementation on musculoskeletal parameters in adolescents one year after trial completion. J Bone Miner Res 2016;31:1473-80.
16.	Parry J, Sullivan E, Scott AC. Vitamin D sufficiency screening in preoperative pediatric orthopaedic patients. J Pediatr Orthop 2011;31:331-3.
17.	Mayes T, Anadio JM, Sturm PF. Prevalence of vitamin D deficiency in pediatric patients with scoliosis preparing for spinal surgery. Spine Deform 2017;5:369-73.
18.	Winzenberg T, Powell S, Shaw KA, Jones G. Effects of vitamin D supplementation on bone density in healthy children: Systematic review and meta-analysis. BMJ 2011;342:c7254.
19.	Doetsch AM, Faber J, Lynnerup N, Wätjen I, Bliddal H, Danneskiold-Samsøe B. The effect of calcium and vitamin D3 supplementation on the healing of the proximal humerus fracture: A randomized placebo-controlled study. Calcif Tissue Int 2004;75:183-8.