Nutritional rickets and osteomalacia are reemerging in Western societies, particularly in young children and in adolescents of African or Asian descent. Hypocalcemic seizures resulting from vitamin D deficiency are rare in adolescents, whereas fractures caused by seizures without evidence of direct trauma have not yet been reported in this population. We present an unusual case of secondary bilateral femoral fractures caused by hypocalcemic seizures in a 17-year-old boy with primary vitamin D deficiency. We examine the epidemiology and the clinical presentation of rickets and osteomalacia in the adolescent population, the risk of secondary injuries in patients with seizures, and the evaluation and management of hypocalcemic seizures and primary vitamin D deficiency.
Although there are no national data on the incidence of rickets or osteomalacia in the United States, several reports have suggested that primary vitamin D deficiency is reemerging in Western societies, particularly in young children and possibly in adolescents of African or Asian origin.1–3 Most adolescents with vitamin D deficiency are asymptomatic. Here we present an unusual case of secondary bilateral femoral fractures caused by hypocalcemic seizures in a 17-year-old black boy with primary vitamin D deficiency.
A 17-year-old black boy was brought to the pediatric emergency department during the wintertime after having a first seizure while sitting on a couch at home. It was witnessed by the patient's mother and described as a 5-minute generalized self-resolving seizure with rhythmic shaking movements of all extremities and backward rolling of the eyes. It occurred at 5 am after a night without sleep. He had been watching television. The patient did not fall from the couch or experience any trauma during the seizure. Paramedics found the patient unresponsive and administered 50 mL of 50% dextrose and 100 mg of thiamine intravenously. On arrival to the emergency department, the patient was somnolent but able to answer questions appropriately. He complained of severe bilateral thigh pain. He reported having felt somewhat weak for the previous few days, although he had been able to play basketball, as he did most days of the week, on the day before admission. He denied any trauma. He had no upper respiratory symptoms, fever, nausea, or vomiting, reported no recent changes in vision or gait, and denied ingestions, medication use, or illicit drug use. His diet consisted of mostly “junk food” and canned soft drinks, with very few fresh fruits, vegetables, or cereals, and less than 1 serving of dairy products per day. He had not traveled recently. He had no significant past medical history, including no history of seizures, and there were no individuals with seizures in his immediate family.
In the emergency department, his vital signs were: temperature, 97.5°F; heart rate, 107 beats per minute; respiratory rate, 20 breaths per minute; blood pressure, 139/63 mmHg; oxygen saturation, 99% on room air; and pain score, 7/10. He was a slender black adolescent boy with prominent musculature. His physical examination was normal except for the musculoskeletal and neurologic components. His extremities revealed contracted quadriceps bilaterally and exquisite pain on palpation of both thighs. The pain prevented him from sitting or walking. On neurologic examination, he was somnolent but arousable and oriented to person, time, and place. He had a generalized increase in muscle tone. Deep-tendon reflexes were brisk all over. Chvostek and Trousseau signs were negative.
One hour after his arrival, the patient had a second generalized tonic-clonic seizure that lasted ∼4 minutes and stopped after intravenous administration of 2 mg of lorazepam. Chemistries were significant for a calcium level of 4.5 mg/dL (reference range: 8.7–10 mg/dL) and ionized calcium level of 0.6 mM/L (reference range: 1.12–1.32 mM/L). His sodium level was 140 mM/L (reference range: 136–146 mM/L), potassium level was 4.0 mM/L (reference range: 3.6–5 mM/L), phosphorus level was 5.0 mg/dL (reference range: 2.5–4.3 mg/dL), and magnesium level was 1.5 mg/dL (reference range: 1.5–2.3 mg/dL). An electrocardiogram showed a normal sinus rhythm with a QTc of 413 milliseconds. He received intravenous calcium gluconate and was transferred to the PICU. Laboratory evaluation revealed normal renal function with a creatinine level of 1.0 mg/dL (reference range: 0.6–1.2 mg/dL) and normal hepatic function (aspartate aminotransferase level: 36 U/L [reference range: 12–38 U/L]; alanine aminotransferase level, 16 U/L [reference range: 7–41 U/L]). His alkaline phosphatase level was 338 U/L (reference range: 33–96 U/L), parathyroid hormone (PTH) level was 515 pg/mL (reference range: 8–51 pg/mL), vitamin D 25-hydroxy level was <5 ng/mL (reference range: 20–57 ng/mL), and vitamin D 1,25-dihydroxy level was <4 pg/mL (reference range: 15–75 pg/mL). Additional workup for malabsorption was negative (negative serology markers for celiac disease and stool negative for fat). The patient was diagnosed with primary vitamin D deficiency.
Radiographs of his legs revealed bilateral femoral-neck fractures (see Figs 1 and 2). A long-bone survey showed normal bone mineralization. Dual radiograph absorptiometry was not performed because of the urgency of surgical management as recommended by the orthopedic surgeons. He underwent open reduction and internal fixation of both femoral heads (see Fig 3). He was discharged on hospital day 12 to a physical rehabilitation facility on calcitriol, calcium carbonate, multivitamins, and ferrous sulfate. Subsequently, he was transitioned to ergocalciferol. A diet with increased calcium intake of at least 2 to 4 servings of dairy per day and daily vitamin D (400 IU) supplementation was recommended and, to the best of our knowledge, has been followed. Seven months after admission the patient had normal PTH and vitamin D levels, and all his medications were discontinued except a standard multivitamin preparation.
Vitamin D deficiency seems to be an unrecognized and prevalent problem in adolescents. School-based studies in the United Kingdom and Finland suggest that a significant proportion of adolescent girls may have subclinical vitamin D deficiency.4, 5 A recent cross-sectional study of 307 healthy teenagers attending an annual physical examination in an adolescent clinic in the northeastern United States showed that vitamin D deficiency was present in 24% of the subjects and that the prevalence was highest in black adolescents.3 The pathophysiology of rickets and osteomalacia in this population may stem from a combination of increased metabolic demands as a result of rapid growth and puberty, poor vitamin D or calcium intake, high soft drink consumption with increased phosphorous content, decreased physical activity, and diminished exposure to sunlight, particularly in individuals with darker skin pigmentation.6
The clinical presentation of rickets and osteomalacia in the adolescent population differs from the presentation in younger patients. Whereas toddlers generally exhibit bony deformities soon after weight-bearing age, most adolescents are asymptomatic. When symptomatic, they tend to present with signs of hypocalcemia such as neuromuscular irritability and, rarely, seizures. Radiographs of the long bones in these patients may not necessarily show radiologic changes of rickets or osteomalacia. It is thought that hypocalcemic symptoms secondary to vitamin D deficiency occur largely in patients with rapid growth rates such as children younger than 1 year and adolescents. In a retrospective review of 65 hospitalized children with vitamin D deficiency in the United Kingdom, Ladhani et al7 reported that hypocalcemic symptoms occurred exclusively in children younger than 3 years or older than 10 years. Narchi et al8 reported 21 cases of symptomatic rickets in adolescents from Saudi Arabia. Most of their patients presented with carpopedal spasm, limb pain, or weakness. The incidence of seizures in adolescents with vitamin D deficiency is unknown. In the Ladhani et al series, 16 patients presented with seizures, but it is unclear how many were in the older age group, whereas none of the adolescent patients in the Narchi et al group had seizures.
Patients with a history of epilepsy seem to be at a higher risk for injuries, including head and dental trauma, lacerations, burns, sprains, and fractures. Surveys and population studies indicate that close to 20% of patients who experience a seizure sustain some kind of injury, and overall, 30% to 35% of patients with seizures have experienced secondary injury as a result of a seizure during their lifetime.9–11 The data in children are limited. A small case-control study in Canada showed that most cognitively intact children with epilepsy have a similar risk of serious injuries compared with their peers without epilepsy.12 A prospective study of 198 consecutive children aged 1 to 16 years with newly diagnosed and untreated seizures noted that serious injuries were uncommon; 12% of their patients with seizures sustained injuries, but only 2% required medical attention.13
However, a recent meta-analysis reported that patients with epilepsy are twice as likely to sustain a fracture as patients without epilepsy,14 which may be a result of (1) increased risk of trauma, (2) decreased bone density caused by the use of antiepileptic drugs, and/or (3) comorbidities. Most of the fractures sustained during seizures are caused by direct trauma and typically involve the skull, nasal bones, and clavicles, but in rare instances, fractures can be caused by the muscular tension of the seizure itself. In these cases, the proximal humerus and the shoulder are more commonly affected.15 Although bilateral femoral fractures caused by electroconvulsive therapy were occasionally encountered in the 1950s and 1960s,16, 17 femoral fractures caused by the muscular tension of a seizure itself seem to be unusual and are described in only a handful of case reports in older adults, patients with renal failure, and skeletally immature patients.18–22 To the best of our knowledge, this is the first reported case of nontraumatic bilateral femoral fractures in an adolescent resulting from hypocalcemic seizures caused by primary vitamin D deficiency.
Laboratory testing after a first unexplained nonfebrile seizure should be considered, particularly in patients with suggestive clinical findings such as vomiting, diarrhea, or dehydration, failure to return to baseline alertness, or increased muscle tone or fractures such as in our patient. The workup should include obtaining electrolyte levels, including calcium, magnesium, and phosphorous. Toxicology screening should be considered if there is a question of drug exposure or substance abuse.23 The differential diagnosis of hypocalcemia in adolescence includes vitamin D deficiency, hypoparathyroidism, hypomagnesemia, malabsorption, and renal and hepatic failure, among others.24 Once hypocalcemia is found, additional laboratory investigations such as obtaining a basic metabolic panel, liver-function tests, and PTH and vitamin D 25-hydroxy and 1,25-dihydroxy levels should be performed. A workup for malabsorption should be undertaken if it is suggested by history or initial laboratory results. The diagnosis of primary vitamin D deficiency is made when low vitamin D levels along with a compatible history are accompanied by high levels of PTH, in the absence of other metabolic or gastrointestinal abnormalities. Dual-beam radiograph–based photon absorptiometry is the most sensitive routine method of detecting and quantifying bone loss and may be considered for patients with vitamin D deficiency.25
Hypocalcemic seizures should be treated with intravenous calcium. In general, calcium gluconate is preferred to calcium chloride because it is less irritating and is less likely to cause tissue necrosis if extravasation occurs. Intravenous therapy with calcium should be continued as long as the patient is symptomatic. Magnesium should be replaced if low levels are identified, and vitamin D replacement in the form of vitamin D2 (ergocalciferol) may be initiated intramuscularly initially and continued orally as long as the patient does not have malabsorption. Phosphate replacement is usually not necessary for vitamin D deficiency, because low levels are a result of the elevated PTH level, which resolves once adequate calcium and vitamin D are supplied. It is important to monitor serum calcium, phosphate, alkaline phosphatase, PTH, and vitamin D levels and the urinary calcium/creatinine ratio during treatment to monitor response and avoid complications of hypocalcemia or hypercalcemia. Every effort should be made to prevent this disease by encouraging adequate diet, sun exposure, and vitamin D supplementation for patients at risk.26
This case illustrates that emergency medicine physicians should carefully evaluate patients with seizures for secondary injuries, both at presentation and after the patient recovers from the postictal stage. Although symptomatic rickets and osteomalacia are rare in the adolescent population, pediatricians, general practitioners, and policy-makers should be aware that subclinical vitamin D deficiency is on the rise in Western urban societies, particularly in individuals of African or Asian origin. Additional research into primary prevention of primary vitamin D deficiency in this population is warranted.
We thank Dr Peter Dayan for careful review of the manuscript.
- Accepted June 12, 2006.
- Address correspondence to David Schnadower, MD, MPH, Division of Pediatric Emergency Medicine, 622 West 168th St, PH-137, New York, NY 10032. E-mail:
The authors have indicated they have no financial relationships relevant to this article to disclose.
- Scanlon K. CDC vitamin D expert panel meeting: October 11–12, 2001; Atlanta, Georgia. Available at: www.cdc.gov/nccdphp/dnpa/nutrition/pdf/Vitamin_D_Expert_Panel_Meeting.pdf. Accessed June 7, 2006
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- ↵Moncrieff MW, Lunt HR, Arthur LJ. Nutritional rickets at puberty. Arch Dis Child.1973;48 :221– 224
- ↵Ladhani S, Srinivasan L, Buchanan C, Allgrove J. Presentation of vitamin D deficiency. Arch Dis Child.2004;89 :781– 784
- ↵Narchi H, El Jamil M, Kulaylat N. Symptomatic rickets in adolescence. Arch Dis Child.2001;84 :501– 503
- ↵Kirsch R, Wirrell E. Do cognitively normal children with epilepsy have a higher rate of injury than their nonepileptic peers? J Child Neurol.2001;16 :100– 104
- ↵Finelli PF, Cardi JK. Seizure as a cause of fracture. Neurology.1989;39 :858– 860
- ↵Kelly JP. Fractures complicating electro-convulsive therapy and chronic epilepsy. J Bone Joint Surg Br.1954;36-B :70– 79
- ↵Powell HD. Stimultaneous bilateral fractures of the neck of the femur. J Bone Joint Surg Br.1960;42-B :236– 252
- ↵Kause J, Parr MJ. Bilateral subcapital neck of femur fractures after eclamptic seizures. Br J Anaesth.2004;92 :590– 592
- ↵Hirtz D, Ashwal S, Berg A, et al. Practice parameter: evaluating a first nonfebrile seizure in children—report of the quality standards subcommittee of the American Academy of Neurology, The Child Neurology Society, and The American Epilepsy Society. Neurology.2000;55 :616– 623
- ↵Singh J, Moghal N, Pearce SH, Cheetham T. The investigation of hypocalcaemia and rickets. Arch Dis Child.2003;88 :403– 407
- ↵Lehtonen-Veromaa MK, Mottonen TT, Nuotio IO, Irjala KM, Leino AE, Viikari JS. Vitamin D and attainment of peak bone mass among peripubertal Finnish girls: a 3-y prospective study. Am J Clin Nutr.2002;76 :1446– 1453
- Copyright © 2006 by the American Academy of Pediatrics