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|Year : 2021 | Volume
| Issue : 6 | Page : 1650-1654
Osteomalacic Myopathy in Children and Adolescents with Vitamin-D Deficiency
Suhalika S Sahni1, Shruti Kakkar1, Ruchika Kumar1, Jatinder S Goraya2
1 Division of Pediatric Neuroloy, Dayanand Medical College & Hospital, Ludhiana, Punjab, India
2 Department of Pediatrics, Dayanand Medical College & Hospital, Ludhiana, Punjab, India
|Date of Submission||30-May-2018|
|Date of Decision||09-May-2020|
|Date of Acceptance||04-Sep-2021|
|Date of Web Publication||23-Dec-2021|
Dr. Jatinder S Goraya
Division of Pediatric Neuroloy, Department of Pediatrics, Dayanand Medical College & Hospital, Ludhiana - 141 001, Punjab
Source of Support: None, Conflict of Interest: None
Background: Osteomalacic myopathy secondary to vitamin-D deficiency is an under-recognized cause of muscle weakness in children and adolescents.
Aim: To describe a cohort of children and adolescents with osteomalacic myopathy.
Settings and Design: Pediatric neurology unit of a tertiary care hospital.
Methods and Material: Charts of children and adolescents with osteomalacic myopathy were retrospectively reviewed for demographics, clinical presentation, laboratory investigations, and treatment response. Diagnosis of vitamin-D deficiency was made on the basis of a combination of clinical, biochemical, and radiographic findings. Response to treatment with vitamin-D confirmed vitamin-D deficiency as the cause of myopathic symptoms.
Results: Twenty-six children—15 girls and 11 boys aged between 20 months and 19 years—with osteomalacic myopathy were identified. Fifteen (58%) children were between 10 years and 19 years of age. Twenty-one (81%) children presented with myopathic symptoms of progressive walking difficulty, with eventual loss of ambulation in six. Four children came to attention through hypocalcemic seizures. One nonambulatory child with cerebral palsy presented with loss of previously attained ability to roll over and sit. All children had proximal muscle weakness on examination. Fifteen (58%) children had clinical signs of rickets. All the children who underwent biochemical (n = 24) and radiographic (n = 16) investigations had results consistent with vitamin-D deficiency. Only in one child, the diagnosis of osteomalacic myopathy was made on the basis of clinical findings. Response to vitamin D was uniformly good.
Conclusions: Vitamin-D deficiency should be considered in the differential diagnosis of proximal myopathy in children and adolescents.
Keywords: Adolescents, children, myopathy, osteomalacia, rickets, Vitamin-D deficiency
Key Messages: Rachitic or osteomalacic myopathy secondary to vitamin D-deficiency is an eminently treatable but under-recognised cause of acquired muscle weakness in children and adolescent. It should be considered in the differential diagnosis in any child who presents with myopathic symptoms. High clinical suspicion and meticulous clinical examination provide important clues to the diagnosis which can easily be confirmed with biochemical and radiological investigations.
|How to cite this article:|
Sahni SS, Kakkar S, Kumar R, Goraya JS. Osteomalacic Myopathy in Children and Adolescents with Vitamin-D Deficiency. Neurol India 2021;69:1650-4
Rickets is the most well-recognized clinical vitamin-D deficiency (VDD) state in children and adolescents. Less commonly, children with VDD may present with neurological symptoms such as irritability, seizures, tetany, or paresthesia secondary to hypocalcemia.,,, Osteomalacic myopathy is a known but uncommon manifestation of VDD in children and is particularly encountered in adolescents.,,,,, Common symptoms of osteomalacic myopathy include progressive walking difficulty, waddling gait, inability to climb stairs, difficulty getting up, and eventually loss of ambulation. Diffuse musculoskeletal pain is a common accompaniment. Clinical signs of rickets may be obvious on clinical examination, especially in younger children.,
Despite being a well-recognized presentation of VDD, osteomalacic myopathy often is not considered in the differential diagnoses of muscular weakness in children, resulting in inappropriate referrals, unnecessary investigations, and undue delays in treatment.,,,, Barring a few case reports, the majority of the studies on osteomalacic myopathies have been published outside neurology journals. The purpose of our study is to describe our experience with osteomalacic myopathy in children and adolescents, highlighting its relevance to the practice of neurology.
| » Material and Methods|| |
We retrospectively reviewed medical records of children and adolescents with a diagnosis of vitamin-D deficiency-associated myopathy, also called rachitic or osteomalacic myopathy, seen over a period of 10 years between February 2010 and March 2020 at a tertiary care hospital of North India. The diagnosis of myopathy was made on the basis of clinical symptoms of progressive walking difficulty, difficulty going upstairs, difficulty rising from sitting, or ability to rise in a bed, and neurological examination showing predominantly proximal weakness. Diagnosis of vitamin-D deficiency was made on the basis of a combination of clinical (presence of signs of rickets), biochemical (raised alkaline phosphatase, low serum phosphate, and low/normal serum calcium), and radiographic signs of rickets and/or osteomalacia. Serum 25-hydroxy vitamin D and serum parathormone (PTH) were not necessary for diagnosis but were noted whenever available. Response to treatment with reversal of symptoms was necessary to attribute myopathy to VDD. All children were treated with 600,000 units of vitamin D given orally as 60,000 units per week for 10 doses along with oral calcium supplementation. Children were followed up clinically till resolution of their symptoms unless underlying illness necessitated continued follow-ups. The study was approved by the institutional review board. Ethical approval obtained; dated 05.04.2014.
| » Results|| |
Twenty-six children aged between 21 months and 19 years were included in the final analysis [Table 1]. Eight (30.7%) children were younger than 5 years of age, three (11.5%) children were 6–9 years of age, and 15 (57.7%) were 10–19 years of age. Thirteen (50%) children had known risk factors for vitamin-D deficiency. These included chronic exposure to antiepileptic medication in six, cerebral palsy in three, celiac disease in three, autism spectrum disorder in two, trisomy 21 in two, and hypothyroidism in two. Ten children had a single risk factor and three had two or more risk factors for vitamin-D deficiency. Additional nutritional deficiencies were identified in eight children and included macrocytic anemia in five, iron deficiency anemia in three, and scurvy in two.
|Table 1: Clinical and laboratory characteristics of patients with vitamin-D deficiency-induced myopathy|
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Progressive walking difficulty, trouble getting up from supine, and difficulty going upstairs were the most common constellation of symptoms at presentation in 21 (80.7%) children, including six who had lost independent ambulation and were wheelchair-bound. In four children, hypocalcemic seizures were the presenting symptom. One adolescent boy with spastic quadriplegia who was nonambulatory but was able to sit by himself presented with inability to roll over and pull himself to sit. Body pains were noted in 13 children. Clinical signs of rickets were present in 15 children [Figure 1] and [Figure 2]. Proximal muscle weakness was detected on physical examination in all the children.
|Figure 1: Wrist swelling representing metaphyseal widening due to rickets in a child with osteomalacic myopathy; similar widening was seen at ankles (not shown)|
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Bone metabolic studies (serum calcium, serum phosphate, and serum alkaline phosphatase) were available in 24 children and were consistent with biochemical alterations of rickets/osteomalacia. Serum 25-hydroxy-vitamin D was available in 19 and was low in 18 (one child with normal value had received vitamin D before presentation but had biochemical and radiographic changes of rickets). Elevated PTH was noted in all seven children who underwent this test. Radiographic examinations were performed in 16 children and all of them had rachitic/osteomalacic changes [Figure 3]. One child had bilateral femoral neck fractures, triggered by hypocalcemic seizure. Overall, 25 children had either radiographic and/or biochemical evidence of vitamin-D deficiency rickets/osteomalacia. The remaining one child aged 36 months was diagnosed on the basis of clinical presentation, positive family history of nutritional rickets, and resolution of symptoms on treatment with vitamin D. Creatine kinase was estimated only in eight children and was minimally elevated in one, and one child had significant elevation. None underwent nerve conduction studies/electromyography or muscle biopsy.
|Figure 3: X-ray wrist showing characteristic radiographic changes or rickets namely flaying (widening), fraying, and cupping of the metaphysis|
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Response to treatment was very gratifying in all. One child was lost to follow up after discharge from the hospital. Significant improvement occurred between 2 and 4 weeks, and complete recovery of muscular weakness was noted between 3 and 6 months. All the six children who had become wheelchair-bound became ambulatory again.
| » Discussion|| |
Vitamin-D deficiency-associated myopathy, called osteomalacic (or rachitic) myopathy, like other primary muscle diseases, results in progressive walking difficulty, waddling gait, difficulty rising from supine or sitting, and trouble going upstairs. Muscle weakness may be severe enough to render patients wheelchair-bound., Proximal muscles and lower limbs are predominantly involved. Body pains secondary to osteomalacia are often present. Despite having been known for a very long time,, osteomalacic myopathy continues to be misdiagnosed as inherited or inflammatory muscle disease, or even as a psychiatric disorder.,, This is because there is nothing specific about osteomalacic myopathy to suggest the diagnosis. Therefore, the diagnosis of rachitic/osteomalacic myopathy requires a very high index of clinical suspicion. Once suspected, the diagnosis can easily be established by appropriate laboratory and radiographic investigations. However, the final confirmation comes from the resolution of myopathic symptoms after treatment with vitamin D.,
In children, osteomalacic myopathy has mostly been recognized in adolescents, attributed in part to increased requirement for vitamin D related to the spurt in physical growth and puberty.,,,,,, Signs of rickets may not be present at this age, making it even more difficult to suspect VDD on clinical examination. In contrast, misdiagnosis of rheumatological disorder, primary muscle disease, or even a psychiatric disorder may be made.,,, In our cohort of 26 children, 15 (58%) were adolescents, aged ≥10 years at the time of presentation. All had presentation consistent with proximal myopathy, although four came to attention through hypocalcemic seizures, a known but uncommon manifestation of VDD in adolescents. In six children, myopathy was severe enough to result in complete loss of ambulation, as has been reported by others as well., Diffuse musculoskeletal pain related to osteomalacia was present in 13 adolescents. One adolescent girl sustained bilateral femoral neck fractures after hypocalcemic seizure, a rare presentation of osteomalacia. Except two children with epilepsy who developed myopathy during treatment with antiepileptic medication while being followed up in our own clinic, all other adolescents in our cohort were referred from outside with suspicion of primary muscle disease.
In our study, in addition to adolescents, we found vitamin-D deficiency-associated myopathy in younger children too. Myopathy due to VDD in young children is not widely reported. In infants who are still developing motor skills, VDD can result in motor delay, which depending upon the age of onset of VDD can manifest as delay in head control, rolling over, sitting, pulling to sit, standing, or walking.,,, In older children who already have attained a certain repertoire of motor skills, VDD results in regression of previously acquired motor milestones. Like in adolescents, due to lack of awareness, the diagnosis of VDD-associated myopathy may not be considered, resulting in investigations for alternative inherited, metabolic, or inflammatory neuromuscular disorders.,,, In the present study, eight children between 21 months and 5 years of age had presentation consistent with proximal myopathy. All the eight children had signs of rickets that were either overlooked or not thought to be related to myopathy by the referring physician.
Muscle-specific investigations, such as serum creatine kinase, nerve conduction/electromyographic studies, and muscle biopsy, are of little help in the diagnosis of VDD-associated myopathy as the results of these investigations are either normal or nonspecific,, Other than clinical signs of rickets, diagnosis is often suggested by the presence of radiographic signs of rickets or abnormal biochemical metabolic bone profile. Resolution of muscle weakness with vitamin D treatment is necessary before the symptoms can be attributed to VDD., Only one child in our series had significantly elevated serum kinase, which was possibly caused by muscle injury secondary to seizure and bilateral femoral neck fractures. We did not perform nerve conduction studies, electromyography, and muscle biopsy in any of the children as the diagnosis of VDD was suspected at the initial presentation only. Therapeutic response helped establish a causal relationship between VDD and muscular weakness.
Vitamin-D deficiency in children is most common at two ages: the first peak comes during infancy and young childhood, and the second peak during adolescence and is attributed to an increased requirement for vitamin D due to physiological growth spurt at this age. In addition, factors such as diet, sun exposure, and skin complexion might have played a role in causing vitamin-D deficiency in our children. Specific risk factors were identified in 13 (50%) children, prominent being antiepileptic medications in six and celiac disease in six. A similar pattern of risk factors has been recognized in earlier studies.,
The main limitation of our study is its retrospective nature and selection bias as patients were recruited from pediatric neurology services and represented severe cases of vitamin-D deficiency. Financial constraints precluded biochemical and radiological monitoring during follow-up. Muscle biopsy and nerve conduction/electromyographic studies were not considered essential given the fact that diagnosis could be easily established on the basis of clinical, radiological, and biochemical parameters, and all the patients responded well to treatment with vitamin D.
To conclude, vitamin-D deficiency in children can present with myopathic symptoms. The diagnosis requires a high index of suspicion and meticulous clinical examination. Once suspected, the diagnosis can be established by biochemical and radiological investigations. Treatment with vitamin D produces an excellent clinical response.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Ladhani S, Srinivasan L, Buchanan C, Allgrove J. Presentations of vitamin D deficiency. Arch Dis Child 2004;89:781-4.
Joiner TA, Foster C, Shope T. Many faces of vitamin D deficiency rickets. Pediatr Rev 2000;21:296-302.
Ward LM, Gaboury I, Ladhani M, Zlotkin S. Vitamin D-deficiency rickets among children in Canada. CMAJ 2007;177:161-6.
Weisberg P, Scanlon KS, Li R, Cogswell ME. Nutritional rickets among children in the United States: Review of cases reported between 1986 and 2003. Am J Clin Nutr 2004;80(suppl):1697S-705S.
Skaria J, Kaliyar BC, Srivastva TP, Dube B. Myopathy and neuropathy associated with osteomalacia. Acta Neurol Scand 1975;5:37-8.
Hadjivassiliou M, Chattopadhyay AK, Grünewald RA, Jarratt JA, Kandler RH, Rao DG, et al
. Myopathy associated with gluten sensitivity. Muscle Nerve 2007;35:443-50.
Kaur K, Singh A, Prabhakar BR. Osteomalacia myopathy. J Indian Med Assoc 1980;74:238-40.
Al-Jurayyan NA, Al Issa SD, Al Otaibi HM, Al Jurayyan AN. Adolescent osteomalacia mimicking neuromuscular disorders. Int J Health Sci Res 2015;5:364-367.
Prabhala A, Garg R, Dandona P. Severe myopathy associated with vitamin D deficiency in western New York. Arch Intern Med 2000;160:1199-203.
Ziambaras K, Dagogo-Jack S. Reversible muscle weakness in patients with vitamin D deficiency. West J Med 1997;167:435-9.
Hartman AL. An 18-month-old who could not walk: A case report. Clin Pediatr 2002;41:731-4.
Torres CF, Forbes GB, Decancq GH. Muscle weakness in infants with rickets: Distribution, course, and recovery. Muscle Nerve 1986;2:95-8.
Fluss J, Kern I, Coulon GD, Gonzalez E, Chehade H. Vitamin D deficiency: A forgotten treatable cause of motor delay and proximal weakness. Brain Dev 2014;36:84-7.
Rajeshwari J, Balasubramanian K, Bhatia V, Sharma VP, Agarwal AK. Aetiology and clinical profile of osteomalacia in adolescents in northern India. Natl Med J India 2003;16:139-42.
Al-Said YA, AL-Rached HS, Al-Qahtani HA, Jan MM. Severe proximal myopathy with remarkable recovery after vitamin D treatment. Can J Neurol Sci 2009;36:336-9.
Al-Otaibi HM, Al-Jurayyan NA, Mohamed S, Salih MA. Osteomalacia in adolescents presenting as proximal myopathy. Curr Pediatr Res 2012;16:57-60.
Irani PF. Electromyography in nutritional osteomalacic myopathy. J Neurol Neurosurg Psych 1976;39:686-93.
Schott GD, Wills MR. Muscle weakness in osteomalacia. Lancet 1976;1:626-9.
Smith R, Stern G. Muscular weakness in osteomalacia and hyperparathyroidism. J Neurol Sci 1969;8:511-20.
Narchi H, Jamil NE, Kulaylat N. Symptomatic rickets in adolescents. Arch Dis Child 2001;84:501-3.
Schnadower D, Agarwal C, Oberfield SE, Fennoy I, Pusic M. Hypocalcemic seizures and secondary bilateral femoral fractures in an adolescent with primary vitamin D deficiency. Pediatrics 2006;118:2226-30.
Carvalho NE, Kenney RD, Carrington PH, Hall DE. Severe nutritional deficiencies in toddlers resulting from health food milk alternatives. Pediatrics 2001;107:e46.
Russell JA. Osteomalacic myopathy. Muscle Nerve 1994;17:578-80.
[Figure 1], [Figure 2], [Figure 3]