Nutritional rickets in Denmark: a retrospective review of children’s medical records from 1985 to 2005

Introduction  This study describes clinical and biochemical characteristics of nutritional rickets and risk factors at diagnosis among children living in Denmark. All medical records from patients with rickets referred to or discharged from hospitals in Southern Denmark from 1985 to 2005 were identified by register search. Materials and methods  Patients included were younger than 15 years of age and fulfilled the diagnostic criteria of primary, nutritional rickets. A total of 112 patients with nutritional rickets were included: 29 were of ethnic Danish origin, and 83 were immigrants. Results  Patients diagnosed before the age of 4 (median 1.4) years displayed the classic clinical signs of rickets, whereas patients diagnosed after the age of 4 (median 12.5) years had few clinical signs and unspecific symptoms. Ethnic Danish patients were only diagnosed before age 24 months, and they accounted for 73% of all cases presenting with hypocalcemic seizures, but biochemically, they did not have more severe rickets. Of patients diagnosed before the age of 4 years, 45% were ethnic Danish. In early childhood, insufficient or no vitamin D supplementation was given in 88% of all cases. Among immigrant girls older than 4 years of age, 78% were veiled. Discussion  Nutritional rickets in Denmark is predominantly a disease among immigrants, but ethnic Danish patients comprised nearly half of all patients diagnosed before the age of 4 years, and they presented more frequently with hypocalcemic seizures. The main risk factors were omitted, such as vitamin D prophylaxis among the youngest patients and veiling among older children/teenagers.     

Nutritional rickets in African American breast-fed infants

OBJECTIVE: To analyze the characteristics of infants and children diagnosed with nutritional rickets at two medical centers in North Carolina in the 1990s. STUDY DESIGN: The physical and radiographic findings, calcium, phosphorus, alkaline phosphatase, and 25-hydroxyvitamin D levels of infants and children diagnosed with nutritional rickets at two medical centers were reviewed. Breast-feeding data were obtained from the North Carolina Women, Infants and Children Program (WIC). RESULTS: Thirty patients with nutritional rickets were first seen between 1990 and June of 1999. Over half of the cases occurred in 1998 and the first half of 1999. All patients were African American children who were breast fed without receiving supplemental vitamin D. The average duration of breast-feeding was 12.5 months. The age at diagnosis was 5 to 25 months, with a median age of 15.5 months. Growth failure was common: length was <5th percentile in 65% of cases, and weight was <5th percentile in 43%. CONCLUSION: Factors that may have contributed to the increase in referrals of children with nutritional rickets include more African American women breast-feeding, fewer infants receiving vitamin D supplements, and mothers and children exposed to less sunlight. We recommend that all dark-skinned breast-fed infants and children receive vitamin D supplementation.     

Deficiency rickets: the current situation in France and Algeria

Persisting vitamin D deficiency rickets in France results from the climatic, environmental and geographic situation of this country. Although systematic administration of vitamin D supplements to infants greatly reduced the prevalence of rickets among infants, clinical and/or biological signs of vitamin D deficiency are still found in children and adolescents, mainly during the winter and in populations vulnerable for economic, cultural or religious reasons. Signs of vitamin D deficiency are also found, during the winter-spring seasons, in pregnant women and their newborns living in urban areas. Such vitamin D deficiencies could be overcome by vitamin D supplementation to susceptible populations. In Algeria, vitamin D deficiency rickets present a continuing public health problem. The persisting high incidence of rickets among children appears to result mainly from economic and cultural factors. Vitamin D supplementation and health education are mandatory to reduce the prevalence of vitamin D deficiency among pregnant women and the occurrence of vitamin D deficiency rickets in infants, whether breast-fed or not.     

Prevalence and risk factors of vitamin D deficiency rickets in Hokkaido, Japan

Background:  Resurgence of vitamin D deficiency rickets has been recognized worldwide. While many cases of this disease have been reported in Hokkaido, the northern island of Japan, no prevalence data is available. Here, we investigated the prevalence and risk factors of vitamin D deficiency rickets in Hokkaido.
Methods:  A specially designed questionnaire was sent to 84 major pediatric departments of hospitals in Hokkaido to collect information of the confirmed cases between July 1999 and June 2004.
Results:  Sixty-seven hospitals responded to the questionnaire. Of these, 20 hospitals reported 31 confirmed cases. All the patients were infants and toddlers, less than 4 years of age. The prevalence of cases in a recent year was estimated to be nine in 100 000 children under four years of age. Most of the 31 cases in our study were breast-fed. Eleven cases showed signs of malnutrition due to unbalanced diet or dietary restriction. Furthermore, the prevalence of cases was higher in the northeastern region than in the southwestern region. The number of cases increased gradually from the end of winter to spring.
Conclusions:  This is the first report ascertaining the prevalence of vitamin D deficiency rickets in Hokkaido, Japan. Limited exposure to sunlight and inadequate diet in early childhood are key risk factors of this disease. Thus, it is crucial to introduce active recommendations for vitamin D supplementation based on age, residential area, and to advocate public awareness for preventing this disease.     

Hypocalcemic Rickets and Dilated Cardiomyopathy: Case Reports and Review of Literature

Internationally, there have been isolated case reports published of children presenting with dilated cardiomyopathy (DCM) in the setting of undiagnosed rickets. Although there has been an increased prevalence of rickets in the United States, there has been only one documented case of associated DCM. At our institution, a hospital database search was conducted from year 1997 to year 2007 to identify patients with confirmed vitamin D deficiency in addition to DCM. Through this search, four exclusively breast-fed African American infants were identified. These infants presented with congestive heart failure secondary to DCM and, at their admission, were found to have laboratory evidence consistent with hypocalcemic rickets. These patients responded dramatically to treatment with vitamin D and calcium, and cardiac function returned to normal within months. Early recognition of vitamin D deficiency was an important factor in these patients’ clinical course. These case reviews present a rare, serious complication of vitamin D-deficient rickets and support evidence for prevention of this nutritional deficiency with vitamin D supplementation in exclusively breast-fed infants.     

Global consensus on nutritional rickets: Implications for Australia

In 2016, a global consensus on the prevention, diagnosis and management of nutritional rickets was published. The bone and mineral working group of the Australasian Paediatric Endocrine Group provides a summary and highlights differences to previous Australian and New Zealand (ANZ) guidelines on vitamin D deficiency and their implications for clinicians. Key points are: (i) The International Consensus document is focused on nutritional rickets, whereas the ANZ guidelines were focused on vitamin D deficiency. (ii) Definitions for the interpretation of 25‐hydroxy vitamin D (25OHD) levels do not differ between statements. (iii) The global consensus recommends that routine 25OHD screening should not be performed in healthy children and recommendations for vitamin D supplementation are not based solely on 25OHD levels. The Australasian Paediatric Endocrine Group bone and mineral working group supports that screening for vitamin D deficiency should be restricted to populations at risk. (iv) Recommendations from the global consensus for vitamin D dosages for the therapy of nutritional rickets (diagnosed based on history, physical examination, biochemical testing and a confirmation by X‐rays) are higher than in ANZ publications. (v) The global consensus recommends the implementation of public health strategies such as universal supplementation with vitamin D from birth to 1 year of age and food fortification. We conclude that updated global recommendations for therapy of nutritional rickets complement previously published position statements for Australia and New Zealand. Screening, management and the implementation of public health strategies need to be further explored for Australia.     

Risk factors for nutritional rickets among children in Kuwait

AIM: To assess the risk factors for nutritional rickets among children in Kuwait. METHODS: One hundred and three children with rickets and 102 control children matched for age and socioethnic characteristics were recruited over a 2 year period (January 1995 to January 1997) in Al-Adan Hospital in Kuwait. Diagnosis was made on clinical, radiologic and biochemical parameters. A specially designed questionnaire was administered by one of the investigators to both mothers of patients and mothers of control subjects to assess the role of social, nutritional and other related factors in the pathogenesis of nutritional rickets. Biochemical investigations included estimation of hemoglobin, serum calcium, serum phosphorus, serum alkaline phosphatase and serum 25-hydroxy vitamin D. RESULTS: The mean birthweights of rickets patients and control subjects were 3.20 +/- 0.46 and 3.19 +/- 0.45 kg, respectively. At the time of diagnosis, bodyweights of the patients and controls were 9.36 +/- 1.50 and 10.15 +/- 2.10 kg, respectively. Heights at the time of diagnosis were 73.58 and 77.24 cm for the patients and the controls, respectively. Mean hemoglobin, serum calcium and serum phosphate were significantly lower in the patients compared with the controls. Alkaline phosphatase was higher among the patients (P < 0.0001). The mean serum 25-hydroxy vitamin D level of the patients was 26.5 nmol/L, compared with 83.5 nmol/L in the controls. The mean age of starting semisolid feeds for the patients was 8.12 months, compared with 5.7 months in the controls. The nutritional quality of semisolid feeds was adequate among 71.6% of the controls as opposed to 13.6% of the patients. CONCLUSION: Nutritional rickets is a multifactorial condition. However, several factors seem to make important contributions. Among these, lack of exposure to sunlight, prolonged breast feeding without supplementation and inadequate weaning practices are important. Maternal education is important as it can influence all of the above factors.     

Rickets in Asian children in Britain

Rickets is common amongst Asian immigrants in Britain. The clinical variants and etiopathogenesis is discussed. Health education and vitamin D supplementation programme initiated at Glasgow has reduced the prevalence of rickets amoug Asians.     

Symptomatic rickets in adolescence.

AIM: To describe 21 cases of symptomatic rickets in adolescents. METHODS: The setting was a primary and secondary care hospital in Saudi Arabia providing medical care to Saudi Arab company employees and their families. Cases of symptomatic rickets diagnosed between January 1996 and December 1997 in adolescents aged 10 to 15 years were assessed with respect to clinical presentation, biochemical and radiological evaluation, dietary assessment, and estimation of sun exposure. RESULTS: Symptomatic rickets developed in 21 adolescents (20 females), with a prevalence rate of 68 per 100 000 children years. Presentation included carpopedal spasms (n = 12), diffuse limb pains (n = 6), lower limbs deformities (n = 2), and generalised weakness (n = 1). Biochemical findings included hypocalcaemia (n = 19), hypophosphoraemia (n = 9), raised serum alkaline phosphatase (n = 21) and parathormone (n = 7), and reduced 25-hydroxyvitamin D concentrations (n = 7). Radiological studies were suggestive of rickets in only eight children. All children had an inadequate dietary calcium and vitamin D intake. All but one had less than 60 minutes sun exposure per day. CONCLUSION: Even in sunny climates, adolescents, especially females, can be at risk of rickets. Hypocalcaemic tetany and limb pains were the most common presenting symptoms. Radiological evidence was not present in every case.     

Adolescent rickets in Saudi Arabia: a rich and sunny country

In this retrospective study from Saudi Arabia, which is a rich and sunny country, we report our experience with 34 adolescents (20 females, 10 males) with rickets. The commonest cause was vitamin D deficiency (58.8%) followed by rickets due to low calcium intake (11.8%) and genetic causes, including possible 25-hydroxylase deficiency (8.8%). The etiology of nutritional rickets is multifactorial, including lack of sun exposure and inadequate calcium intake. The clinical symptoms were nonspecific and therefore cases in this country are either underdiagnosed or missed. Vitamin D deficient patients needed an average of 19 months of treatment before recovery. High dose vitamin D plus calcium supplementation are recommended for treatment. Measures to prevent rickets in all age groups including adolescents are suggested. Further studies on nutritional and genetic forms of rickets are recommended.     

Reemerging nutritional rickets: a historical perspective

Recent case reports highlight the resurgence of rickets in certain groups of breastfed infants. Infants residing in the North, irrespective of skin color, and dark-skinned African American infants residing anywhere in the United States are most vulnerable to nutritional rickets if they are exclusively breastfed past age 6 months without vitamin D supplementation. At the turn of the 20th century, rickets was nearly universal among African American infants living in the North. The discovery of vitamin D, the initiation of public health campaigns to fortify infant foods with vitamin D, and the supplementation of vitamin D to breastfed infants were responsible for overcoming the rickets scourge. We review a classic nutritional study by Alfred F. Hess, one of the greatest clinical nutritional researchers of the early 20th century, in the context of the resurgence of rickets, especially among dark-skinned infants. The Columbus Hill district, a black community of New York, NY, served as the setting for the study. Sixty-five infants (aged 1-17 months) entered a 6-month open-label trial of daily cod liver oil therapy. Participants were assessed for signs of rickets at recruitment and at 2, 4, and 6 months. Cod liver oil prevented the development of rickets in 34 (92%) of 37 infants treated for 6 months and in 7 (58%) of 12 treated for 4 months. Of the 16 infants who did not take the prescribed treatment, rickets progressed unremittingly in 15. Hess translated his success into a public health campaign leading to the development of the first rickets clinic in 1917. This was the first step in the conquest of the rickets epidemic of the early 20th century.     

Presentation of vitamin D deficiency.

AIMS: To describe the various ways in which vitamin D deficiency presents in children in selected districts of London and to identify which factors, if any, determine the mode of presentation. METHODS: Retrospective review of patients presenting to Newham General, Royal London, Great Ormond Street, and King's College Hospitals between 1996 and 2001 with either hypocalcaemia or rickets caused by vitamin D deficiency. Children with plasma 25-hydroxyvitamin D levels <25 nmol/l (10 ng/ml) were considered to have vitamin D deficiency. RESULTS: Sixty five children, mostly from Black or Asian ethnic minority groups, were identified, 29 of whom had hypocalcaemic symptoms. Seventeen of these had no radiological evidence of rickets. The remainder (48 children) had radiological evidence of rickets with or without clinical signs. Symptoms and signs reverted to normal in all cases with vitamin D supplementation. All children who presented with symptomatic hypocalcaemia were aged either <3 or >10 years. There was a strong correlation between age at presentation and population growth velocity reference data. CONCLUSIONS: Rickets remains a problem in the UK especially in "at risk" ethnic minority groups. Symptomatic hypocalcaemia is an important, but under-recognised presenting feature. Growth rate is likely to be an important factor in determining the mode of presentation. Unexplained hypocalcaemia should be attributed to vitamin D deficiency in "at risk" ethnic minority groups until proved otherwise.     

Presentation of vitamin D deficiency

Aims: To describe the various ways in which vitamin D deficiency presents in children in selected districts of London and to identify which factors, if any, determine the mode of presentation. Methods: Retrospective review of patients presenting to Newham General, Royal London, Great Ormond Street, and King''s College Hospitals between 1996 and 2001with either hypocalcaemia or rickets caused by vitamin D deficiency. Children with plasma 25-hydroxyvitamin D levels <25 nmol/l (10 ng/ml) were considered to have vitamin D deficiency. Results: Sixty five children, mostly from Black or Asian ethnic minority groups, were identified, 29 of whom had hypocalcaemic symptoms. Seventeen of these had no radiological evidence of rickets. The remainder (48 children) had radiological evidence of rickets with or without clinical signs. Symptoms and signs reverted to normal in all cases with vitamin D supplementation. All children who presented with symptomatic hypocalcaemia were aged either <3 or >10 years. There was a strong correlation between age at presentation and population growth velocity reference data. Conclusions: Rickets remains a problem in the UK especially in "at risk" ethnic minority groups. Symptomatic hypocalcaemia is an important, but under-recognised presenting feature. Growth rate is likely to be an important factor in determining the mode of presentation. Unexplained hypocalcaemia should be attributed to vitamin D deficiency in "at risk" ethnic minority groups until proved otherwise.     

Rickets in exclusively breast fed babies

Articles appear periodically in Indian and western literature, about occurrence of vitamin D deficiency in exclusively breast fed babies. Some countries have formulated guidelines for prevention of vitamin D deficiency in such babies. In this study, twenty cases of nutritional rickets were diagnosed in exclusively breast fed babies between December 2003 and December 2006. None of them received vitamin D supplementation. Through this study, we hope to initiate further research and debate among the policymakers on whether or not vitamin supplementation should be given to all exclusively breast fed babies and lead to a formulation of clear cut guidelines in the Indian context.     

A comparison of breastfed children with nutritional rickets who present during and after the first year of life

This study compares the patient characteristics of breastfed children in Baltimore, Maryland from 1990 to 2000 diagnosed with nutritional rickets at 12 months or younger to those older than 12 months to gain a better understanding of nutritional and environmental factors. All 30 of the patients were African American. Patients 12 months or younger (n=15) compared to those older than 12 months (n=15) were more likely to be born during the summer and to present with seizures and hypocalcemia. We recommend vitamin D supplementation of all breastfed infants at an early age and that supplementation continue throughout the duration of breastfeeding.     

Nutritional rickets at puberty

Four adolescent Asians with vitamin D deficiency rickets were seen in Derby in the 5 years 1967 to 1971. They had an extremely low intake of vitamin D, and this, combined with the extra metabolic demands of puberty, was judged to be the main cause of the rickets. However, since investigation of their sibs revealed 4 further cases of rickets, it is possible that some of these children had an inherited disability in the metabolism of vitamin D. 2 cases of iron deficiency anaemia were found among their sibs. We suspect that nutritional deficiencies may be widespread in the Asian community in Britain and that prevention depends on dietary education.     

Nutritional rickets in San Diego

Despite the ability of infants to synthesize vitamin D through exposure to sunlight, nutritional rickets occasionally develops in infants even in areas with perennially sunny climates. In San Diego, a 1-year-old breast-fed infant presented with classic signs of nutritional rickets. Unsupplemented breast milk, limited exposure to sunlight, and darkly pigmented skin were predisposing factors. Because of this occurrence, we conducted a survey of vitamin supplementation practices among pediatricians in San Diego. Twenty-nine percent of 160 respondents do not prescribe vitamin D supplements for breast-fed infants. Those in practice less than ten years were even less likely to prescribe a vitamin supplement compared with their older colleagues. The patient report, coupled with a literature review, suggest the need for vitamin D supplementation for all nursing infants.     

Nutritional rickets around the world: causes and future directions

INTRODUCTION: Nutritional rickets has been described from at least 59 countries in the last 20 years. Its spectrum of causes differs in different regions of the world. METHODS: We conducted a systematic review of articles on nutritional rickets from various geographical regions published in the last 20 years. We extracted information about the prevalence and causes of rickets. RESULTS: Calcium deficiency is the major cause of rickets in Africa and some parts of tropical Asia, but is being recognised increasingly in other parts of the world. A resurgence of vitamin D deficiency has been observed in North America and Europe. Vitamin D-deficiency rickets usually presents in the 1st 18 months of life, whereas calcium deficiency typically presents after weaning and often after the 2nd year. Few studies of rickets in developing countries report values of 25(OH)D to permit distinguishing vitamin D from calcium deficiency. CONCLUSIONS: Rickets exists along a spectrum ranging from isolated vitamin D deficiency to isolated calcium deficiency. Along the spectrum, it is likely that relative deficiencies of calcium and vitamin D interact with genetic and/or environmental factors to stimulate the development of rickets. Vitamin D supplementation alone might not prevent or treat rickets in populations with limited calcium intake.     

Unique form of rickets with low serum 25-hydroxyvitamin D in two normally nourished children

We present an unusual type of rickets involving two children: a 2 year old boy and a 15 month old boy, who presented with marked bowing of the lower extremities and bulging of costochondral junctions. Both children had normal growth, with their height and body weight greater than the 50th and 97th percentile for age. Roentgenograms of their extremities showed the typical changes of vitamin D refractory rickets. Serum alkaline phosphatase levels were elevated and serum levels of calcium and phosphate were both within the normal range. No primary cause for the rickets, including nutritional deficiencies, was found in the two patients. Characteristic findings were persistently low serum 25-hydroxyvitamin D (25-OH-D) and normal 1,25-dihydroxyvitamin D (1,25-(OH)2-D). Improvements in clinical and X-ray findings were observed after either oral administration of 1 α-(OH)-D3 (9–15 μg per day) or massive vitamin D2 therapy (600 000 IU single injection). The low serum levels of 25-OH-D did not increase unless massive vitamin D2 therapy was also given. These two cases represent a unique form of rickets that does not meet the criteria for any type of previously known rickets.     

Clinical and radiographic improvement of rickets in Bangladeshi children as a result of nutritional advice

BACKGROUND: Calcium-deficiency rickets is common in south-east Bangladesh and responds to calcium supplementation. AIM: To evaluate the healing effect on active rickets of a five-component nutritional advice programme aimed at doubling dietary calcium intakes. METHODS: Forty-nine children aged <10 years with mild lower limb deformities and active rickets were followed over a period of 12 months. All were provided with a five-component nutritional advice programme advocating (i) the routine addition of 1 g limestone/kg rice, (ii) consuming small fish (including bones) instead of large ones, and (iii) daily consumption of 5 g ground sesame seeds, (iv) 100 g leafy vegetables and, if possible, (v) 100 ml of milk. RESULTS: Radiographic scores improved in 90% of children. The response was positively associated with age (r=0.34, n=48, p=0.01) and severity of radiographic score at baseline (r=0.85, n=49, p<0.0001). CONCLUSIONS: Despite the lack of a statistically significant association between radiographic improvement and compliance with nutritional advice, in mild calcium-deficiency active rickets, nutritional advice may be a cost-effective treatment and possibly a valuable long-term solution to the problem.