Nutritional and metabolic rickets

Nutritional rickets is casued by vitamin D deficiency due to lack of exposure to sunlight. Neonatal rickets occurs only in infants born to mothers with very severe osteomalacia. Calcium deficiency alone does not cause mineralisation defects. It only causes osteoporosis and secondary hyperparathyroidism with raised plasma, 1,25 (OH)₂D and osteocalcin. Low 25-OHD, increased IPTH, increased alkaline phosphatase in plasma and decreased calcium and increased hydroxyproline in urine are diagnostic of rickets. Low or undetectable plasma levels of 25-OHD, in presence of high plasma 1,25(OH)₂D and IPTH are often observed during treatment with vitamin D. Even the marginal intakes of fluoride (> 2.5 mg/day) cause rickets in calcium deficient children. Indian children often need high dose of vitamin D due to severely depleted D stores, high IPTH and severe bone disease (radiologic and histomorphometric) for treatment.     

Osteomalacia of the mother —rickets of the newborn

During the last 4 years we observed four cases of neonatal rickets. The mothers of the infants suffered from osteomalacia for 1–3 years prior to its diagnosis shortly after the birth of their children. All four infants were born with craniotabes, and one infant had, in addition, a radial fracture. The diagnoses were confirmed by radiological and laboratory tests which revealed a rarefied bone structure, decreased serum 25-hydroxy-vitamin D and increased alkaline phosphatase levels in all patients. The disorder regressed under low-dose vitamin D₃ therapy. As osteomalacia seems to be predominant in oriental women living in Berlin, it is necessary to consider vitamin D deficiency when clinical symptoms of this disease arise and to treat these women at least during pregnancy.     

25-Hydroxyvitamin D and total calcium: extraordinarily low plasma concentrations in Saudi mothers and their neonates

Venous blood was obtained from 100 consecutive and unselected Saudi Arabian mothers and their neonates within 48 h after delivery. Plasma levels of 25-hydroxyvitamin D (25-OHD) and total calcium were measured in paired samples. Fifty-nine mothers and 70 neonates had subnormal (less than 10 ng/ml) 25-OHD levels. Plasma Ca concentrations were low in 61% of the mothers and 59% of the newborns consisting of 10 preterm and 38 full term babies. There were significant correlation between the plasma levels of maternal and neonatal 25-OHD (r = 0.54; P = 0.0001), maternal 25-OHD and Ca (r = -0.22; P = 0.03), neonatal 25-OHD and Ca (r = -0.28; P = 0.0009), and maternal and neonatal calcium levels (r = 0.46; P = 0.0001). Nevertheless, maternal 25-OHD was not invariably higher than that in the infant. Normocalcemia was observed in 29 neonates and 26 mothers (20 mother/baby pairs) in the presence of subnormal maternal 25-OHD. Twenty babies and 16 mothers including nine mother/baby pairs had hypocalcemia in the presence of normal levels of 25-OHD. This indicates that vitamin D plays a crucial, but not exclusive, role in calcium homeostasis during pregnancy. This study revealed that vitamin D deficiency is very prevalent during pregnancy in Saudi Arabia. It also showed that asymptomatic hypocalcemia in full term babies is far commoner than is generally appreciated. It is considered that vitamin D deficiency is primarily due to lack of exposure to sunlight. Encouragement to obtain sunlight exposure and fortification of food are the only alternative measures.     

Vitamin D Status of term exclusively breastfed infants and their mothers from India

Objectives: (i) To measure 25‐OH vitamin D levels in term infants at 10 weeks and 6 months and to correlate with maternal vitamin D levels at 10‐week postpartum (ii) To evaluate infants at 6 months for rickets. Patients and methods: A total of 179 exclusively breastfed infant–mother pairs 96 appropriate‐for‐gestational age (Group 1) and 83 small‐ for‐ gestational age infants (Group 2) recruited at 10 weeks. At 6 months, 52 in group 1 and 45 in group 2 were evaluated. Venous blood sample were collected at 10 weeks and 6 months in infants and at 10 weeks in mothers for calcium, phosphorus, alkaline phosphatase and 25‐OH vitamin D estimation. Results: Mean 25‐OH vitamin D levels of infants (n = 97) were 11.55 ± 7.17 ng/mL at 10 weeks and 16.96 ± 13.33 ng/mL at 6 months (p < 0.001). Mean vitamin D levels of infants in group 1 and group 2 did not differ at recruitment and 6 months (p > 0.05)). Maternal vitamin D levels in group 1 and group 2 were 8.89 ± 5.97 and 9.87 ± 6.44 ng/mL, respectively (p = 0.44). Significant correlation was observed between 25‐OH vitamin D of infants and mothers (p < 0.05). At 10 weeks, 55.67% infants, 70% mothers and at 6 months, 44.33% infants had vitamin D < 11 ng/mL. At 6 months, 16.49% infants developed rickets. Conclusions: Exclusively breastfed infants and their mothers are Vitamin D deficient, hence the need to improve vitamin D status.     

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.     

Vitamin D dependent rickets: Decreased sensitivity to 1,25-dihydroxyvitamin D

A patient with vitamin D dependent rickets with decreased sensitivity to 1,25-Dihydroxyvitamin D was observed. She suffered from bone pain of two years duration beginning at 12 years of age and was found to be suffering from hypocalcemia, secondary hyperparathyroidism and osteomalacia. Laboratory findings revealed normal serum 25-hydroxyvitamin D (27 ng/ml) and markedly elevated serum 1,25-dihydroxyvitamin D (131.9 pg/ml). The hypocalcemia was refractory in spite of administration of 25,000 units of vitamin D₂, but therapy with high doses of oral 1-hydroxyvitamin D₃ resulted in significant elevation of the serum calcium level. The clinical findings and course of the patient's disease were quite different from those of other patients with vitamin D dependent rickets reported by other authors.     

Maternal compared with infant vitamin D supplementation.

Vitamin D metabolites were studied in mother-infant pairs at delivery and eight and 15 weeks after that to evaluate the possibility of vitamin D supplementation of infant through the mother. Healthy mothers (n = 49) delivering in January received daily either 2000 IU (group 1), 1000 IU (group 2), or no (group 3) vitamin D. Their infants were exclusively breast fed, and those in group 3 received 400 IU of vitamin D a day. After eight weeks of lactation the infantile vitamin D concentrations were similar in groups 1 and 3 but significantly lower in group 2. The serum 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations were also lower in group 2. The mean mineral, parathyroid hormone, and alkaline phosphatase values showed no intergroup differences at any point. No infants showed any clinical or biochemical signs of rickets, and their growth was equal. In conclusion, a daily postpartum maternal supplementation with 2000 IU of vitamin D, but not with 1000 IU, seems to normalise the vitamin D metabolites of breast fed infants in winter. Maternal safety with such supplementation over prolonged periods, however, should be examined.     

Profile of rickets in hilly areas of himachal pradesh

Eighty four children of vitamin D deficiency rickets were studied. Most of the children belonged to families of poor socio-economic status and over half were malnourished. Thirteen infants aged 1 to 9 months presented with tetany, They had lower serum calcium (7.5 mg/dl) than patients with rickets but no tetany (serum calcium 8.4 to 9.8 mg/dl) Clinical features of hypocalcemia were also more marked and more common in patients with tetany. Important etiological factors were poor diet of the mothers, prevaling practices of rearing such as prolonged breast feeding without supplement and lack of exposure to sun due to excessive clothing to protect against the cold weather.     

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.     

Case-control study of breast milk calcium in mothers of children with and without nutritional rickets

Aim: Despite similarly low calcium intakes and normal vitamin D status, only some Nigerian children develop nutritional rickets. We hypothesized that mothers with children who had developed rickets might have lower breast-milk calcium concentration than mothers with normal children and compared the breast-milk calcium concentration of mothers who had had children with rickets with those who had not (controls). Methods: We collected breast milk from 35 Nigerian mothers who had previously had children with nutritional rickets. For each case mother, we collected breast milk from three matched control mothers at the same stage of lactation (±4 weeks) who had had no children with rickets. Data were collected about parity, stage of lactation, and the infant's intake. The mother's bone density was measured. Results: The mean breast milk calcium concentration of mothers of children with rickets (4.30±1.24 mmol/L) was less than that of control mothers (4.65±1.03 mmol/L; P=0.034 in multivariate regression controlling for duration of lactation and resumption of menses). Forearm bone mineral content was significantly related to breast milk calcium concentration (r = 0.20) after adjusting for height, weight, and bone area (P=0.028). Conclusion: : Reduced breast-milk calcium concentration may contribute to a reduced calcium intake in infancy and predispose children to nutritional rickets.     

Congenital rickets

Although rickets in premature newborns is known to occur, term babies presenting at birth is uncommon. We report a term baby born to a mother with osteomalacia, and presented at birth with signs of florid rickets which was confirmed biochemically. After 4 weeks of treatment, radiological signs of healing were seen.     

Low breast milk phosphorus concentration in familial hypophosphatemia

We report breast milk mineral concentrations in a mother with familial hypophosphatemia that was untreated due to poor compliance with medical advice. Milk phosphorus content was extremely low despite normal maternal serum phosphorus concentrations. Milk calcium concentrations were only modestly decreased so that the ratio of calcium to phosphorus was greatly elevated. It appears that mothers with this disorder who breast feed should have their milk mineral content carefully monitored during lactation. If milk mineral content is abnormal despite maternal therapy with phosphorus and vitamin D, infants may require supplementation of mineral intake.     

Vitamin D deficiency rickets in breast-fed infants presenting with hypocalcaemic seizures

At the Aga Khan Hospital (AKUH), 65 infants presented with hypocalcaemic seizures, subsequently found to have rickets. Forty-six infants less than 6 months were totally or predominantly breast fed. In a subgroup of 15 mothers and their infants, we found very low plasma levels of 25(OH) vitamin D of < 5 /ig/1 and 7.53.3$uMg/l, respectively. Neither mothers nor infants received vitamin D supplementation. Maternal vitamin D deficiency and non-supplementation in the infants were the likely causes of rickets in our patients. Prophylactic vitamin D 400 i.u. administered to infants up to 2 years and 800 i.u. to women in pregnancy and during lactation is recommended to prevent vitamin D deficiency.     

Effect of combined maternal and infant vitamin D supplementation on vitamin D status of exclusively breastfed infants

Severe vitamin D deficiency in mothers and their breastfed infants is a significant health problem in the Middle East. Supplementation of the breastfed infant alone with the recommended dose of vitamin D may be insufficient in high‐risk population. We investigated the effect of combined maternal and infant vitamin D supplementation on vitamin D status of the breastfed infant. We examined also the effect of supplementation on vitamin D antirachitic activity of breast milk in a subset of mothers. Healthy breastfeeding mothers (n = 90) were randomly assigned to 2000 IU daily (group 1) or 60 000 IU monthly (group 2) of vitamin D₂, and all their infants (n = 92) received 400 IU daily of vitamin D₂ for 3 months. Most infants had vitamin D deficiency – 25‐hydroxyvitamin D [25(OH)D] ≤ 37.5 nmol L^?1– at study entry. Serum 25(OH)D concentrations at 3 months increased significantly from baseline in infants of mothers in group 1 (13.9 ± 8.6 vs. 49.6 ± 18.5 nmol L^?1, P < 0.0001) and group 2 (13.7 ± 12.1 vs. 44.6 ± 15.0 nmol L^?1, P < 0.0001). Maternal and infant serum 25(OH)D concentrations correlated positively at baseline (r = 0.36, P = 0.01) and 3 months (r = 0.46, P = 0.002). Milk antirachitic activity increased from undetectable (<20 IU L^?1) to a median of 50.9 IU L^?1. In conclusion, combined maternal and infant vitamin D supplementation was associated with a threefold increase in infants’ serum 25(OH)D concentrations and a 64% reduction in the prevalence of vitamin D deficiency without causing hypervitaminosis D.     

Rickets in Asian immigrants

Although rickets is considered to have practically disappeared in developed countries, there is increasing evidence of widespread vitamin D deficiency among immigrants. Many studies report rickets and osteomalacia in Asian infants, adolescents and pregnant women moving to developed countries with a cooler climate. The etiopathogenesis of this disorder of calcium and D vitamin metabolism depend mainly on environmental and sociocultural factors, associated with low exposure to sunlight and low calcium intake, among other dietary factors. Given the recent increase in the number of immigrants to Spain, the prevention and treatment of this disease in Asian children and adolescents should be reviewed.     

Subclinical hypovitaminosis D among exclusively breastfed young infants

OBJECTIVE: To determine Vitamin D status of mother-newborn diads at birth and of their exclusively breastfed (EBF) infants at 3 months. DESIGN: Longitudinal study. METHODS: Exclusively breastfed infants born at term with birth weight > 2.5 kg to normal, healthy mothers followed till 3 months. Serum calcium, phosphorous, heat labile alkaline phosphatase (HLAP) and 25(OH)D estimated in 42 mother / cord blood diads and in 35 (EBF) infants followed up at 3 months. Twenty five (OH)D < 15 ng/mL was considered low and 15 to 25 ng/mL low to normal. RESULTS: Ca, P, HLAP were significantly higher in cord blood (P < 0.001) but mean 25 (OH)D, 19.36 ng/mL was comparable to maternal level of 22.9 ng/mL (r = 0.82, P < 0.001). At 3 months only HLAP was significantly higher compared to cord blood. Higher 25 (OH)D at 3 months correlated with higher 25 (OH)D values in cord blood (r = +0.616, P < 0.001) as well as higher antenatal maternal levels (r = + 0.552, P < 0.001). Serum 25 (OH)D values < 25 ng/mL was observed in 50 % mothers, 62 % cord blood specimens and 80 % infants at 3 months. CONCLUSIONS: Subnormal maternal vitamin D status is associated with vitamin D deficiency in newborns and persists in exclusively breastfed infants.     

Endocrine control and disturbances of calcium and phosphate metabolism in children

Most disorders of extracellular calcium and phosphate metabolism in childhood can be attributed to primary increased or decreased secretion/action of 1,25-dihydroxyvitamin D₃ and parathyroid hormone or primary increased or decreased urinary excretion of phosphate and calcium. Based on this pathogenetic classification the most important diseases related to calcium and phosphate metabolism will be discussed.Abbreviations PTH parathyroid hormone - 1,25(OH)₂D₃ 1,25-dihydroxyvitamin D₃ - 25(OH)D₃ 25-hydroxyvitamin D₃ - 24,25(OH)₂D₃ 24,25-dihydroxyvitamin D₃ - VDR vitamin D deficiency rickets - VDDR vitamin D dependency rickets - MEN multiple endocrine neoplasia - HP hypoparathyroidism - PHP pseudohypoparathyroidism - AHO Albright's hereditary osteodystrophy - XLH X-linked familial hypophosphataemic rickets     

Varying role of vitamin D deficiency in the etiology of rickets in young children vs. adolescents in northern India

The relative importance of calcium vs. vitamin D deficiency in the etiology of nutritional rickets in the tropics may be different in children compared with adolescents. We studied calcium intake, sun exposure, serum alkaline phosphatase, and 25 hydroxyvitamin D in 24 children and 16 adolescents with rickets/osteomalacia. The values were compared with those obtained in control subjects (34 children and 19 adolescents). We found that young children with rickets had lower calcium intake compared with controls (285 +/- 113 vs. 404 +/- 149 mg/day, p < 0.01), but similar sun exposure (55 +/- 28 vs. 56 +/- 23 min x m2/day) and 25 hydroxyvitamin D (49 +/- 38 vs. 61 +/- 36 nmol/l). Sixteen of 24 children with rickets had 25 hydroxyvitamin D above the rachitic range (> 25 nmol/l), in contrast to one of 16 adolescents. Adolescent patients had low calcium intake vs. controls (305 +/- 196 vs. 762 +/- 183 mg, p < 0.001), and lower sunshine exposure (16 +/- 15 vs. 27 +/- 17 min x m2/day, p < 0.01) and serum 25 hydroxyvitamin D (12.6 +/- 7.1 vs. 46 +/- 45.4 nmol/l, p < 0.001). The odds ratio for developing rickets with a daily calcium intake below 300 mg was 4.8 (95 per cent CI, 1.9 - 12.4, p = 0.001). Subjects with rickets were randomized to receive 1 g calcium daily, with or without vitamin D. Children showed complete healing in 3 months, whether they received calcium alone or with vitamin D. Adolescents showed no response to calcium alone, but had complete healing with calcium and vitamin D in 3-9 months (mean 5.3 months). Thus deficient calcium intake is universal among children and adolescents with rickets/osteomalacia. Inadequate sun exposure and vitamin D deficiency are important in the etiology of adolescent osteomalacia.     

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.     

Dilated cardiomyopathy secondary to nutritional rickets

Two 9-month-old breastfed infants presented with congestive heart failure secondary to dilated cardiomyopathy. No underlying aetiology was found, except for the presence of advanced rickets. Following treatment with vitamin D and calcium supplements, both infants quickly recovered normal myocardial function.