Although rarely seen in the United States and Europe, rickets is still a problem in many parts of the world. It is currently ranked among the top five childhood diseases in developing countries. Inadequate vitamin D—from dietary sources or sunlight—has long been thought to be the cause of rickets. Recent studies and case reports, however, have found that children with rickets respond to calcium supplementation. To pursue this observation, Thacher and colleagues performed a trial to evaluate calcium supplementation with and without vitamin D in children with rickets.

Children were followed at a clinic in Nigeria. They enrolled in the study if they were between one and 14 years of age and found to have radiographic characteristics of rickets that included genu varum, genu valgum and widened wrists. Rickets was considered to be active if the child had cupping or fraying of metaphyseal margins or if the epiphyseal plates were wider than normally expected for age. Excluded were children who had taken calcium or vitamin D supplements in the prior 12 weeks and those who had any other chronic illnesses such as renal disease, liver disease or tuberculosis.

For each child enrolled, a healthy control subject of the same age, sex and weight (within 1 to 2 kg [2.2 to 4.4 lb]) was also enrolled. The primary outcome variables were changes in serum calcium, alkaline phosphatase and improvements on radiographs.

The baseline estimate of the children's calcium intake was determined from the parents at two separate interviews about daily food intake. Children who met eligibility criteria were randomized into three groups: the first group received 600,000 U of intramuscular vitamin D initially and at week 12 plus daily doses of placebo tablets; the second group was given 1,000 mg of oral calcium daily along with two placebo injections of mineral oil; the third group of children received 1,000 mg of oral calcium daily plus two 600,000 U injections of vitamin D.

Laboratory data obtained at baseline included serum calcium, phosphorus, alkaline phosphatase, albumin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels. These data were obtained again at weeks 12 and 24. Radiographs of the wrists and knees were obtained at baseline and again at weeks 12 and 24. A 10-point scoring system to assess radiographic changes of the radius, ulna, femur and tibia was used. A score of less than 1.5 by week 24 was considered to be consistent with complete resolution of the abnormalities of rickets. Three physicians who were blinded to the treatment status of the children read the radiographs.

Of 297 children who were initially screened, 123 were included after exclusion criteria were applied. The median age of the children was 44 months, with a similar distribution of males and females. The children with rickets were significantly shorter and weighed less than the control children. Of note, the median intake of dietary calcium at baseline was only 203 mg in the treatment group and 196 mg in the control subjects. The initial radiographic scores in the children with rickets correlated with their lower serum alkaline phosphatase levels and calcium intake. The mean alkaline phosphatase level was 812 U per L in the children with rickets and 245 U per L in the control group. The calcium levels were 7.7 and 9 mg per dL, respectively.

After 24 weeks, the percentage of children with adequate healing on radiographs (score: less than 1.5) who had a serum alkaline phosphatase level of less than 350 U per L was similar in the calcium and the calcium-vitamin D groups (61 and 58 percent). Just 19 percent of the children who were given only vitamin D had comparable healing. The serum calcium levels for the first two groups of children increased from approximately 7.7 to 9 mg per dL. In the children who were given only vitamin D, the calcium level increased to 8.3 mg per dL (2.07 mmol per L) at 24 weeks. Subjective improvement was noted in 86 percent of children who received calcium, 93 percent who had calcium and vitamin D, and 83 percent who were given vitamin D alone. Of six fractures, four were in the children who received only vitamin D.

The authors conclude that calcium supplementation alone or in combination with vitamin D is an effective treatment for rickets. These findings support their hypothesis that a deficiency of calcium plays a major role in the occurrence of rickets in children.

editor's note: Although rickets is not a significant problem in the United States, this study lends additional support to the benefits of dietary calcium. In an accompanying editorial, Bishop discusses the issue of calcium intake for children, with his final words of advice being “drink up your milk, and go play outside.”