Gopal P. Moodley

Rickets in children of rural origin in South Africa: is low dietary calcium a factor?

Studies of nine children 4 7/12 to 13 years of age who had rickets are presented. No evidence of renal abnormalities, vitamin D deficiency, or of the inherited varieties of rickets was found. The salient features were their rural origins, mild hypocalcemia with evidence of secondary hyperparathyroidism, and improvement with a normal diet that contained an average of 944 mg calcium/24 hours. It is proposed that the etiology of the rickets is related to low calcium intake with or without a high oxalate concentration in the diet.

Differences in mineral homeostasis, volumetric bone mass and femoral neck axis length in black and white South African women.

In South Africa, appendicular and lumbar spine bone mineral density (BMD) have been found to be similar in black and white women. However, femoral BMD has been found to be higher in black than in white women. Two different techniques were used to recalculate BMD to eliminate the possible confounding influence of ethnic differences in height on areal BMD measurements. Volumetric bone mineral apparent density (BMAD) values were calculated and bone mineral content (BMC) was corrected for body and bone size. This report analyses differences in BMD (corrected for height and weight), BMAD, BMC (corrected for body and bone size), femoral neck axis length (FNAL), mineral homeostasis and bone turnover (BT) in a group of 20 to 49-year-old premenopausal (105 whites and 74 blacks) and 45 to 64-year-old postmenopausal (50 whites and 65 blacks) female South African nurses. The corrected BMD and BMC findings were congruous, showing that both pre- and postmenopausal blacks and whites have similar distal radius and lumbar spine bone mass but that whites have lower femoral neck bone mass than blacks. In contrast, BMAD findings suggest that pre- and postmenopausal whites have lower bone mass at the lumbar spine and femoral neck than blacks but similar bone mass at the distal radius to blacks. There is a greater rate of decline in BMD in postmenopausal whites than in blacks. BMD at the femoral neck was 12.1% lower in premenopausal whites and 16.5% lower in postmenopausal whites than in blacks. There was a positive association between femoral neck BMD and weight in premenopausal blacks (R2=0.5,p=0.0001) but not in whites. Blacks had shorter FNAL than whites in both the pre- and postmenopausal groups. Blacks had lower serum 25-hydroxyvitamin D (25-(OH)D) and higher 1,25-dihydroxyvitamin D (1,25-(OH)2D) levels than whites. There were no ethnic differences in biochemical markers of bone formation (serum alkaline phosphatase and osteocalcin) or bone resorption (urine hydroxyproline and pyridinoline), or in dietary calcium intake in either the pre- or postmenopausal groups. In the postmenopausal group, whites had higher ionized serum calcium (p=0.003), similar serum albumin, lower serum parathyroid hormone (p=0.003) and higher urinary calcium excretion (p=0.0001) than blacks. These results suggest that the higher peak femoral neck BMD in South African blacks than in whites might be determined by greater weight-bearing in blacks and that the significantly lower femoral neck BMD in postmenopausal whites than in blacks is determined by lower peak femoral neck BMD and a faster postmenopausal decline in BMD in whites. The higher incidence of femoral neck fractures in South African whites than in blacks is probably determined by the lower femoral neck BMD and longer FNAL in whites. The greater rate of decline in BMD in postmenopausal whites than in blacks is associated with an increase in urinary calcium excretion in whites. Measurement of biochemical markers of BT has not contributed to the understanding of ethnic differences in BMD and skeletal metabolism in our subjects.

Appendicular Bone Mass in Children with a High Prevalence of Low Dietary Calcium Intakes

We have previously documented evidence of dietary calcium deficiency in black children living in a rural community in the eastern part of South Africa. The present study determined the bone mass of the distal one‐third of the radius in a random sample of children living in the same community and compared their bone mass measurements with those of black children living in a similar rural community but without evidence of dietary calcium deficiency. Further, factors (weight, height, serum corrected total calcium, phosphorus, and alkaline phosphatase [ALP]) that might influence appendicular bone mass were assessed and correlated with the bone mass measurements. A random sample of 306 boys and 345 girls between the ages of 1 and 20 years were included in the study. Hypocalcemia was found in 6.5% of the boys and 5% of the girls, while elevated ALP values were recorded in 20 and 26% of the boys and girls, respectively. After adjusting for differences in age, weight, and height, bone mineral density (BMD) and bone mineral apparent density (BMAD) were significantly lower and bone width (BW) greater in study than control children. In a stepwise regression analysis, weight and/or height accounted for the majority of the observed variance in BMC, BW, and BMD; however, a significant effect of serum calcium (positively) and ALP (negatively) on BMC and BMD was also found. In boys, but not girls, serum ALP also had a positive effect on BW. BMAD was negatively correlated to ALP and positively correlated to serum calcium in both boys and girls. Those children with hypocalcemia or elevated ALP levels had significantly lower BMC, BMD, and BMAD and a trend toward greater BW than children with normal biochemistry. The findings suggest that low dietary calcium intake may have a detrimental effect on appendicular bone density in rural black children. Whether or not these effects are disadvantageous in the long‐term is not known.

Bone mineralization and mineral homeostasis in very low-birth-weight infants fed either human milk or fortified human milk.

Abnormalities in bone mineral metabolism are frequently found in very low-birth-weight infants, especially if fed breast milk. To assess the efficacy of a breast-milk fortifier in the feeding of these very small infants, very low-birth-weight babies (between 1,000 g-1,500 g at birth) were randomly assigned to one of two groups on day 4 of life. The fortified group received the fortifier mixed in equal proportions with their own mothers milk, while the breast-milk group received only their own mothers milk. All infants received an oral vitamin D supplement of 750 IU/day. The study was continued until the infants weighed 1,800 g, at which stage breast feeding was encouraged. Thirty infants in the breast-milk group and 29 in the fortified group completed the study. Infants in the fortified group had significantly lower alkaline phosphatase values, a greater bone mineral content (BMC) and BMC/bone width ratio, and lower urinary calcium excretion than the breast-milk group at a weight of 1,800 g. At follow-up study 3 months after delivery, when most of the infants in both groups had been breast fed for at least 6 weeks, the breast-milk groups biochemical and BMC abnormalities were almost totally corrected and were now similar to those of the fortified group. Thus, the addition of the fortifier to breast milk during the first 4–6 weeks of life decreased the biochemical evidence of abnormal bone mineral homeostasis and increased BMC in very low-birth-weight infants. By 3 months of age, however, the breast-milk group had almost totally corrected its abnormalities.

Endemic skeletal fluorosis in children: hypocalcemia and the presence of renal resistance to parathyroid hormone

Although endemic skeletal fluorosis has been reported in children, hypocalcemia has not been previously noted. In a prevalence study of 260 schoolchildren living in an endemic fluorosis area in South Africa (water fluoride content 8-12 ppm), hypocalcemia was documented in 23%. Furthermore in a separate study of nine children with skeletal symptoms due to endemic fluorosis, hypocalcemia was found in six. 1,25-Dihydroxyvitamin D levels were elevated in the seven children in whom it was measured. Parathyroid hormone (PTH) stimulation tests on admission revealed evidence of impaired phosphaturic responses, typical of acquired pseudohypoparathyroidism type II, and a direct correlation between serum calcium values and the degree of phosphaturia was noted. Repeat tests performed in two of the children after correction of the hypocalcemia by dietary means, revealed a return of normal renal responsiveness. Serum calcium values also correlated inversely with the degree of osteomalacia on iliac crest bone histomorphometry. It is suggested that low dietary calcium intakes might exacerbate the severity of the bone lesions in children living in areas of endemic fluorosis.

Serum osteocalcin has limited usefulness as a diagnostic marker for rickets

Abstract Serum alkaline phosphatase (AP), the bone fraction of which is secreted by osteoblasts, is elevated in rickets. Both normal and elevated levels of serum osteocalcin (OC), a bone-specific marker secreted by osteoblasts, have been reported in rickets. Expression of the OC gene is enhanced by 1,25-dihydroxyvitamin D (1,25(OH)2D) in experimental models. This study assessed serum OC levels in 14 controls and 41 patients with active rickets divided into a phosphopenic (n=20) and a calciopenic (n=21) group. Phosphopenic subjects were older (9.5 versus 5.7 years, P=0.03) with higher median serum calcium level (2.35 versus 2.16 mmol/l, P=0.0002) and serum 25-hydroxyvitamin D level (15.4 versus 10.4 ng/l, P=0.003); and lower serum phosphate (0.80 versus 1.51 mmol/l, P=0.0001), serum 1,25(OH)2D (43.0 versus 95.6 pg/ml, P=0.0001) and intact serum parathyroid hormone level (45.0 versus 141.5 ng/l, P=0.01) than calciopenic subjects. There were no differences in median serum AP (774 versus 1430 IU/l, P=0.17) and OC (14.5 versus 13.4 ng/ml, P=0.6) between the two groups. The mean OC value for the 41 rickets subjects was 15.1 ± 6.2 ng/ml and 17.4 ± 7.8 ng/ml for the 14 control subjects. In the face of markedly elevated serum AP levels in the rickets subjects, all of the serum OC values in the study fell within two standard deviations of the mean for normals. There was no association between serum OC and 1,25-(OH)2D in either the phosphopenic or the calciopenic group. Conclusion These results show that serum osteocalcin levels are not elevated in all forms of active rickets and that, unlike serum alkaline phosphatase, serum osteocalcin cannot be used in the diagnosis of rickets.

Bone disease in African children with slipped capital femoral epiphysis : Histomorphometry of iliac crest biopsies

African teenagers with slipped capital femoral epiphysis (SCFE) not infrequently also have genu valgum (knock-knee). Because we had previously demonstrated metabolic bone disease attributable to dietary calcium deficiency in black teenagers with genu valgum, we examined 29 black teenagers (15 male, 14 female) with SCFE for metabolic bone disease. Each patient had an iliac crest bone biopsy taken (after double tetracycline labeling) for routine histomorphometry, and blood and urine samples for bone biochemistry. Spinal bone mineral density was measured in 13 patients. Compared to reported data, we found our patients to be sexually more immature, older, at least as obese, and to have more severe and more frequently bilateral hip disease. Eighty percent of the children took dairy products only once or twice a week or less frequently, and 37.9% had genu valgum. Compared with race- and age-matched South Africans, bone biopsies in our patients showed lower bone volume (BV/TV, p = 0.0003), wall thickness (p = 0.0002), and trabecular thickness (Tb.Th, p = 0.0002), and a tendency to greater trabecular spacing (Tb.Sp, p = 0.053). Lower osteoid volume (OV/BV, p = 0.0001), osteoid surface (OS/BS, p = 0.0001), osteoid thickness (O.Th, p = 0.0002), double labeled surface (dLS/BS, p = 0.029), and bone formation rate (BFR/BS, p = 0.037) suggested poorer bone forming capacity in our patients. No evidence of hyperparathyroid bone disease or osteomalacia was found. BV/TV was below the reference range (14.2%) in 65.5% of cases; these patients had lower values for Tb.Th (p = 0.037) and Tb.N (p = 0.0003), greater Tb.Sp (p = 0.0002), a tendency to lower adjusted apposition rate (Aj.AR, p = 0.057), and had had less frequent intake of dairy products than those with normal BV/TV (p = 0.024). Furthermore, months since menarche correlated with histomorphometric variables BV/TV (r = 0.667, p = 0.009), Tb.Th (r = 0.745, p = 0.002), Tb.Sp (r = -0.549, p = 0.042), O.Th (r = 0.784, p = 0.0009), and Aj.AR (r = 0.549, p = 0.042). The correlation between Tb.Th and spinal bone mineral content (r = 0.656, p = 0.015) suggests that the reduced trabecular thickness reflected a generalized bone condition. A greater than normal proportion of patients had spinal bone mineral density values below -1 standard deviation (SD) of the mean (osteopenia) (p = 0.001). Patients tested for parathyroid hormone and 25-hydroxyvitamin D levels were found to have normal values. Parathyroid hormone correlated with Aj.AR (r = 0.661, p = 0.038) and serum phosphorus (r = -0.764, p = 0.010). We conclude that sexual immaturity and possibly past dietary calcium deficiency contributed to osteopenia, and that this, together with obesity, led to the development of more severe and more frequently bilateral SCFE in our patients than in reported series of black and white children.

Serum calcium and phosphate disturbances during rehydration in acute dehydrating gastroenteritis

Alterations in serum ionized and total calcium, magnesium, and phosphate concentrations, during recovery from acute dehydrating gastroenteritis, were studied. Fifteen children with acute dehydrating gastroenteritis had serum concentrations of ionized and total calcium, magnesium, phosphate, sodium, potassium, chloride, urea, creatinine, and albumin, as well as acid-base status, evaluated during rehydration and up to 72-h postadmission. The total serum calcium corrected for albumin did not change significantly during rehydration and remained within the normal range. Although serum ionized calcium fell significantly at 24 and 72 h, its concentration was not sufficiently decreased to cause symptomatic hypocalcemia. Serum ionized calcium correlated significantly with pH (r −0.57), bicarbonate (r = −0.63), and albumin (r = +0.65), but not with total serum calcium, magnesium, and phosphate. Serum magnesium remained within the normal range during the study period. Serum phosphate was increased on admission (2.64 ± 0.77 mmol/L), decreased by 12 h (to 0.84 ± 0.32 mmol/L), and then followed by a gradual increase. This study suggests that changes in serum ionized calcium in dehydrating gastroenteritis are not of clinical significance. However, changes in serum phosphate concentration need further evaluation.