Case-control study of factors associated with nutritional rickets in Nigerian children.

OBJECTIVE: Because the causes of nutritional rickets in tropical countries are poorly understood, we conducted a case-control study to determine factors associated with rickets in Nigerian children. STUDY DESIGN: We compared 123 Nigerian children who had rickets with matched control subjects. Dietary, demographic, anthropometric, and biochemical data were collected to assess factors related to calcium and vitamin D status, which might predispose children to rickets. RESULTS: Mean (+/- SD) daily dietary calcium intake was low in both children with rickets and control children (217 +/- 88 mg and 214 +/- 77 mg, respectively; P =.64). Children with rickets had a greater proportion of first-degree relatives with a history of rickets (14.6% vs 3.1%; P <.001), a shorter mean duration of breast-feeding (16.0 vs 17.3 months; P =.041), and a delayed age of walking (14 vs 12 months; P <.001). Among children with rickets, biochemical features suggestive of calcium deficiency included hypocalcemia, extremely low calcium excretion, and elevated 1, 25-dihydroxyvitamin D and parathyroid hormone values. Median 25-hydroxyvitamin D concentrations were 32 and 50 nmol/L (13 and 20 ng/mL) in children with rickets and control children, respectively (P <.0001). Only 46 subjects with rickets (37%) had 25-hydroxyvitamin D values <30 nmol/L (12 ng/mL). CONCLUSIONS: Vitamin D deficiency appears unlikely to be the primary etiologic factor of rickets in African children. Moreover, low dietary calcium intake alone does not account for rickets. Insufficient dietary calcium probably interacts with genetic, hormonal, and other nutritional factors to cause rickets in susceptible children.

Chemical, pathological and toxicological studies of the effects of RICOM-1013-J of Ricinus communis var minor on women volunteers and rodents.

RICOM-1013-J (Ricinus communis var minor) administered orally once to each of 12 women volunteers at a dose of 2.5-2.7 g per 8 months, protected against pregnancy over a period of 7-8 months of study. A study of the effect of a contraceptive dose (20 mg/kg) on metabolic parameters in rat (food and water in-take, urine and faecal output and body weight) over a period of 4 months showed a slight decrease in all the parameters in the first 1-8 weeks. This effect was reversible attaining pretreatment levels from week 16. The LD(50) in an acute toxicity test in mice was 63.1 +/- 16.0 g/kg s.c. Determination of blood urea, sodium (Na(+)), potassium (K(+)), chloride (Cl(-)) and bicarbonate (HCO$_¿3¿ ¿-¿$)as a measure of renal function and alkaline phosphatase (ALP), transaminases (GPT and GOT) and transpeptidases (GGT) as a measure of liver function showed that liver function profiles in pretreated rats were not significantly different from control (p < 0.05) on day 21 to day 150. However, serum levels of ALP and GGT at day 120 to day 150 were moderately but significantly elevated (p > 0.05) compared with the control. There were no significant changes in renal function profiles in pretreated rats (p < 0.05) compared with the control. The results of the liver and renal function profiles in women volunteers showed that there were no significant (p < 0.05) changes in renal functions on day 206 following RICOM-1013-J administration. However, serum levels of ALP and GGT showed a slight rise in about 70% of volunteers, whereas bilirubin and transaminases levels were normal. The present results indicate a very high efficacy and margin of safety of RICOM-1013-J in women volunteers. The increase in ALP and GGT in both animal and women volunteers suggest mild intrahepatic cholestatic changes which may be attributed to an oestrogenic effect of RICOM-1013-J.

Preliminary clinical investigation of the contraceptive efficacy and chemical pathological effects of RICOM-1013-J of Ricinus communis var minor on women volunteers.

The seeds of Ricinus communis Linn, RICOM-1013-J, administered as a single oral dose of 2.3-2.5 g once per 12 months protected against pregnancy in 50 women volunteers for a period of one year. The antifertility and contraceptive efficacy of the seed was demonstrated in this study. Clinical observation revealed very minimal side effects. Some of the side effects investigated included headache, nausea, vomiting, weight gain, loss of appetite, raised blood pressure and dysmenorrhoea. Furthermore, both the renal and liver functions were not affected as revealed by urea, electrolyte and creatinine values as well as total bilirubin, conjugated bilirubin, serum albumin, total protein and transaminases values when compared with control values. In addition cholesterol and phospholipids were not significantly altered. When all these results are considered together, it seems unlikely that the antifertility and contraceptive efficacy of RICOM-1013-J is due to hormonal mechanisms alone since side effects, renal and liver function, and cholesterol effects attributable to oestrogen and/or progesterone were minimal in the volunteers.

A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children.

BACKGROUND: Nutritional rickets remains prevalent in many tropical countries despite the fact that such countries have ample sunlight. Some postulate that a deficiency of dietary calcium, rather than vitamin D, is often responsible for rickets after infancy. METHODS: We enrolled 123 Nigerian children (median age, 46 months) with rickets in a randomized, double-blind, controlled trial of 24 weeks of treatment with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of vitamin D and calcium. We compared the calcium intake of the children at enrollment with that of control children without rickets who were matched for sex, age, and weight. We measured serum calcium and alkaline phosphatase and used a 10-point radiographic score to assess the response to treatment at 24 weeks. RESULTS: The daily dietary calcium intake was low in the children with rickets and the control children (median, 203 mg and 196 mg, respectively; P=0.64). Treatment produced a smaller increase in the mean (+/-SD) serum calcium concentration in the vitamin D group (from 7.8+/-0.8 mg per deciliter [2.0+/-0.2 mmol per liter] at base line to 8.3+/-0.7 mg per deciliter [2.1+/-0.2 mmol per liter] at 24 weeks) than in the calcium group (from 7.5+/-0.8 [1.9+/-0.2 mmol per liter] to 9.0+/-0.6 mg per deciliter [2.2+/-0.2 mmol per liter], P<0.001) or the combination-therapy group (from 7.7+/-1.0 [1.9+/-0.25 mmol per liter] to 9.1+/-0.6 mg per deciliter [2.3+/-0.2 mmol per liter], P<0.001). A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphatase concentration of 350 U per liter or less and radiographic evidence of nearly complete healing of rickets (61 percent, 58 percent, and 19 percent, respectively; P<0.001). CONCLUSIONS: Nigerian children with rickets have a low intake of calcium and have a better response to treatment with calcium alone or in combination with vitamin D than to treatment with vitamin D alone.

PIP: A randomized, double-blind, controlled trial was conducted to compare the efficacy of calcium, vitamin D, and a combination of both in the treatment of nutritional rickets among Nigerian children. Subjects included 123 Nigerian children with the deformity characteristics of rickets. For each child who was enrolled, a parent or guardian was asked to recruit a control child with the same sex, age, weight, and who had no clinical signs of rickets. Children with rickets were under treatment for 24 weeks with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of both. Then the serum calcium and alkaline phosphates were measured and a 10-point radiographic score was used to assess the response to the 24-week treatment. The results revealed a low dietary calcium intake in children with rickets and in control children. Children under vitamin D treatment appeared to have a small increase in the mean serum calcium concentration when compared to children under calcium treatment or a combination of both vitamin D and calcium. A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphates concentration of 350 U/liter or less and radiographic evidence of nearly complete healing of rickets. Overall, compliance ranged from 92% to 96% across the three groups. Since Nigerian children with rickets had low calcium intake, treatment should focus on dietary supplementation with calcium or a combination of calcium and vitamin D.

Absence of vitamin D deficiency in young Nigerian children.

OBJECTIVE: To determine the prevalence of vitamin D deficiency in young Nigerian children residing in an area where nutritional rickets is common. STUDY DESIGN: A randomized cluster sample of children aged 6 to 35 months in Jos, Nigeria. RESULTS: Of 218 children evaluated, no child in the study had a 25-hydroxyvitamin D (25-OHD) concentration <10 ng/mL (the generally held definition of vitamin D deficiency). Children spent an average of 8.3 hours per day outside of the home. Twenty children (9.2%) had clinical findings of rickets. Children with clinical signs of rickets were more likely to be not currently breast fed and have significantly lower serum calcium concentrations than those without signs of rickets (9.1 vs 9.4 mg/dL, respectively, P =.01). Yet, 25-OHD levels were not significantly different between those children with clinical signs of rickets and those without such clinical signs. CONCLUSION: Vitamin D deficiency was not found in this population of young children in whom clinical rickets is common. This is consistent with the hypothesis that dietary calcium insufficiency, without preexisting vitamin D deficiency, accounts for the development of clinical rickets in Nigerian children.

PIP: Deficiencies of either calcium or vitamin D can cause nutritional rickets. Findings are reported from a study conducted to assess the prevalence of vitamin D deficiency in young Nigerian children living in an area where nutritional rickets is common. A random sample of 218 children aged 6-35 months in Jos, Nigeria, was evaluated. The children were of mean age 22 months. No child had a 25-hydroxyvitamin D (25-OHD) concentration of less than 10 ng/ml, the generally held definition of vitamin D deficiency. Children spent an average of 8.3 hours/day outside of the home, and 20 children (9.2%) had clinical findings of rickets. Children with clinical signs of rickets were more likely to be not currently breast-fed and have significantly lower serum calcium concentrations than those with no signs of rickets. 25-OHD levels were not significantly different between children with clinical signs of rickets and those without such clinical signs. The failure to find vitamin D deficiency in this population of young children in whom clinical rickets is common is consistent with the hypothesis that dietary calcium insufficiency, without preexisting vitamin D deficiency, accounts for the development of rickets in Nigerian children.

Calcium supplements increase the serum levels of crosslinked N-telopeptides of bone collagen and parathyroid hormone in rachitic Nigerian children.

OBJECTIVES: Biochemical markers of bone turnover were measured in the sera of 16 controls and 10 children with calcium-deficiency rickets, during a 12-week course of calcium supplementation (1 g CaCO3/d) that was effective in healing the bone lesions of the rachitic children. DESIGN AND METHODS: Serum levels of crosslinked N-telopeptides of bone collagen (NTx), parathyroid hormone (PTH), alkaline phosphatase (ALP), and urinary deoxypyridinoline (LP) were assayed at baseline and during the course of calcium therapy and compared with data of the 16 non-rachitic controls. RESULTS: Calcium therapy suppressed serum NTx and PTH levels in the rachitic children within 24 h; however, after the first week, PTH and NTx levels increased to the extent that at 12 weeks both were elevated when compared with controls or to baseline levels. Serum levels of NTx and PTH were correlated in the controls and experimental subjects (r = 0.63, p < 0.001). CONCLUSIONS: The rate of bone resorption, as estimated by serum NTx concentration, is increased during the healing of rachitic lesions.

Serum levels of the pyridinoline crosslinked carboxyterminal telopeptide of type I collagen (ICTP) and osteocalcin in rachitic children in Nigeria.

OBJECTIVES: We measured the levels of the pyridinoline crosslinked carboxyterminal telopeptide of type I collagen (ICTP) and osteocalcin (OC) in the serum of 12 rachitic and 27 healthy Nigerian children, and compared the performance of these relatively new markers of bone metabolism with established laboratory parameters of skeletal disease. DESIGN AND METHODS: Active rickets was diagnosed on the basis of clinical and biochemical criteria. Serum calcium and phosphorus concentration and alkaline phosphatase activity were determined using clinically accepted methods. Radioimmunoassay was performed to quantify parathyroid hormone, 1-,25-dihydroxyvitamin D, OC, and ICTP. RESULTS: The rachitic children had statistically significant serum elevations of ICTP and osteocalcin as compared with age- and sex-matched controls. Serum levels of ICTP correlated with alkaline phosphate activity. CONCLUSIONS: As a marker of abnormal bone metabolism, ICTP performs at least as well as alkaline phosphate. ICTP and OC are valuable additions to the growing repertoire of bone markers.

Thyroidectomy and thyroxine administration alter serum calcium levels in rat.

The effects of thyroidectomy and thyroxine on serum calcium concentration were studied in adult albino Wistar strain rats using the technique described by Baginski et al. (1973) as used by Lorentz [10]. Thyroidectomy decreased serum calcium concentration from 2.28 +/- 0.02 mmol/l to 1.61 +/- 0.01 mmol/l. Chronic administration of thyroxine (6-8 micrograms/100 g body wt/day) for 35 days caused an increased serum calcium concentrations from 2.28 +/- 0.02 mmol/l to 2.98 +/- 0.05 mmol/l. These findings suggest that thyroidectomy and the dose of thyroxine used affected calcium metabolism in rats.