Does inadequate diet during childhood explain the higher high fracture rates in the Southern United States?

SUMMARY: Southern states have the highest age-adjusted hip fracture rates among older adults in the United States. Regional hip fracture rates in the United States in 1986-1993 correlate with death rates from rickets in the 1940s. Historical patterns of bone nutrition early in life might explain contemporary geographic patterns in bone fragility. INTRODUCTION: State of residence early in life is a better predictor of the risk of hip fracture after age 65 than state of current residence. Therefore, the geography of rickets mortality in the United States before 1950 was compared with the geography of hip fracture rates among older adults in the United States during 1986-1993. METHODS: Vital statistics data for the US white population for 1942-1948 allowed calculation of the ratio of deaths from rickets to live births for each geographic division of the USA. These ratios were correlated with previously published, standardized hip fracture rates among whites 65-89 years old during 1986-1993 by census division. RESULTS: During 1942-1948, the rickets mortality ratio among whites was 3.11 in the South, 1.91 in the Northeast, 1.75 in the Midwest, and 1.04 in the West. The correlation of mortality with risk of hip fracture was 0.71 (p = 0.03) for both sexes combined and 0.86 (p = 0.01) for women. CONCLUSIONS: Inadequate nutrition during skeletal formation early in life might explain the higher incidence of hip fracture among older adults in the South.

Regulation of gene expression by dietary Ca2+ in kidneys of 25-hydroxyvitamin D3-1 alpha-hydroxylase knockout mice.

BACKGROUND: Pseudovitamin D deficiency rickets (PDDR) is an autosomal disease, characterized by undetectable levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), rickets and secondary hyperparathyroidism. Mice in which the 25-hydroxyvitamin D3-1 alpha-hydroxylase (1 alpha-OHase) gene was inactivated, presented the same clinical phenotype as patients with PDDR. METHODS: cDNA Microarray technology was used on kidneys of 1 alpha-OHase knockout mice to study the expression profile of renal genes in this Ca2+-related disorder. Genome wide molecular events that occur during the rescue of these mice by high dietary Ca2+ intake were studied by the use of 15K cDNA microarray chips. RESULTS: 1 alpha-OHase knockout mice fed a normal Ca2+ diet developed severe hypocalcemia, rickets and died with an average life span of 12 +/- 2 weeks. Intriguingly, 1 alpha-OHase-/- mice supplemented with an enriched Ca2+ diet were normocalcemic and not significantly different from wild-type mice. Inactivation of the 1 alpha-OHase gene resulted in a significant regulation of +/- 1000 genes, whereas dietary Ca2+ supplementation of the 1 alpha-OHase-/- mice revealed +/- 2000 controlled genes. Interestingly, 557 transcripts were regulated in both situations implicating the involvement in the dietary Ca2+-mediated rescue mechanism of the 1 alpha-OHase-/- mice. Conspicuous regulated genes encoded for signaling molecules like the PDZ-domain containing protein channel interacting protein, FK binding protein type 4, kinases, and importantly Ca2+ transporting proteins including the Na+-Ca2+ exchanger, calbindin-D28K and the Ca2+ sensor calmodulin. CONCLUSION: Dietary Ca2+ intake normalized disturbances in the Ca2+ homeostasis due to vitamin D deficiency that were accompanied by the regulation of a subset of renal genes, including well-known renal Ca2+ transport protein genes, but also genes not previously identified as playing a role in renal Ca2+ handling.

Hypoglycemia spiking mortality syndrome in broilers with rickets and a subsequent investigation of feed restriction as a contributing factor.

Several cases of elevated mortality with neurologic signs in 14-to-16-day-old broilers were presented to the Poultry Diagnostic and Research Center from one local integrated company. Suspected of "spiking mortality" associated with hypoglycemia, blood glucose levels were <150 mg/dl overall, with several birds with blood glucose levels as low as 30 mg/dl. Tissues, submitted for histopathology, revealed rickets in 50% of the birds. Virus isolation and serology for reovirus and infectious bursal disease virus were negative. After evaluation of these cases, a brief investigation was conducted to determine the effects of feed restriction on the induction of rickets and resulting hypoglycemia. One-hundred 1-day-old broilers were randomly assigned to three treatment groups of: 1) ad libitum feed, 2) 25% restriction, and 3) 50% restriction. Restriction began on the fifth day of age and continued to 21 days of age. Samples collected during the course of the study included whole blood for blood glucose measurements and proximal tibiotarsus for histopathologic examination for rickets. We were unable to reproduce the clinical signs of spiking mortality, neurologic changes, or hypoglycemia experimentally. Histopathology of the growth plates of the proximal tibiotarsus did indicate mild changes consistent with rickets, but the changes were not significant between treatment groups.

Long-term outcome of paediatric patients with hereditary tubular disorders.

BACKGROUND: An increasing number of children with hereditary tubular disorders (HTD) reach adult life due to diagnostic and therapeutic advances which results in growing need to manage these patients by adult centres. Data on the prevalence and the late clinical problems of these patients are limited. METHODS: We observed 177 paediatric patients with isolated or complex HTD between 1969 and 1994. The median age at the time of diagnosis was 3 (range 0-18) years and the median observation period 10 (range 1-43) years. The long-term outcomes with respect to renal function, bone disease, and body growth were analyzed. RESULTS: The prevalence of HTD was 3.2% of all patients observed in our renal unit and 14% of those patients with chronic renal failure and/ or end-stage renal disease. The three most frequent disorders observed were nephropathic cystinosis (n = 34), X-linked hypophosphataemic rickets (n = 26), and idiopathic hypercalciuria (n = 17). At the last observation, 12% of the patients with isolated HTD and 30% of those with complex HTD had developed preterminal chronic renal failure; end-stage renal disease was observed in 5 and 25%, respectively (p < 0.001). Progressive disease occurred mainly in patients having cystinosis, primary hyperoxaluria, the syndrome of hypomagnesaemia/hypercalciuria, primary Fanconi syndrome, Fanconi-Bickel syndrome, and methylmalonic aciduria. Nephrocalcinosis was found in 42%, urolithiasis in 14%, bone deformities and/or fractures in 28%, and other extrarenal alterations in 29% of all patients. The median body height at last observation was 2.0 SD below the normal mean (range from -10.4 to +2. 6), and the adult height was subnormal in 48% of 67 grown-up patients. Growth retardation was more severe in complex than in isolated HTD. The mortality decreased from 17% in 1969-1981 to 12% in 1982-1994. CONCLUSION: Although HTD are rare nephropathies, their frequently progressive course associated with extrarenal complications requires the attention of nephrologists beyond the paediatric age.

Severe rickets in a children's hospital in Addis Ababa.

A retrospective, case-controlled study of rachitic patients admitted to Ethio-Swedish Children's Hospital (ESCH), Addis Ababa, Ethiopia, over a ten-year period (1979-1988) is presented. Clinical records of 131 patients with clinical and radiological evidence of rickets and an equal number of randomly selected, age and sex matched controls with no rickets were analysed. Rickets was found to be more common in males (2:1) and at 6 to 18 months of age (79%). Associated findings were infectious diseases (90%), protein-energy malnutrition (75%), anaemia (39%), and congestive heart failure (16). Mortality was much higher in rachitic patients. The admission rates show a progressive increase over the study period. The need for early diagnosis and treatment, continued nutrition and health education, and further study to elucidate the relation between protein-energy malnutrition (PEM) and rickets is suggested.