Ascorbic Acid Deficiency, Iron Overload and Alcohol Abuse Underlie the Severe Osteoporosis in Black African Patients with Hip Fractures — A Bone Histomorphometric Study
MRC Mineral Metabolism Research Unit, University of the Witwatersrand, Johannesburg, South Africa. Calcified Tissue International
(Impact Factor: 3.27).
02/2005; 76(2):79-89. DOI: 10.1007/s00223-004-0053-9
Osteoporosis and femoral neck fractures (FNF) are uncommon in black Africans although osteoporosis accompanying iron overload (from traditional beer brewed in iron containers) associated with ascorbic acid deficiency (oxidative catabolism by iron) has been described from sub-Saharan Africa. This study describes histomorphometric findings of iliac crest bone biopsies and serum biochemical markers of iron overload and of alcohol abuse and ascorbic acid levels in 50 black patients with FNFs (29 M, 21 F), age 62 years (40-95) years (median [min-max]), and in age- and gender-matched black controls. We found evidence of iron overload in 88% of patients and elevated markers of alcohol abuse in 72%. Significant correlations between markers of iron overload and of alcohol abuse reflect a close association between the two toxins. Patients had higher levels of iron markers, i.e., siderin deposits in bone marrow (P < 0.0001), chemical non-heme bone iron (P = 0.012), and serum ferritin (P = 0.017) than controls did. Leukocyte ascorbic acid levels were lower (P = 0.0008) than in controls. The alcohol marker mean red blood cell volume was elevated (P = 0.002) but not liver enzymes or uric acid. Bone volume, trabecular thickness, and trabecular number were lower, and trabecular separation was greater in patients than in controls, all at P < 0.0005; volume, surface, and thickness of osteoid were lower and eroded surface was greater, all at P < 0.0001. There was no osteomalacia. Ascorbic acid deficiency accounted significantly for decrease in bone volume and trabecular number, and increase in trabecular separation, osteoid surface, and eroded surface; iron overload accounted for a reduction in mineral apposition rate. Alcohol markers correlated negatively with osteoblast surface and positively with eroded surface. Relative to reported data in white FNF patients, the osteoporosis was more severe, showed lower osteoid variables and greater eroded surface; FNFs occurred 12 years earlier and were more common among men. We conclude that the osteoporosis underlying FNFs in black Africans is severe, with marked uncoupling of resorption and formation in favor of resorption. All three factors--ascorbic acid deficiency, iron overload, and alcohol abuse--contributed to the osteoporosis, in that order.
Available from: Barbara Brodziak
- "In the group of femoral neck fractures in 50 black patients, occurred in 88% of the population increased iron content. The authors noted that iron overload accounted for a reduction in the rate of bone mineralization while ascorbic acid deficiency caused a decrease in bone volume . "
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ABSTRACT: Manganese and iron are elements that constitute components of bone tissue. The aim of this study was to determine presence of manganese and iron in hip joint tissue and interdependencies between these elements. The objects of the research were hip joint elements from people residing in cities on the territory of the Upper Silesian Industrial District. The number of people in the study group was 91 samples, including 66 samples from women and 25 from a man. The examined tissues were obtained intraoperatively during hip replacement procedures. The content of manganese and iron was determined using the atomic absorption spectrophotometry (AAS) method. The lowest content of manganese and iron was found in the cortical bone, and the largest, in the case of manganese, in the articular cartilage, whereas in the case of iron in a fragment of the cancellous bone from the intertrochanteric area. The content of iron in selected elements of the hip joint decreased with age. Higher content of manganese in hip joint tissue of women compared to men was confirmed. What is more, higher content of iron in hip joint tissue of men was confirmed as well.
Available from: mohammad perwaiz iqbal Iqbal
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ABSTRACT: SUMMARY Vitamin C (L-ascorbic acid) is a water soluble vitamin which is an antioxidant and has a wide variety of biological functions for growth and development of the human body. It is essential for maintaining good health. The objective of this review is to share with the scientific community, the status of vitamin C in the South Asian populations compared to other populations in the world. The focus in this review is on populations from Pakistan, India, Thailand, Malaysia, Nepal and Singapore. Mean plasma levels of vitamin C of Indians/South Asians living abroad did not vary much compared to other ethnic groups, however, there was a significant decrease in these levels among those living in Pakistan and India. In general, males, smokers, persons using drugs of abuse, individuals infected with H. pylori or parasitic infections and those with low-HDL cholesterol have lower plasma levels of vitamin C when compared to females, non-smokers and normal healthy subjects free from drugs of abuse and infections (parasitic as well as H. pylori) and having normal levels of HDL cholesterol. In winter, plasma levels of vitamin C are, generally, higher compared to summer. Availability of non-sweet fruits, namely oranges, grape fruit, guava, lime and strawberries in winter could be the reason for that. There is a positive relationship between serum haptoglobin (Hp) levels and serum vitamin C concentrations. Individuals carrying a Hp2-2 phenotype (less stable Hp) have lower levels of vitamin C. The prevalence of vitamin C deficiency (plasma levels < 2 µg/ml) is highest among Indians and people of South Asian origin compared to other races except the Mexican population. Lower intake of fresh fruits and vegetables and over-cooking of food by South Asians might contribute to the high prevalence of vitamin C deficiency in these populations. The high proportion of individuals with low levels of vitamin C in Pakistani, Indian, Malay and Chinese populations compared to most Western populations might explain higher rates of cardiovascular disease and cancer among South Asians.
Available from: onlinelibrary.wiley.com
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ABSTRACT: Using a mouse mutant that fractures spontaneously and dies at a very young age, we identified that a deletion of the GULO gene, which is involved in the synthesis of vitamin C, is the cause of impaired osteoblast differentiation, reduced bone formation, and development of spontaneous fractures.
A major public health problem worldwide, osteoporosis is a disease characterized by inadequate bone mass necessary for mechanical support, resulting in bone fracture. To identify the genetic basis for osteoporotic fractures, we used a mouse model that develops spontaneous fractures (sfx) at a very early age.
Skeletal phenotype of the sfx phenotype was evaluated by DXA using PIXImus instrumentation and by dynamic histomorphometry. The sfx gene was identified using various molecular genetic approaches, including fine mapping and sequencing of candidate genes, whole genome microarray, and PCR amplification of candidate genes using cDNA and genomic DNA as templates. Gene expression of selected candidate genes was performed using real-time PCR analysis. Osteoblast differentiation was measured by bone marrow stromal cell nodule assay.
Femur and tibial BMD were reduced by 27% and 36%, respectively, in sfx mice at 5 weeks of age. Histomorphometric analyses of bones from sfx mice revealed that bone formation rate is reduced by >90% and is caused by impairment of differentiated functions of osteoblasts. The sfx gene was fine mapped to a 2 MB region containing approximately 30 genes in chromosome 14. By using various molecular genetic approaches, we identified that deletion of the gulonolactone oxidase (GULO) gene, which is involved in the synthesis of ascorbic acid, is responsible for the sfx phenotype. We established that ascorbic acid deficiency caused by deletion of the GULO gene (38,146-bp region) contributes to fractures and premature death because the sfx phenotype can be corrected in vivo by treating sfx mice with ascorbic acid and because osteoblasts derived from sfx mice are only able to form mineralized nodules when treated with ascorbic acid. Treatment of bone marrow stromal cells derived from sfx/sfx mice in vitro with ascorbic acid increased expression levels of type I collagen, alkaline phosphatase, and osteocalcin several-fold.
The sfx is a mutation of the GULO gene, which leads to ascorbic acid deficiency, impaired osteoblast cell function, and fractures in affected mice. Based on these and other findings, we propose that ascorbic acid is essential for the maintenance of differentiated functions of osteoblasts and other cell types.
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