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Nature and distribution of mineral-binding, keratan sulfate-containing glycoconjugates in rat and rabbit bone.

The presence of keratan sulfate (KS) and KS proteoglycans in bone has been demonstrated in birds and rabbits but comparison with other animal species has not been investigated. The nature and distribution of mineral-binding, KS-containing glycoconjugates in rat and rabbit bone were investigated with a monoclonal antibody (MAb 5D4) specific for KS. Mineral-binding proteins were extracted from the mineralized bone with 0.4 M EDTA without guanidine-HCl (E-extract). On Western blot analysis of SDS-polyacrylamide gel electrophoresis, rat E-extract gave a weak 5D4-reactive band, M(r) 66,000-68,000, whereas rabbit E-extract produced two major reactive populations of small and large molecular size; one population consisted of two closely spaced bands at M(r) 61,000-63,000 and 66,000-68,000, and the other population consisted of one band at approximately M(r) 200,000. The identity of KS chains was further established by the sensitivity of these bands to keratanase II (Bacillus sp. Ks 36) and endo-beta-galactosidase. Immunocytochemistry with MAb 5D4 showed that, in rat bone, staining associated with the mineral phase was limited to the walls of osteocytic lacunae and bone canaliculi, whereas the remainder of the mineralized matrix lacked staining. In contrast, in rabbit bone the staining was distributed over the entire portion of the mineralized matrix with focal accumulation of staining in the wall of the lacunocanalicular system. These results indicate that rat bone contains a mineral-binding, KS-containing glycoconjugate with preferential localization in the wall of the lacunocanalicular system, whereas rabbit bone contains at least two or possibly three types of KS-containing glycoconjugates distributed over the entire portion of the mineralized matrix.

Animals↗

Mineral water intake reduces blood pressure among subjects with low urinary magnesium and calcium levels.

BACKGROUND: Several previous epidemiological studies have shown a relation between drinking water quality and death in cardiovascular disease whereas others have not found such a relationship. An intervention study was undertaken to evaluate the effect of water with added magnesium and natural mineral water on blood pressure. METHODS: A group of 70 subjects with borderline hypertension was recruited and consumed 1) a water low in minerals, 2) magnesium enriched water or 3) natural mineral water, in a random, double blind fashion during four weeks. RESULTS: Among persons with an initial low excretion of magnesium or calcium in the urine, the urinary excretion of magnesium was increased in the groups consuming the two waters containing magnesium after 4 weeks. A significant decrease in blood pressure was found in the group consuming mineral water at 2 and 4 weeks. CONCLUSION: The results suggest that minerals taken in water are significant for the body burden and that an intake of mineral water among persons with a low urinary excretion of magnesium or calcium may decrease the blood pressure. Further studies should investigate the extent of mineral deficiency in different populations and the efficiency of different vehicles for supplying minerals, particularly magnesium and calcium.

Blood Chemical Analysis↗

Diet and bone mineral content at term in premature infants.

Premature infants are at risk of developing metabolic bone disease mainly because of low calcium and phosphorus intake. We have examined the effect of different mineral supplements on bone mineral content at term in 127 premature infants with gestational age <32 wk in a double-blinded randomized trial. We used either phosphate supplementation of human milk as recommended by the European Society of Pediatric Gastroenterology and Nutrition or fortified supplementation with protein, calcium, and phosphorus or preterm formula as recommended by the American Academy of Pediatrics. The intervention period was from 1 week old until 36 wk of gestational age, and the infants were fed approximately 200 mL x kg(-1) x d(-1). Bone mineral content was measured at term by dual-energy x-ray absorptiometry scan. Surprisingly, neither phosphate, fortifier, nor preterm formula supplementation had any significant effect on bone mineral content at term compared with infants fed their own mother's milk only. There was a tendency to higher total bone mineral content in infants fed preterm formula compared with infants fed their own mother's milk only (p = 0.05), but when the bone mineral content was corrected for the size of the infant, there was no difference (p = 0.68). Infants fed preterm formula had a significantly higher weight at term compared with infants fed their own mother's milk only (p = 0.02), but did not differ significantly in length or head circumference. In a regression analysis, the amount of supplemented phosphorus was significantly associated with weight at term (p = 0.008). We conclude that when feeding 200 mL x kg(-1) x d(-1), mineral supplementation of human milk or use of preterm formula does not significantly improve bone mineralization outcome at term.

Absorptiometry, Photon↗

Is idiopathic recurrent calcium urolithiasis in males a cellular disease? Laboratory findings in plasma, urine and erythrocytes, emphasizing the absence and presence of stones, oxidative and mineral metabolism: an observational study.

BACKGROUND: The site of origin of idiopathic recurrent calcium urolithiasis (IRCU)--a disorder characterized by stones composed of calcium oxalate (CaOx) and/or calcium phosphate (CaPi)--is uncertain, because in urine such risk factors for stones as disturbed Ox, Ca and Pi are not regularly observed. AIMS: To evaluate whether imbalance of antioxidants and oxidants might be present in IRCU patients that is then followed by abnormal urine, plasma and intracellular mineral homeostasis, and stones. METHODS: Males were investigated in the laboratory under standardized conditions, and three trials were organized. Trial 1 was cross-sectional, comparing IRCU patients with (n = 111) and without stones in situ (n = 126), focussing on abnormalities of oxypurines and minerals in urine and plasma, and metabolic activity (MA) of the disease. Trial 2 was partly controlled (n = 14 healthy subjects; n = 53 IRCU patients), comparing the plasma levels of total antioxidant status (TAS) and uric acid, the major antioxidant in humans, using the subsets Low (n = 26) and High (n = 27) TAS among IRCU patients in terms of plasma levels of uric acid, ascorbic acid, albumin, alpha-tocopherol and minerals, urinary minerals, CaOx and CaPi (hydroxyapatite) supersaturation. Trial 3, comprising stone-free IRCU patients (n = 8) and healthy controls (n = 8), compared minerals and mineral ratios in plasma and red blood cells (RBCs). Established analytical methodologies were used throughout. RESULTS: In trial 1, uricemia, hypoxanthinuria and proteinuria were elevated, fractional urinary clearance (FE) of uric acid was decreased in stone-bearing patients, and MA correlated positively with uricemia and urinary total protein excretion. In trial 2, TAS was significantly decreased in IRCU patients vs. healthy controls; low TAS coincided with low plasma uric acid and albumin, unchanged ascorbic acid, alpha-tocopherol and parathyroid hormone, but increased FE-uric acid and Pi excretion; the latter correlated negatively with TAS. In trial 3, plasma minerals were significantly decreased in IRCU patients vs. controls, and Ca/Pi, (Ca/Pi)/Mg and (Ca/Pi)/Na molar ratios increased; the latter ratio was also increased in RBCs, and correlated highly positively with the same ratio in plasma. CONCLUSIONS: In IRCU 1) renal stones in situ in combination with high fasting uricemia, high hypoxanthinuria and protein-uria, and high MA suggest that a systemic metabolic anomaly underlies stone formation; 2) antioxidant deficit is frequent, unrelated to the presence or absence of stones but apparently related to poor renal uric acid recycling, low uricemia and albuminemia, exaggerated urinary Pi excretion, and low MA; 3) the combination of low plasma TAS, disordered Ca/Pi and other mineral ratios in urine, plasma and RBCs, but unchanged urinary Ca salt supersaturation is compatible with the view that CaPi solid and Ca microlith formation start inside oxidatively damaged cells.

Adult↗

Mineralization of organic contaminants in sludge-soil mixtures.

The mineralization of 14C-labeled linear alkylbenzene sulfonate (LAS), nonylphenol (NP), nonylphenol-di-ethoxylate (NP2EO), di-(2-ethylhexyl)phthalate (DEHP), pyrene, and 1,4-dichlorobenzene (DCB) was investigated in different sludge-soil mixtures and soils. Under aerobic conditions, the mineralization of LAS, NP, and NP2EO was between 50 and 81% of the added amounts after two months, while DEHP and pyrene were mineralized more slowly. The mineralization of the model chemicals was indirectly affected by the amount of sludge in the test mixtures. A higher content of sludge in the mixtures reduced the overall concentration of oxygen, which resulted in a decrease of the mineralization of several of the model chemicals. In sludge-soil mixtures with predominantly anaerobic conditions, the mineralization was slower for all of the chemicals with the exception of DEHP and DCB. The mineralization of DCB was enhanced in mixtures with a high sludge content. No pronounced difference in the mineralization of the model chemicals (except DEHP) was observed when the sludge was mixed with three different agricultural soils.

Aerobiosis↗

The post-translational chemistry and molecular packing of mineralizing tendon collagens.

Using cross-linking stereochemistry as indicators, the molecular environment of two collagens in the turkey leg Achilles tendon were compared. The tendon from one year old turkeys was dissected into nonmineralized, fully mineralized and transitionally mineralized portions. Amino acid composition and cyanogen bromide peptide mapping of these portions indicated that the collagens were essentially type I throughout. The fully mineralized compartment had a lysine hydroxylation level similar to turkey or mammalian bone collagen. The non- and transitionally mineralized collagens had a significantly higher lysine hydroxylation, typical of tendon or ligament. However, unlike mammalian tendon, the collagen cross-links were essentially derived from the carboxy-terminal ends of the molecules. The predominant cross-link in this portion was pyridinoline having a high content of 0.95 +/- 0.09 res/mole of collagen. The cross-links in the fully mineralized collagen were also essentially derived from carboxy-terminal aldehyde. However, here significant amounts of the lysyl analog of pyridinoline and lysine-involved bifunctional cross-links were present. The molecular loci of pyridinoline in nonmineralized collagen and the lysyl analog of pyridinoline in mineralized collagen were found to be identical. The total trifunctional cross-link level in the mineralized collagen, 0.55 +/- 0.05 res/mole of collagen, was virtually identical to that observed in old mammalian bone and dentin, and in long term in vitro incubation studies of predentin. We have tentatively concluded that the post-translational chemistry and molecular environments are different in these two turkey tendon fibrils. However, a relative paucity of amino-terminal based cross-links is a feature they have in common. The possible involvement of the amino-terminal telopeptides in collagen mineralization is discussed.

Amino Acids↗

Mineral characterization in calcifying tissues: atomic, molecular and macromolecular perspectives.

This paper presents a general overview of calcification and involves aspects of the chemical, physical, and biological nature of mineral crystals in invertebrate and vertebrate tissues, with selected examples of the latter. Two broad areas are described: mineral structure and composition. Mineral formation is detailed in an incidental fashion. Both classical research and recent data appropriate to mineralization studies are noted in order to convey basic principles, as well as the sense and direction of current investigations on the mineral phases of calcified tissues. In this context, novel analytical and imaging techniques from a number of different laboratories lately have helped characterize crystal size, shape, and composition; mineral association with respect to collagen; atomic lattice structure of crystal surfaces; interrelationships between non-collagenous matrix components and mineral; and stereochemical organization of putative matrix nucleation sites. Together, this work has provided a more complete understanding of the mineral-matrix atomic, molecular, and macromolecular interactions that underlie the general mechanism of calcification in biological tissues.

Animals↗

[Synthetic mineral fibers].

The group of man-made mineral fibres includes slagwool, glasswool, rockwool, glass filaments and microfibres, as well as refractory ceramic fibres. The toxicity of mineral fibres is determined by several factors such as the diameter (< or = 3-3.5 microns) and the length of the fibres (< 100 microns), their biopersistence, which is much shorter for man-made mineral fibres than for asbestos fibres, their physicochemical structure and surface properties, and the exposure level. The chemical composition of the various types of man-made mineral fibres depends directly on the raw material used to manufacture them. While naturally occurring fibres are crystalline in structure, most man-made mineral fibres are amorphous silicates combined with various metal oxides and additives. Observations using intracavitary administration have provided evidence that some types of man-made mineral fibres are bioactive in cellular and animal experiments and may induce lung tumours and mesothelioma. It is difficult to extrapolate these results to humans since they bypass inhalation, deposition, clearance and translocation mechanisms. Inhalation studies show more realistic results but differences are observed between animal species regarding their sensibility to tumours. There is no firm evidence that exposure to various wools is associated with lung fibrosis, pleural lesions or nonspecific respiratory disease in humans. A possible exception may be mentioned for refractory ceramic fibres. A slightly elevated standard mortality ratio for lung cancer has been documented in large cohorts of workers (USA, Europe and Canada) exposed to man-made mineral fibres, especially in the early technological phase. It is not possible to determine from these data whether the risk of lung cancer is due to the man-made mineral fibres themselves, in particular due to the lack of data on smoking habits. No increased risk of mesothelioma has been demonstrated in these cohorts. Epidemiological data are insufficient at this time concerning neoplastic diseases in refractory ceramic fibres.

Animals↗

[The effect of dentin phosphoprotein on inducing mineralization].

OBJECTIVE: To investigate the effect of dentin phosphoprotein (DPP) in inducing dentinal mineralization. METHODS: Human DPP was combined with EAH-Sepharose 4B beads and its function of inducing mineralization was studied in mineralization system in-vitro. The mineral formed on the surface of the beads was analyzed by scanning electron microscopy (SEM) and the structure was analyzed by X-ray diffraction and plasma emission spectrum. RESULTS: There was mineral formed on the beads with combined DPP and the mineral was calcium phosphates whose ratio of calcium to phosphate was 1.33. The diffractogram of the formed mineral was more similar to hydroxyapatite than to other calcium phosphates. CONCLUSION: When tightly combined with certain support substance, human DPP can induce mineralization.

Calcium Phosphates↗

[Simulation of nitrogen mineralization and immobilization of crop straw during its initial decomposition in soil].

The nitrogen (N) transformation of crop straw during its initial decomposition in soil was simulated by Model-maker software. A good fit was obtained between the simulated and measured data of 6 variables, including the amount of soil ammonium N, nitrate N, microbial biomass N and their 15N atom %. The simulation results indicated that the main N form immobilized by soil microbes was ammonium, while the immobilization of nitrate was very small. N mineralization occurred dominantly in crop straw but very small in humus. The N mineralization of crop straw could be better described by first order than zero order kinetics. N re-mineralization occurred later than N immobilization. The assumptions on the absence of N re-mineralization or the simultaneous presence of re-mineralization and immobilization during straw decomposition led to a serious error in calculating the gross N mineralization and immobilization; while no consideration of nitrification and volatilization losses led to a low estimation of gross N mineralization. The occurrence of net N mineralization or net N immobilization depended not only on the C/N of straw, but also on the duration of straw decomposition.

Edible Grain↗

Levamisole and inorganic pyrophosphate inhibit beta-glycerophosphate induced mineralization of bone formed in vitro.

The addition of the organic phosphate, beta-glycerophosphate, to the culture media of osteoid forming cells or tissues will induce formation of mineralized bone. The mechanisms behind this phenomenon are not clearly understood. In order to gain new understanding of organic phosphate induced mineralization of bone it was decided to attempt to inhibit this process in two fundamentally different ways. Firstly, the reversible inhibitor of alkaline phosphatase, Levamisole, was used to help define the role of alkaline phosphatase in mineralization in vitro. Secondly, inorganic pyrophosphate, a known inhibitor of hydroxyapatite (HA) formation was also used. It was hypothesized that inorganic pyrophosphate, in addition to its ability to block HA formation, might also interfere with organic phosphate access to alkaline phosphatase and thereby prevent mineralization. The data show that mineralization is blocked when alkaline phosphatase activity is inhibited by Levamisole prior to but not after osteoid maturation. Inorganic pyrophosphate blocks organic phosphate induced mineralization whether added before or after osteoid formation. Organic phosphate effects on alkaline phosphatase activity are reversed by the addition of inorganic pyrophosphate either before or after osteoid formation. These findings suggest a role for alkaline phosphatase in organic phosphate induced mineralization. The data show further that inorganic pyrophosphate may effect mineralization of bone not only by blocking apatite formation but possibly by modulating organic phosphate metabolism.

Animals↗

Mineral uptake by the femora of older female X-linked hypophosphatemic (HYP) mice but not older male HYP mice.

X-linked hypophosphatemic (Hyp) mice are a model of human sex-linked vitamin D-resistant rickets. Young adult Hyp mice are characterized by osteomalacia and decreased bone mineral content. However, older heterozygous Hyp female mice increase in bone mineral content with age so that by one year of age the bone mass/mm femoral length equals or exceeds normal females. To test for the occurrence of this mineral accretion in Hyp male mice and in homozygous Hyp female mice, femora from all 3 Hyp genotypes as well as normal male and female mice were analyzed at various ages from one to 52 weeks of age. Compared to normal mice, all three Hyp genotypes were depressed in bone ash, femoral length, and ash/length ratio at 13 weeks of age. After that age the femora of both heterozygous and homozygous Hyp females showed a slow mineral accretion and, by 52 weeks of age, a normal ash/length ratio. However, the femora of Hyp males, as well as those of normal males, failed to increase in bone mineral content or ash/length ratio after 13 weeks of age. The differences between male and female Hyp mice could not be explained by differences in the plasma levels of calcium, phosphate, or alkaline phosphatase. Increased bone mineral content in older Hyp mice was seen in both heterozygous and homozygous females but not in hemizygous males. Thus, the basis for this increase is not incomplete dominance of the Hyp gene in females nor the Lyon hypothesis. The accretion of mineral in older female Hyp mice despite lifelong reduced plasma phosphate levels suggests that there are factors other than phosphate that also regulate mineral accretion in this bone disease.

Aging↗

Disposition of preformed mineral in matrix vesicles. Internal localization and association with alkaline phosphatase.

Studies were made on the disposition of mineral ions in matrix vesicles (MV) and their relationship to alkaline phosphatase by treatment of MV-enriched microsomes (MVEM) with graded levels of Ca2+-chelating agents to complex accessible ions, fractionation of MVEM on hypertonic sucrose gradients at two different pH values (7.5 and 8.0) to evaluate for the presence of calcium phosphate mineral, and passage of MVEM through cation-exchange columns to determine the accessibility of the Ca2+. The effect of removal of Ca2+ and Pi on subsequent ability of MVEM to induce mineral formation from synthetic cartilage lymph was also determined. Passage through cation-exchange columns revealed that MV Ca2+ was not freely exchangeable, but coeluted in the void volume with alkaline phosphatase. However, upon incubation in synthetic cartilage lymph, progressively more Ca2+ was retained by the column. These findings indicate that, initially, the majority of Ca2+ in MVEM is internal and not readily exchangeable, but as Ca2+ accumulates, progressively more becomes external. The mineral in MV is labile and readily susceptible to loss; treatment with graded levels of EGTA removed major portions of the original Ca2+ and Pi. 45Ca uptake by these mineral-depleted MV was markedly reduced, even in the presence of alkaline phosphatase substrates. Sucrose gradient fractionation of MVEM caused extensive loss of Pi, but not Ca2+, from the low-density alkaline phosphatase-rich fractions. This reveals that Ca2+ and Pi are not initially coupled together: Pi is largely soluble, whereas Ca2+ must be tightly bound. In the high-density vesicles, large amounts of both Ca2+ and Pi are present. The slightly enhanced recovery at higher pH suggests the presence of a solid mineral phase. During mineralization by MV, Ca2+ became externalized, and concomitantly alkaline phosphatase activity declined. This suggests that a direct association exists between the enzyme and the developing mineral.

Alkaline Phosphatase↗

Selected minerals in foods surveys, 1974 to 1981/82.

The levels of 11 essential minerals in food commodity groups and total diets of adult males, infants, and toddlers were summarized from the Selected Minerals in Foods Survey, Fiscal Years (FY) 1974 through mid-1982, of the Food and Drug Administration (FDA) to evaluate the sources and adequacy of those minerals in the diets. The three diets were adequate in calcium, phosphorus, magnesium, potassium, manganese, and selenium; low in copper; and elevated in sodium and iodine. Iron was adequate in adult male but not in infant or toddler diets, and zinc was adequate in infant but somewhat low in adult male and toddler diets. Dairy products; meat, fish, and poultry; grain and cereal products; and fruits and vegetables were the major sources of the 11 minerals. Some statistically significant differences in mineral levels were found among years for total diets and food commodity groups. Regression analysis indicated several linear trends in the mineral content of food commodity groups but no linear trends in the mineral levels of total diets. FDA continues to monitor the levels of minerals in food and diets through the revised Total Diet Study program, which began in mid-FY82.

Adult↗

[Formation of an organic matrix in the traction method of bone regeneration and characteristics of its mineralization in experimental tibia lengthening].

Stretching of dog crus was carried out using transbone distractional osteosynthesis method by Ilizarov. Distribution of calcium, phosphorus and organic substances in zones of regenerating tissue was studied within 1 and 2 months after stretching and within 2 months after the subsequent fixation of the leg in the apparatus. Zones of non-mineralized osteoids were not found already during destruction. In the zones content of minerals varied only slightly and the less mineralized middle zone contained about 66% of calcium and phosphorus as compared with their level in mature compact bone tissue. Crystals of hydroxyapatite were found in zones close to bone fragments using electron microscopy. The data obtained suggest that under optimal conditions of regeneration provided by the method the newly formed bone matrix is partially mineralized during its synthesis. Reverse correlation was detected between contents of minerals and glycosaminoglycans. Middle zones with a slightly higher concentration of glycosaminoglycans were less mineralized. Within 2 months after stopping of distraction differences between zones were decreased, content of glycosaminoglycans was lowered as minerals accumulated; content of minerals became higher than in spongy bone tissue but slightly lower as compared with compact bone.

Animals↗

[Mineral balance during nutritional recuperation of infants with protein deficiency].

Mineral requirements of normal infants change according to growth velocity. They are directly associated to needs for obtaining an adequate composition of new tissue, assure an optimal bone mineralization and for maintaining normal plasma mineral levels. Nutritional rehabilitation of malnourished infants determines increased mineral requirements, which may be not satisfied with usual infant formulas. We studied mineral retention (Ca, P, Mg, Zn and Cu) during nutritional recovery of 9 malnourished male infants (age: 2-7 mo; weight/age < 70%), fed two formulas, both with 85 Kcal/dL (356 KJoule/dL): the first based on whole cow's milk (LP) and the second on a modified cow's milk containing mineral recommendations for normal infants (LPM); balances were compared to normal for age and for length. Infants received each formula for 6 days, with the last 3 days on a metabolic balance Ca, Mg, and P showed high intakes and very low urinary excretions, calcium retention (68.5 +/- 22.7 and 61.4 +/- 16.7 mg/kg/d, for LP and LPM, respectively) were 3 times over normal mean for age (130 mg/d) and 2.5 times over the normal for length (155 mg/d). Mg retention (7.4 +/- 2.0 and 3.4 +/- 1.2 mg/kg/d)), for LP and LPM) were higher than normal for age (2.7 mg/d) or length (3.3 mg/d) and also those of P (LP: 74.8 +/- 7.1; LPM: 52.2 +/- 9.3 mg/kg/d), compared to a mean of 66 mg/d for the same age, or 79 mg/d for length. Zn retentions were comparable with both formulas (LP: 0.14 +/- 0.07 vs LPM: 0.18 +/- 0.06 mg/kg/d) and over normal requirements for age (0.3 mg/d) or length (0.5 mg/d). Copper retentions were significantly lower with LP than LPM (13.8 +/- 14.0 vs 40.0 +/- 13.2 micrograms/kg/d; p < 0.01), due to low intake with LP. We conclude that a high mineral retention is observed in infants recovering from malnutrition, when they are fed formulas with mineral content over its normal recommendations.

Calcium↗

Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception.

BACKGROUND: Several studies report an association between depot medroxyprogesterone acetate (DMPA) injectable contraception and decreased bone mineral density. Adolescents, who are still gaining bone, may be particularly affected, but there has been little study of the association in adolescent users and none following discontinuation. OBJECTIVE: To evaluate bone mineral density changes in adolescents using and discontinuing use of DMPA contraception. DESIGN: A population-based prospective cohort study. PARTICIPANTS: One hundred seventy adolescent women, aged 14 to 18 years; 80 baseline DMPA users and 90 age-similar, unexposed comparison women. Sixty-one participants discontinued DMPA use during follow-up. MAIN OUTCOME MEASURE: Bone mineral density, measured every 6 months for 24 to 36 months at the hip, spine, and whole body, comparing mean bone mineral density changes in DMPA users and discontinuers with nonusers. RESULTS: Among DMPA users, bone mineral density declined significantly relative to nonusers at the hip and spine but not the whole body. Annualized mean percentage changes, adjusted for covariates, were hip, -1.81% vs -0.19%; P<.001; spine, -0.97% vs 1.32%; P<.001, and whole body, 0.73% vs 0.88%; P = .78 for DMPA users vs nonusers, respectively. New users lost bone mineral density more rapidly than prevalent users. Discontinuers experienced significantly increased bone mineral density relative to nonusers at all anatomical sites; annualized mean percentage changes were hip, 1.34% vs -0.19%; P = .004; spine, 2.86% vs 1.32%; P = .004; and whole body, 3.56% vs 0.88%; P<.001. CONCLUSIONS: Use of DMPA contraception in adolescents was associated with significant continuous losses of bone mineral density at the hip and spine. However, significant gains postdiscontinuation provide evidence that the loss of bone mass is apparently reversed.

Absorptiometry, Photon↗

Respiratory outcomes among South African coal miners at autopsy.

BACKGROUND: Studies of dose-response relationships between respiratory outcomes at autopsy and coal dust exposure are limited. The Pathology Automation System (PATHAUT) database of South African miners, is one of the largest autopsy databases of occupational lung disease. This study described the prevalence of respiratory outcomes among South African coal miners at autopsy, and determined whether dose response relationships existed between emphysema and exposure. METHODS: Autopsies conducted from 1975 to 1997 on coal miners with exclusive coal mining exposure and having exposure duration information (n = 3,167) were analyzed from PATHAUT. Logistic regression was used to determine relationships between exposure and outcomes, controlling for race, smoking and age on a subset for whom smoking history was available (n = 725). RESULTS: The mean duration of exposure was 11.0 years. Most were black miners (75.3%) with significant differences in the mean ages of black and white miners (37.9 and 55.3 years, respectively). Only 22.9% of cases had information on smoking. The prevalence of silicosis, tuberculosis (TB), coal workers' pneumoconiosis (CWP), and moderate and marked emphysema were 10.7%, 5.2%, 7.3%, and 6.4%, respectively. All diseases, except TB, were associated with exposure duration. Black miners had 8.3 and 1.2 fold greater risks for TB and CWP, respectively, than white miners. White miners had an increased risk of 1.4 and 5.4 for silicosis and moderate to marked emphysema, respectively. In models unadjusted for age, and including smoking, moderate to marked emphysema was strongly associated with exposure duration (OR = 3.4; 95% CI = 1.9-5.9 for highest tercile of exposure duration). Exposure-related risk estimates were reduced when age was introduced into the model. However, age and duration of exposure were highly correlated, (r = 0.68) suggesting a dilution of the exposure effect by age. CONCLUSIONS: There were significant dose related associations of disease, including emphysema, with coal dust exposure.

Adolescent↗