The independent and interactive associations of physical activity intensity and vitamin D status with bone mineral density in prepubertal children: the PANIC Study.

It is unclear how physical activity intensity and vitamin D status are related to bone health in prepubertal children. We found positive associations between vitamin D status and moderate-to-vigorous physical activity with bone in boys and girls. This highlights the importance of lifestyle factors for skeletal health prepuberty. INTRODUCTION: The sex-specific independent and interactive associations of physical activity (PA) intensity and serum 25-hydroxyvitamin D (25(OH)D) levels with areal bone mineral density (aBMD) were investigated in prepubertal children. METHODS: The participants were 366 prepubertal Finnish children (190 boys, 176 girls) aged 6-8 years. Linear regression analysed the associations of sedentary time (ST), light PA (LPA), moderate PA (MPA), moderate-to-vigorous PA (MVPA) and vigorous PA (VPA) measured by accelerometery, and serum 25(OH)D with total body less head (TBLH) and lower-limb aBMD, measured by dual-energy X-ray absorptiometry. RESULTS: There was no interaction between PA intensity or serum 25(OH)D and sex with aBMD. MPA and MVPA were positively associated with TBLH and lower-limb aBMD (ß = 0.11, 95% CI 0.02-0.20, p = 0.01). Serum 25(OH)D was positively associated with TBLH and lower-limb aBMD (ß = 0.09, 95% CI 0.01-0.18, p = 0.03). There were no interactions between PA intensity and serum 25(OH)D with aBMD. CONCLUSION: Vitamin D status, MPA and MVPA levels in active prepubertal children were positively associated with aBMD. The influence of MVPA is due to the MPA component, though our findings regarding the role of VPA should be interpreted with caution, as shorter accelerometer epochs are needed to more accurately assess VPA. This study adds evidence to the promotion of MPA and behaviours to encourage optimal vitamin D status in supporting skeletal health in childhood, though these need not be used in conjunction to be beneficial, and a sex-specific approach is not necessary in prepubertal children. TRIAL REGISTRATION NUMBER: NCT01803776 . Date of registration: 4/03/2013.

Approaches to assess IgE mediated allergy risks (sensitization and cross-reactivity) from new or modified dietary proteins.

The development and introduction of new dietary protein sources has the potential to improve food supply sustainability. Understanding the potential allergenicity of these new or modified proteins is crucial to ensure protection of public health. Exposure to new proteins may result in de novo sensitization, with or without clinical allergy, or clinical reactions through cross-reactivity. In this paper we review the potential of current methodologies (in silico, in vitro degradation, in vitro IgE binding, animal models and clinical studies) to address these outcomes for risk assessment purposes for new proteins, and especially to identify and characterise the risk of sensitization for IgE mediated allergy from oral exposure. Existing tools and tests are capable of assessing potential crossreactivity. However, there are few possibilities to assess the hazard due to de novo sensitization. The only methods available are in vivo models, but many limitations exist to use them for assessing risk. We conclude that there is a need to understand which criteria adequately define allergenicity for risk assessment purposes, and from these criteria develop a more suitable battery of tests to distinguish between proteins of high and low allergenicity, which can then be applied to assess new proteins with unknown risks.

The application of post-market monitoring to novel foods.

The role of post-market monitoring (PMM) in the safety assessment of novel foods is critically discussed in order to derive guidelines as to in which situations the application of PMM might be warranted. Available data sources on food consumption and health status, and the methodologies for generating such data are reviewed. The paper suggests improvements to make them more applicable for PMM purposes. It is concluded that any PMM programme must be a hypothesis-driven scientific exercise. PMM can have a role as a complement to, but not as a replacement for, a comprehensive pre-market safety assessment. Its use may be appropriate to confirm that product use is as predicted in the pre-market assessment; to provide reassurance that effects observed in the pre-market assessment occur with no greater frequency or intensity in the post-market phase than anticipated; and to investigate the significance of any adverse effects reported by consumers after market-launch. However PMM is insufficiently powerful to test the hypothesis that any effects seen in the pre-market assessment are absent in the post-market phase. Current methodologies place limitations on what PMM can achieve. PMM should only be used when triggered by or when the focus is on specific evidence-based questions.

History of safe use as applied to the safety assessment of novel foods and foods derived from genetically modified organisms.

Very few traditional foods that are consumed have been subjected to systematic toxicological and nutritional assessment, yet because of their long history and customary preparation and use and absence of evidence of harm, they are generally regarded as safe to eat. This 'history of safe use' of traditional foods forms the benchmark for the comparative safety assessment of novel foods, and of foods derived from genetically modified organisms. However, the concept is hard to define, since it relates to an existing body of information which describes the safety profile of a food, rather than a precise checklist of criteria. The term should be regarded as a working concept used to assist the safety assessment of a food product. Important factors in establishing a history of safe use include: the period over which the traditional food has been consumed; the way in which it has been prepared and used and at what intake levels; its composition and the results of animal studies and observations from human exposure. This paper is aimed to assist food safety professionals in the safety evaluation and regulation of novel foods and foods derived from genetically modified organisms, by describing the practical application and use of the concept of 'history of safe use'.

Modelling Southern Ocean ecosystems: krill, the food-web, and the impacts of harvesting.

The ecosystem approach to fisheries recognises the interdependence between harvested species and other ecosystem components. It aims to account for the propagation of the effects of harvesting through the food-web. The formulation and evaluation of ecosystem-based management strategies requires reliable models of ecosystem dynamics to predict these effects. The krill-based system in the Southern Ocean was the focus of some of the earliest models exploring such effects. It is also a suitable example for the development of models to support the ecosystem approach to fisheries because it has a relatively simple food-web structure and progress has been made in developing models of the key species and interactions, some of which has been motivated by the need to develop ecosystem-based management. Antarctic krill, Euphausia superba, is the main target species for the fishery and the main prey of many top predators. It is therefore critical to capture the processes affecting the dynamics and distribution of krill in ecosystem dynamics models. These processes include environmental influences on recruitment and the spatially variable influence of advection. Models must also capture the interactions between krill and its consumers, which are mediated by the spatial structure of the environment. Various models have explored predator-prey population dynamics with simplistic representations of these interactions, while others have focused on specific details of the interactions. There is now a pressing need to develop plausible and practical models of ecosystem dynamics that link processes occurring at these different scales. Many studies have highlighted uncertainties in our understanding of the system, which indicates future priorities in terms of both data collection and developing methods to evaluate the effects of these uncertainties on model predictions. We propose a modelling approach that focuses on harvested species and their monitored consumers and that evaluates model uncertainty by using alternative structures and functional forms in a Monte Carlo framework.

Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.

Unintended effects and their detection in genetically modified crops.

The commercialisation of GM crops in Europe is practically non-existent at the present time. The European Commission has instigated changes to the regulatory process to address the concerns of consumers and member states and to pave the way for removing the current moratorium. With regard to the safety of GM crops and products, the current risk assessment process pays particular attention to potential adverse effects on human and animal health and the environment. This document deals with the concept of unintended effects in GM crops and products, i.e. effects that go beyond that of the original modification and that might impact primarily on health. The document first deals with the potential for unintended effects caused by the processes of transgene insertion (DNA rearrangements) and makes comparisons with genetic recombination events and DNA rearrangements in traditional breeding. The document then focuses on the potential value of evolving "profiling" or "omics" technologies as non-targeted, unbiased approaches, to detect unintended effects. These technologies include metabolomics (parallel analysis of a range of primary and secondary metabolites), proteomics (analysis of polypeptide complement) and transcriptomics (parallel analysis of gene expression). The technologies are described, together with their current limitations. Importantly, the significance of unintended effects on consumer health are discussed and conclusions and recommendations presented on the various approaches outlined.

Guidance for the safety assessment of botanicals and botanical preparations for use in food and food supplements.

There is a growing interest by both consumers and industry for the development of food products with 'functional' properties, or health benefits. These products may take the form of dietary supplements or of foods. The health benefits are given by particular ingredients, and in many cases these are derived from botanicals. The variety of plants providing these functions is large, ranging from staple food sources such as cereals, fruits and vegetables, to herbals as used in traditional medicine. The food or ingredient conferring health properties may consist of the plants themselves, extracts thereof, or more purified components. The scientific literature is abundant with articles not only on the beneficial properties, but also on possible adverse health effects of plants and their components. The present report discusses the data required to determine the safe use of these types of ingredients, and provides advice on the development of risk assessment strategies consistent with due diligence under existing food regulations. Product specifications, composition and characterisation of standardised and authentic materials, documented history of use and comparison to existing products (taking into account the effect of industrial processing), description of the intended use and consequent exposure are highlighted as key background information on which to base a risk evaluation. The extent of experimental investigation required, such as in vitro, animal, and/or human studies, depends on the adequacy of this information. A decision tree is presented as an aid to determine the extent of data requirements based on product comparison. The ultimate safety in use depends on the establishment of an adequate safety margin between expected exposure and identified potential hazards. Health hazards may arise from inherent toxicities or contaminants of the plant materials, including the mechanism of the intended beneficial effect. A lower safety margin may therefore be expected than for food ingredients or additives where no physiological effects are intended. In rare cases, post launch monitoring programmes may be envisaged to confirm expected exposures and adequacy of the safety margin. This guidance document was elaborated by an expert group of the Natural Toxin Task Force of the European Branch of the International Life Sciences Institute--ILSI Europe and discussed with a wider audience of scientists at a workshop held on 13-15 May 2002 in Marseille, France.

Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic activity.

Epidemiological studies have found an inverse association between coffee consumption and the risk of certain types of cancers such as colorectal cancers. Animal data support such a chemopreventive effect of coffee. Substantial research has been devoted to the identification of coffee components that may be responsible for these beneficial effects. In animal models and cell culture systems, the coffee diterpenes cafestol and kahweol (C+K) were shown to produce a broad range of biochemical effects resulting in a reduction of the genotoxicity of several carcinogens including 7,12-dimethylbenz[a]anthracene (DMBA), aflatoxin B(1) (AFB(1)), benzo[a]pyrene (B[a]P) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Different mechanisms appear to be involved in these chemoprotective effects: an induction of conjugating enzymes (e.g. glutathione S-transferases, glucuronosyl S-transferases), an increased expression of proteins involved in cellular antioxidant defense (e.g. gamma-glutamyl cysteine synthetase and heme oxygenase-1) and an inhibition of the expression and/or activity of cytochromes P450 involved in carcinogen activation (e.g. CYP2C11, CYP3A2). In animal models, the C+K-mediated induction of conjugating and antioxidant enzymes has been observed in hepatic, intestinal and kidney tissues. In the small intestine, these inductions were shown to be mediated by Nrf2-dependent transcriptional activation. In vitro investigations obtained in cell cultures of human origin indicate that the effects and mechanisms observed in animal test systems with C+K are likely to be of relevance for humans. In human liver epithelial cell lines transfected to express AFB(1)-activating P450s, C+K treatment resulted in a reduction of AFB(1)-DNA binding. This protection was correlated with an induction of GST-mu, an enzyme known to be involved in AFB(1) detoxification. In addition, C+K was found to inhibit P450 2B6, one of the human enzymes responsible for AFB(1) activation. Altogether, the data on the biological effects of C+K provide a plausible hypothesis to explain some of the anticarcinogenic effects of coffee observed in human epidemiological studies and in animal experiments.

Mutational analysis of the liver, colon and kidney of Big Blue rats treated with 2-amino-3-methylimidazo[4,5-f]quinoline.

The heterocyclic aromatic amine (HAA) 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) induces intestinal tumours and hepatocellular carcinomas in rats, but no tumourigenic effects have been identified in the kidney. The tissue-specific mutagenicity of IQ was studied at the lacI locus in the liver, colon and kidney of Big Blue transgenic rats. At the highest dosing regime of IQ (20 mg/kg for 5 consecutive days) the mean mutant frequencies were significantly increased above background (P < 0.05) and were highest in the liver (12.9 +/- 6.2 x 10(-5)), followed by colon (7.4 +/- 1.4 x 10(-5)) and kidney (5.9 +/- 0.8 x 10(-5)). The mutational spectra from the livers of IQ-treated rats was statistically significantly different to that from the livers of control rats (P < 0.01). The lacI mutation spectra of the liver, colon and kidney from IQ-treated rats were similar. These were characterized by an increase in GC transversions in the liver and colon and an increase in the proportion of 1 bp G:C deletions in the liver and kidney. A single G deletion in the sequence 5'-CGGGA-3', characteristic of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine exposure, was detected in the liver and colon. A 2 bp GC deletion was identified at an identical position in the liver, colon and kidney. The colon was the only organ to contain two larger deletions of 13 and 33 bp. A preference was observed for base substitution mutations at guanine in the sequence 5'-CGC/T-3' and for 1 bp deletions at the guanine doublet in the sequence 5'-CGGA-3', especially in the liver and colon. Using the lacI gene as marker in the Big Blue rat model, the mutations identified in the IQ spectra have similarities to those identified for other HAAs studied in the same experimental system, but not to mutations identified in IQ-induced tumours.

Interspecies differences in metabolism of heterocyclic aromatic amines by rat and human P450 1A2.

The catalytic efficiences of cytochrome P450 (P450)-mediated N-oxidation of the 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by recombinant human P450 1A2 were 10-19-fold higher than rat P450 1A2, while methoxyresorufin O-demethylation activity was comparable for both P450s. Similar findings were observed with rat and human liver microsomal samples. Interspecies differences in P450 enzyme expression and catalytic activities may be significant and must be considered when assessing human health risk.

Evaluation of Escherichia coli DJ4309 expressing human P450 1A2 in mutagenicity testing of complex food mixtures.

Heterocyclic aromatic amines (HAAs) are potent bacterial mutagens and potential human carcinogens formed in heat processed proteins. The Ames test (strain TA98) is a useful mutagenicity test system to screen food products for these compounds. HAAs require activation to their genotoxic forms, and in the Ames test, a rat liver S-9 preparation is normally used. In order to better understand the mechanisms of mutagen activation with respect to human metabolism, new bacterial strains containing human cytochrome P450s and other metabolic enzymes have recently been developed. We have investigated the capacity of one of these strains, DJ4309 [Josephy et al., Chem. Res. Toxicol. 11 (1998) 70-74] as a screening tool for mutagens in food products. DJ4309 expresses the human P450 1A2, human NADPH cytochrome reductase and the bacterial acetyl CoA:arylamine N-acetyltransferase. This strain is as sensitive as the Ames system to the mutagenic effects of the heterocyclic aromatic amines 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline and 2-amino-3,8-dimethylimidazo[4, 5-f]quinoxaline, but less sensitive to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. However, the mutagenicity of the arylamine 2-aminofluorene is considerably higher in DJ4309 than in the Ames test system. Meat extracts with a total HAA content ranging from less than 2 ng/g to 20 ng/g are efficiently detected by the Ames TA98 strain with rat liver S-9 activation. DJ4309 is less sensitive, with fewer revertants induced over the same dose range. Unknown compounds present in the meat extracts appear to inhibit the activity of the P450 1A2 enzyme in the DJ4309 strain. We have therefore demonstrated that although DJ4309 is a useful tool for mechanistic studies in chemical carcinogenesis, the screening of complex food matrices for HAAs by this bacterial strain must be conducted with caution.

DMSO induction of the leukotriene LTC4 by Lewis rat Schwann cells.

Schwann cells are capable of producing many immunomodulatory molecules, which indicates that they may play an active role in autoimmune diseases of the peripheral nervous system. We have previously reported production of the prostanoids prostaglandin E2 and thromboxane A2, products of arachidonic acid metabolism, by Schwann cells. This study reports that Schwann cells are capable of producing leukotriene C4, also a product of arachidonic acid metabolism. Production of leukotriene C4 was in response to pre-incubation of the Schwann cells with the cytokines interferon-gamma and tumour necrosis factor-alpha followed by incubation with dimethylsulfoxide. The cytokines alone did not elicit a response nor did stimulation with calcium ionophore, phorbol ester or lipopolysaccharide.

The coffee-specific diterpenes cafestol and kahweol protect against aflatoxin B1-induced genotoxicity through a dual mechanism.

The diterpenes cafestol and kahweol (C&K) have been identified in animal models as two potentially chemoprotective agents present in green and roasted coffee beans. It has been postulated that these compounds may act as blocking agents by producing a co-ordinated modulation of multiple enzymes involved in carcinogen detoxification. In this study, we investigated the effects of C&K against the covalent binding of aflatoxin B1 (AFB1) metabolites to DNA. Male Sprague-Dawley rats were treated with increasing amounts of a mixture of C&K in the diet (0-6200 p.p.m.) for 28 and 90 days. A dose-dependent inhibition of AFB1 DNA-binding was observed using S9 and microsomal subcellular fractions from C&K-treated rat liver in an in vitro binding assay. Significant inhibition was detected at 2300 p.p.m. and maximal reduction of DNA adduct formation to nearly 50% of the control value was achieved with 6200 p.p.m. of dietary C&K. Two complementary mechanisms may account for the chemopreventive action of cafestol and kahweol against aflatoxin B1 in rats. A decrease in the expression of the rat activating cytochrome P450s (CYP2C11 and CYP3A2) was observed, as well as a strong induction of the expression of the glutathione-S-transferase (GST) subunit GST Yc2, which is known to detoxify highly the most genotoxic metabolite of AFB1. These data and the previously demonstrated effects of C&K against the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis at various tissue sites suggest the potential widespread effect of these coffee components against chemical carcinogenesis.

Activation of heterocyclic aromatic amines by rat and human liver microsomes and by purified rat and human cytochrome P450 1A2.

The dietary mutagens 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are activated to genotoxins by rat and human liver cytochrome P450 (P450) 1A1- and 1A2-mediated N-oxidation. Immunoquantitation of 51 human liver samples revealed a wide range in P450 1A2 expression (10-250 pmol/mg of microsomal protein, median 71 pmol/mg), with 39% of the livers containing >100 pmol/mg of protein. There was no evidence for expression of P450 1A1 (<1 pmol/mg of protein). P450 1A2 levels were correlated to MeIQx and PhIP N-oxidation rates (r = 0.83, 0.73, respectively). In male Fischer-344 and Sprague-Dawley rats, hepatic P450 1A2 ranged from 5 to 35 pmol/mg of protein, while P450 1A1 was <1 pmol/mg. Animal pretreatment with 3-methylcholanthrene, beta-naphthoflavone, or polychlorinated biphenyls (PCB) resulted inasmuch as 340-fold and >1000-fold induction of P450 1A2 and 1A1, respectively, and a 220-fold increase in N-oxidation activity. Approximately 20% of the human samples were as active in N-oxidation and conversion of MeIQx to bacterial mutagens as microsomes of PCB-pretreated rats [3-4 nmol of NHOH-MeIQx formed min-1 (mg of protein)-1]. In contrast, microsomes from PCB-treated rats displayed higher rates of PhIP N-oxidation and activation to mutagens than the most active human liver microsomes [8-24 vs 2-4 nmol of HNOH-PhIP formed min-1 (mg of protein)-1]. Recombinant human P450 1A2 showed catalytic efficiencies of MeIQx and PhIP N-oxidation that were 10-19-fold higher than purified rat P450 1A2. Cytochrome P450 1A2 expression in rodent and human liver tissue varies greatly and there are considerable differences between the enzymes in the two species in the activation of some heterocyclic aromatic amines, which must be considered when assessing human health risk.

Multiparity and bone mass.

OBJECTIVE: To investigate the influence of multiparity on bone mass of the axial skeleton in a population of women of high parity. DESIGN: Open study of Omani women. SETTING: Medical physics department and clinical physiology department of a third degree referral (university) hospital. PARTICIPANTS: A consecutive series of 159 normal women referred with low back pain over a period of six months. RESULTS: The bone mineral density was measured with dual-photon absorptiometry and the mean was found to be 0.984 (+/-0.166) (+/- SD) g cm-2. The age ranged from 20 to 70 years with a mean age of 43.4 (+/- 12.5) years. The number of children per woman ranged from 0 to 14 with a mean of 5.1 (+/- 3.5). There was no statistically significant influence of the number of children per woman on bone mineral density but there was a strong correlation with age and body size variables. CONCLUSION: Multiparity does not influence lumbar spine bone mineral density in normal women.

Antimutagenicity and catechin content of soluble instant teas.

The antimutagenic properties of soluble instant teas were examined using the bacterial Ames assay. Inhibition of the numbers of revertants induced from a number of known mutagens indicates that aqueous extracts of instant teas have antimutagenic activity and antioxidative properties, and can inhibit nitrosation reactions. Despite a significant reduction in the amounts of major green tea catechins, quantified using reversed-phase HPLC with electro-chemical detection, no differences in antimutagenicity were observed between the instant teas, a black fermented tea and a green tea. Oxidation of polyphenolic compounds which occurs during the production of instant tea does not therefore decrease the antioxidant, free radical scavenging and antimutagenic properties. This suggests that catechins are not the only compounds responsible for the protective effects of teas.

Detection and classification of Streptococcus thermophilus bacteriophages isolated from industrial milk fermentation.

In the last 30 years, 81 Streptococcus thermophilus bacteriophage isolates were collected from industrial yogurt (n = 40) and cheese (n = 41) fermentation. Forty-six distinct restriction patterns of phage DNA (11 in yogurt and 35 in cheese) were observed. The phages were investigated for host range, serological properties, and DNA homology to study whether these three independent techniques can be used to classify the phages into taxonomic groups. Yogurt factory-derived phages were classified into the same two subgroups by serology, host range analysis, and hybridization with subgroup-specific DNA sequences. Cheese factory-derived phages, however, could not be classified: the 35 cheese phage isolates with distinct restriction patterns showed 34 different host ranges. All but one cheese phage isolate showed serological cross-reactivity with yogurt phages. A phage DNA fragment that hybridized with all phage DNA samples was cloned, establishing the genetic relatedness of all S. thermophilus phages from our collection. With the sequence information from an unusually conserved S. thermophilus phage DNA element (H. Brüssow, A. Probst, M. Frémont, and J. Sidoti, Virology 200:854-857, 1994), a PCR-based phage detection method was developed for cheese whey from a factory that produced mozzarella cheese with complex undefined starter mixes. PCR allowed the detection of phages in cheese whey (detection limit, 10(3) PFU/ml) which could not be detected by dot blot hybridization techniques (detection limit, 10(7) PFU/ml).

Isolation and characterisation of promoter regions from Streptococcus thermophilus.

Four promoter regions required for the expression of a promoterless antibiotic resistance gene (cat194) in Streptococcus thermophilus were isolated by random chromosomal cloning experiments. These were shown to be functional in vivo, and their sequences were determined. Each region expressed different amounts of Cat protein as determined by enzyme activities. One region, STP10, was found to contain the 5' coding region of the large ribosomal subunit protein L20.

A study of bone mineral density versus age in Omani women and a comparison with normal British women.

Dual photon absorptiometry (DPA) of the lumbar spine (2nd, 3rd and 4th lumbar vertebrae) was carried out using a Norland 2600 bone densitometer on 194 Omani women (OW). The exclusion criteria were (1) any medical treatment known to affect calcium metabolism or bone mass, (2) osteomalacia or secondary osteoporosis, (3) the presence of osteophytes or compression fractures of the lumbar vertebrae and (4) the presence of aortic calcifications. The bone mineral density (BMD) results showed a peak value occurring in the 30-35 year old age range (mean 1.1 g cm-2, standard deviation 0.1). The data were compared with a group of 165 normal British women (BW) with a similar age distribution whose peak BMD (obtained with dual X-ray absorptiometry) occurred in the 40-45 year old age range. The two groups were compared in each 10 year age range and the BMD of the OW group was found to be significantly lower in the 40-49 year old age range (P < 0.01) as well as the 50-59 and 60-69 year old age ranges (P < 0.001).