Grass pea consumption & present scenario of neurolathyrism in Maharashtra State of India.

BACKGROUND & OBJECTIVES: Neurolathyrism is a non progressive motor neuron disorder engendered by the prolonged over-consumption of Lathyrus sativus (grass pea) seeds which contain a neurotoxic amino acid, ß-N oxalyl- L-α, ß-diaminopropionic acid (ß-ODAP). It is characterized by spastic paraparesis in the hind limbs. The present study was conducted in 105 households (HHs) of Gondia district in Maharashtra, India, where grass pea is cultivated and consumed to assess the health implication of its consumption. METHODS: Across-sectional survey was carried out in 105 HHS in five villages and grass pea samples were collected for ß-ODAP estimation. Amino acid analysis was also done, neurolathyrism cases were identified by snowball sampling method and neurological examination was carried out. RESULTS: The study revealed that 61 per cent of population was consuming this pulse as a part of diet. ß-ODAP concentration in grass pea was high in Bora village (1254.5 ± 528.21 mg %) and less in Malgaon village (413.6±415.79 mg %). The nutritional status of the people was within the normal range (BMI 18± 3.40 kg/m2) in the surveyed households. Consumption of grass pea was observed to be less than 25 g. CONCLUSIONS: The cases of neurolathyrism declined in all the studied villages due to reduced ß-ODAP exposure through Lathyrus sativus consumption, however, the grass pea was cultivated and consumed in Gondia district of Maharashtra State.

New insights into the mechanism of neurolathyrism: L-ß-ODAP triggers [Ca2+]i accumulation and cell death in primary motor neurons through transient receptor potential channels and metabotropic glutamate receptors.

Neurolathyrism is a motor neuron (MN) disease caused by ß-N-oxalyl-L-α,ß-diaminopropionic acid (L-ß-ODAP), an AMPA receptor agonist. L-ß-ODAP caused a prolonged rise of intracellular Ca(2+) ([Ca(2+)]i) in rat spinal cord MNs, and the [Ca(2+)]i accumulation was inversely proportional to the MN's life span. The [Ca(2+)]i rise induced by L-ß-ODAP or (S)-AMPA was antagonized completely by NBQX, an AMPA-receptor blocker. However, blocking the L-type Ca(2+) channel with nifedipine significantly lowered [Ca(2+)]i induced by (S)-AMPA, but not that by L-ß-ODAP. Tetrodotoxin completely extinguished the [Ca(2+)]i rise induced by (S)-AMPA or kainic acid, whereas that induced by L-ß-ODAP was only attenuated by 65.6±6% indicating the prominent involvement of voltage-independent Ca(2+) entry. The tetrodotoxin-resistant [Ca(2+)]i induced by L-ß-ODAP was blocked by 2-APB, Gd(3+), La(3+), 1-(ß-[3-(4-methoxy-phenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SKF-96365) and flufenamic acid, which all are blockers of the transient receptor potential (TRP) channels. Blockers of group I metabotropic glutamate receptors (mGluR I), 7-(hydroxyiminocyclopropan[b]chromen-1α-carboxylate ethyl ester (CPCCPEt) and 2-methyl-6-(phenylethynyl)-pyridine (MPEP) also lowered the [Ca(2+)]i rise by L-ß-ODAP. MN cell death induced by L-ß-ODAP was prolonged significantly with SKF-96365 as well as NBQX. The results show the involvement of TRPs and mGluR I in L-ß-ODAP-induced MN toxicity through prolonged [Ca(2+)]i mobilization, a unique characteristic of this neurotoxin.

[Altered collagene characteristics and lysyl oxidase activity in lathyrism].

Experiments were carried out on rats with lathyrism, which was induced by adding semicarbazide (0.075%) into drinking water for 45 days. The data obtained show a 30% reduction in the body weight and an increase in.organ weight coefficients. Semicarbazide intake led to the pelvic limb paralysis, scoliosis, bone tissue degradation, cartilage growth, 46% decrease of the calcium level in the femur. It has been detected essential structural changes in extracellular matrix based on the collagen cross-links reduction. The activity of lysyl oxidase, a key enzyme for the collagen development, showed 5-fold decrease in the aorta tissues. The level of formaldehyde, a nonenzymic cross-links developer, has been measured in the liver tissue by the aldehyde trap (5,5-dimethyleyclohexane-1,3-dione) administration and then fluorimetric determination of formaldimedone. Under semicarbazide load, the formaldehyde level in the liver tissue was reduced by 47%. Therefore, semicarbazide influences not only the enzymic development of aldehyde groups in collagen, but the level of other aldehydes, which can cause cross-links. This experimental model of lathyrism is appropriate for investigation of the lysyl oxidase inhibitors effect on extracellular matrix.

L-ß-N-oxalyl-α,ß-diaminopropionic acid toxicity in motor neurons.

The excitatory amino acid L-ß-N-oxalyl-α,ß-diaminopropionic acid (L-ß-ODAP) in Lathyrus sativus L. is proposed as the causative agent of the neurodegenerative disease neurolathyrism. We investigated the effect of L-ß-ODAP on [Ca2+]i handling, redox homeostasis, and cell death in rat spinal motor neurons. L-ß-ODAP and L-glutamate triggered [Ca2+]i transients, which were inhibited by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor blockers; 2,3-dioxo-6-nitro-1,2,3, 4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide and 1-naphthyl acetylspermine, the latter specifically blocking Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors. In addition, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, and to a lesser extent 1-naphthyl acetylspermine, protected the neurons against cell death induced by L-ß-ODAP or L-glutamate. Methionine and cysteine were also protective against neuronal cell death. We conclude that deregulation of [Ca2+]i homeostasis and oxidative stress contribute to motor neuron cell death in neurolathyrism.

Studies on neurolathyrism in Ethiopia: dietary habits, perception of risks and prevention.

This study describes the correlation of traditional perceptions and dietary habits with the incidence of neurolathyrism to propose preventive measures. Therefore, 118 households of South Wollo and North Gondar (Amhara Regional State, Ethiopia), of which one third had at least one neurolathyrism affected member, were interviewed. Most of the affected families in this study had one neurolathyrism victim, being predominantly male and of younger age. The incidence among youngsters (boys and girls) was significantly correlated with the consumption of green unripe seeds (eshet), confirming this as a risk factor for developing neurolathyrism. The consumption of other popular grass pea preparations was not age related. Neurolathyrism patients did not attempt any medication as most people knew that neurolathyrism is incurable, but the consumption of grass pea was abandoned after developing the disease. The minority 'Woito' tribe was virtually unaffected. They were the only people reporting to consume fish which is rich in amino acids such as methionine and using metallic kitchen utensils in addition to clay pots. This observation points to the correlation between low neurolathyrism incidence and a better balanced diet as well as metallic kitchen utensils, suggesting a new approach for neurolathyrism prevention.

Grass pea and neurolathyrism: farmers' perception on its consumption and protective measure in North Shewa, Ethiopia.

Neurolathyrism in Ethiopia is caused by food dependency on grass pea (Lathyrus sativus L.). In the study area, a large proportion of the farmers are growing grass pea since it can withstand harsh environments. Socio-economic factors (poverty; lack of money to buy other food legumes) and environmental problems (such as water logging and frost hazards) influence consumption of grass pea. Most of the respondents have the idea that some chemical contained in grass pea causes a health problem. Different processing and preparation methods are used to prepare grass pea into different food forms. The major processing methods include washing and soaking, as the farmers apply these methods mainly because they assume that the chemical that causes lathyrism, scientifically known as ß-ODAP (ß-N-oxalyl-L-α,ß-diaminopropionic acid) is reduced through washing and soaking. The farmers adopt different strategies to avoid the problem of lathyrism such as avoiding consumption of grass pea in the form that they suspect to cause the problem, blending/mixing with other crops, applying different processing/detoxification methods. Since grass pea is consumed with a fear of lathyrism, future research should concentrate either on developing grass pea varieties with safe level of ß-ODAP content or improving the traditional/indigenous processing methods.

Brain glutathione as a target for aetiological factors in neurolathyrism and konzo.

Both neurolathyrism and konzo are associated with the nutritional dependence of human populations on a single plant food. These diseases express themselves as chronic disorders of upper motor neurones, leading to signs and symptoms that characterise amyotrophic lateral sclerosis (motor neurone disease). The plant food associated with neurolathyrism is grass pea, which contains the neurotoxic ß-N-oxalyl-α,ß-diaminopropionic acid (ß-ODAP). The plant food associated with konzo is cassava, which may contain significant concentrations of cyanogenic glycosides and their degradation products. A monotonous diet of grass pea is likely to generate nutritional deficiencies; it is proposed that one of these, plasma methionine deficiency, may predispose neurones to the neurotoxic effects of ß-ODAP. Subjects suffering from konzo also have low concentrations of plasma methionine as a result of a dietary deficiency of this amino acid. However, the plasma cystine concentration is also compromised because cyanide released from cyanogenic glycosides in cassava probably reacts with plasma cystine non-enzymatically. The product of this reaction is 2-imino-4-thiazolidine carboxylic acid. Since both plasma methionine and cystine are used for glutathione synthesis it seems likely that one common feature that leads to motor neurone death in neurolathyrism and konzo is the depletion of glutathione in the central nervous system.

A new unifying hypothesis for lathyrism, konzo and tropical ataxic neuropathy: nitriles are the causative agents.

Konzo and lathyrism are associated with consumption of cassava and grass pea, respectively. Cassava consumption has also been associated with a third disease, tropical ataxic neuropathy (TAN). This review presents a new unifying hypothesis on the causative agents for these diseases: namely, that they are nitriles, compounds containing cyano groups. The diseases may be caused by different but similar nitriles through direct neurotoxic actions not mediated by systemic cyanide release. Both cassava and Lathyrus contain nitriles, and other unidentified nitriles can be generated during food processing or in the human body. Available data indicate that several small nitriles cause a variety of neurotoxic effects. In experimental animals, 3,3'-iminodipropionitrile (IDPN), allylnitrile and cis-crotononitrile cause sensory toxicity, whereas hexadienenitrile and trans-crotononitrile induce selective neuronal degeneration in discrete brain regions. IDPN also induces a neurofilamentous axonopathy, and dimethylaminopropionitrile is known to cause autonomic (genito-urinary) neurotoxicity in both humans and rodents. Some of these actions depend on metabolic bioactivation of the parental nitriles, and sex- and species-dependent differences in susceptibility have been recorded. Recently, neuronal degeneration has been found in rats exposed to acetone cyanohydrin. Taken together, the neurotoxic properties of nitriles make them excellent candidates as causative agents for konzo, lathyrism and TAN.

Unraveling the mechanism of ß-N-oxalyl-α,ß-diaminopropionic acid (ß-ODAP) induced excitotoxicity and oxidative stress, relevance for neurolathyrism prevention.

ß-N-Oxalyl-α,ß-diaminopropionic acid (ß-ODAP) is a plant metabolite present in Lathyrus sativus (L. Sativus) seeds that is proposed to be responsible for the neurodegenerative disease neurolathyrism. This excitatory amino acid binds to α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors and several lines of evidence indicate that ß-ODAP triggers motor neuron degeneration by inducing excitotoxic cell death and increasing oxidative stress. In addition, this toxin is known to disturb the mitochondrial respiration chain and recent data indicate that ß-ODAP may inhibit the uptake of cystine thereby compromising the cells' abilities to cope with oxidative stress. Recent work from our group furthermore suggests that ß-ODAP disturbs the cellular Ca(2+) homeostasis machinery with increased Ca(2+) loading in the endoplasmic reticulum (ER)-mitochondrial axis. In this review, we aim to integrate the various mechanistic levels of ß-ODAP toxicity into a consistent pathophysiological picture. Interestingly, the proposed cascade contains several aspects that are common with other neurodegenerative diseases, for example amyotrophic lateral sclerosis (ALS). Based on these mechanistic insights, we conclude that dietary supplementation with methionine (Met) and cysteine (Cys) may significantly lower the risk for neurolathyrism and can thus be considered, in line with epidemiological data, as a preventive measure for neurolathyrism.

Factors affecting ß-ODAP content in Lathyrus sativus and their possible physiological mechanisms.

A neuroexcitatory non-protein amino acid, ß-N-oxalyl-L-α,ß-diaminopropionic acid (ß-ODAP), present in the seeds of the hardy legume crop grass pea (Lathyrus sativus L.), was considered responsible for human lathyrism. The levels of ß-ODAP were reported to vary in different tissues during plant development, and to be affected by a wide range of environmental stresses. In this paper, dynamic changes in ß-ODAP level at specific stages of plant development as well as the influences of various environmental factors, including nutrient deficiency, drought, salinity, toxic heavy metals, and Rhizobium symbiosis on ß-ODAP levels were analyzed, highlighting the relationship between changes in ß-ODAP concentrations and Rhizobium growth. Possible mechanisms underlying ß-ODAP accumulation are proposed and future research is suggested.

Assessing diet in populations at risk for konzo and neurolathyrism.

Although both konzo and neurolathyrism are diseases associated with diet, we know surprising little about the diets of the groups at risk. The objective of this paper is to discuss methods for assessing dietary intake in populations at risk for konzo and lathyrism. These methods include weighed food records and interview based techniques like 24-h recalls and food frequency questionnaires (FFQs). Food records have the potential to provide accurate information on food quantities, and are generally the method of choice. Interview based methods provide less precise information on the quantities of foods ingested, and are subject to recall bias, but may be useful in some studies or for surveillance. Sample size needs to be adequate to account for day-to-day and seasonal variability in food intake, and differences between age and sex groups. Adequate data on the composition of foods, as actually consumed, are needed to evaluate the food intake information. This is especially important in the case of cassava and grass pea where the toxins in the diet is a function of processing. Biomarkers for assessing the cyanogen exposure from cassava-based diets are available; biomarkers for the ß-ODAP exposure from grass pea diets need development.

The nutritive value of grasspea (Lathyrus sativus) and allied species, their toxicity to animals and the role of malnutrition in neurolathyrism.

The safe use of grasspea (Lathyrus sativus) and allied species (L. cicera, L. clymenum and L. ochrus) requires a better understanding of the factors that are involved in the development of neurolathyrism. A suitable animal model is needed. The nutritional quality, seed chemical composition, the role of malnutrition, synergistic action of antinutritional factors, the toxicity of both seed and forage to animals, metabolism and tissue distribution of the toxic amino acid beta-N-oxalyl-alpha,beta-L-diaminopropionic acid (ODAP) in mammals are reviewed. Malnutrition is not necessary for the development of neurolathyrism, however, the supply of sulfur amino acids by Lathyrus spp. is limited by the combined action of several antinutritional factors and the low inherent levels in the seeds. Metabolism or excretion of ODAP and clearance from the central nervous system appear to function well under normal circumstances, while species differences exist. Interruptions to these processes and excessive concurrent demands for reduced sulfur amino acids are likely to be conducive to the onset of neurotoxicity.

Sulfur amino acids deficiency caused by grass pea diet plays an important role in the toxicity of L-ß-ODAP by increasing the oxidative stress: studies on a motor neuron cell line.

Neurolathyrism is a motor neuron disease caused by the overconsumption of grass pea (Lathyrus sativus L.) containing L-ß-ODAP. The precise mechanism to cause motor neuron degeneration has yet to be elucidated, but should agree with the epidemiological backgrounds. Considering the amino acid content of the legume, and the epidemiological link with prolonged unbalanced nutrition, the shortage of sulfur amino acids methionine and cysteine could affect the toxicity of L-ß-ODAP. We analyzed the effect of these amino acids in the media on the toxicity using primary motor neuron culture and a motor neuron cell line NSC-34. Deprivation of both methionine and cysteine exacerbated the toxicity of L-ß-ODAP by 66% compared to the complete medium. The glutathione content of these cells was greatly decreased in sulfur amino acid-deprived medium. L-ß-ODAP further lowered the content in the deprived media to be 32-44% of the controls compared to normal media being 62-74%. The increased motor neuron toxicity in this medium was neutralized by the addition of reduced glutathione ethyl ester or N-acetylcysteine suggesting the importance of the mitochondrial oxidative stress induced by L-ß-ODAP under sulfur amino acid-deficient conditions.

Genetic improvement of grass pea for low neurotoxin (ß-ODAP) content.

Grass pea is a promising crop for adaptation under climate change because of its tolerance to drought, water-logging and salinity, and being almost free from insect-pests and diseases. In spite of such virtues, global area under its cultivation has decreased because of ban on its cultivation in many countries. The ban is imposed due to its association with neurolathyrism, a non-reversible neurological disorder in humans and animals due to presence of neurotoxin, ß-N-oxalyl-L-α,ß-diaminopropionic acid (ß-ODAP) in its seedlings and seeds. The traditional varieties of grass pea contain 0.5-2.5% ß-ODAP. Exploitable genetic variability for ß-ODAP has been observed for development of low ODAP varieties, which along with improved agronomic and detoxification practices can help reduce the risk of lathyrism. Collaborative efforts between ICARDA and NARS have resulted in development of improved varieties such as Wasie in Ethiopia, Ratan, Prateek and Mahateora in India, and BARI Khesari-1 and BARI Khesari-2 in Bangladesh with <0.10% ß-ODAP. Soil application of 15-20 kg ha(-1) zinc sulphate, early planting, and soaking seeds in water have shown significant effects on ß-ODAP. Because of the often cross-pollination nature, the current breeding procedures being followed in grass pea requires paradigm shift in its approach for a possible genetic breakthrough.

Effect of environmental factors on the biosynthesis of the neuro-excitatory amino acid ß-ODAP (ß-N-oxalyl-L-α,ß-diaminopropionic acid) in callus tissue of Lathyrus sativus.

Habituated callus tissues derived from leaf explants of Lathyrus sativus L. (grass pea) were cultured under different environmental conditions such as drought, salinity and deficiency or oversupply of micronutrients. The biosynthesis of the neuro-excitatory ß-ODAP (ß-N-oxalyl-L-α,ß-diaminopropionic acid) was induced by feeding the precursor BIA, (ß-isoxazolin-5-on-2-yl)-alanine, to those calli habituated under different stress conditions. Conversion of BIA into ß-ODAP was reduced by Zn(2+) at different levels of Fe(2+) supplements while excess of Fe(2+) enhanced it at different Zn(2+) levels in the media. The biosynthesis of ß-ODAP was increased by both oversupply and deficiency of Mn(2+) manganese while B(3+) as well as Co(2+) increased it significantly by oversupply. Al(3+) enhanced the conversion of BIA into ß-ODAP significantly in a concentration-dependent way. Cu(2+) also reduced the formation of ß-ODAP when increased in the media. Mo(6+) had no apparent effect. NaCl decreased the conversion of BIA into ß-ODAP proportionately with the increase in salinity. ß-ODAP was increased with increasing mannitol concentration till -0.23MPa while at this osmotic potential created with PEG-20,000 the formation of ß-ODAP is completely inhibited in low toxin calli. These experiments demonstrate the importance of environmental factors, especially micronutrients and salinity, on the biosynthesis of ß-ODAP.

A look at the brighter facets of ß-N-oxalyl-l-α,ß-diaminopropionic acid, homoarginine and the grass pea.

The low incidence of neurolathyrism, its absence in several communities traditionally consuming Lathyrus sativus and the likely benefits of its inclusion as part of a normal diet are reviewed. The metabolism/detoxification of ODAP which is unique to humans may be a crucial factor in this regard. The presence of homoarginine in the pulse which has received scant attention in the past could make this an invaluable pulse since it could contribute to a sustained generation of NO. NO is well recognized for its role in cardiovascular physiology and general well-being and thus a daily dietary intake of homoarginine through small quantities of L. sativus may be of advantage and deserves to be exploited. The detoxification of ODAP in humans could spotlight the pulse further for its non-neurotoxic attributes. Activation of PKC by ODAP adds a new dimension to explore its possible therapeutic potentials in areas such as Alzheimer's disease, hypoxia, and long term potentiation. These novel approaches to both ODAP and homoarginine might entirely change our perception of this poor man's pulse.

The effect of lathyrism on dentin structure of the rat incisors: a morphometric and scanning electron microscopic investigation.

BACKGROUND: The present study was designed to study the effect of beta-aminopropionitrile (beta-APN), present in Lathyrus sativus grass pea consumed in drought prone areas, on dentin of the continuously erupting rat incisors. METHODS: Eighteen adult male rats were used. In the experimental group (18 rats), lathyrism was induced by a once daily subcutaneous administration of beta-APN for 40 days. The maxillary and mandibular incisors were examined ultrastructurally and morphometrically. RESULTS: The mean number of patent tubules, the mean area, perimeter and the area percent of the tubules were analyzed. Ultrastructurally, the dentinal tubules of both coronal and radicular dentin in the lathyritic group were narrower or even obliterated compared with those in the control. The coronal and radicular dentin of the lathyritic group exhibited an irregular lattice of non-mineralized small branching collagen fibrils obliterating the dentinal tubules. The mean number of patent tubules in the control and lathyritic groups revealed an insignificant difference. The mean area of the tubules showed a statistically significant difference in lathyritic radicular dentin (P = 0.0353). The percentage of the total surface area of the dentinal tubules significantly decreased in the radicular dentin of the lathyritic group (P = 0.024). CONCLUSIONS: These findings indicated a deleterious effect of lathyrism on dentin, with a possible negative impact on developing teeth integrity.

Hind-limb paraparesis in a rat model for neurolathyrism associated with apoptosis and an impaired vascular endothelial growth factor system in the spinal cord.

Neurolathyrism is a motor neuron disease characterized by lower limb paraparesis. It is associated with ingestion of a plant excitotoxin, beta-N-oxalyl-L-alphabeta-diaminopropionic acid (L-beta-ODAP), an agonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate-type glutamatergic receptors. Previously, a limited model of neurolathyrism was reported for the rat. To improve upon the model, we stressed rat pups by separation from their mothers, followed by the subcutaneous L-beta-ODAP treatment, resulting in a 4.6-fold higher incidence (14.0-15.6%) of the paraparesis compared with the prior study. The number and size of motor neurons in these rats were decreased only in the lumbar and sacral cord segments, at approximately 13-36 weeks after treatment. Only lumbar and sacral spinal cord tissue revealed pathological insults typical of physical and ischemic spinal cord injury in the surviving motor neurons. In addition, extensive but transient hemorrhage occurred in the ventral spinal cord parenchyma of the rat, and numerous TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive cells were also observed. In parallel, vascular endothelial growth factor receptor (VEGFR)-2 (Flk-1) levels were significantly lowered in the lumbosacral spinal cord of the paraparetic rats compared with their controls, suggesting a failure of the VEGF system to protect neurons against L-beta-ODAP toxicity. We propose, based on these data, a novel pathological process of motor neuron death induced by peripheral L-beta-ODAP. For the first time, we present a model of the early molecular events that occur during chemically induced spinal cord injury, which can potentially be applied to other neurodegenerative disorders.

Ultrastructural and histomorphometric alterations of rat jaw bones after experimental induction of lathyrism.

OBJECTIVE: The aim of this study was to investigate the effect of beta-aminopropionitrile (beta-APN), present in Lathyrus sativus (L. sativus) seeds consumed in drought prone areas, on the maxillary and mandibular bones of rats. DESIGN: Eighteen rats were used; they were divided into experimental group (12 rats) and a control group (6 rats). In the experimental group, lathyrism was induced by a once daily subcutaneous administration of beta-APN at a dose of 5mg in 0.4ml distilled water per 100g of body weight for 40 days. The specimens were examined histologically, histomorphometrically and ultrastructurally. RESULTS: Histopathological examination of lathyritic rats showed that both mandible and maxillae were significantly affected. Irregular bone trabeculae with wide medullary cavities and abundant marrow spaces were observed. Focal resorptive areas lined with osteoclasts were also present. Histomorphometric analysis showed a decrease in the area percentage of bone in lathyritic rats as compared to the control. This decrease was statistically significant only in the mandible (p=0.018). Moreover, a significant increase in the number of osteoclasts (p=0.014, 0.012) and resorptive bays (p=0.013, 0.002) was detected in the maxillae and mandible of the experimental group, respectively. Ultrastructurally, there was a significant difference in the microarchitecture of the collagen fibres in lathyritic rats compared to the control. The collagen fibres in the lathyritic group appeared disorganized, fewer in number and more spaced. CONCLUSIONS: This study provided evidence for lathyritic disturbances in bone architecture. These disturbances are likely to affect mineralization and bone strength as well.